Chemical Profiling, Antioxidant, and Anti-Inflammatory Activities of Hyoseris radiata L., a Plant Used in the Phytoalimurgic Tradition.

Hyoseris radiata L. (Asteraceae), known as "wild chicory", is a perennial herbaceous plant native to the Mediterranean region, North Africa, and West Asia. Collected from the wild, the plant is largely used in Italy for culinary purposes and in popular medicine, so that it can be included in the list of phytoalimurgic plants. The present study aimed to investigate for the first time the plant's chemical profile, through a combined UHPLC-HR-ESI-Orbitrap/MS and NMR approach, and its potential healthy properties, focusing on antioxidant and anti-inflammatory activities. The LC-MS/MS analysis and the isolation through chromatographic techniques of the plant's hydroalcoholic extract allowed the authors to identify 48 compounds, including hydroxycinnamic acids, flavonoids, megastigmane glucosides, coumarins, and lignans, together with several unsaturated fatty acids. The quantitative analysis highlighted a relevant amount of flavonoids and hydroxycinnamic acids, with a total of 12.9 ± 0.4 mg/g DW. NMR-based chemical profiling revealed the presence of a good amount of amino acids and monosaccharides, and chicoric and chlorogenic acids as the most representative polyphenols. Finally, the antioxidant and anti-inflammatory activities of H. radiata were investigated through cell-free and cell-based assays, showing a good antioxidant potential for the plant extract and a significant reduction in COX-2 expression.

Characterization of Health Beneficial Components in Discarded Leaves of Three Escarole (Cichorium endivia L.) Cultivar and Study of Their Antioxidant and Anti-Inflammatory Activities.

Plants of genus Cichorium (Asteraceae) can be used as vegetables with higher nutritional value and as medicinal plants. This genus has beneficial properties owing to the presence of a number of specialized metabolites such as alkaloids, sesquiterpene lactones, coumarins, unsaturated fatty acids, flavonoids, saponins, and tannins. Cichorium endivia L., known as escarole, has achieved a common food status due to its nutritionary value, bitter taste, and the presence of healthy components, and is eaten cooked or raw in salads. Presently, wastes derived from the horticultural crops supply chain are generated in very large amounts. Vegetable waste comprises the discarded leaves of food sources produced during collection, handling, transportation, and processing. The external leaves of Cichorium endivia L. are a horticultural crop that is discarded. In this work, the phytochemical profile, antioxidant, and anti-inflammatory activities of hydroalcoholic extract obtained from discarded leaves of three cultivars of escarole (C. endivia var. crispum 'Capriccio', C. endivia var. latifolium 'Performance' and 'Leonida') typical horticultural crop of the Campania region were investigated. In order to describe a metabolite profile of C. endivia cultivars, the extracts were analysed by HR/ESI/Qexactive/MS/MS and NMR. The careful analysis of the accurate masses, the ESI/MS spectra, and the 1H NMR chemical shifts allowed for the identification of small molecules belonging to phenolic, flavonoid, sesquiterpene, amino acids, and unsaturated fatty acid classes. In addition, the antioxidant potential of the extracts was evaluated using cell-free and cell-based assays, as well as their cytotoxic and anti-inflammatory activity. All the extracts showed similar radical-scavenging ability while significant differences between the three investigated cultivars emerged in the cell-based assays. The obtained data were ascribed to the content of polyphenols and sesquiterpenes in the extracts. Accordingly, C. endivia by-products can be deemed an interesting material for healthy product formulations.

Autonomic dysfunction in progressive supranuclear palsy.

BACKGROUND: The degree of involvement of the autonomic nervous system in progressive supranuclear palsy (PSP) has been investigated in several studies, often providing conflicting results. There is a need for a better characterization of autonomic dysfunction in PSP, to enhance our understanding of this highly disabling neurodegenerative disease including patients' needs and possibly be of value for clinicians in the differential diagnosis among Parkinsonian syndromes. METHODS: We applied a systematic methodology to review existing literature on Pubmed regarding autonomic nervous system involvement in PSP. RESULTS: PSP reported quite frequently symptoms suggestive of autonomic dysfunction in all domains. Cardiovascular autonomic testing showed in some cases a certain degree of impairment (never severe). There was some evidence suggesting bladder dysfunction particularly in the storage phase. Dysphagia and constipation were the most common gastrointestinal symptoms. Instrumental tests seemed to confirm sudomotor and pupillomotor disturbances. CONCLUSIONS: PSP patients frequently reported visceral symptoms, however objective testing showed that not always these reflected actual autonomic impairment. Further studies are needed to better delineate autonomic profile and its prognostic role in PSP.

The Bologna motor and non-motor prospective study on parkinsonism at onset (BoProPark): study design and population.

