Liquid biopsy in organ damage: introduction of an innovative tool for assessing the complexity of blunt splenic injury.

Liquid biomarkers are essential in trauma cases and critical care and offer valuable insights into the extent of injury, prognostic predictions, and treatment guidance. They can help assess the severity of organ damage (OD), assist in treatment decisions and forecast patient outcomes. Notably, small extracellular vesicles, particularly those involved in splenic trauma, have been overlooked.

Regulatory T Cell Inhibition by P60 Combined with Adenoviral AFP Transduced Dendritic Cells for Immunotherapy of Hepatocellular Carcinoma.

Background & Aims: Vaccination with tumor-associated antigen-pulsed dendritic cells leads to specific T-cell response against hepatocellular carcinoma. However, clinical response has been shown to be limited. High regulatory T-cell count is associated with poor prognosis and seems to mediate immune tolerance in hepatocellular carcinoma.

Current view of liver cancer cell-of-origin and proposed mechanisms precluding its proper determination.

Hepatocellular carcinoma and intrahepatic cholangiocarcinoma are devastating primary liver cancers with increasing prevalence in many parts of the world. Despite intense investigation, many aspects of their biology are still largely obscure. For example, numerous studies have tackled the question of the cell-of-origin of primary liver cancers using different experimental approaches; they have not, however, provided a clear and undisputed answer.

Small Extracellular Vesicles and Their Involvement in Cancer Resistance: An Up-to-Date Review.

In recent years, tremendous progress has been made in understanding the roles of extracellular vesicles (EVs) in cancer. Thanks to advancements in molecular biology, it has been found that the fraction of EVs called exosomes or small EVs (sEVs) modulates the sensitivity of cancer cells to chemotherapeutic agents by delivering molecularly active non-coding RNAs (ncRNAs). An in-depth analysis shows that two main molecular mechanisms are involved in exosomal modified chemoresistance: (1) translational repression of anti-oncogenes by exosomal microRNAs (miRs) and (2) lack of translational repression of oncogenes by sponging of miRs through long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs).

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.

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.

Are there different patterns of detrusor overactivity which are clinically relevant? ICI-RS 2018.

Introduction: Different patterns of detrusor overactivity (DO) have been described and included in several standardization terminology documents. However, it is unclear if these different patterns have any clinical significance.

Methods: This is a report of the proceedings of Proposal 3: "Are there different patterns of detrusor overactivity which are clinically relevant?" from the annual International Consultation on Incontinence-Research Society (ICIRS) meeting, which took place from 14 to 16 June 2018, in Bristol, UK.

Fibroblastic reticular cells enhance T cell metabolism and survival via epigenetic remodeling.

Lymph node fibroblastic reticular cells (FRCs) respond to signals from activated T cells by releasing nitric oxide, which inhibits T cell proliferation and restricts the size of the expanding T cell pool. Whether interactions with FRCs also support the function or differentiation of activated CD8 T cells is not known. Here we report that encounters with FRCs enhanced cytokine production and remodeled chromatin accessibility in newly activated CD8 T cells via interleukin-6.

Extracellular Vesicles in Liver Diseases: Meeting Report from the International Liver Congress 2018.

Extracellular vesicles (EVs) are small and heterogeneous membrane-bound structures released by cells and found in all biological fluids. They are effective intercellular communicators, acting on a number of close and/or distant target cells. EV cargo may reflect the cell of origin as well as the specific stress that induces their formation and release.

Extracellular Vesicles in Liver Diseases: Diagnostic, Prognostic, and Therapeutic Application.

Extracellular vesicles, comprising exosomes, microvesicles, and apoptotic bodies, represent an emerging field in disease diagnostics and prognosis. They can be isolated from peripheral blood of patients as well as from other body fluids and can therefore be considered a minimally invasive liquid biopsy screening tool. Especially their surface antigen composition can reveal information about disease backgrounds.

Large Extracellular Vesicles: Have We Found the Holy Grail of Inflammation?

The terms microparticles (MPs) and microvesicles (MVs) refer to large extracellular vesicles (EVs) generated from a broad spectrum of cells upon its activation or death by apoptosis. The unique surface antigens of MPs/MVs allow for the identification of their cellular origin as well as its functional characterization. Two basic aspects of MP/MV functions in physiology and pathological conditions are widely considered.

Novel therapeutic approaches in primary hyperoxaluria.

: Currently, three types of primary hyperoxaluria (PH I-III) are known, all based on different gene-mutations affecting the glyoxylate metabolism in the liver. Disease hallmark is an increased endogenous oxalate production and thus massively elevated urinary excretion of oxalate and other type-specific metabolites. Hyperoxaluria induces the formation of calcium-oxalate kidney stones and/or nephrocalcinosis.

Targeting kidney inflammation as a new therapy for primary hyperoxaluria?

The primary hyperoxalurias (PHs) are inborn errors of glyoxylate metabolism characterized by endogenous oxalate overproduction in the liver, and thus elevated urinary oxalate excretion. The urinary calcium-oxalate (CaOx) supersaturation and the continuous renal accumulation of insoluble CaOx crystals yield a progressive decline in renal function that often ends with renal failure. In PH Type 1 (AGXT mutated), the most frequent and severe condition, patients typically progress to end-stage renal disease (ESRD); in PH Type 2 (GRHPR mutated), 20% of patients develop ESRD, while only one patient with PH Type 3 (HOGA1 mutated) has been reported with ESRD so far.

An NLRP3-specific inflammasome inhibitor attenuates crystal-induced kidney fibrosis in mice.

Intrarenal crystal formation activates the Nlrp3 inflammasome in myeloid cells and triggers a profound inflammatory response. Here, we studied whether a specific inhibitor of the Nlrp3 inflammasome, CP-456,773, can prevent kidney fibrosis in a murine model of crystal nephropathy induced by diets rich in oxalate or adenine. Inflammasome activation in renal dendritic cells and the resulting interleukin (IL)-1β and IL-18 production were markedly reduced by CP-456,773 treatment both ex vivo and in vivo.