Cardiac Differentiation Promotes Focal Adhesions Assembly through Vinculin Recruitment.

Cells of the cardiovascular system are physiologically exposed to a variety of mechanical forces fundamental for both cardiac development and functions. In this context, forces generated by actomyosin networks and those transmitted through focal adhesion (FA) complexes represent the key regulators of cellular behaviors in terms of cytoskeleton dynamism, cell adhesion, migration, differentiation, and tissue organization. In this study, we investigated the involvement of FAs on cardiomyocyte differentiation.

Response to erenumab assessed by Headache Impact Test-6 is modulated by genetic factors and arterial hypertension: An explorative cohort study.

Background And Purpose: Response predictors to erenumab (ERE) in migraine patients would benefit their clinical management. We investigate associations between patients' clinical characteristics and polymorphisms at calcitonin receptor-like receptor (CALCRL) and receptor activity-modifying protein 1 (RAMP1) genes and response to ERE treatment measured as clinically meaningful improvement on the Headache Impact Test-6 (HIT-6) score.

Methods: This post hoc analysis of a prospective, multicenter, investigator-initiated study involves 110 migraine patients starting ERE 70 mg/month.

Progression patterns and therapeutic sequencing following immune checkpoint inhibition for hepatocellular carcinoma: An international observational study.

Background And Aims: Different approaches are available after the progression of disease (PD) to immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC), including the continuation of ICI, treatment switching to tyrosine kinase inhibitors (TKIs) and cessation of anticancer therapy. We sought to characterise the relationship between radiological patterns of progression and survival post-ICI, also appraising treatment strategies.

Methods: We screened 604 HCC patients treated with ICIs, including only those who experienced PD by data cut-off.

Peptide-Based Hydrogels and Nanogels Containing Gd(III) Complexes as Relaxation Agents.

New peptide-based hydrogels incorporating Gd(III) chelates with different hydration states, molecular structures and overall negative charges ([Gd(BOPTA)]2−), [Gd(DTPA)]2−, and ([Gd(AAZTA)]−) were prepared and characterized. N-terminal Fmoc- or acetyl-derivatized hexapeptides (K1, K2 and K3) containing five aliphatic amino acids (differently ordered Gly, Ala, Val, Leu and Ile) and a charged lysine at the amidated C-terminal were used for the formation of the hydrogels. Particular attention was paid to the investigation of the morphological and rheological properties of the nanoparticles, in addition to the assessment of the ability (relaxivity) of the confined complexes to accelerate the longitudinal relaxation rate of the water protons localized in the polymeric network.

Maternal ApoE genotype and risk of recurrent pregnancy loss: An updated systematic review and meta-analysis.

Background: In order to clarify the role of the maternal apolipoprotein E (ApoE) genotype and the risk of recurrent pregnancy loss (RPL), we herein performed an updated systematic review and meta-analysis to reevaluate the evidence on this association.

Methods: A comprehensive literature search was performed on PubMed, Web of Knowledge and the Cochrane library up to September 2022. Methodological study quality was assessed using the Newcastle-Ottawa Scale and the credibility of significant pooled odds ratios (ORs) was estimated by the false positive report probability and the Bayesian false discovery probability.

Assessing the interactions between nanoparticles and biological barriers in vitro: a new challenge for microscopy techniques in nanomedicine.

Nanoconstructs intended to be used as biomedical tool must be assessed for their capability to cross biological barriers. However, studying in vivo the permeability of biological barriers to nanoparticles is quite difficult due to the many structural and functional factors involved. Therefore, the in vitro modeling of biological barriers -2D cell monocultures, 2D/3D cell co-cultures, microfluidic devices- is gaining more and more relevance in nanomedical research.

The power of a novel combined anticancer therapy: challenge and opportunity of micotherapy in the treatment of Glioblastoma Multiforme.

Glioblastoma (GBM) is the most common and mortal primary brain tumor in human. After standard therapies, that include surgical resection followed by radiotherapy and chemotherapy, it is difficult to completely remove the tumor and the development of relapses and resistance is almost inevitable. The chemotherapy now available also show important side effects, to overcame those limitation, new platinum-based drugs are being synthetized, Pt(IV)Ac-POA, (OC-6-44)-acetate-diamine-chloride(2-(2-propynyl)octanoato)platinum(IV), a prodrug having an Histone-3-DeAcetylase-Inhibitor as axial ligands, is one of them.

Regenerative Potential of A Bovine ECM-Derived Hydrogel for Biomedical Applications.

