144 research outputs found
ComunitaÌ energetiche e territorio, binomio indissolubile
Lâemergenza climatica ed energetica stanno focalizzando lâattenzione per le comunitaÌ energetiche rinnovabili (CER), costituite da cittadini che diventano produttori e consumatori di energia (âprosumerâ) ma anche piccole e medie imprese e amministrazioni comunali, al fine della distribuzione locale di energia prodotta da fonti rinnovabili, portando una serie di benefici ambientali, economici e sociali a livello territoriale e contribuendo a ridurre la povertaÌ energetica quale obiettivo di sviluppo sostenibile ed al raggiungimento del comune obiettivo di âdecarbonizzazioneâ richiesto dal futuro sistema energetico dellâUnione Europea. EÌ quindi immediata lâesigenza di pianificazione, per cui lâarticolo espone delle riflessioni conseguenti, con particolare riferimento alla pianificazione paesaggistica, basandosi sul caso di studio del Comune di Corsano (Lecce). Dai processi di decentramento e localismo energetico, emergono alcune prospettive che convergono sul distretto energetico come proiezione della comunitaÌ energetica locale e che sembrano valorizzarne una piuÌ sistemica e dimensione strategica della pianificazione energetica a scala urbana
Autophagy modulation in lymphocytes from COVID-19 patients. new therapeutic target in SARS-COV-2 infection
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the novel coronavirus, causing coronavirus disease 2019 (COVID-19). During virus infection, several pro-inflammatory cytokines are produced, leading to the âcytokine storm.â Among these, interleukin (IL)-6, tumor necrosis factorâα (TNFâα), and IL-1ÎČ seem to have a central role in the progression and exacerbation of the disease, leading to the recruitment of immune cells to infection sites. Autophagy is an evolutionarily conserved lysosomal degradation pathway involved in different aspects of lymphocytes functionality. The involvement of IL-6, TNFâα, and IL-1ÎČ in autophagy modulation has recently been demonstrated. Moreover, preliminary studies showed that SARS-CoV-2 could infect lymphocytes, playing a role in the modulation of autophagy. Several anti-rheumatic drugs, now proposed for the treatment of COVID-19, could modulate autophagy in lymphocytes, highlighting the therapeutic potential of targeting autophagy in SARS-CoV-2 infection
Flexible Bioelectronic Devices Based on Micropatterned Monolithic Carbon Fiber Mats
Polymer-derived carbon can serve as an electrode material in multimodal neural stimulation, recording, and neurotransmitter sensing platforms. The primary challenge in its applicability in implantable, flexible neural devices is its characteristic mechanical hardness that renders it difficult to fabricate the entire device using only carbon. A microfabrication technique is introduced for patterning flexible, cloth-like, polymer-derived carbon fiber (CF) mats embedded in polyimide (PI), via selective reactive ion etching. This scalable, monolithic manufacturing method eliminates any joints or metal interconnects and creates electrocorticography electrode arrays based on a single CF mat. The batch-fabricated CF/PI composite structures, with critical dimension of 12.5 ”m, are tested for their mechanical, electrical, and electrochemical stability, as well as to chemicals that mimic acute postsurgery inflammatory reactions. Their recording performance is validated in rat models. Reported CF patterning process can benefit various carbon microdevices that are expected to feature flexibility, material stability, and biocompatibility
Tofacitinib May Inhibit Myofibroblast Differentiation from Rheumatoid-Fibroblast-like Synoviocytes Induced by TGF-ÎČ and IL-6
During rheumatoid arthritis (RA), the pathogenic role of resident cells within the synovial membrane is suggested, especially for a population frequently referred to as fibroblast-like synoviocytes (FLSs). In this study, we assess the markers of myofibroblast differentiation of RA-FLSs by ex vivo observations and in vitro evaluations following the stimulation with both TGF-ÎČ and IL-6. Furthermore, we investigated the possible inhibiting role of tofacitinib, a JAK inhibitor, in this context. Myofibroblast differentiation markers were evaluated on RA synovial tissues by immune-fluorescence or immune-histochemistry. RA-FLSs, stimulated with transforming growth factor (TGF-ÎČ) and interleukin-6 (IL-6) with/without tofacitinib, were assessed for myofibroblast differentiation markers expression by qRT-PCR and Western blot. The same markers were evaluated following JAK-1 silencing by siRNA assay. The presence of myofibroblast differentiation markers in RA synovial tissue was significantly higher than healthy controls. Ex vivo, α-SMA was increased, whereas E-Cadherin decreased. In vitro, TGF-ÎČ and IL-6 stimulation of RA-FLSs promoted a significant increased mRNA expression of collagen I and α-SMA, whereas E-Cadherin mRNA expression was decreased. In the same conditions, the stimulation with tofacitinib significantly reduced the mRNA expression of collagen I and α-SMA, even if the Western blot did not confirm this finding. JAK-1 gene silencing did not fully prevent the effects of stimulation with TGF-ÎČ and IL-6 on these features. TGF-ÎČ and IL-6 stimulation may play a role in mediating myofibroblast differentiation from RA-FLSs, promoting collagen I and α-SMA while decreasing E-Cadherin. Following the same stimulation, tofacitinib reduced the increases of both collagen I and α-SMA on RA-FLSs, although further studies are needed to fully evaluate this issue and confirm our results
CD4 T lymphocyte autophagy is upregulated in the salivary glands of primary Sjögrenâs syndrome patients and correlates with focus score and disease activity
Background: Primary Sjögrenâs syndrome (pSS) is a common chronic autoimmune disease characterized by
lymphocytic infiltration of exocrine glands and peripheral lymphocyte perturbation. In the current study, we
aimed to investigate the possible pathogenic implication of autophagy in T lymphocytes in patients with pSS.
