56 research outputs found
Olive Leaf Extract (OLE) as a Novel Antioxidant That Ameliorates the Inflammatory Response in Cystic Fibrosis
No full textThe deletion of phenylalanine at position 508 (F508del) produces a misfolded CFTR protein that is retained in the ER and degraded. The lack of normal CFTR channel activity is associated with chronic infection and inflammation which are the primary causes of declining lung function in Cystic Fibrosis (CF) patients. Moreover, LPS-dependent oxidative stress downregulates CFTR function in airway epithelial cells. Olive leaf extract (OLE) is used in traditional medicine for its effects, including anti-oxidant and anti-inflammatory ones. We found that OLE decreased the intracellular ROS levels in a dose-response manner in CFBE cells. Moreover, OLE attenuates the inflammatory response to LPS or IL-1 beta/TNF alpha stimulation, mimicking the infection and inflammatory status of CF patients, in CFBE and primary nasal epithelial (HNE) cells. Furthermore, we demonstrated that OLE restored the LPS-mediated decrease of Trikfafta (TM)-dependent F508del-CFTR function in CFBE and HNE cultures. These findings provide strong evidence of OLE to prevent redox imbalance and inflammation that can cause chronic lung damage by enhancing the antioxidant activity and attenuating inflammation in CF airway epithelial cells. Additionally, OLE might be used in combination with CFTR modulators therapy to improve their efficacy in CF patients
Cheiromyia laselva Brooks, sp. nov.
No full textCheiromyia laselva Brooks sp. nov. (Figs. 5 A–D, 8 B) Recognition (male). This species is very similar to C. brevitarsis Brooks sp. nov. (see above), but can be distinguished from that species based on the following features: left apv epandrial lobe with acute apicodorsal process (Fig. 5 A); face slightly wider. Description. Male: Body length: 4.6 mm, wing length: 3.8–3.9 mm. Head: Postocular setae: upper 5–7 dark, lower setae pale, lowermost 1–2 setae dark. Frons subrectangular (wider than high), dark with bluegreen and violet metallic reflections. Face silvery white, relatively broad (slightly wider than C. brevitarsis, cf. Fig. 2 B), sides convergent below. Clypeus concolorous with face, subquadrate. Palpus pale, ovoid, bare above, with several fine elongate setulae on lower edge. Proboscis: anterior surface of each labellar lobe with close-set row of 3 fine elongate hairs. Antenna: similar to C. brevitarsis and C. palmaticornis (cf. Fig. 1 B), scape, pedicel and base of postpedicel pale, apical part of postpedicel and stylus dark; scape obconical, with acute medial and ventral process; pedicel short; postpedicel ovoid basally with digitiform, pubescent apex, outer surface with 5 pubescent digitiform projections, basalmost projection broader, projections occasionally bifurcate; stylus dorsal, before middle of dorsal margin of postpedicel, basal article elongate, extending to tip of postpedicel, distal article strongly pubescent. Thorax: Scutum mainly metallic green with violet reflections or vice versa, dark bronze area above notopleuron immediately posterior to suture. Scutellum mainly metallic green with violet reflections or vice-versa. Mesopleuron gray pruinose with brownish background coloration and metallic green reflections. Legs: Mainly pale except as noted below. I: CxI infuscate; TI slightly swollen; tarsus I with pronounced outward bend, It 2 shorter than It 3, It 3–4 with row of erect setae on inner margin, setae more closely set on It 4, It 3–5 with pale velvety pile on ventral surface, claws enlarged and stout (often crossed in preserved specimens). II: CxII with lateral surface and outer margin of anterior surface dark; tarsus II weakly infuscate from tip of IIt 1- 5. III: CxIII with lateral surface dark; tarsus III weakly infuscate from tip of IIIt 1-5. Wing: Hyaline; with pronounced arc beyond bend, similar to C. brevitarsis (cf. Fig. 2 D). Abdomen: Tergites 1–5 metallic green, with silverish pruinosity laterally. Hypopygium (Figs. 5 A–D): Epandrium with bv epandrial lobe not developed; apv epandrial lobe projecting ventrally, with 2 long apicolateral setae, apicolateral margin forming a darkened crest narrowing to dentiform process apicoventrally, medial surface with bulging weakly sclerotized to membranous lobe, left apv epandrial lobe broader and longer than right lobe with acute apicodorsal projection, right lobe without with acute apicodorsal projection. Surstylus: dorsal arm with sac-like medioventral lobe, with short finger-like dorsal process bearing apical seta, apex with microtrichia ventrally; ventral arm with stout curved apical seta, subapical crest present. Postgonite digitiform. Cercus mainly pale with dark outer margin, subquadrate. Hypandrium with medial notch apically. Phallus slightly widened preapically, preapical flap-like dorsal process with weak longitudinal serrate ridges basally. Ejaculatory apodeme straight. Female: Unknown. Type material. HOLOTYPE 3, labelled: “ COSTA RICA: Heredia,/ La Selva Biological Station/ 10 ° 26 'N 84 °01'W, 50–150m,/ INBio-OET, 15.vii. 1993 / M/02/ 153 ”; “ HOLOTYPE / Cheiromyia laselva / Brooks” [red label] (INBC). PARATYPE: COSTA RICA: 13 Heredia, La Selva Research Station, 11– 17.vi. 1986, W. Hanson, G. Bohart (EMUS). Distribution. Cheiromyia laselva is only known from the holotype and paratype, both of which were collected at La Selva Biological Station (Fig. 8 B). Remarks. The morphological differences between C. laselva and C. brevitarsis are slight, but in our opinion, consistent and sufficient enough to warrant the recognition of two separate species. Etymology. This new species name is derived from La Selva Biological Station, where the type series was collected.Published as part of Brooks, Scott E., Cumming, Jeffrey M. & Pollet, Marc A. A., 2010, Revision of the Neotropical genus Cheiromyia Dyte (Diptera: Dolichopodidae), pp. 41-58 in Zootaxa 2333 on pages 50-52, DOI: 10.5281/zenodo.19313
