Liquid Biopsy in Hepatocellular Carcinoma: Challenges, Advances, and Clinical Implications.

Hepatocellular carcinoma (HCC) is an aggressive primary liver malignancy often diagnosed at an advanced stage, resulting in a poor prognosis. Accurate risk stratification and early detection of HCC are critical unmet needs for improving outcomes. Several blood-based biomarkers and imaging tests are available for early detection, prediction, and monitoring of HCC.

Novel Biomarkers for Early Detection of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality globally. Most patients present with late diagnosis, leading to poor prognosis. This narrative review explores novel biomarkers for early HCC detection.

Hematin- and Hemin-Induced Spherization and Hemolysis of Human Erythrocytes Are Independent of Extracellular Calcium Concentration.

Pathologies such as malaria, hemorrhagic stroke, sickle cell disease, and thalassemia are characterized by the release of hemoglobin degradation products from damaged RBCs. Hematin (liganded with OH) and hemin (liganded with Cl)-are the oxidized forms of heme with toxic properties due to their hydrophobicity and the presence of redox-active Fe. In the present study, using the original LaSca-TM laser particle analyzer, flow cytometry, and confocal microscopy, we showed that both hematin and hemin induce dose-dependent RBC spherization and hemolysis with ghost formation.

Fat and inflammation: adipocyte-myeloid cell crosstalk in atherosclerosis.

Adipose tissue inflammation has been implicated in various chronic inflammatory diseases and cancer. Perivascular adipose tissue (PVAT) surrounds the aorta as an extra layer and was suggested to contribute to atherosclerosis development. PVAT regulates the function of endothelial and vascular smooth muscle cells in the aorta and represent a reservoir for various immune cells which may participate in aortic inflammation.

Platelets provide robustness of spatial blood coagulation to the variation of initial conditions.

Activated platelets provide phospholipid surface and secrete coagulation factors, enhancing blood clotting. We investigated the role of platelets in the regulation of blood coagulation spatial dynamics. We activated blood clotting with tissue factor-bearing (TF) surface in platelet-rich plasma (PRP) or platelet-free plasma (PFP).

Recent advances in the management of hepatocellular carcinoma.

Liver cancer remains a challenge of global health, being the 4th leading cause of cancer death worldwide. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and is usually precipitated by chronic viral infections (hepatitis B and C), non-alcoholic steatohepatitis, heavy alcohol use, and other factors which may lead to chronic inflammation and cirrhosis of the liver. There have been significant advances in the systemic treatment options for HCC over the past decades, with several approvals of both immune checkpoint inhibitors and tyrosine kinase inhibitors in patients with preserved liver function.

Platelet functional abnormalities in pediatric patients with kaposiform hemangioendothelioma/Kasabach-Merritt phenomenon.

Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor of infancy that is commonly associated with a life-threatening thrombocytopenic condition, Kasabach-Merritt phenomenon (KMP). Platelet CLEC-2, tumor podoplanin interaction is considered the key mechanism of platelet clearance in these patients. Here, we aimed to assess platelet functionality in such patients.

Predictive Biomarkers for Immune-Checkpoint Inhibitor Treatment Response in Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) has one of the highest mortality rates among solid cancers. Late diagnosis and a lack of efficacious treatment options contribute to the dismal prognosis of HCC. Immune checkpoint inhibitor (ICI)-based immunotherapy has presented a new milestone in the treatment of cancer.

The Study of the Association of Polymorphisms in , , , , , and Genes with the Risk and Outcome of Ischemic Stroke in the Russian Population.

To date, there has been great progress in understanding the genetic basis of ischemic stroke (IS); however, several aspects of the condition remain underexplored, including the influence of genetic factors on post-stroke outcomes and the identification of causative loci. We proposed that an analysis of the results obtained from animal models of brain ischemia could be helpful. To this end, we developed a bioinformatic approach for exploring single-nucleotide polymorphisms (SNPs) in human orthologs of rat genes expressed differentially after induced brain ischemia.

[A study of genetic variants in patients with ischemic stroke in human rat gene orthologues].

Objective: To study the associations of nine genetic variants with the risk and dynamics of recovery (outcome) of ischemic stroke (IS) using the developed protocol for the search for genomic markers based on a bioinformatic approach to the study of single nucleotide polymorphisms (SNPs) in human orthologues of rat genes differentially expressed under conditions of induced cerebral ischemia.

Material And Methods: We identified and analyzed nine SNPs in 553 Russians (331 IS patients and 222 controls). The National Institutes of Health Stroke Scale (NIHSS) was used to assess stroke severity.

TET1 and TDG Suppress Inflammatory Response in Intestinal Tumorigenesis: Implications for Colorectal Tumors With the CpG Island Methylator Phenotype.

Background & Aims: Aberrant DNA methylation is frequent in colorectal cancer (CRC), but underlying mechanisms and pathologic consequences are poorly understood.

