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Objectives: COVID-19 lockdowns were introduced to control the pandemic, however, they resulted in a global disruption of daily life and of individual and global health. Reduced accessibility of health services, unavailability of food and drugs, and mental health challenges had a huge impact on older people and on people living with disabling conditions such as Parkinson's disease (PD). We assessed whether and to what extent the more disabled and vulnerable people with Parkinson's (PwP) were affected by lockdowns., Method: We analysed responses collected through a web-based survey of PwP according to their self-sufficiency [self-sufficient (SS); nearly self-sufficient (nSS); non-self-sufficient, cared for by family (NSS/F); non-self-sufficient, needs professional care (NSS/PC)]., Results: Fears due to COVID-19 and difficulties with food supply were highest in NSS/F PwP. Difficulties with the supply of Parkinson's medication or other drugs were apparently not an issue, while problems accessing primary care physicians and neurologists were similar across all patient groups. On the contrary, difficulties with daily and motor activities were higher in NSS/F and NSS/PC PwP. PwP symptoms worsened in all groups, with NSS/F and NSS/PC participants experiencing the worst deterioration. Notably, the deterioration of PwP symptoms was specifically related to changes in daily and motor activities, with participants who reported less engagement in daily and motor activities experiencing the worst deterioration., Conclusion: Findings strongly support the need for decision-makers and healthcare providers to carefully re-evaluate the risk-benefit ratio of limiting healthcare accessibility for PwP, since evidence shows that lockdown measures primarily impact the groups who are most fragile and vulnerable.

Aim: Early biomarkers of phenoconversion to neurodegeneration are crucial to identify individuals at high risk. In patients with idiopathic REM sleep behavior disorder (iRBD), the strongest risk factor for neurodegeneration, CD4 + T cells exhibit a peculiar transcription factor pattern. Objective: To assess transcription factor mRNA levels in CD4 + T cells as predictive biomarkers of phenoconversion in iRBD patients. Methods: iRBD patients were followed prospectively. ROC curve analysis and Kaplan-Meier curves were used to assess the discrimination between converters and non-converters. Results: CD4 + T cells from converters had higher STAT1 , and lower GATA3 and FOXP3 mRNA levels. Hazard ratio was 58.3 (95% CI: 6.2-547.1) for higher STAT1 , 101.2 (95% CI: 16.8-609.4) for lower GATA3 and 15.7 (2.7-91.4) for lower FOXP3 . Conclusion: STAT1 , GATA3 and FOXP3 mRNA levels in CD4 + T cells are promising predictive biomarkers of phenoconversion in iRBD patients.

Dopamine (DA) affects immune functions in healthy subjects (HS) and during disease by acting on D1-like (D1 and D5) and D2-like (D2, D3 and D4) dopaminergic receptors (DR); however, its effects on human polymorphonuclear leukocytes (PMN) are still poorly defined. We investigated DR expression in human PMN and the ability of DA to affect cell migration and reactive oxygen species (ROS) production. Experiments were performed on cells from HS and from patients (Pts) with bacterial infections as well, during the acute phase and after recovery. Some experiments were also performed in mice knockout (KO) for the DRD5 gene. PMN from HS express both D1-like and D2-like DR, and exposure to DA results in inhibition of activation-induced morphological changes, migration and ROS production which depend on the activation of D1-like DR. In agreement with these findings, DA inhibited migration of PMN obtained from wild-type mice, but not from DRD5KO mice. In Pts with bacterial infections, during the febrile phase D1-like DRD5 on PMN were downregulated and DA failed to affect PMN migration. Both D1-like DRD5 expression and DA-induced inhibition of PMN migration were however restored after recovery. Dopaminergic inhibition of human PMN is a novel mechanism which is likely to play a key role in the regulation of innate immunity. Evidence obtained in Pts with bacterial infections provides novel clues for the therapeutic modulation of PMN during infectious disease., (© 2022 The Authors. Immunology published by John Wiley & Sons Ltd.)

This study tests the hypothesis that in isolated human polymorphonuclear leukocytes (PMN) adrenergic ligands can affect neutrophil extracellular trap (NET) formation. We have previously shown that, in PMN, adrenaline (A), through the activation of adrenergic receptors (AR), reduces stimulus-dependent cell activation; we have, therefore, planned to investigate if AR are involved in NET production. PMN were obtained from venous blood of healthy subject. The ability of adrenergic ligands to affect reactive oxygen species (ROS) production, NET production, and cell migration was investigated in cells cultured under resting conditions or after activation with N-formyl-methionyl-leucyl-phenylalanine (fMLP), LPS, or IL-8. Stimuli-induced NET production measured as ROS, microscopic evaluation, and elastase production was reverted by A and this effect was blocked by the selective β 2 -AR antagonist ICI-118,551. The stimulus-induced ROS generation and migration was prevented by A and by isoprenaline (ISO), and these effects were counteracted only by ICI-118,551 and not by the other two selective ligands for the β 1 and β 3 -AR. Finally, the presence of the β-ARs on PMN was confirmed, by means of microscopy and flow cytometry. The data of the present study suggest that adrenergic compounds, through the interaction of mainly β 2 -AR, are able to affect neutrophil functions. These data are suggestive of a possible therapeutic role of β 2 -AR ligands (in addition to their classical use), promoting the possible therapeutic relevance of adrenergic system in the modulation of innate immunity proposing their possible use as anti-inflammatory drugs., (©2018 Society for Leukocyte Biology.)

