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1.
EMBO J ; 40(4): e105120, 2021 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-33368531

RESUMEN

Autophagy is a lysosome-dependent degradation pathway essential to maintain cellular homeostasis. Therefore, either defective or excessive autophagy may be detrimental for cells and tissues. The past decade was characterized by significant advances in molecular dissection of stimulatory autophagy inputs; however, our understanding of the mechanisms that restrain autophagy is far from complete. Here, we describe a negative feedback mechanism that limits autophagosome biogenesis based on the selective autophagy-mediated degradation of ATG13, a component of the ULK1 autophagy initiation complex. We demonstrate that the centrosomal protein OFD1 acts as bona fide autophagy receptor for ATG13 via direct interaction with the Atg8/LC3/GABARAP family of proteins. We also show that patients with Oral-Facial-Digital type I syndrome, caused by mutations in the OFD1 gene, display excessive autophagy and that genetic inhibition of autophagy in a mouse model of the disease, significantly ameliorates polycystic kidney, a clinical manifestation of the disorder. Collectively, our data report the discovery of an autophagy self-regulated mechanism and implicate dysregulated autophagy in the pathogenesis of renal cystic disease in mammals.


Asunto(s)
Proteínas Reguladoras de la Apoptosis/metabolismo , Autofagosomas/fisiología , Familia de las Proteínas 8 Relacionadas con la Autofagia/metabolismo , Autofagia , Proteínas Asociadas a Microtúbulos/metabolismo , Enfermedades Renales Poliquísticas/patología , Proteínas/metabolismo , Animales , Proteínas Reguladoras de la Apoptosis/genética , Familia de las Proteínas 8 Relacionadas con la Autofagia/genética , Humanos , Lisosomas/metabolismo , Lisosomas/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas Asociadas a Microtúbulos/genética , Enfermedades Renales Poliquísticas/etiología , Enfermedades Renales Poliquísticas/metabolismo , Proteínas/genética
2.
Int Ophthalmol ; 44(1): 93, 2024 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-38367121

RESUMEN

BACKGROUND: The most common retinal complications after glaucoma surgery are choroidal detachment, hypotony maculopathy, malignant glaucoma, vitreous hemorrhage, endophthalmitis and retinal detachment. However, if glaucoma surgery is a risk factor for the ERM development needs to be clarified. This study aims to assess the incidence of epiretinal membrane (ERM) in 2 years of follow-up in patients with primary open-angle glaucoma (POAG) treated with Ex-Press shunt implant. METHODS: A prospective, consecutive, single-center, case-control study. We enrolled patients affected by POAG and scheduled for Ex-Press device implant with or without concomitant cataract surgery. The control group was the contralateral eyes which continues anti-glaucomatous eyedrops. Complete ophthalmologic evaluation and spectral-domain optical coherence tomography were performed before surgery, at 6 months and 24 months of follow-up. RESULTS: Eighty-two eyes of 41 consecutive patients, 18 males and 23 females with a mean age of 70, 29 ± 8,45, were analyzed at 24 months. 39.1% of eyes developed ERM: 29.3% were cellophane macular reflex (CMR) and 9.8% were pre-macular fibrosis (PMF). In the control group, 19.5% of eyes developed ERM: 17.1% were CMR and 2.4% were PMF. No statistically significant difference was reported (p = 0.121) between treated and control group. ERM development did not affect significantly the central foveal thickness (260.13 ± 35.01 µm at baseline, 265.03 ± 34.90 µm at 6 months and 275.18 ± 33.31 µm at 24 months) and macular volume (7.75 ± 0.43 mm3 at baseline, 7.77 ± 0.48 mm3 at 6 months and 7.77 ± 0.46 mm3 at 24 months), remained comparable to reported average measures in healthy individuals during the follow-up. Concomitant cataract surgery did not increase the ERM incidence. CONCLUSION: Ex-Press implant may increase the ERM incidence regardless concomitant cataract surgery, accelerating or inducing a posterior vitreous detachment, such as other ocular surgical procedure. Nevertheless, the vast majority of ERM are CMR, not affecting the macular profile.