OBJECTIVE: The Bologna motor and non-motor prospective study on parkinsonism at onset (BoProPark) was designed to prospectively characterize motor and non-motor features in patients with a progressive neurodegenerative disease starting with parkinsonism since early disease stage and to investigate their diagnostic and prognostic role in the differential diagnosis of Parkinson's disease from atypical parkinsonisms. The aim of this paper is to describe the method and population of the BoProPark study. METHODS: Patients referred to our Department with parkinsonism within 3 years from motor onset were recruited. Secondary causes of parkinsonism were excluded. Each patient underwent a comprehensive evaluation of motor and non-motor symptoms, assessed by means of quantitative, objective instrumental tests in addition to scales and questionnaires. The evaluations were performed at enrolment (T0), after 16 months (T1) and after 5 years (T2). Diagnoses were made according to consensus criteria. RESULTS: We recruited 150 patients, with mean age 61.5 ± 9.8 years and mean disease duration 20 ± 9 months. H&Y stage was 1 in 47.3% and 2 in 46.7% of cases. Mean UPDRS-III was 17.7 ± 9.2. Fifty-four patients were on dopaminergic treatment with median levodopa equivalent daily dose (LEDD) of 200 mg. CONCLUSIONS: We expect that the prospective nature of the BoProPark study as well as the comprehensive, instrumental evaluation of motor and non-motor symptoms in patients with parkinsonism will provide important new insights for both clinical practice and research. Our data could be used for comparison with other cohorts and shared with national and international collaborators to develop new innovative projects.

Pulmonary Hypertension in COVID-19 Pneumoniae: It Is Not Always as It Seems.

A patient affected by COVID-19 pneumonia may develop pulmonary hypertension (PH) and secondary right ventricular (RV) involvement, due to lung parenchymal and interstitial damage and altered pulmonary haemodynamics, even in non-advanced phases of the disease. This is a consequence of hypoxic vasoconstriction of the pulmonary circulation, the use of positive end-expiratory pressure (PEEP) in mechanical ventilation, pulmonary endothelial injury, and local inflammatory thrombotic and/or thromboembolic processes. We report the case of a young man admitted with a diagnosis of COVID-19 pneumoniae with PH unrelated to viral infection and in whom partial anomalous pulmonary venous drainage (PAPVD) was eventually diagnosed. LEARNING POINTS: COVID-19 patients, even if previously well, can have pulmonary hypertension due to other causes.The cause of pulmonary hypertension should always be sought and not assumed, even in COVID-19 patients.

Quantitative and qualitative effect of gH625 on the nanoliposome-mediated delivery of mitoxantrone anticancer drug to HeLa cells.

The present work investigates in vitro the delivery of the anticancer drug mitoxantrone (MTX) to HeLa cancer cells by means of polyethylene glycol (PEG) liposomes functionalized with the novel cell penetrating peptide gH625. This hydrophobic peptide enhances the delivery of doxorubicin (Doxo) to the cytoplasm of cancer cells, while the mechanism of this enhancement has not yet been understood. Here, in order to get a better insight into the role of gH625 on the mechanism of liposome-mediated drug delivery, we treated HeLa cells with liposomes functionalized with gH625 and loaded with MTX; functionalized and not liposome were characterized in terms of their physico-chemical properties and drug release kinetics. To quantify the MTX uptake and to study the subcellular drug distribution and interaction, we took advantage of the intrinsic fluorescence of MTX and of the fluorescence-based techniques like fluorescence-activated cell sorting (FACS) and confocal spectral imaging (CSI). FACS data confirmed that gH625 increases the total intracellular MTX content. CSI data indicated that when liposomes are decorated with gH625 an enhanced staining of the internalized drug is observed mainly in hydrophobic regions of the cytoplasm, where the increased presence of an oxidative metabolite of the drug is observed. The cytotoxicity on HeLa cell line was higher for functionalized liposomes within 4-6h of treatment. To summarise, the MTX delivery with gH625-decorated nanoliposomes enhances the quantity of both the intracellular drug and of its oxidative metabolite and contributes to higher anticancer efficacy of the drug at the delay of 4-6h.

Management of arthropathy in inflammatory bowel diseases.

