Magnetic nanoradiotracers for targeted neutrophil detection in pulmonary arterial hypertension.

Background: Pulmonary arterial hypertension (PAH) is a severe disease characterized by elevated blood pressure in the pulmonary artery that can ultimately damage the right ventricle of the heart. PAH is pathophysiologically heterogeneous, which makes early diagnosis and treatment difficult. Inflammation is thought to be an important factor in the development and progression of this disease and may explain some of the observed interindividual differences.

PCNA molecular recognition of different PIP motifs: Role of Tyr211 phosphorylation.

The coordination of enzymes and regulatory proteins for eukaryotic DNA replication and repair is largely achieved by Proliferating Cell Nuclear Antigen (PCNA), a toroidal homotrimeric protein that embraces the DNA duplex. Many proteins bind PCNA through a conserved sequence known as the PCNA interacting protein motif (PIP). PCNA is further regulated by different post-translational modifications.

HIF-1α inhibitor PX-478 preserves pancreatic β cell function in diabetes.

During progression of type 2 diabetes, pancreatic β cells are subjected to sustained metabolic overload. We postulated that this state mediates a hypoxic phenotype driven by hypoxia-inducible factor-1α (HIF-1α) and that treatment with the HIF-1α inhibitor PX-478 would improve β cell function. Our studies showed that the HIF-1α protein was present in pancreatic β cells of diabetic mouse models.

PI3K-regulated Glycine N-methyltransferase is required for the development of prostate cancer.

Glycine N-Methyltransferase (GNMT) is a metabolic enzyme that integrates metabolism and epigenetic regulation. The product of GNMT, sarcosine, has been proposed as a prostate cancer biomarker. This enzyme is predominantly expressed in the liver, brain, pancreas, and prostate tissue, where it exhibits distinct regulation.

Unusual sensory-motor neuropathies in post-COVID-19 patients admitted in rehabilitation hospitals: a case-series.

Background: Several neurological complications occurred in SARS-CoV-2 disease (COVID-19), mainly related to inflammatory and vascular disorders. The involvement of the peripheral nervous system (PNS) has been mostly reported as Guillain-Barré Syndrome, while focal peripheral neuropathies have been rarely described.

Case Report: We report the cases of ten patients hospitalized in Rehabilitation Units after COVID-19, who presented severe focal motor involvement.

The commensal bacterium imprints innate memory-like responses in mononuclear phagocytes.

Gut microbiota is a constant source of antigens and stimuli to which the resident immune system has developed tolerance. However, the mechanisms by which mononuclear phagocytes, specifically monocytes/macrophages, cope with these usually pro-inflammatory signals are poorly understood. Here, we show that innate immune memory promotes anti-inflammatory homeostasis, using as model strains of the commensal bacterium .

Hypoxia reduces cell attachment of SARS-CoV-2 spike protein by modulating the expression of ACE2, neuropilin-1, syndecan-1 and cellular heparan sulfate.

A main clinical parameter of COVID-19 pathophysiology is hypoxia. Here we show that hypoxia decreases the attachment of the receptor-binding domain (RBD) and the S1 subunit (S1) of the spike protein of SARS-CoV-2 to epithelial cells. In Vero E6 cells, hypoxia reduces the protein levels of ACE2 and neuropilin-1 (NRP1), which might in part explain the observed reduction of the infection rate.

The dystrophia myotonica WD repeat-containing protein DMWD and WDR20 differentially regulate USP12 deubiquitinase.

Despite its potential clinical relevance, the product of the DMWD (dystrophia myotonica, WD repeat containing) gene is a largely uncharacterized protein. The DMWD amino acid sequence is similar to that of WDR20, a known regulator of the USP12 and USP46 deubiquitinases (DUBs). Here, we apply a combination of in silico and experimental methods to investigate several aspects of DMWD biology.

Hypoxia compromises the mitochondrial metabolism of Alzheimer's disease microglia via HIF1.