Asunto(s)
Catarata , Membrana Epirretinal , Glaucoma de Ángulo Abierto , Glaucoma , Masculino , Femenino , Humanos , Recién Nacido , Membrana Epirretinal/diagnóstico , Membrana Epirretinal/cirugía , Estudios de Casos y Controles , Glaucoma de Ángulo Abierto/cirugía , Glaucoma de Ángulo Abierto/complicaciones , Estudios Prospectivos , Estudios Retrospectivos , Glaucoma/complicaciones , Tomografía de Coherencia Óptica , Catarata/complicaciones
3.
Health Econ ; 31(5): 729-759, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35001469

RESUMEN

Air pollution has been shown to have adverse effects on many health outcomes including respiratory effects, cardiovascular effects, and mortality. However, evidence on the effects of prenatal exposure is still limited. We investigate the causal impact of prenatal exposure to air pollution on neonatal health in Italy in the 2000s. We exploit variation in rainfall shocks to instrument for non-random air pollution exposure. Our empirical setting combines detailed information on mother's residential location from birth certificates with PM10 concentrations from air pollution monitors. Ten additional units in the average PM10 level (approximately one standard deviation) would decrease birth weight by about 0.5% and gestational age by 0.16%; it would increase the prevalence of low birth weight by 22% and of preterm birth by 16%. The effects are stronger in magnitude for third trimester exposure and for less educated mothers. These findings suggest that the health impacts of air pollution on newborns are unequally distributed in the population.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Nacimiento Prematuro , Efectos Tardíos de la Exposición Prenatal , Contaminantes Atmosféricos/toxicidad , Contaminación del Aire/estadística & datos numéricos , Femenino , Humanos , Salud del Lactante , Recién Nacido , Embarazo , Nacimiento Prematuro/epidemiología
4.
Health Econ ; 31(8): 1770-1799, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35709182

RESUMEN

We investigate the impact of the Great Recession in Italy on the incidence of chronic diseases using new individual longitudinal data from Electronic Health Records. We exploit the exogenous shock in the economic conditions occurred in 2008 to estimate heterogeneous effects of an unprecedented rise in local unemployment rates in an individual fixed-effects model. Our results document that harsh economic downturns have a negative long-lasting effect on cardiovascular disease and a temporary effect on depression. This effect is heterogeneous across gender, increases with age and is stronger right before the retirement age. An important policy recommendation emerging from this study is that prolonged economic downturns constitute an additional external risk for individual health and not a temporary benefit.


Asunto(s)
Recesión Económica , Registros Electrónicos de Salud , Estado de Salud , Humanos , Jubilación , Desempleo
5.
Nucleic Acids Res ; 48(D1): D416-D421, 2020 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-31598703

RESUMEN

CancerGeneNet (https://signor.uniroma2.it/CancerGeneNet/) is a resource that links genes that are frequently mutated in cancers to cancer phenotypes. The resource takes advantage of a curation effort aimed at embedding a large fraction of the gene products that are found altered in cancer cells into a network of causal protein relationships. Graph algorithms, in turn, allow to infer likely paths of causal interactions linking cancer associated genes to cancer phenotypes thus offering a rational framework for the design of strategies to revert disease phenotypes. CancerGeneNet bridges two interaction layers by connecting proteins whose activities are affected by cancer drivers to proteins that impact on the 'hallmarks of cancer'. In addition, CancerGeneNet annotates curated pathways that are relevant to rationalize the pathological consequences of cancer driver mutations in selected common cancers and 'MiniPathways' illustrating regulatory circuits that are frequently altered in different cancers.


Asunto(s)
Bases de Datos Genéticas , Neoplasias/genética , Proteínas/genética , Algoritmos , Antineoplásicos/farmacología , Gráficos por Computador , Humanos , Terapia Molecular Dirigida , Neoplasias/tratamiento farmacológico , Fenotipo , Interfaz Usuario-Computador
6.
Nucleic Acids Res ; 48(D1): D504-D510, 2020 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-31665520

RESUMEN

The SIGnaling Network Open Resource 2.0 (SIGNOR 2.0) is a public repository that stores signaling information as binary causal relationships between biological entities. The captured information is represented graphically as a signed directed graph. Each signaling relationship is associated to an effect (up/down-regulation) and to the mechanism (e.g. binding, phosphorylation, transcriptional activation, etc.) causing the up/down-regulation of the target entity. Since its first release, SIGNOR has undergone a significant content increase and the number of annotated causal interactions have almost doubled. SIGNOR 2.0 now stores almost 23 000 manually-annotated causal relationships between proteins and other biologically relevant entities: chemicals, phenotypes, complexes, etc. We describe here significant changes in curation policy and a new confidence score, which is assigned to each interaction. We have also improved the compliance to the FAIR data principles by providing (i) SIGNOR stable identifiers, (ii) programmatic access through REST APIs, (iii) bioschemas and (iv) downloadable data in standard-compliant formats, such as PSI-MI CausalTAB and GMT. The data are freely accessible and downloadable at https://signor.uniroma2.it/.