The most common extra-intestinal manifestation in patients with inflammatory bowel disease (IBD) is articular involvement, with a prevalence ranging between 17% and 39%. It is frequently characterized by an involvement of the axial joints but may also be associated with peripheral arthritis. The target of therapy in the management of arthritis associated with IBD is to reduce the inflammation and prevent any disability and/or deformity. This requires active cooperation between gastroenterologist and rheumatologist. The treatment of axial involvement has focused on the combination of exercise with nonsteroidal anti-inflammatory drugs. Immunomodulators have been efficacious in patients with peripheral arthritis and other extra-intestinal manifestations, but they are not effective for the treatment of axial symptoms of spondylitis. Tumor necrosis factor (TNF) α inhibitors have been proven to be highly effective in the treatment of IBD patients which are steroid-dependent or refractory to conventional therapy and in patients with associated articular manifestations. The treatment of peripheral involvement and/or enthesitis and/or dactylitis is based on local steroid injections, while sulfasalazine and/or low doses of systemic steroids may be useful in case of inadequate response to intra-articular steroids. Sulfasalazine induces only a little improvement in peripheral arthritis. Immunomodulators such as methotrexate, azathioprine, cyclosporine and leflunomide show their efficacy in some patients with peripheral arthritis and other extra-intestinal components. TNF-α inhibitors should be considered the first-line therapeutic approach when moderate-to-severe luminal Crohn's disease or ulcerative colitis is associated with polyarthritis. The aim of this review is to provide a fair summary of current treatment options for the arthritis associated with IBD.

Extra-articular manifestations in psoriatic arthritis patients.

Psoriatic arthritis (PsA) is an inflammatory rheumatic disorder, associated with skin and/or nail psoriasis. It has been included in the spondyloarthropathies (SpA) group, with which it shares clinical, radiologic, and serologic features and familial and genetic relationship. Inclusion of disease among SpA is also based on their striking points of similarity for extra-articular manifestations (EAMs). The aim of study was to describe the EAMs in patients with PsA, evaluating the prevalence and clinical features associated with established and early PsA. The study was a retrospective analysis of case records of 387 PsA patients. Data recorded were demographic data, disease properties, laboratory tests, drug use, and presence of EAMs. Of 387 PsA patients, 190 have shown EAMs: 33.16 % had bowel involvement, 32.63 % ocular, 28.42 % cardiovascular, 25.79 % urogenital, 8.42 % skin (excluding psoriasis), 1.05 % pulmonary, and 0.53 % renal. A higher prevalence of EAMs was found in axial subset (p < 0.0001) and in established PsA patients (p = 0.03). The disease activity in PsA patients with EAMs was significantly higher (p < 0.0005). Smoker PsA patients had a significantly higher prevalence of EAMs than nonsmoker PsA patients (p < 0.0005). EAMs in PsA patients are common than expected and frequently associated with established form and axial subset. EAMs were more frequent in male gender, and the contemporary presence of male gender and axial subset showed a higher risk to develop EAMs. EAMS were more frequent in patients with a long disease duration and active disease. Moreover, these results suggest that in PsA patients, an initial checkup and a regular screening for EAMs are requested to ensure an appropriate management.

Thalassemic trait prevalence in patients affected by psoriatic arthritis in anti-TNF treatment.

Thalassemic trait (Thal) is associated with rheumatic disease, particularly a mild form of seronegative polyarthritis resembling rheumatoid arthritis (RA), but not with other rheumatic diseases. The aim of this study was to estimate the frequency of Thal in patients with psoriatic arthritis (PsA) and to evaluate the efficacy of anti-tumor necrosis factor alpha (TNF-α) therapy in patients with PsA and Thal. We performed a retrospective study in 321 patients with PsA who started therapy with TNF-α blockers. For all patients included in the study, at baseline and every 3 months for the 1 year of follow up, data concerning PsA activity and ferritin levels were registered. In our group of PsA patients, a total of 27 (8%) with concomitant Thal were identified and included in the study. In patients without Thal, all variables improved significantly after 6 months of therapy, while in patients with Thal, the same variables showed a significant decrease after 12 months.: Our study shows that PsA is significantly associated with Thal, but further studies are needed to address this issue. The presence of Thal could be a negative predictor of achieving remission during treatment with TNF-α-blockers.

Osteoporosis and psoriatic arthritis.

Osteoporosis (OP) is a skeletal disorder characterized by compromised bone strength that predisposes to an increased risk of fracture. The prevalence of OP in the general population is very high as established in several studies, and OP represents one of the possible aspects of bone involvement in arthritis. In psoriatic arthritis this involvement is particularly complex because it affects not only mechanisms of bone loss but also of bone formation. We will discuss these aspects and the available epidemiological data.

Imatinib treatment inhibit IL-6, IL-8, NF-KB and AP-1 production and modulate intracellular calcium in CML patients.

