Prevalence of hybrid TLR4M2 monocytes/macrophages in peripheral blood and lung of systemic sclerosis patients with interstitial lung disease.

Introduction: Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease characterized by microvascular damage, immune system reactivity and progressive fibrosis of skin and internal organs. Interstitial lung disease is the leading cause of death for SSc patients (SSc-ILD), and the process of lung fibrosis involves also circulating monocytes and alveolar macrophages.

Methods: Current study aimed to identify monocyte/macrophage phenotypes in lung and peripheral blood of SSc-ILD patients by immunostaining and flow cytometry, respectively.

The intervention of macrophages in progressive fibrosis characterizing systemic sclerosis: A systematic review.

Background And Aim: Systemic sclerosis (SSc) is an immune mediated connective tissue disease characterized by microvascular dysfunction, aberrant immune response, and progressive fibrosis. Although the immuno-pathophysiological mechanisms underlying SSc are not fully clarified, they are often associated with a dysfunctional macrophage activation toward an alternative (M2) phenotype induced by cytokines [i.e.

The epigenetic effects of glucocorticoids, sex hormones and vitamin D as steroidal hormones in rheumatic musculoskeletal diseases.

Chronic rheumatological diseases are multifactorial conditions in which both the neuroendocrine hormone pathway, including cortisol, sex hormones and active vitamin D3 (calcitriol), all deriving from cholesterol, and the epigenetic modifications that they cause play an important role. In fact, epigenetics modulates the function of the DNA of immune cells, through three main mechanisms: DNA methylation, modifications to the histones that make up chromatin and production of non-coding RNAs (microRNA - miRNA). In this narrative review, the main data regarding the epigenetic modifications induced by cortisol, 17β-oestradiol, progesterone, testosterone and calcitriol on immune cells were collected, discussing how these can interfere in the predisposition and course of chronic rheumatological diseases (i.

Nintedanib downregulates the profibrotic M2 phenotype in cultured monocyte-derived macrophages obtained from systemic sclerosis patients affected by interstitial lung disease.

Background: Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by vasculopathy and progressive fibrosis of skin and several internal organs, including lungs. Macrophages are the main cells involved in the immune-inflammatory damage of skin and lungs, and alternatively activated (M2) macrophages seem to have a profibrotic role through the release of profibrotic cytokines (IL10) and growth factors (TGFβ1). Nintedanib is a tyrosine kinase inhibitor targeting several fibrotic mediators and it is approved for the treatment of SSc-related interstitial lung disease (ILD).

Developmental and Nutritional Dynamics of Malpighian Tubule Autofluorescence in the Asian Tiger Mosquito .

Malpighian tubules (MTs) are arthropod excretory organs crucial for the osmoregulation, detoxification and excretion of xenobiotics and metabolic wastes, which include tryptophan degradation products along the kynurenine (KYN) pathway. Specifically, the toxic intermediate 3-hydroxy kynurenine (3-HK) is metabolized through transamination to xanthurenic acid or in the synthesis of ommochrome pigments. Early investigations in larval fat bodies revealed an intracellular autofluorescence (AF) that depended on tryptophan administration.

Understanding the Immune-Endocrine Effects of Vitamin D in SARS-CoV-2 Infection: A Role in Protecting against Neurodamage.

Calcitriol and hydroxyderivatives of lumisterol and tachisterol are secosteroid hormones with immunomodulatory and anti-inflammatory properties. Since the beginning of the COVID-19 pandemic, several studies have correlated deficient serum concentrations of vitamin D3 (calcifediol) with increased severity of the course of SARS-CoV-2 infection. Among systemic complications, subjective (anosmia, ageusia, depression, dizziness) and objective (ischemic stroke, meningoencephalitis, myelitis, seizures, Guillain-Barré syndrome) neurological symptoms have been reported in up to 80% of severe COVID-19 patients.

A Systematic Review of Aminaphtone from Pathophysiology to Clinical Applications: Focus on New Rheumatological Acquisitions.

Aminaphtone is a chemical drug that has been used for more than thirty years to treat a variety of vascular disorders, with good clinical results and a satisfying safety profile. In the last two decades, multiple clinical studies have reported the efficacy of the drug in different clinical scenarios of altered microvascular reactivity, describing the downregulation of adhesion molecules (i.e.

Vitamin D and COVID-19: Narrative Review after 3 Years of Pandemic.

Active vitamin D [1,25(OH)D-calcitriol] is a secosteroid hormone whose receptor is expressed on all cells of the immune system. Vitamin D has a global anti-inflammatory effect and its role in the management of a SARS-CoV-2 infection has been investigated since the beginning of the COVID-19 pandemic. In this narrative review, the laboratory and clinical results of a vitamin D supplementation have been collected from both open-label and blinded randomized clinical trials.

Adult vaccination uptake strategies in low- and middle-income countries: A systematic review.

Background: Evidence-based strategies can maximize vaccination intent and uptake among adults. This systematic review summarizes the existing literature on strategies to improve vaccination intent and uptake among adults in low- and middle-income countries (LMICs) to inform future implementation in various populations and contexts.

Methods: Eligible studies were identified through a systematic search in Medline, Embase, Cochrane Libraries, as well as grey literature databases published between January 2010 and March 2021.

The Role of M1/M2 Macrophage Polarization in Rheumatoid Arthritis Synovitis.