Asunto(s)
Bases de Datos Factuales , Transducción de Señal , Programas Informáticos , Animales , Humanos , Mapas de Interacción de Proteínas
7.
Aging Clin Exp Res ; 32(5): 935-950, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-31347102

RESUMEN

BACKGROUND: More than 60% of patients affected by pancreatic cancer are ≥ 65 years of age. Surgery represents the only potentially curative treatment for malignant pancreatic neoplasia and a useful treatment for benign diseases. AIM: To evaluate outcomes in elderly patients with ASA risk score 4 who underwent pancreatic resection compared to younger patients and elderly patients with lower anesthesiological risk. METHODS: A consecutive series of 345 patients underwent pancreatic resection between 2010 and 2017 was reviewed. We compared three groups based on age at the time of surgery: < 65 years (group A), 65-74 years (group B), and ≥ 75 years (group C). Patients in group C were split into two subgroups, ASA 1-3 versus ASA 4, and compared. RESULTS: Group A consisted of 117 (34%) patients, group B 128 (37%) patients, and group C 100 (29%) patients. Group C had a significantly higher incidence of comorbidity and ASA 4 status (p < 0.05), and of overall post-operative complications (p < 0.01), because of the higher incidence of post-operative medical complications. No differences in terms of overall surgical complications and post-operative mortality were reported. The mean overall survival was significantly lower for group C (p < 0.01), with no difference in mortality for cancer. Within group C, no differences were reported regarding surgical complications (p = 0.59), mortality (p = 0.34), and mean overall survival (p = 0.53) between ASA 1-3 and ASA 4 patients. CONCLUSIONS: Advanced age should not preclude elderly patients with pancreatic diseases from being treated surgically, and ASA 4 in subjects aged ≥ 75 years should not be an absolute contraindication.


Asunto(s)
Pancreatectomía , Centros de Atención Terciaria , Anciano , Anciano de 80 o más Años , Anestesiólogos , Comorbilidad , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pancreatectomía/efectos adversos , Neoplasias Pancreáticas/cirugía , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Estados Unidos
8.
Small ; 15(49): e1904399, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31592571

RESUMEN

As the hole transport layer (HTL) for perovskite solar cells (PSCs), poly(3-hexylthiophene) (P3HT) has been attracting great interest due to its low-cost, thermal stability, oxygen impermeability, and strong hydrophobicity. In this work, a new doping strategy is developed for P3HT as the HTL in triple-cation/double-halide ((FA1-x-y MAx Csy )Pb(I1-x Brx )3 ) mesoscopic PSCs. Photovoltaic performance and stability of solar cells show remarkable enhancement using a composition of three dopants Li-TFSI, TBP, and Co(III)-TFSI reaching power conversion efficiencies of 19.25% on 0.1 cm2 active area, 16.29% on 1 cm2 active area, and 13.3% on a 43 cm2 active area module without using any additional absorber layer or any interlayer at the PSK/P3HT interface. The results illustrate the positive effect of a cobalt dopant on the band structure of perovskite/P3HT interfaces leading to improved hole extraction and a decrease of trap-assisted recombination. Non-encapsulated large area devices show promising air stability through keeping more than 80% of initial efficiency after 1500 h in atmospheric conditions (relative humidity ≈ 60%, r.t.), whereas encapsulated devices show more than >500 h at 85 °C thermal stability (>80%) and 100 h stability against continuous light soaking (>90%). The boosted efficiency and the improved stability make P3HT a good candidate for low-cost large-scale PSCs.

9.
BMC Bioinformatics ; 17(Suppl 19): 506, 2016 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-28155642

RESUMEN

BACKGROUND: Macrophages cover a major role in the immune system, being the most plastic cell yielding several key immune functions. METHODS: Here we derived a minimalistic gene regulatory network model for the differentiation of macrophages into the two phenotypes M1 (pro-) and M2 (anti-inflammatory). RESULTS: To test the model, we simulated a large number of such networks as in a statistical ensemble. In other words, to enable the inter-cellular crosstalk required to obtain an immune activation in which the macrophage plays its role, the simulated networks are not taken in isolation but combined with other cellular agents, thus setting up a discrete minimalistic model of the immune system at the microscopic/intracellular (i.e., genetic regulation) and mesoscopic/intercellular scale. CONCLUSIONS: We show that within the mesoscopic level description of cellular interaction and cooperation, the gene regulatory logic is coherent and contributes to the overall dynamics of the ensembles that shows, statistically, the expected behaviour.


