Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality in industrialized countries. Coronary artery disease (CAD) represents the most prevalent form of cardiovascular disease and remains a leading cause of morbidity, mortality, and long-term disability worldwide. Therefore, the identification of early biomarkers and clarification of the mechanism of action of pharmacological adjuvants is urgently needed.
View Article and Find Full Text PDFGram-negative bacterium , which is increasingly prevalent in elderly individuals, is associated with cognitive decline and gut-brain axis dysfunction. Here, we present a comprehensive structural characterization of lipopolysaccharide (LPS), a key modulator of immune recognition and the main component of its outer membrane. Using a multidisciplinary approach combining chemical, spectroscopic, spectrometric, biophysical and computational methods, we unveil a unique O-antigen characterized by a trisaccharide repeating unit containing rhamnose and glucosamine, displaying nonstoichiometric O-acetylation and a terminal methylated rhamnose capping the saccharide chain.
View Article and Find Full Text PDFHigh mobility group box 1 (HMGB1) is a non‑histone protein widely expressed in the nucleus of mammalian cells, and it can be released by both immune and tumor cells. In the extracellular context HMGB1 can act as a proinflammatory mediator and boosting cancer progression. High HMGB1 mRNA expression levels are usually observed in various malignant diseases, including breast cancer (BC).
View Article and Find Full Text PDFIntroduction: Prostate cancer (PC) is a leading cause of cancer-related deaths among men, often progressing to castration-resistant prostate cancer (CRPC) after androgen deprivation therapy (ADT). A subset of CRPC evolves into treatment-emergent neuroendocrine prostate cancer (t-NEPC), an aggressive form characterized by poor prognosis. Currently, there is no reliable biomarker for early detection of t-NEPC.
View Article and Find Full Text PDFCancer participates in the immune response by releasing several factors, such as cytokines and chemokines, which can alter the ability of the immune system to identify and eradicate cancer. Notably, the role of thymic stromal lymphopoietin (TSLP) in breast cancer (BC) is currently controversial and unclear. The present study characterized the role of TSLP in BC and its interaction with peripheral blood mononuclear cells, focusing on the CD14CD16 monocyte population via the secretome released by BC cells.
View Article and Find Full Text PDFThyroid cancer (TC) is the most prevalent endocrine malignancy, and is categorized into well-differentiated and aggressive anaplastic types. Novel therapeutic modalities are needed for TC. Nanomedicine is a promising strategy for the development of precision medicine.
View Article and Find Full Text PDFAims: The last released European guidelines on the management of heart failure (HF) recommend in patients with chronic HF with reduced ejection fraction (HFrEF) a pharmacological approach based on four fundamental drugs to be rapidly implemented and then uptitrated to modify disease progression. The aim of the Optimization of Therapy in the Italian Management of Heart Failure (OPTIMA-HF) registry is to collect data on chronic HF outpatients in different settings of care. In the present analysis, we report the first analysis of the OPTIMA-HF registry, focusing on the real-life use of guideline-directed medical therapy in patients affected by HFrEF.
View Article and Find Full Text PDFLAG3 plays a regulatory role in immunity and emerged as an inhibitory immune checkpoint molecule comparable to PD-L1 and CTLA-4 and a potential target for enhancing anti-cancer immune responses. We generated 3D cancer cultures as a model to identify novel molecular biomarkers for the selection of patients suitable for α-LAG3 treatment and simultaneously the possibility to perform an early diagnosis due to its higher presence in breast cancer, also to achieve a theragnostic approach. Our data confirm the extreme dysregulation of LAG3 in breast cancer with significantly higher expression in tumor tissue specimens, compared to non-cancerous tissue controls.
View Article and Find Full Text PDFDiagnostics (Basel)
August 2024
Craniosynostoses (CRS) are caused by the premature fusion of one or more cranial sutures, with isolated nonsyndromic CRS accounting for most of the clinical manifestations. Such premature suture fusion impacts both skull and brain morphology and involves regions far beyond the immediate area of fusion. The combined use of different neuroimaging tools allows for an accurate depiction of the most prominent clinical-radiological features in nonsyndromic CRS but can also contribute to a deeper investigation of more subtle alterations in the underlying nervous tissue organization that may impact normal brain development.
View Article and Find Full Text PDFBiobanks are valuable service units that ensure the usage of high-quality biological samples. They contribute to translational research, and their support may improve future therapeutic approaches. They store biological samples that can be used to examine circulation biomarkers, immune cells, and immunohistochemistry aspects of illnesses and further in-depth examinations using NGS techniques.