Innate and adaptive immunity represent a harmonic counterbalanced system involved in the induction, progression, and possibly resolution of the inflammatory reaction that characterize autoimmune rheumatic diseases (ARDs), including rheumatoid arthritis (RA). Although the immunopathophysiological mechanisms of the ARDs are not fully clarified, they are often associated with an inappropriate macrophage/T-cell interaction, where classical (M1) or alternative (M2) macrophage activation may influence the occurrence of T-helper (Th)1 or Th2 responses. In RA patients, M1/Th1 activation occurs in an inflammatory environment dominated by Toll-like receptor (TLR) and interferon (IFN) signaling, and it promotes a massive production of pro-inflammatory cytokines [i.

Immune response to one dose of BNT162b2 mRNA Covid-19 vaccine followed by SARS-CoV-2 infection: An Italian prospective observational study.

Introduction: A mass vaccination campaign against SARS-CoV-2 was initiated in European countries on December 27, 2020. This study compared the antibody response in a sample of healthcare workers (HCWs) who, after the first dose of the BNT162b2 mRNA vaccine, were infected with SARS-CoV-2 (infection group) with the response in a control group of HCWs immunized with two doses (vaccine group).

Methods: This two-arm observational cohort study was carried out using routine health surveillance data obtained from HCWs at Bari Policlinico General Hospital (Italy).

CTLA4-Ig treatment induces M1-M2 shift in cultured monocyte-derived macrophages from healthy subjects and rheumatoid arthritis patients.

Background: In rheumatoid arthritis (RA), macrophages play an important role in modulating the immunoinflammatory response through their polarisation into "classically" (M1) or "alternatively activated" (M2) phenotypes. In RA, CTLA4-Ig (abatacept) reduces the inflammatory activity of macrophages by interacting with the costimulatory molecule CD86. The study aimed to investigate the efficacy of CTLA4-Ig treatment to induce an M2 phenotype both in M1-polarised monocyte-derived macrophages (MDMs) obtained from healthy subjects (HS) and in cultured MDMs obtained from active RA patients.

Post-Marketing Active Surveillance of Adverse Reactions Following Influenza Cell-Based Quadrivalent Vaccine: An Italian Prospective Observational Study.

Since the influenza season 2018/19, the Italian Ministry of Health recommended a dose of cell-based quadrivalent vaccine (Flucelvax Tetra) for HCWs (healthcare workers), because this vaccine seemed more efficacious in the prevention of AH3N2 virus. Due to the lack of pre-registration data, the safety profile of this new vaccine must be investigated in post-marketing surveillance. The aim of our study is to evaluate, through a post-marketing active surveillance program developed during the 2019/20 influenza season, any Adverse Events Following Immunization (AEFIs) that happened in the 7 days after immunization with Flucelvax Tetra.

Apremilast interferes with the TGFβ1-induced transition of human skin fibroblasts into profibrotic myofibroblasts: in vitro study.

Objectives: Fibroblast-to-myofibroblast transition and extracellular matrix overproduction represent progressive events in chronic inflammatory and fibrotic diseases, in which TGFβ1 is one of the key mediators. Phosphodiesterase 4 (PDE4) acts as a proinflammatory enzyme through the degradation of cyclic adenosine monophosphate and it is overexpressed in skin fibroblasts. The study investigated how apremilast (a PDE4 inhibitor) interferes with the intracellular signalling pathways responsible for the TGFβ1-induced fibroblast-to-myofibroblast transition and profibrotic extracellular matrix protein synthesis.

Altered expression of RXFP1 receptor contributes to the inefficacy of relaxin-based anti-fibrotic treatments in systemic sclerosis.

Objectives: Relaxin is a potent anti-fibrotic hormone that has been tested to ameliorate fibrosis in systemic sclerosis (SSc), but with controversial results. The aim of the study is to sequence relaxin receptor gene RXFP1 and to assess its mRNA expression and protein levels in the skin of SSc patients and healthy subjects.

Methods: Fibroblasts were isolated from unaffected/affected skin samples of (n=16) limited-cutaneous-SSc-(LcSSc) and from affected ones of (n=4) diffuse-cutaneous-SSc-(DcSSc) patients.

Antibodies against specific extractable nuclear antigens (ENAs) as diagnostic and prognostic tools and inducers of a profibrotic phenotype in cultured human skin fibroblasts: are they functional?

Background: The importance of systemic sclerosis (SSc) autoantibodies for diagnosis has become recognized by their incorporation into the 2013 ACR/EULAR classification criteria. Clear prognostic and phenotypic associations with cutaneous subtype and internal organ involvement have been also described. However, little is known about the potential of autoantibodies to exert a direct pathogenic role in SSc.

Correlation between circulating fibrocytes and dermal thickness in limited cutaneous systemic sclerosis patients: a pilot study.

The objective is to detect any possible correlation between the modified Rodnan skin score (mRSS) and dermal thickness (DT) measured by skin high-frequency ultrasound (US) and the percentage of circulating fibrocytes in patients with limited cutaneous systemic sclerosis (lcSSc). Eight lcSSc patients and five healthy subjects (control group, CNT) were enrolled. The skin involvement was evaluated by mRSS and US (18 and 22 MHz probes) in all 13 subjects in the 17 standard skin areas evaluated by mRss.