Dopamine (DA) is a neurotransmitter in the central nervous system as well as in peripheral tissues. Emerging evidence however points to DA also as a key transmitter between the nervous system and the immune system as well as a mediator produced and released by immune cells themselves. Dopaminergic pathways have received so far extensive attention in the adaptive branch of the immune system, where they play a role in health and disease such as multiple sclerosis, rheumatoid arthritis, cancer, and Parkinson's disease. Comparatively little is known about DA and the innate immune response, although DA may affect innate immune system cells such as dendritic cells, macrophages, microglia, and neutrophils. The present review aims at providing a complete and exhaustive summary of currently available evidence about DA and innate immunity, and to become a reference for anyone potentially interested in the fields of immunology, neurosciences and pharmacology. A wide array of dopaminergic drugs is used in therapeutics for non-immune indications, such as Parkinson's disease, hyperprolactinemia, shock, hypertension, with a usually favorable therapeutic index, and they might be relatively easily repurposed for immune-mediated disease, thus leading to innovative treatments at low price, with benefit for patients as well as for the healthcare systems.

Objective: Sample manipulation to obtain isolated granulocytes represents a key, and often necessary, step in the in vitro studies. We investigated by the means of flow cytometry and microscopic techniques (both optical microscopy [OM] and scanning electron microscopy [SEM]), the granulocyte-endothelium adhesion and the role of sample manipulation., Methods: By means of a co-culture method, we have analysed the adhesion of human leukocytes, originated from two different blood samples (fresh venous blood [FB] and buffy coat [BC]), to the human umbilical venous endothelial cell (HUVEC) monolayer. Cultured HUVEC were analysed for adhesion molecule expression by means of flow cytometry, while the morphological changes were evaluated by means of SEM. Cell adhesion was evaluated by means of flow cytometry and both OM and SEM., Results: HUVEC expressed under resting conditions the adhesion molecules ICAM-1, VCAM-1 and E-selectin and their expression was upregulated by stimulation with TNF-α (0.1-10ng/ml) as well as with LPS (1μg/ml). SEM analysis showed that stimulation with both stimuli profoundly affect cell morphology. Flow cytometric evaluation of cell adhesion showed that the ability of cells to adhere to HUVEC monolayer was quite different in the two preparations, with the lowest adhesion for FB in all the cell subsets analysed. Finally, isolated granulocytes were able to adhere to HUVEC monolayer more than cells identified in FB or BC and the adhesion was increased during activation of HUVEC with 10ng/ml of TNF-α., Conclusion: Our data showed that cell manipulation necessary for the isolation of specific immune cells from whole blood profoundly affect the ability of these cells to adhere to the HUVEC monolayer although their functional properties remain unchanged., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Cyclic RGD peptidomimetics containing a bifunctional diketopiperazine scaffold are a novel class of high-affinity ligands for the integrins αVβ3 and αVβ5. Since integrins are a promising target for the modulation of normal and pathological angiogenesis, the present study aimed at characterizing the ability of the RGD peptidomimetic cyclo[DKP-RGD] 1 proliferation, migration and network formation in human umbilical vein endothelial cells (HUVEC)., Methods: Cell viability was assessed by flow cytometry and annexin V (ANX)/propidium iodide (PI) staining. Cell proliferation was evaluated by the ELISA measurement of bromodeoxyuridine (BrdU) incorporation. Network formation by HUVEC cultured in Matrigel-coated plates was evaluated by optical microscopy and image analysis. Integrin subunit mRNA expression was assessed by real time-PCR and Akt phosphorylation by western blot analysis., Results: Cyclo[DKP-RGD] 1 does not affect cell viability and proliferation either in resting conditions or in the presence of the pro-angiogenic growth factors VEGF, EGF, FGF, and IGF-I. Addition of cyclo[DKP-RGD] 1 however significantly decreased network formation induced by pro-angiogenic growth factors or by IL-8. Cyclo[DKP-RGD] 1 did not affect mRNA levels of αV, β3 or β5 integrin subunits, however it significantly reduced the phosphorylation of Akt., Conclusions: Cyclo[DKP-RGD] 1 can be a potential modulator of angiogenesis induced by different growth factors, possibly devoid of the adverse effects of cytotoxic RGD peptidomimetic analogues.