Asunto(s)
Diferenciación Celular , Redes Reguladoras de Genes , Macrófagos/citología , Macrófagos/metabolismo , Modelos Estadísticos , Biología de Sistemas/métodos , Regulación de la Expresión Génica , Humanos
10.
J Thromb Thrombolysis ; 41(4): 606-12, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26255069

RESUMEN

Prognostic stratification of acute pulmonary embolism (PE) remains a challenge in clinical practice. Simplified PESI (sPESI) score is a practical validated score aimed to stratify 30-day mortality risk in acute PE. Whether prognostic value of sPESI score differs according to sex has not been previously investigated. Therefore the aim of our study was to provide information about it. Data records of 452 patients, 180 males (39.8 %) and 272 females (60.2 %) discharged for acute PE from Internal Medicine wards of Tuscany (Italy) were analysed. sPESI was retrospectively calculated. Variables enclosed in sPESI score, all cause in-hospital mortality and overall bleedings were compared between sexes. Moreover, predictive ability of sPESI score as prognosticator of all cause in-hospital mortality was tested and compared between sexes. sPESI score 0 (low risk) was found in 17.7 % of males and 13.6 % of females (p = 0.2323). We didn't find significant difference in sPESI scoring distribution. Age ≥80 years (51.4 vs. 33.8 %, p = 0.0003) and heart rate ≥110 bpm (23.5 vs. 14.4 %, p = 0.0219) were found significantly more prevalent in females, whereas active cancer (23.8 vs. 39.4 %, p = 0.0004) and cardio-respiratory diseases (19.8 vs. 27.7 %, p = 0.0416) were in males. All cause in-hospital mortality was 0 % in both genders for sPESI score 0, whereas it was 5.4 % in females and 13.6 % in males with sPESI score 1-2 (p = 0.0208) and 22 % in females and 19.3 % in males with sPESI score ≥3 (p = 0.7776). Overall bleedings were significantly more frequent in females compared with males (4.77 vs. 0.55 %, p = 0.0189). In females overall bleedings ranged from 2.7 % in sPESI score 0 to 6 % in sPESI score ≥3. Predictive ability of sPESI score as prognosticator of all cause in-hospital mortality was higher in females compared to males (AUC 0.72 vs. 0.67, respectively). In real life different co-morbidity burdens in females compared to males. Females seems to be at lower risk of all cause in-hospital mortality for sPESI score ≤2 but at higher risk of bleeding, irrespective from sPESI scoring. Predictive ability of sPESI score seems better in females.


Asunto(s)
Embolia Pulmonar/mortalidad , Caracteres Sexuales , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Cardiopatías/mortalidad , Hemorragia/mortalidad , Mortalidad Hospitalaria , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Neoplasias/mortalidad , Prevalencia , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Tasa de Supervivencia
11.
Nanotechnology ; 26(49): 494002, 2015 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-26574237

RESUMEN

The past few years have witnessed remarkable progress in solution-processed methylammonium lead halide (CH3NH3PbX3, X = halide) perovskite solar cells (PSCs) with reported photoconversion efficiency (η) exceeding 20% in laboratory-scale devices and reaching up to 13% in their large area perovskite solar modules (PSMs). These devices mostly employ mesoporous TiO2 nanoparticles (NPs) as an electron transport layer (ETL) which provides a scaffold on which the perovskite semiconductor can grow. However, limitations exist which are due to trap-limited electron transport and non-complete pore filling. Herein, we have employed TiO2 nanorods (NRs), a material offering a two-fold higher electronic mobility and higher pore-filing compared to their particle analogues, as an ETL. A crucial issue in NRs' patterning over substrates is resolved by using precise Nd:YVO4 laser ablation, and a champion device with η ∼ 8.1% is reported via a simple and low cost vacuum-vapor assisted sequential processing (V-VASP) of a CH3NH3PbI3 film. Our experiments showed a successful demonstration of NRs-based PSMs via the V-VASP technique which can be applied to fabricate large area modules with a pin-hole free, smooth and dense perovskite layer which is required to build high efficiency devices.