Recent advancements in regenerative medicine have enhanced the development of biomaterials as multi-functional dressings, capable of accelerating wound healing and addressing the challenge of chronic wounds. Hydrogels obtained from decellularized tissues have a complex composition, comparable to the native extracellular environment, showing highly interesting characteristics for wound healing applications. In this study, a bovine pericardium decellularized extracellular matrix (dECM) hydrogel was characterized in terms of macromolecules content, and its immunomodulatory, angiogenic and wound healing potential has been evaluated.

Microplastic contamination of supraglacial debris differs among glaciers with different anthropic pressures.

Microplastic (MP) contamination is ubiquitous and widespread in terrestrial and aquatic ecosystems, including remote areas. However, information on the presence and distribution of MPs in high-mountain ecosystems, including glaciers, is still limited. The present study aimed at investigating presence, spatial distribution, and patterns of contamination of MPs on three glaciers of the Ortles-Cevedale massif (Central Alps, Northern Italy) with different anthropic pressures, i.

In Vitro Models of Biological Barriers for Nanomedical Research.

Nanoconstructs developed for biomedical purposes must overcome diverse biological barriers before reaching the target where playing their therapeutic or diagnostic function. In vivo models are very complex and unsuitable to distinguish the roles plaid by the multiple biological barriers on nanoparticle biodistribution and effect; in addition, they are costly, time-consuming and subject to strict ethical regulation. For these reasons, simplified in vitro models are preferred, at least for the earlier phases of the nanoconstruct development.

Resveratrol and Its Analogue 4,4'-Dihydroxy-trans-stilbene Inhibit Lewis Lung Carcinoma Growth In Vivo through Apoptosis, Autophagy and Modulation of the Tumour Microenvironment in a Murine Model.

Lung cancer is the most prevalent cancer worldwide. Despite advances in surgery and immune-chemotherapy, the therapeutic outcome remains poor. In recent years, the anticancer properties of natural compounds, along with their low toxic side effects, have attracted the interest of researchers.

Butyrate Inhibits Colorectal Cancer Cell Proliferation through Autophagy Degradation of β-Catenin Regardless of and β-Catenin Mutational Status.

Colorectal cancer (CRC) pathogenesis is mainly driven by alterations in WNT signaling, which results in altered transcriptional activity of β-Catenin. Mutations in (Adenomatous Polyposis Coli) are reflected in β-Catenin hyperactivation and loss of proliferation control. Certain intestinal bacteria metabolites have shown the ability to limit CRC cell proliferation and CRC pathogenesis.

Do the Current Guidelines for Heart Failure Diagnosis and Treatment Fit with Clinical Complexity?

Heart failure (HF) is a clinical syndrome defined by specific symptoms and signs due to structural and/or functional heart abnormalities, which lead to inadequate cardiac output and/or increased intraventricular filling pressure. Importantly, HF becomes progressively a multisystemic disease. However, in August 2021, the European Society of Cardiology published the new Guidelines for the diagnosis and treatment of acute and chronic HF, according to which the left ventricular ejection fraction (LVEF) continues to represent the pivotal parameter for HF patients' evaluation, risk stratification and therapeutic management despite its limitations are well known.

Analysis of LINE1 Retrotransposons in Huntington's Disease.

Transposable elements (TEs) are mobile genetic elements that made up about half the human genome. Among them, the autonomous non-LTR retrotransposon long interspersed nuclear element-1 (L1) is the only currently active TE in mammals and covers about 17% of the mammalian genome. L1s exert their function as structural elements in the genome, as transcribed RNAs to influence chromatin structure and as retrotransposed elements to shape genomic variation in somatic cells.

Clinic and genetic predictors in response to erenumab.

Background And Purpose: Erenumab (ERE) is the first anticalcitonin gene-related peptide receptor monoclonal antibody approved for migraine prevention. A proportion of patients do not adequately respond to ERE.

Methods: Prospective multicenter study involving 110 migraine patients starting ERE 70 mg monthly.

Clinical Outcomes and Toxic Effects of Single-Agent Immune Checkpoint Inhibitors Among Patients Aged 80 Years or Older With Cancer: A Multicenter International Cohort Study.

Importance: Geriatric (aged ≥80 years) patients are historically underrepresented in cancer clinical trials. Little is known about the efficacy of immune checkpoint inhibitors (ICIs) in geriatric patients. These agents are associated with immune-related adverse events (irAEs), which may be particularly associated with morbidity in this population.

The Multiple Faces of Integrin-ECM Interactions in Inflammatory Bowel Disease.