IL-17 family members exert an autocrine pro-inflammatory loop in CF respiratory epithelial cells ex vivo
No full textBackground: Lungs of people with Cystic Fibrosis (pwCF) are characterized by chronic inflammation and infection with P. aeruginosa. High levels of IL-17 A and F have been observed in sputum of pwCF and the interleukin-17(IL17) family (A-to-F) has been suggested to play a key role in CF pulmonary disease. Methods: We measured mRNA levels of IL-17 receptors (IL-17R) by RT-qPCR in CF bronchial epithelial (CFBE) cultured cells upon infection with P. aeruginosa PAO1 strain or clinical exoproducts (EXO) isolated from pwCF. We measured IL-17 mRNA expression by RT-qPCR and the release of cytokines by ELISA and Bioplex from CF primary nasal epithelial (HNE) cultured cells. Results: Infection of CFBE cells with PAO1 or EXO isolated from 15 pwCF significantly increased mRNA expression of all IL-17R, except IL-17RD. Infection of HNE cells with EXO isolated from the correspondent donor significantly increased the mRNA levels of all the IL-17 cytokines and receptors, except for IL-17D and IL-17RD, and the release of the cytokines IL-17 A, IL-17B, IL-17C, IL-17E and IL-17F. HNE exposed to IL-17 A and F were induced to release pro-inflammatory cytokines (IL-1R, IL-6, TNF-alpha), neutrophil chemokines (IL-8, G-CSF) and cytokines known to be involved in chloride and bicarbonate secretion, together with mucin upregulation (IL-4, IL-13). Conclusion: These results highlight a wider expression of IL-17 family member in respiratory epithelial cells, which can play a role as an autocrine inflammatory amplification loop in CF airways. These in-vitro studies using patient-derived cultures underline the relevant role of IL-17 family members in CF pulmonary immune response
Phenotyping rare cftr mutations reveal functional expression defects restored by trikaftatm
No full textThe rare Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mutations, c.1826A > G (H609R) and c.3067_3072delATAGTG (I1023_V1024del), are associated with severe lung disease. Despite the existence of four CFTR targeted therapies, none have been approved for individuals with these mutations because the associated molecular defects were not known. In this study we examined the consequences of these mutations on protein processing and channel function in HEK293 cells. We found that, similar to F508del, H609R and I1023_V1024del-CFTR exhibited reduced protein processing and altered channel function. Because the I1023_V1024del mutation can be linked with the mutation, I148T, we also examined the protein conferred by transfection of a plasmid bearing both mutations. Interestingly, together with I148T, there was no further reduction in channel function exhibited by I1023-V1024del. Both H609R and I1023_V1024del failed to exhibit significant correction of their functional expression with lumacaftor and ivacaftor. In contrast, the triple modulator combination found in TRIKAFTATM, i.e., tezacaftor, elexacaftor and ivacaftor rescued trafficking and function of both of these mutants. These in-vitro findings suggest that patients harbouring H609R or I1023_V1024del, alone or with I148T, may benefit clinically from treatment with TRIKAFTATM
Improvement of Refractory Dysphagia in Patients with Idiopathic Inflammatory Myopathies Receveing Immunoglobulin Intravenous Therapy
No full textEfficacy of a soy rich diet in preventing postmenopausal osteoporosis: the Menfis randomized trial
No full textEfficacy of a soy rich diet in preventing postmenopausal osteoporosis: the Menfis randomized trial
No full textOP0129 Drug survival on anti-tnf-alpha in psoriatic arthritis patients with axial involvement and analysis of predictors
No full textLung Disease Management by Iloprost-Loaded Nanoparticles to Address Hyperinflammation Associated with Cystic Fibrosis
No full textHere, iloprost-loaded polymeric nanoparticles were embedded into mannitol microparticles by the nano into micro (NiM) strategy and were proposed as an inhalable formulation for the management of hyperinflammation associated with cystic fibrosis (CF). To do this, a polymeric derivate was synthesized by functionalization of alpha,beta-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA) with 3.2 mol % of poly(lactic-co-glycolic acid) (PLGA) and 4.5 mol % of poly(ethylene glycol) (PEG), which was used as a starting material to produce iloprost-loaded pegylated nanoparticles (NP_PEG+Ilo) by nanoprecipitation. These nanoparticles showed colloidal size (similar to 150 nm) and negative zeta potential; thanks to the high surface pegylation degree (35 molecules/100 nm(2)), they did not interact with mucins and were able to ensure a sustained release of the entrapped drug in a simulated physiological fluid (55 wt % after 24 h incubation). Then, the NP_PEG+Ilo particles were embedded in mannitol-based microparticles by spray-drying. The obtained NiM showed adequate characteristics for pulmonary administration in CF patients, such as spherical shape, micrometric size (similar to 2 mu m), the capability to not interact with the components of CF artificial mucus, and, once dispersed with water, the ability to rapidly dissolve and release the NP_PEG+Ilo. Moreover, the NP_PEG+Ilo, entrapped into NiM particles, exhibited high cytocompatibility and a pronounced anti-inflammatory effect toward CFBE cells overexpressing F508del CFTR (CFBE-F508del) in terms of reduction of IL-1 beta, TNF-alpha, IL-6, and IL-8 gene expression, thus demonstrating that this formulation could represent a potential pulmonary carrier for iloprost
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