12.
J Clin Med ; 13(11)2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38893053

RESUMEN

Background: The aim of this study was to determine if the rise in new surgical procedures for glaucoma is changing the baseline features of patients. Methods: In this retrospective study, we reviewed the baseline features of patients undergoing their first glaucoma surgery in 2011 and 2021, collecting data regarding intraocular pressure (IOP), visual field (VF) parameters, stage of disease, and the type of surgery. Results: In the study, 455 patients were included in the analysis. From these, 230 eyes had glaucoma surgery performed in 2011 (Group A) and 225 eyes in 2021 (Group B). When considering the baseline features, Group A was older than Group B (72.7 ± 10.7 and 70 ± 12.4 years; p = 0.02, respectively), and showed a significantly more advanced VF mean defect (-16.4 ± 8.8 and -13.8 ± 8.7 dB; p < 0.01, respectively) and a higher IOP (25.9 ± 6.6 and 24.9 ± 7.8 mmHg; p = 0.02, respectively). Overall, severe VF damage at the time of surgery was more frequent in Group A (74.3%) than in Group B (60.8%) (p < 0.01). The overall number of traditional glaucoma surgeries was 211 in 2011, reducing to 94 ten years later, with similar severe pre-operative VF defects. In 2021, minimally invasive bleb surgery (MIBS) represented 58% of all surgeries. Conclusions: In the last ten years, patients receiving glaucoma surgery for the first time were younger, had less severe disease, and a more contained IOP. The baseline feature modifications were probably related to the diffusion of new procedures, especially MIBS, which allowed for treating patients at an earlier stage, reserving traditional procedures for advanced cases.

13.
Nanomaterials (Basel) ; 14(3)2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38334553

RESUMEN

A water-processable and low-cost nanocomposite material, based on gelatin and graphene, has been used to fabricate an environmentally friendly temperature sensor. Demonstrating a temperature-dependent open-circuit voltage between 260 and 310 K, the sensor effectively detects subzero ice formation. Notably, it maintains a constant temperature sensitivity of approximately -19 mV/K over two years, showcasing long-term stability. Experimental evidence demonstrates the efficient regeneration of aged sensors by injecting a few drops of water at a temperature higher than the gelation point of the hydrogel nanocomposite. The real-time monitoring of the electrical characteristics during the hydration reveals the initiation of the regeneration process at the gelation point (~306 K), resulting in a more conductive nanocomposite. These findings, together with a fast response and low power consumption in the range of microwatts, underscore the potential of the eco-friendly sensor for diverse practical applications in temperature monitoring and environmental sensing. Furthermore, the successful regeneration process significantly enhances its sustainability and reusability, making a valuable contribution to environmentally conscious technologies.

14.
Comput Struct Biotechnol J ; 21: 4706-4716, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37841333

RESUMEN

In recent years, research on long non-coding RNAs (lncRNAs) has gained considerable attention due to the increasing number of newly identified transcripts. Several characteristics make their functional evaluation challenging, which called for the urgent need to combine molecular biology with other disciplines, including bioinformatics. Indeed, the recent development of computational pipelines and resources has greatly facilitated both the discovery and the mechanisms of action of lncRNAs. In this review, we present a curated collection of the most recent computational resources, which have been categorized into distinct groups: databases and annotation, identification and classification, interaction prediction, and structure prediction. As the repertoire of lncRNAs and their analysis tools continues to expand over the years, standardizing the computational pipelines and improving the existing annotation of lncRNAs will be crucial to facilitate functional genomics studies.

15.
Biomedicines ; 11(2)2023 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-36830948

RESUMEN

MYC oncoprotein deregulation is a common catastrophic event in human cancer and limiting its activity restrains tumor development and maintenance, as clearly shown via Omomyc, an MYC-interfering 90 amino acid mini-protein. MYC is a multifunctional transcription factor that regulates many aspects of transcription by RNA polymerase II (RNAPII), such as transcription activation, pause release, and elongation. MYC directly associates with Protein Arginine Methyltransferase 5 (PRMT5), a protein that methylates a variety of targets, including RNAPII at the arginine residue R1810 (R1810me2s), crucial for proper transcription termination and splicing of transcripts. Therefore, we asked whether MYC controls termination as well, by affecting R1810me2S. We show that MYC overexpression strongly increases R1810me2s, while Omomyc, an MYC shRNA, or a PRMT5 inhibitor and siRNA counteract this phenomenon. Omomyc also impairs Serine 2 phosphorylation in the RNAPII carboxyterminal domain, a modification that sustains transcription elongation. ChIP-seq experiments show that Omomyc replaces MYC and reshapes RNAPII distribution, increasing occupancy at promoter and termination sites. It is unclear how this may affect gene expression. Transcriptomic analysis shows that transcripts pivotal to key signaling pathways are both up- or down-regulated by Omomyc, whereas genes directly controlled by MYC and belonging to a specific signature are strongly down-regulated. Overall, our data point to an MYC/PRMT5/RNAPII axis that controls termination via RNAPII symmetrical dimethylation and contributes to rewiring the expression of genes altered by MYC overexpression in cancer cells. It remains to be clarified which role this may have in tumor development.