Methods: Thirty consecutive pSS patients were recruited together with 20 patients affected by sicca syndrome a
nd/or chronic sialoadenitis and 30 healthy controls. Disease activity and damage were evaluated according to SS
disease activity index, EULAR SS disease activity index, and SS disease damage index. T lymphocytes were analyzed
for the expression of autophagy-specific markers by biochemical, molecular, and histological assays in peripheral
blood and labial gland biopsies. Serum interleukin (IL)-23 and IL-21 levels were quantified by enzyme-linked
immunosorbent assay.
Results: Our study provides evidence for the first time that autophagy is upregulated in CD4+ T lymphocyte salivary
glands from pSS patients. Furthermore, a statistically significant correlation was detected between lymphocyte
autophagy levels, disease activity, and damage indexes. We also found a positive correlation between autophagy
enhancement and the increased salivary gland expression of IL-21 and IL-23, providing a further link between innate
and adaptive immune responses in pSS.
Conclusions: These findings suggest that CD4+ T lymphocyte autophagy could play a key role in pSS pathogenesis.
Additionally, our data highlight the potential exploitation of T cell autophagy as a biomarker of disease activity and
provide new ground to verify the therapeutic implications of autophagy as an innovative drug target in pSS
Anti-D4GDI antibodies activate platelets in vitro. a possible link with thrombocytopenia in primary antiphospholipid syndrome
Background: Thrombocytopenia is a manifestation associated with primary antiphospholipid syndrome (PAPS), and many studies have stressed the leading role played by platelets in the pathogenesis of antiphospholipid syndrome (APS). Platelets are highly specialized cells, and their activation involves a series of rapid rearrangements of the actin cytoskeleton. Recently, we described the presence of autoantibodies against D4GDI (Rho GDP dissociation inhibitor beta, ARHGDIB) in the serum of a large subset of SLE patients, and we observed that anti-D4GDI antibodies activated the cytoskeleton remodeling of lymphocytes by inhibiting D4GDI and allowing the upregulation of Rho GTPases, such as Rac1. Proteomic and transcriptomic studies indicate that D4GDI is very abundant in platelets, and small GTPases of the RHO family are critical regulators of actin dynamics in platelets. Methods: We enrolled 38 PAPS patients, 15 patients carrying only antiphospholipid antibodies without clinical criteria of APS (aPL carriers) and 20 normal healthy subjects. Sera were stored at - 20 °C to perform an ELISA test to evaluate the presence of anti-D4GDI antibodies. Then, we purified autoantibodies anti-D4GDI from patient sera. These antibodies were used to conduct in vitro studies on platelet activation. Results: We identified anti-D4GDI antibodies in sera from 18/38 (47%) patients with PAPS, in sera from 2/15(13%) aPL carriers, but in no sera from normal healthy subjects. Our in vitro results showed a significant 30% increase in the activation of integrin αIIbÎČ3 upon stimulation of platelets from healthy donors preincubated with the antibody anti-D4GDI purified from the serum of APS patients. Conclusions: In conclusion, we show here that antibodies anti-D4GDI are present in the sera of PAPS patients and can prime platelet activation, explaining, at least in part, the pro-thrombotic state and the thrombocytopenia of PAPS patients. These findings may lead to improved diagnosis and treatment of APS
Novel analgesic/anti-inflammatory agents: 1,5-diarylpyrrole nitrooxyalkyl ethers and related compounds as cyclooxygenase-2 inhibiting nitric oxide donors
A series of 3-substituted 1,5-diarylpyrroles bearing a nitrooxyalkyl side chain linked to different spacers were designed. New classes of pyrrole-derived nitrooxyalkyl inverse esters, carbonates, and ethers (7-10) as COX-2 selective inhibitors and NO donors were synthesized and are herein reported. By taking into account the metabolic conversion of nitrooxyalkyl ethers (9, 10) into corresponding alcohols, derivatives 17 and 18 were also studied. Nitrooxy derivatives showed NO-dependent vasorelaxing properties, while most of the compounds proved to be very potent and selective COX-2 inhibitors in in vitro experimental models. Further in vivo studies on compounds 9a,c and 17a highlighted good anti-inflammatory and antinociceptive activities. Compound 9c was able to inhibit glycosaminoglycan (GAG) release induced by interleukin-1ÎČ (IL-1ÎČ), showing cartilage protective properties. Finally, molecular modeling and (1)H- and (13)C-NMR studies performed on compounds 6c,d, 9c, and 10b allowed the right conformation of nitrooxyalkyl ester and ether side chain of these molecules within the COX-2 active site to be assessed
PREVALENCE OF HELICOBACTER PYLORI TEN YEARS AGO COMPARED TO THE CURRENT PREVALENCE IN PATIENTS UNDERGOING UPPER ENDOSCOPY
CD4 T lymphocyte autophagy is upregulated in the salivary glands of primary Sjögrenâs syndrome patients and correlates with focus score and disease activity
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