Genetic Alzheimer's disease (AD) risk factors associate with reduced defensive amyloid β plaque-associated microglia (AβAM), but the contribution of modifiable AD risk factors to microglial dysfunction is unknown. In AD mouse models, we observe concomitant activation of the hypoxia-inducible factor 1 (HIF1) pathway and transcription of mitochondrial-related genes in AβAM, and elongation of mitochondria, a cellular response to maintain aerobic respiration under low nutrient and oxygen conditions. Overactivation of HIF1 induces microglial quiescence in cellulo, with lower mitochondrial respiration and proliferation.

Selective modulation by PARP-1 of HIF-1α-recruitment to chromatin during hypoxia is required for tumor adaptation to hypoxic conditions.

Background: The adaptation to hypoxia is mainly controlled by the HIF transcription factors. Increased expression/activity of HIF-1α correlates with poor prognosis in cancer patients. PARP-1 inhibitors are used in the clinic to treat BRCAness breast/ovarian cancer and have been shown to regulate the hypoxic response; therefore, their use could be expanded.

Borrelia burgdorferi infection induces long-term memory-like responses in macrophages with tissue-wide consequences in the heart.

Lyme carditis is an extracutaneous manifestation of Lyme disease characterized by episodes of atrioventricular block of varying degrees and additional, less reported cardiomyopathies. The molecular changes associated with the response to Borrelia burgdorferi over the course of infection are poorly understood. Here, we identify broad transcriptomic and proteomic changes in the heart during infection that reveal a profound down-regulation of mitochondrial components.

Genomic and Functional Regulation of TRIB1 Contributes to Prostate Cancer Pathogenesis.

Prostate cancer is the most frequent malignancy in European men and the second worldwide. One of the major oncogenic events in this disease includes amplification of the transcription factor cMYC. Amplification of this oncogene in chromosome 8q24 occurs concomitantly with the copy number increase in a subset of neighboring genes and regulatory elements, but their contribution to disease pathogenesis is poorly understood.

MicroRNA Nanotherapeutics for Lung Targeting. Insights into Pulmonary Hypertension.

In this review, the potential future role of microRNA-based therapies and their specific application in lung diseases is reported with special attention to pulmonary hypertension. Current limitations of these therapies will be pointed out in order to address the challenges that they need to face to reach clinical applications. In this context, the encapsulation of microRNA-based therapies in nanovectors has shown improvements as compared to chemically modified microRNAs toward enhanced stability, efficacy, reduced side effects, and local administration.

The Dysphagia in Multiple Sclerosis Questionnaire Correlates with Fiber-Optic Endoscopic Examination for Detecting Swallowing Deficits in MS.

Multiple sclerosis (MS) refers to chronic inflammation of the central nervous system including the brain and spinal cord. Assessing for the presence of dysphagia in subjects with MS represents a challenge for neurologists in clinical practice. The aim of the present study was to verify the relationship between DYMUS scores, a patient-reported scale, and objective symptoms using the Dysphagia Outcome Severity Score (DOSS), based on fiber-optic endoscopy.

Effects of THC/CBD oromucosal spray on spasticity-related symptoms in people with multiple sclerosis: results from a retrospective multicenter study.

Introduction: The approval of 9-δ-tetrahydocannabinol (THC)+cannabidiol (CBD) oromucosal spray (Sativex®) in Italy as an add-on medication for the management of moderate to severe spasticity in multiple sclerosis (MS) has provided a new opportunity for MS patients with drug-resistant spasticity. We aimed to investigate the improvement of MS spasticity-related symptoms in a large cohort of patients with moderate to severe spasticity in daily clinical practice.

Materials And Methods: MS patients with drug-resistant spasticity were recruited from 30 Italian MS centers.

Home blood pressure monitoring and e-Health: investigation of patients' experience with the Hy-Result system.

Background: Hy-Result is a validated system designed to help patients complying with the home blood pressure monitoring (HBPM) protocol and understanding their blood pressure (BP) readings. It is available as a standalone web application or within a wireless BP monitor app.

Objective: The aim of the study was to explore patients' experience with Hy-Result.