Inflammatory Bowel Disease (IBD) comprises a series of chronic and relapsing intestinal diseases, with Crohn's disease and ulcerative colitis being the most common. The abundant and uncontrolled deposition of extracellular matrix, namely fibrosis, is one of the major hallmarks of IBD and is responsible for the progressive narrowing and closure of the intestine, defined as stenosis. Although fibrosis is usually considered the product of chronic inflammation, the substantial failure of anti-inflammatory therapies to target and reduce fibrosis in IBD suggests that fibrosis might be sustained in an inflammation-independent manner.

Myogenic Potential of Extracellular Matrix Derived from Decellularized Bovine Pericardium.

Skeletal muscles represent 40% of body mass and its native regenerative capacity can be permanently lost after a traumatic injury, congenital diseases, or tumor ablation. The absence of physiological regeneration can hinder muscle repair preventing normal muscle tissue functions. To date, tissue engineering (TE) represents one promising option for treating muscle injuries and wasting.

Gene polymorphism association studies in cluster headache: A field synopsis and systematic meta-analyses.

Background: A plethora of studies have attempted to identify genetic determinants of disease susceptibility and treatment response of patients with cluster headache (CH), but results are often conflicting, and no comprehensive overview with a quantitative summary of the evidence in this field is available.

Methods: A systematic search of relevant publications was performed without any language restrictions on PubMed, Web of Knowledge, Cochrane Library, and OpenGrey, up to December 2020. A standardized data extraction form was used to collect relevant data from each included study.

Inhibition of the Histone Methyltransferase EZH2 Enhances Protumor Monocyte Recruitment in Human Mesothelioma Spheroids.

Malignant pleural mesothelioma (MPM) is a highly aggressive cancer with a long latency period and dismal prognosis. Recently, tazemetostat (EPZ-6438), an inhibitor of the histone methyltransferase EZH2, has entered clinical trials due to the antiproliferative effects reported on MPM cells. However, the direct and indirect effects of epigenetic reprogramming on the tumor microenvironment are hitherto unexplored.

Heme catabolism by tumor-associated macrophages controls metastasis formation.

Although the pathological significance of tumor-associated macrophage (TAM) heterogeneity is still poorly understood, TAM reprogramming is viewed as a promising anticancer therapy. Here we show that a distinct subset of TAMs (F4/80CD115C3aRCD88), endowed with high rates of heme catabolism by the stress-responsive enzyme heme oxygenase-1 (HO-1), plays a critical role in shaping a prometastatic tumor microenvironment favoring immunosuppression, angiogenesis and epithelial-to-mesenchymal transition. This population originates from F4/80HO-1 bone marrow (BM) precursors, accumulates in the blood of tumor bearers and preferentially localizes at the invasive margin through a mechanism dependent on the activation of Nrf2 and coordinated by the NF-κB1-CSF1R-C3aR axis.

A New Platinum-Based Prodrug Candidate for Chemotherapy and Its Synergistic Effect With Hadrontherapy: Novel Strategy to Treat Glioblastoma.

Glioblastoma (GBM) is the most common tumor of the central nervous system. Current therapies, often associated with severe side effects, are inefficacious to contrast the GBM relapsing forms. In trying to overcome these drawbacks, (-6-44)-acetatodiamminedichlorido(2-(2-propynyl)octanoato)platinum(IV), also called Pt(IV)Ac-POA, has been recently synthesized.

A Comparative Study of the Effects of Platinum (II) Complexes on β-Amyloid Aggregation: Potential Neurodrug Applications.

Herein the effects of three platinum complexes, namely (-4-2)-(2,2'-bipyridine)dichloridoplatinum(II), Pt-bpy, (-4-2)-dichlorido(1,10-phenanthroline) platinum(II), Pt-phen, and (-4-2)-chlorido(2,2':6',2''-terpyridine)platinum(II) chloride, Pt-terpy, on the aggregation of an amyloid model system derived from the C-terminal domain of Aβ peptide (Aβ) were investigated. Thioflavin T (ThT) binding assays revealed the ability of Pt(II) compounds to repress amyloid aggregation in a dose-dependent way, whereas the ability of Aβ peptide to interfere with ligand field of metal complexes was analyzed through UV-Vis absorption spectroscopy and electrospray ionization mass spectrometry. Spectroscopic data provided micromolar EC values and allowed to assess that the observed inhibition of amyloid aggregation is due to the formation of adducts between Aβ peptide and complexes upon the release of labile ligands as chloride and that they can explore different modes of coordination toward Aβ with respect to the entire Aβ polypeptide.