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Topic Review
FXIII in Acute VTE
Coagulation factor XIII (FXIII) is converted by thrombin into its active form, FXIIIa, which cross-links fibrin fibers, rendering clots more stable and resistant to degradation. FXIII affects fibrin clot structure and function leading to a more prothrombotic phenotype with denser networks, char-acterizing patients at risk of venous thromboembolism (VTE). Mechanisms regulating FXIII acti-vation and its impact on fibrin structure in patients with acute VTE encompassing pulmonary embolism (PE) or deep vein thrombosis (DVT) are poorly elucidated. Reduced circulating FXIII levels in acute PE were reported over 20 years ago. Similar observations indicating decreased FXIII plasma activity and antigen levels have been made in acute PE and DVT with their subse-quent increase after several weeks since the index event. Plasma fibrin clot proteome analysis con-firms that clot-bound FXIII amounts associated with plasma FXIII activity are decreased in acute VTE. Reduced FXIII activity has been associated with impaired clot permeability and hypofibri-nolysis in acute PE.
  • 743
  • 01 Mar 2021
Topic Review
Tumor Immune Microenvironment
Since the efficacy of ICIs depends on the tumor immune microenvironment, it is necessary to elucidate the immune environment of HCC to select appropriate ICIs. 
  • 743
  • 07 Jun 2021
Topic Review
Inflammasome-Mediated Cytokines
Liver cancer is one of the most lethal malignancies and is commonly diagnosed as hepatocellular carcinoma (HCC), a tumor type that affects about 90% of patients. Non-alcoholic steatohepatitis (NASH) and obesity are both risk factors for this disease. HCC initiation and progression are deeply linked with changes in the hepatic microenvironment, with cytokines playing key roles. The understanding of the pathogenic pathways that connect these disorders to liver cancer remains poor.
  • 743
  • 07 Feb 2023
Topic Review
SHED-Dependent Oncogenic Signaling of the PEAK3 Pseudo-Kinase
The human kinome is composed of about 50 pseudo-kinases with unclear function, because they are predicted to be catalytically inactive; however, they are shown to play an important role in cancer, similar to active kinases. Understanding how these pseudo-kinases promote tumor formation despite their catalytic inactivity is a great challenge, which may lead to innovative anti-cancer therapies. The PEAK1 and 2 pseudo-kinases have emerged as important components of the protein tyrosine kinase pathway implicated in cancer progression. They can signal using a scaffolding mechanism via a conserved split helical dimerization (SHED) module.
  • 742
  • 11 Jan 2022
Topic Review
Extracellular Vesicles and Their Relationship with the Uremia
Extracellular vesicles (EVs) have been widely investigated for their role in intercellular communication and as potential biomarkers; and could be a promising tool to improve the quality of care in kidney disease patients. Our research group previously demonstrated that the EVs can be related to endothelial dysfunction and are formed when UTs are in contact with the endothelial monolayer. Thus, this review addresses the relationship between these vesicles, cardiorenal syndrome, and uremia.
  • 741
  • 26 Nov 2021
Topic Review
Prothrombotic Phenotype in COVID-19
COVID-19 infection is associated with a broad spectrum of presentations, but alveolar capillary microthrombi have been described as a common finding in COVID-19 patients, appearing as a consequence of a severe endothelial injury with endothelial cell membrane disruption. These observations clearly point to the identification of a COVID-19-associated coagulopathy, which may contribute to thrombosis, multi-organ damage, and cause of severity and fatality. One significant finding that emerges in prothrombotic abnormalities observed in COVID-19 patients is that the coagulation alterations are mainly mediated by the activation of platelets and intrinsically related to viral-mediated endothelial inflammation. Beyond the well-known role in hemostasis, the ability of platelets to also release various potent cytokines and chemokines has elevated these small cells from simple cell fragments to crucial modulators in the blood, including their inflammatory functions, that have a large influence on the immune response during infectious disease. Indeed, platelets are involved in the pathogenesis of acute lung injury also by promoting NET formation and affecting vascular permeability. Specifically, the deposition by activated platelets of the chemokine platelet factor 4 at sites of inflammation promotes adhesion of neutrophils on endothelial cells and thrombogenesis, and it seems deeply involved in the phenomenon of vaccine-induced thrombocytopenia and thrombosis. Importantly, the hyperactivated platelet phenotype along with evidence of cytokine storm, high levels of P-selectin, D-dimer, and, on the other hand, decreased levels of fibrinogen, von Willebrand factor, and thrombocytopenia may be considered suitable biomarkers that distinguish the late stage of COVID-19 progression in critically ill patients. 