Prevalence of dysphagia in a consecutive cohort of subjects with MS using fibre-optic endoscopy.

Introduction: Multiple sclerosis (MS) refers to chronic inflammation of the central nervous system including the brain and spinal cord. Dysphagia is a symptom that represents challenges in clinical practice. The aim of the present study was to evaluate the prevalence of dysphagia in an Italian cohort of subjects with MS using the Dysphagia Outcome Severity Score (DOSS), based on fibre-optic endoscopy, and determine factors that correlate with the presence of swallowing problems.

OnabotulinumtoxinA Reduces Temporal Pain Processing at Spinal Level in Patients with Lower Limb Spasticity.

Spasticity is a muscle tone disorder associated with different neurological conditions. Spasticity could be associated with pain, high disability, poor functional recovery, and reduced quality of life. Botulinum neurotoxin type A (BoNT-A) is considered a first-line treatment for spasticity and, more recently, it also represents a therapeutic option for various chronic pain conditions.

The Effects of Transcutaneous Spinal Direct Current Stimulation on Neuropathic Pain in Multiple Sclerosis: Clinical and Neurophysiological Assessment.

: Central neuropathic pain represents one of the most common symptoms in multiple sclerosis (MS) and it seriously affects quality of life. Spinal mechanisms may contribute to the pathogenesis of neuropathic pain in MS. Converging evidence from animal models and neurophysiological and clinical studies in humans suggests a potential effect of transcranial direct current stimulation (tc-DCS) on neuropathic pain.

Body Weight Support Combined With Treadmill in the Rehabilitation of Parkinsonian Gait: A Review of Literature and New Data From a Controlled Study.

Gait disorders represent disabling symptoms in Parkinson's Disease (PD). The effectiveness of rehabilitation treatment with Body Weight Support Treadmill Training (BWSTT) has been demonstrated in patients with stroke and spinal cord injuries, but limited data is available in PD. The aim of the study is to investigate the efficacy of BWSTT in the rehabilitation of gait in PD patients.

SUMOylation regulates LKB1 localization and its oncogenic activity in liver cancer.

Background: Even though liver kinase B1 (LKB1) is usually described as a tumor suppressor in a wide variety of tissues, it has been shown that LKB1 aberrant expression is associated with bad prognosis in Hepatocellular Carcinoma (HCC).

Methods: Herein we have overexpressed LKB1 in human hepatoma cells and by using histidine pull-down assay we have investigated the role of the hypoxia-related post-translational modification of Small Ubiquitin-related Modifier (SUMO)ylation in the regulation of LKB1 oncogenic role. Molecular modelling between LKB1 and its interactors, involved in regulation of LKB1 nucleocytoplasmic shuttling and LKB1 activity, was performed.

Therapeutic drug monitoring-guided definition of adherence profiles in resistant hypertension and identification of predictors of poor adherence.

Aims: Arterial hypertension is an important cardiovascular risk factor. A substantial proportion of patients show resistance to antihypertensive treatment but poor adherence to medication regimens is also a significant cause of treatment failure. In this context, therapeutic drug monitoring (TDM) could be useful.

Impact of psychological profile on drug adherence and drug resistance in patients with apparently treatment-resistant hypertension.

Purpose: Patients with apparent treatment-resistant hypertension (a-TRH) are often poorly adherent to drug treatment and have an unusual personal history and psychological profile. The aim of this study was to identify predictors of drug adherence and drug resistance in a cohort of patients with aTRH, with emphasis on psychological characteristics.

Methods: All patients with confirmed aTRH on standardized antihypertensive treatment were eligible.

Effectiveness of Renal Denervation in Resistant Hypertension: A Meta-Analysis of 11 Controlled Studies.

Introduction: Early uncontrolled studies reported large blood pressure reductions in subjects with resistant hypertension treated with renal denervation, however these results were not confirmed in several of the latest publications.

Aim: The aim of the current study was to evaluate the effectiveness of RDN in controlled studies comparing RDN to either a sham procedure or to medical therapy.

Method: Only controlled studies were included in the analysis.