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Integrative meta-analysis identifies microRNA-regulated networks in infantile hemangioma.

BackgroundHemangioma is a common benign tumor in the childhood; however our knowledge about the molecular mechanisms of hemangioma development and progression are still limited. Currently, microRNAs (miRNAs) have been shown as gene expression regulators with an important role in disease pathogenesis. Our goals were to identify miRNA-mRNA expression networks associated with infantile hemangioma.MethodsWe performed a meta-analysis of previously published gene expression datasets including 98 hemangioma samples. Deregulated genes were further used to identify microRNAs as potential regulators of

Improving Kidney Disease Care: One Giant Leap for Nephrology.

Nephrology is an ever-evolving field of medicine. The importance of such a discipline is related to the high clinical impact of kidney disease. In fact, abnormalities of kidney function and/or structure are common in the general population, reaching an overall prevalence of about 10%. More importantly, the onset of kidney damage is related to a strikingly high risk of cardiovascular events, mortality, and progression to kidney failure which, in turn, compromises quality and duration of life. Attempts to comprehend the pathogenesis and molecular mechanisms involved in kidney disease occurrence

Pulmonary hypertension in patients with multiple myeloma: A comprehensive review.

Multiple myeloma (MM) is a common hematological malignancy resulting from clonal proliferation of plasma cells and is defined by criteria set forth by the international myeloma working group. Pulmonary hypertension (PH) is defined by an elevated mean pulmonary artery pressure >20 mmHg measured during right heart catheterization. Echocardiography-diagnosed PH is relatively common in patients with MM and has been associated with increased mortality, morbidity, and poor stem cell transplant outcomes. PH in patients with MM (PH-MM) is usually multifactorial in origin. MM disease-specific factors,

A review of sitaxsentan sodium in patients with pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a life threatening, progressive condition which eventually leads to fatal right heart failure. Endothelin-1 (ET-1), a potent vasoconstrictor peptide, is increased in the pulmonary arteries of patients with pulmonary hypertension. Endothelin-1 acts through the stimulation of 2 subtypes of receptors (endothelin receptor subtypes A [ET(A)] and B [ET(B)]). In PAH patients, ETRAs block the deleterious vasoconstrictor effects of ET-1, and ETRA treatment in PAH patients has been shown to be safe and efficacious. Sitaxsentan is an orally active, highly ET(A) se

Immune Dysfunction in Uremia 2020.

Cardiovascular disease and infections are major causes for the high incidence of morbidity and mortality of patients with chronic kidney disease. Both complications are directly or indirectly associated with disturbed functions or altered apoptotic rates of polymorphonuclear leukocytes, monocytes, lymphocytes, and dendritic cells. Normal responses of immune cells can be reduced, leading to infectious diseases or pre-activated/primed, giving rise to inflammation and subsequently to cardiovascular disease. This review summarizes the impact of kidney dysfunction on the immune system. Renal failur

Molecular mechanisms and clinical management of cancer bone metastasis.

As one of the most common metastatic sites of malignancies, bone has a unique microenvironment that allows metastatic tumor cells to grow and flourish. The fenestrated capillaries in the bone, bone matrix, and bone cells, including osteoblasts and osteoclasts, together maintain the homeostasis of the bone microenvironment. In contrast, tumor-derived factors act on bone components, leading to subsequent bone resorption or excessive bone formation. The various pathways involved also provide multiple targets for therapeutic strategies against bone metastases. In this review, we summarize the curr

Ixazomib for Desensitization (IXADES) in Highly Sensitized Kidney Transplant Candidates: A Phase II Clinical Trial.

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Treatment of Cancer Pain by Targeting Cytokines.