  • 741
  • 30 Dec 2021
Topic Review
Amyloid-like Aggregation as Common Cause of Diseases
Amyloids were conventionally referred to as extracellular and intracellular accumulation of Aβ42 peptide, which causes the formation of plaques and neurofibrillary tangles inside the brain leading to the pathogenesis in Alzheimer’s disease. Subsequently, amyloid-like deposition was found in the etiology of prion diseases, Parkinson’s disease, type II diabetes, and cancer, which was attributed to the aggregation of prion protein, α-Synuclein, islet amyloid polypeptide protein, and p53 protein, respectively. Hence, traditionally amyloids were considered aggregates formed exclusively by proteins or peptides. However, since the last decade, it has been discovered that other metabolites, like single amino acids, nucleobases, lipids, glucose derivatives, etc., have a propensity to form amyloid-like toxic assemblies. Several studies suggest direct implications of these metabolite assemblies in the patho-physiology of various inborn errors of metabolisms like phenylketonuria, tyrosinemia, cystinuria, and Gaucher’s disease, to name a few. 
  • 741
  • 13 Jul 2023
Topic Review
Fabry Cardiomyopathy
Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the galactosidase A (GLA) gene that result in deficient galactosidase A enzyme and subsequent accumulation of glycosphingolipids throughout the body. The result is a multi-system disorder characterized by cutaneous, corneal, cardiac, renal, and neurological manifestations. Increased left ventricular wall thickness represents the predominant cardiac manifestation of FD. As the disease progresses, patients may develop arrhythmias, advanced conduction abnormalities, and heart failure. 
  • 740
  • 22 Jun 2021
Topic Review
Quadruplex Ligands in Cancer Therapy
Nucleic acids can adopt alternative secondary conformations including four-stranded structures known as quadruplexes. To date, quadruplexes have been demonstrated to exist both in human chromatin DNA and RNA. Quadruplexes are associated with key biological processes ranging from transcription and translation of several oncogenes and tumor suppressors to telomeres maintenance and genome instability. In this context, quadruplexes have prompted investigations on their possible role in cancer biology and the evaluation of small-molecule ligands as potential therapeutic agents.
  • 739
  • 19 Jul 2021
Topic Review
Mast Cells in Cardiac Remodeling
In response to various stressors, cardiac chambers undergo structural remodeling. Long-term exposure of the right ventricle (RV) to pressure or volume overload leads to its maladaptive remodeling, associated with RV failure and increased mortality. While left ventricular adverse remodeling is well understood and therapeutic options are available or emerging, RV remodeling remains underexplored, and no specific therapies are currently available. 
  • 739
  • 28 Feb 2024
Topic Review
Nectria pseudotrichia Associated with Camellia Canker Disease
Camellia japonica is a native tree species with high economic value that is widely cultivated in southern China. Canker disease was a serious threat to the growth of camellia trees. However, the pathogen causing this disease in China has not yet been reported. 
  • 738
  • 01 Aug 2023
Topic Review
Ceruloplasmin Deamidation in Neurodegeneration
Neurodegenerative disorders can induce modifications of several proteins; one of which is ceruloplasmin (Cp), a ferroxidase enzyme found modified in the cerebrospinal fluid (CSF) of neurodegenerative diseases patients.
  • 737
  • 23 Feb 2021
Topic Review
Biomarker of Age-Related Macular Degeneration
According to the epigenetic hypothesis, a number of environmental stimuli can, through miRNAs, influence the phenotype of an organism. Discovering the phenomena of miRNAs regulation enables understanding of AMD pathomechanism. The characteristic profile of changes in miRNA expression levels may be helpful in early diagnosis. However, the role of miRNAs as biomarkers is not yet clear.  