View Article and Find Full Text PDFPurpose: Craniosynostosis (CRS) is a rare congenital cranial malformation in which 1 or more cranial or facial sutures are fused in utero or rapidly fused in early infancy. The cranial sutures separate the skull bone plates and enable rapid growth of the skull in the first 2 years of life, in which growth is largely dictated by growth of the brain. CRS is a rare disease that occurs in 1 in 2100 to 1 in 2500 births and may be either nonsyndromic (also referred to as isolated) or syndromic.
View Article and Find Full Text PDFMembers of the KCTD protein family play key roles in fundamental physio-pathological processes including cancer, neurodevelopmental/neuropsychiatric, and genetic diseases. Here, we report the crystal structure of the KCTD1 P20S mutant, which causes the scalp-ear-nipple syndrome, and molecular dynamics (MD) data on the wild-type protein. Surprisingly, the structure unravels that the N-terminal region, which precedes the BTB domain (preBTB) and bears the disease-associated mutation, adopts a folded polyproline II (PPII) state.
View Article and Find Full Text PDFPediatric B-cell acute lymphoblastic leukemia (B-ALL) is a serious disease for which a better understanding of prognostic factors and new therapeutic targets is needed. Circular RNAs (circRNAs) are promising markers due to their stability and differential expression patterns in various diseases. However, their role in pediatric B-ALL patients, particularly in risk stratification and relapse prediction, remains poorly understood.
View Article and Find Full Text PDFBackground: Paediatric acute B-cell lymphoblastic leukaemia is the most common cancer of the paediatric age. Although the advancement of scientific and technological knowledge has ensured a huge step forward in the management of this disease, there are 15%-20% cases of recurrence leading to serious complications for the patient and sometimes even death. It is therefore necessary to identify new and increasingly personalised biomarkers capable of predicting the degree of risk of B-ALL in order to allow the correct management of paediatric leukaemia patients.
View Article and Find Full Text PDFDexamethasone (DEX) is a synthetic analogue of cortisol commonly used for the treatment of different pathological conditions, comprising cancer, ocular disorders, and COVID-19 infection. Its clinical use is hampered by the low solubility and severe side effects due to its systemic administration. The capability of peptide-based nanosystems, like hydrogels (HGs) and nanogels (NGs), to serve as vehicles for the passive targeting of active pharmaceutical ingredients and the selective internalization into leukemic cells has here been demonstrated.
View Article and Find Full Text PDFBreast cancer is one of the most spread and monitored pathologies in high-income countries. After breast biopsy, histological tissue is stored in paraffin, sectioned and mounted. Conventional inspection of tissue slides under benchtop light microscopes involves paraffin removal and staining, typically with H&E.
View Article and Find Full Text PDFKCTD ((K)potassium Channel Tetramerization Domain-containing) proteins constitute an emerging class of proteins involved in fundamental physio-pathological processes. In these proteins, the BTB domain, which represents the defining element of the family, may have the dual role of promoting oligomerization and favoring functionally important partnerships with different interactors. Here, by exploiting the potential of recently developed methodologies for protein structure prediction, we report a comprehensive analysis of the interactions of all KCTD proteins with their most common partner Cullin 3 (Cul3).
View Article and Find Full Text PDFBreast cancer is the leading cause of cancer-related death in women worldwide. It is well known that breast cancer shows significant alterations in the tumor microenvironment (TME), which is composed of a variety of immune cells, including natural killer (NK) cells, that have a key role in tumor development or anti-tumor responses in breast cancer patients. Luminal B (BT474) and triple-negative breast cancer (HS578T) cell lines were cultured in 2D and 3D model systems.
View Article and Find Full Text PDFAplasia cutis congenita (ACC) is a congenital epidermal defect of the midline scalp and has been proposed to be due to a primary keratinocyte abnormality. Why it forms mainly at this anatomic site has remained a long-standing enigma. KCTD1 mutations cause ACC, ectodermal abnormalities, and kidney fibrosis, whereas KCTD15 mutations cause ACC and cardiac outflow tract abnormalities.
View Article and Find Full Text PDFAcute leukemia is the most common pediatric cancer. In most cases, this disease results from the malignant transformation of either the B-cell (B-ALL) or, less frequently, T-cell progenitors (T-ALL). Recently, a marked overexpression of KCTD15, a member of the emerging class of the potassium (K) channel tetramerization domain-containing proteins (KCTDs) has been detected in both patients and continuous cell lines as in vitro model systems.
View Article and Find Full Text PDFHydrogel nanoparticles, also known as nanogels (NGs), have been recently proposed as alternative supramolecular vehicles for the delivery of biologically relevant molecules like anticancer drugs and contrast agents. The inner compartment of peptide based NGs can be opportunely modified according to the chemical features of the cargo, thus improving its loading and release. A full understanding of the intracellular mechanism involved in nanogel uptake by cancer cells and tissues would further contribute to the potential diagnostic and clinical applications of these nanocarriers, allowing the fine tuning of their selectivity, potency, and activity.
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