Inflammation is one of the most important causes of the majority of cancer symptoms, including pain, fatigue, cachexia, and anorexia. Cancer pain affects 17 million people worldwide and can be caused by different mediators which act in primary efferent neurons directly or indirectly. Cytokines can be aberrantly produced by cancer and immune system cells and are of particular relevance in pain. Currently, there are very few strategies to control the release of cytokines that seems to be related to cancer pain. Nevertheless, in some cases, targeted drugs are available and in use for other diseas

Global first-in-class drugs approved in 2023-2024: Breakthroughs and insights.

First-in-class (FIC) drugs are considered the main drivers of new drug discovery and have novel targets and mechanisms. The proportion of FIC drugs among new drugs provides fundamental guidance for both academic and pharmaceutical research. From a global perspective, 81 FIC drugs were approved in 2023 and 2024. Among them, small-molecule drugs account for a greater percentage (51.9%), illustrating the discovery of new chemical entities. Macromolecule drugs (48.1%), which mainly consist of antibody analogs, represent a growing trend as new biotechnology techniques have emerged. In terms of FIC

IgA Vasculitis (Henoch-Schönlein Purpura): An Update on Treatment.

Objective: IgA vasculitis (IgAV), previously named as Henoch-Schönlein purpura, is the most frequent systemic vasculitis in children. In adults, IgAV is less common although it is associated with more severe disease. In fact, the frequency of glomerulonephritis (referred to as IgAV nephritis) in adults is higher than in children and tends to present more severely, with around 10-30% of those affected eventually progressing to end-stage renal disease. In this review, we describe the pathophysiology, main clinical features, diagnosis of the disease, and latest clinical data regarding IgAV therap

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… Endothelin Receptor Antagonists Endothelins (ETs) are potent endogenous pressor agents comprising a family of three peptides, each one consisting of 21 amino acids: endothelin-1 (ET1), endothelin-2 (ET2), and endothelin-3 (ET3). …

Systemic Sclerosis: From Pathophysiology to Novel Therapeutic Approaches.

Systemic sclerosis (SSc) is a systemic, immune-mediated chronic disorder characterized by small vessel alterations and progressive fibrosis of the skin and internal organs. The combination of a predisposing genetic background and triggering factors that causes a persistent activation of immune system at microvascular and tissue level is thought to be the pathogenetic driver of SSc. Endothelial alterations with subsequent myofibroblast activation, excessive extracellular matrix (ECM) deposition, and unrestrained tissue fibrosis are the pathogenetic steps responsible for the clinical manifestati

Novel Treatment Paradigms: Primary IgA Nephropathy.

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Approximately 30% to 45% of patients progress to kidney failure (KF) within 20 to 25 years of diagnosis, and there has long been a lack of effective treatments. The therapeutic landscape in IgAN is rapidly evolving, driven in large part by the acceptance of the surrogate clinical trial end point of proteinuria reduction by regulatory authorities for the accelerated approval of new therapies. Two drugs, targeted release formulation (TRF)-budesonide (nefecon) and sparsentan, have recently been approved under this sch

Cancer metastasis to the bone: Mechanisms and animal models (Review).

The majority of cancer-related deaths result from tumor metastasis, with bone metastasis occurring in almost all types of malignant tumors. Understanding the mechanism by which tumors metastasize to bone is critical for the identification of novel therapeutic targets. A large amount of research has been carried out using animal models, and these models have been crucial in advancing the fundamental understanding of cancer. However, current models are limited; although they can mimic specific stages of the metastatic process, they are not able to replicate the entire process from tumorigenesis

Role of Ceramide from Glycosphingolipids and Its Metabolites in Immunological and Inflammatory Responses in Humans.

Glycosphingolipids (GSLs) are composed of hydrophobic ceramide and hydrophilic sugar chains. GSLs cluster to form membrane microdomains (lipid rafts) on plasma membranes, along with several kinds of transducer molecules, including Src family kinases and small G proteins. However, GSL-mediated biological functions remain unclear. Lactosylceramide (LacCer, CDw17) is highly expressed on the plasma membranes of human phagocytes and mediates several immunological and inflammatory reactions, including phagocytosis, chemotaxis, and superoxide generation. LacCer forms membrane microdomains with the Sr

Emerging Modes of Treatment of IgA Nephropathy.