  • 737
  • 23 Aug 2021
Topic Review
Sex-Specific Medicine in Human Physiopathology
A prodigious increment of scientific evidence in both preclinical and clinical studies is narrowing a major gap in knowledge regarding sex-specific biological responses observed in numerous branches of clinical practices. Some paradigmatic examples include neurodegenerative and mental disorders, immune-related disorders such as pathogenic infections and autoimmune diseases, oncologic conditions, and cardiovascular morbidities. The male-to-female proportion in a population is expressed as sex ratio and varies eminently with respect to the pathophysiology, natural history, incidence, prevalence, and mortality rates.
  • 730
  • 24 Mar 2022
Topic Review
Implications of CD47 in Tumor Biology
Cancer is a leading cause of death worldwide. Despite treatment advances, high rates of tumor recurrence emphasize the need for new therapeutic strategies. Tumors often acquire mechanisms to avoid detection by the immune system, allowing them to develop and metastasize. Immunotherapy is a type of treatment designed to overcome these mechanisms by reactivating the immune system to eliminate tumors. CD47 is a cell surface protein and marker of “self” expressed on cells throughout the body and prevents them from being “eaten” by cells of the immune system. CD47 has also been described to have immune-independent functions in normal and malignant cells which could contribute to tumor growth and progression.
  • 728
  • 10 Nov 2023
Topic Review
Extracellular Vesicles, Exercise and Depression
It sheds light on the triad "physical exercise-extracellular vesicles-depression" and suggests new avenues in this novel emerging field.
  • 727
  • 22 Sep 2021
Topic Review
Adverse Events of Biological Drugs
The aim of this study is to know the biological therapy drugs that are related to adverse events, what dental treatments are associated with the appearance of these events, their severity, and how they are resolved.
  • 727
  • 08 Jun 2021
Topic Review
CARD9 Deficiency Increases Hippocampal Injury
Caspase recruitment domain containing family member 9 (CARD9) is an adaptor protein that delivers signals through immunoreceptor tyrosine-based activation motif (ITAM)-coupled or hemITAM-bearing C-type lectin receptors (CLRs), including Dectin-1, Dectin-2 and Mincle. The Syk/CARD9 signaling axis triggered by engagement of Dectin-1, Dectin-2, or Mincle was recently shown to contribute to early innate responses against certain viruses, but also against bacteria, parasites and fungal pathogens. Viruses, such as vesicular stomatitis virus (VSV), encephalomyocarditis virus and vaccinia virus, which are sensed by the cytosolic nucleic sensors RIG-I, MDA5 and RAD50, respectively, were shown to engage CARD9 for inflammatory cytokine production. However, in contrast to the predominant protective effect observed in fungal diseases, CARD9 signaling seems to play an ambivalent role in viral disorders, with beneficial effects by promoting antiviral responses (e.g., VSV, vaccinia virus) and detrimental effects by triggering virus-induced immunopathology (e.g., influenza virus, coxsackievirus) being described in animal experiments.
  • 724
  • 18 Nov 2021
Topic Review
Intratumoral Platelets
The tumor microenvironment (TME) has gained considerable interest because of its decisive impact on cancer progression, response to treatment, and disease recurrence. The TME can favor the proliferation, dissemination, and immune evasion of cancer cells. Likewise, there is accumulating evidence that intratumoral platelets could favor the development and aggressiveness of solid tumors, notably by influencing tumor cell phenotype and shaping the vascular and immune TME components. Yet, in contrast to other tumor-associated cell types like macrophages and fibroblasts, platelets are still often overlooked as components of the TME. This might be due, in part, to a deficit in investigating and reporting the presence of platelets in the TME and its relationships with cancer characteristics. 
  • 721
  • 07 May 2022
Topic Review
Extracellular Vesicles in Airway Homeostasis and Pathophysiology
The epithelial–mesenchymal trophic unit (EMTU) is a morphofunctional entity involved in the maintenance of the homeostasis of airways as well as in the pathogenesis of several diseases, including asthma and chronic obstructive pulmonary disease (COPD). The “muco-microbiotic layer” (MML) is the innermost layer of airways made by microbiota elements (bacteria, viruses, archaea and fungi) and the surrounding mucous matrix. The MML homeostasis is also crucial for maintaining the healthy status of organs and its alteration is at the basis of airway disorders. Nanovesicles produced by EMTU and MML elements are probably the most important tool of communication among the different cell types, including inflammatory ones. 
  • 719
  • 08 Nov 2021
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