Methods: We disrupted active DNA demethylation genes Tet1 and/or Tdg from Apc mice and characterized the methylome and transcriptome of colonic adenomas. Data were compared to human colonic adenocarcinomas (COAD) in The Cancer Genome Atlas.

[An overview of risk factors for stroke].

Stroke is a heterogeneous syndrome, and the definition of risk factors, treatment and prevention tactics depends on the specific pathogenesis of the disease. Risk factors for ischemic and hemorrhagic stroke are similar, but at the same time there are significant differences. The concept of stroke triggers is discussed separately.

Immune and inflammatory mechanisms of abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease. Immune-mediated infiltration and a destruction of the aortic wall during AAA development plays significant role in the pathogenesis of this disease. While various immune cells had been found in AAA, the mechanisms of their activation and function are still far from being understood.

IL27 Signaling Serves as an Immunologic Checkpoint for Innate Cytotoxic Cells to Promote Hepatocellular Carcinoma.

Unlabelled: Although inflammatory mechanisms driving hepatocellular carcinoma (HCC) have been proposed, the regulators of anticancer immunity in HCC remain poorly understood. We found that IL27 receptor (IL27R) signaling promotes HCC development in vivo. High IL27EBI3 cytokine or IL27RA expression correlated with poor prognosis for patients with HCC.

Examination of Genetic Variants Revealed from a Rat Model of Brain Ischemia in Patients with Ischemic Stroke: A Pilot Study.

Although there has been great progress in understanding the genetic bases of ischemic stroke (IS), many of its aspects remain underexplored. These include the genetics of outcomes, as well as problems with the identification of real causative loci and their functional annotations. Therefore, analysis of the results obtained from animal models of brain ischemia could be helpful.

Hypercoagulation detected by routine and global laboratory hemostasis assays in patients with infective endocarditis.

Background: Coagulation system is heavily involved into the process of infective endocarditis (IE) vegetation formation and can facilitate further embolization. In this study we aimed to assess the coagulation and platelet state in IE implementing a wide range of standard and global laboratory assays. We also aim to determine whether prothrombotic genetic polymorphisms play any role in embolization and mortality in IE patients.

Epigenetic Plasticity Enables CNS-Trafficking of EBV-infected B Lymphocytes.

Subpopulations of B-lymphocytes traffic to different sites and organs to provide diverse and tissue-specific functions. Here, we provide evidence that epigenetic differences confer a neuroinvasive phenotype. An EBV+ B cell lymphoma cell line (M14) with low frequency trafficking to the CNS was neuroadapted to generate a highly neuroinvasive B-cell population (MUN14).

Act Locally, Act Globally-Microbiota, Barriers, and Cytokines in Atherosclerosis.

Atherosclerosis is a lipid-driven chronic inflammatory disease that is characterized by the formation and progressive growth of atherosclerotic plaques in the wall of arteries. Atherosclerosis is a major predisposing factor for stroke and heart attack. Various immune-mediated mechanisms are implicated in the disease initiation and progression.

Determination of fibrin clot growth and spatial thrombin propagation in the presence of different types of phospholipid surfaces.

In this work, we present a new method-Thrombodynamics-4D-for the assessment of both plasma and platelet contributions to clotting. Thrombodynamics-4D potentially allows for the determination of plasma or platelet disorders and the effects of various drugs on plasma clotting or on platelet procoagulant function. In this assay, clot formation in platelet-rich plasma or platelet-free plasma supplemented with phospholipids is activated with tissue factor immobilized on a surface.

IL-27 receptor-regulated stress myelopoiesis drives abdominal aortic aneurysm development.

Abdominal aortic aneurysm (AAA) is a prevalent life-threatening disease, where aortic wall degradation is mediated by accumulated immune cells. Although cytokines regulate inflammation within the aorta, their contribution to AAA via distant alterations, particularly in the control of hematopoietic stem cell (HSC) differentiation, remains poorly defined. Here we report a pathogenic role for the interleukin-27 receptor (IL-27R) in AAA, as genetic ablation of IL-27R protects mice from the disease development.

An enhanced clot growth rate before in vitro fertilization decreases the probability of pregnancy.

Background: The shift towards hypercoagulation during in vitro fertilization (IVF) can lead to the impairment of embryo implantation and placental blood circulation, which is believed to be a factor in an unsuccessful IVF cycle.

Objectives: To assess coagulation in women with infertility before the start of an IVF cycle and during treatment to reveal the association between coagulation imbalance and IVF outcome.

Patients/methods: We conducted a prospective cohort observational study including 125 participants who underwent fresh IVF cycles.

[Genetic characteristics of stroke].

In the recent years there is a growing interest in identification of additional genetic factors of stroke. A growing body of evidence supports the role of genetic factors in determining the risk of both hemorrhagic and ischemic stroke. The article considers the main genes associated with susceptibility to stroke and genetic polymorphisms associated with the disease.