IgA nephropathy is the most common primary glomerulonephritis with potentially serious outcome leading to end stage renal disease in 30 to 50% of patients within 20 to 30 years. Renal biopsy, which might be associated with risks of complications (bleeding and others), still remains the only reliable diagnostic tool for IgA nephropathy. Therefore, the search for non-invasive diagnostic and prognostic markers for detection of subclinical types of IgA nephropathy, evaluation of disease activity, and assessment of treatment effectiveness, is of utmost importance. In this review, we summarize treat

Reciprocal interactions between osteoclasts and nociceptive sensory neurons in bone cancer pain.

Many common cancers such as breast, prostate, and lung cancer metastasize to bones at advanced stages, producing severe pain and functional impairment. At present, the current pharmacotherapies available for bone cancer pain are insufficient to provide safe and efficacious pain relief. In this narrative review, we discuss the mechanisms used by cancer cells within the bone tumor microenvironment (TME) to drive bone cancer pain. In particular, we highlight the reciprocal interactions between tumor cells, bone-resorbing osteoclasts, and pain-sensing sensory neurons (nociceptors), which drive bon

Tumor metastasis to bone.

Establishment of skeletal metastasis involves bidirectional interactions between the tumor cell and the cellular elements in the bone microenvironment. A better understanding of the pathophysiology of bone metastasis will be critical in developing the means to prevent bone metastasis or inhibit its progression. The receptor activator of nuclear factor-kappaB (RANK)/RANK ligand pathway has emerged as the key pathway regulating osteolysis in skeletal metastasis. A number of candidate factors, including the Wnt (wingless int) proteins, endothelin-1, and bone morphogenetic proteins, have been impl

Role of the Bone Microenvironment in the Development of Painful Complications of Skeletal Metastases.

Cancer-induced bone pain (CIBP) is the most common and painful complication in patients with bone metastases. It causes a significant reduction in patient quality of life. Available analgesic treatments for CIBP, such as opioids that target the central nervous system, come with severe side effects as well as the risk of abuse and addiction. Therefore, alternative treatments for CIBP are desperately needed. Although the exact mechanisms of CIBP have not been fully elucidated, recent studies using preclinical models have demonstrated the role of the bone marrow microenvironment (e.g., osteoclast

Resveratrol and Curcumin for Chagas Disease Treatment-A Systematic Review.

Chagas disease (CD) is a neglected protozoan infection caused by Trypanosoma cruzi, which affects about 7 million people worldwide. There are two available drugs in therapeutics, however, they lack effectiveness for the chronic stage-characterized mainly by cardiac (i.e., cardiomyopathy) and digestive manifestations (i.e., megaesophagus, megacolon). Due to the involvement of the immuno-inflammatory pathways in the disease's progress, compounds exhibiting antioxidant and anti-inflammatory activity seem to be effective for controlling some clinical manifestations, mainly in the chronic phase. Re

Targeted therapy in the treatment of malignant gliomas.

Malignant gliomas are invasive tumors with the potential to progress through current available therapies. These tumors are characterized by a number of abnormalities in molecular signaling that play roles in tumorigenesis, spread, and survival. These pathways are being actively investigated in both the pre-clinical and clinical settings as potential targets in the treatment of malignant gliomas. We will review many of the therapies that target the cancer cell, including the epidermal growth factor receptor, mammalian target of rapamycin, histone deacetylase, and farnesyl transferase. In additi

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… Spinella F Rosano S DiCastor V Endothelin-1 and endothelin-3 promote invasive behavior via hypoxia-inducible factor-1alpha in human melanoma cells Cancer Res 2007 67 4 1725 1734 17308114 10.1158/0008-5472.CAN-06-2606 90. …