Imatinib (IM) is considered the gold standard for chronic myeloid leukemia (CML) treatment, although resistance is emerging as a significant problem. The proinflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8) play an important role in cell proliferation, survival, and resistance to glucocorticoid-mediated cell death. Several transcription factors such as NF-KB and AP-1 are activated in response to physiopathological increases and modulation of intracellular calcium levels. Our previous study demonstrated that lymphocytes from CML patients showed dysregulated calcium homeostasis and oxidative stress. Alteration in ionized calcium concentration in the cytosol has been implicated in the initiation of secretion, contraction, and cell proliferation. In this study, we hypothesized that IL-6, IL-8, NF-kB, AP-1, and intracellular calcium may be used as selective and prognostic factors to address the follow-up in CML patients treated with imatinib. Our results demonstrated a significant down-regulation in IL-6 and IL-8 release as well as NF-kB and AP-1 activation in lymphomonocytes from Imatinib-treated patients, compared to samples from untreated patients. In parallel, IM treatment, in vivo and in vitro, were able to modulate the intracellular calcium concentration of peripheral blood mononuclear cells of CML patients by acting at the level of InsP(3) receptor in the endoplasmic reticulum and at the level of the purinergic receptors on plasma membrane. The results of this study show that measurements of NF-kB, AP-1, IL-6, IL-8, and intracellular calcium in CML patients treated with Imatinib may give important information to the hematologist on diagnostic criteria and are highly predictive in patients with newly diagnosed CML.

A peptide derived from herpes simplex virus type 1 glycoprotein H: membrane translocation and applications to the delivery of quantum dots.

Cell membranes are impermeable to most molecules that are not actively imported by living cells, including all macromolecules and even small molecules whose physiochemical properties prevent passive membrane diffusion. However, recently, we have seen the development of increasingly sophisticated methodology for intracellular drug delivery. Cell-penetrating peptides (CPPs), short peptides believed to enter cells by penetrating cell membranes, have attracted great interest in the hope of enhancing gene therapy, vaccine development and drug delivery. Nevertheless, to achieve an efficient intracellular delivery, further strategies to bypass the endocytotic pathway must be investigated. We report on a novel peptide molecule derived from glycoprotein gH of herpes simplex type I virus that is able to traverse the membrane bilayer and to transport a cargo into the cytoplasm with novel properties in comparison with existing CPPs. We use as cargo molecule quantum dots that do not significantly traverse the membrane bilayer on their own. FROM THE CLINICAL EDITOR: Cell-penetrating peptides have recently attracted great interest in optimizing gene therapy, vaccine development and drug delivery. In this study, a peptide derived from glycoprotein gH of herpes simplex I is investigated from this standpoint.

Rheumatic complaints in women taking aromatase inhibitors for treatment of hormone-dependent breast cancer.

BACKGROUND: The rheumatic adverse effects accompanying treatment with aromatase inhibitors (AIs) in hormone-dependent breast cancer represent an area of clinical relevance and emerging concern. This report describes these rheumatic complaints detailing their clinical pattern. METHODS: During 1-year period, 18 consecutive postmenopausal women (mean age, 58.33 years; range, 52-66 years) in treatment with AIs for hormone-dependent breast cancer (mean duration of therapy, 12.0 months; range, 9.1-17.7 months) were referred for evaluation in the outpatient clinic of the rheumatology unit in relation to rheumatic complaints. According to a routine protocol planned with oncologists, patient evaluations consisted of a complete clinical examination with careful assessment of rheumatic complaints and related physical symptoms, followed by laboratory testing and a bone scintiscan. In no cases were rheumatic complaints present before AI therapy. RESULTS: On the basis of clinical data and investigations and by applying accepted diagnostic criteria, a diagnosis of an undifferentiated spondyloarthropathy was reached in 10 (55.5%) of the 18 patients studied, and an oligoarthritis was shown in 2 more patients (11.1%), whereas a simple arthralgia was found in the remaining 6 patients (33.3%). In the patients meeting criteria as belonging to a spondyloarthritic subset, a family history positive for psoriasis and celiac disease was shown in 2 and 1 instance, respectively, whereas HLA-CW6 and HLA-B27 were detected in 3 and 1 case. A high serum level of anti-cyclic citrullinated peptide antibodies was shown in 1 patient with oligoarthritis. Most of the patients (16/18) were treated with nonsteroidal anti-inflammatory drugs or with corticosteroids. Methotrexate (10 mg weekly) was added in 3 of these patients, nonresponders. Aromatase inhibitor discontinuation was needed in the remaining 2 cases with spontaneous resolution of symptoms over time. CONCLUSIONS: Data from the present study emphasize a previously unsuspected high prevalence of defined arthritides underlying these rheumatic complaints. Therefore, investigative efforts should be addressed to better clarify the clinical and pathogenetic significance of these important consequences of AI therapy. An accurate monitoring of rheumatic complaints has to be suggested to patients taking AI therapy, with a rapid referral to a rheumatologist in the case of consistent suspicion of an inflammatory arthritis.