16.
J Glaucoma ; 32(5): 420-425, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-36795513

RESUMEN

PRCIS: Ultrasound cyclo plasty (UCP) using high-intensity focused ultrasound is an effective and safe procedure in lowering intraocular pressure (IOP) in patients with glaucoma, even in those with high myopia. PURPOSE: This study aimed to evaluate the efficacy and safety of UCP in glaucoma patients with high myopia. MATERIALS AND METHODS: In this retrospective, single-center study, we enrolled 36 eyes divided into 2 groups based on axial length: group A (≥26.00 mm) and group B (<26.00 mm). We collected data about visual acuity, Goldmann applanation tonometry, biomicroscopy, and visual field before the procedure and at 1, 7, 30, 60, 90, 180, and 365 days after the procedure. RESULTS: Mean IOP significantly decreased in both groups after treatment ( P <0.001). Mean IOP reduction from baseline to the last visit was 9.8±6.6 mmHg (38.7%) in group A and 9.6±6.3 mmHg (34.8%) in group B ( P <0.001). Mean IOP at the last visit was 15.8±4.1 mmHg in the myopic group and 18.1±5.6 mmHg in the non-myopic one. Regarding the number of IOP-lowering eyedrops being taken by our patients, statistically significant differences were found between groups A and B neither at baseline (2.8±0.9 and 2.6±1.0; P =0.568) nor 1 year after the procedure (2.5±1.1 and 2.6±1.1; P =0.762). No major complications occurred. All minor adverse events resolved within a few days. CONCLUSION: UCP seems to be an effective and well-tolerated strategy to lower IOP in glaucoma patients with high myopia.


Asunto(s)
Glaucoma de Ángulo Abierto , Glaucoma , Miopía , Humanos , Glaucoma de Ángulo Abierto/complicaciones , Glaucoma de Ángulo Abierto/diagnóstico , Glaucoma de Ángulo Abierto/cirugía , Presión Intraocular , Estudios Retrospectivos , Glaucoma/cirugía , Tonometría Ocular , Cuerpo Ciliar/cirugía , Miopía/complicaciones , Miopía/diagnóstico , Miopía/cirugía , Resultado del Tratamiento
17.
Autophagy ; 19(1): 24-43, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35613303

RESUMEN

Macroautophagy/autophagy is a self-degradative process necessary for cells to maintain their energy balance during development and in response to nutrient deprivation. Autophagic processes are tightly regulated and have been found to be dysfunctional in several pathologies. Increasing experimental evidence points to the existence of an interplay between autophagy and cilia. Cilia are microtubule-based organelles protruding from the cell surface of mammalian cells that perform a variety of motile and sensory functions and, when dysfunctional, result in disorders known as ciliopathies. Indeed, selective autophagic degradation of ciliary proteins has been shown to control ciliogenesis and, conversely, cilia have been reported to control autophagy. Moreover, a growing number of players such as lysosomal and mitochondrial proteins are emerging as actors of the cilia-autophagy interplay. However, some of the published data on the cilia-autophagy axis are contradictory and indicate that we are just starting to understand the underlying molecular mechanisms. In this review, the current knowledge about this axis and challenges are discussed, as well as the implication for ciliopathies and autophagy-associated disorders.


Asunto(s)
Autofagia , Ciliopatías , Humanos , Autofagia/fisiología , Cilios/metabolismo , Ciliopatías/metabolismo , Microtúbulos , Proteínas Mitocondriales/metabolismo
18.
Cell Biosci ; 13(1): 207, 2023 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-37957701

RESUMEN

BACKGROUND: Paediatric-type diffuse High-Grade Gliomas (PDHGG) are highly heterogeneous tumours which include distinct cell sub-populations co-existing within the same tumour mass. We have previously shown that primary patient-derived and optical barcoded single-cell-derived clones function as interconnected networks. Here, we investigated the role of exosomes as a route for inter-clonal communication mediating PDHGG migration and invasion. RESULTS: A comprehensive characterisation of seven optical barcoded single-cell-derived clones obtained from two patient-derived cell lines was performed. These analyses highlighted extensive intra-tumour heterogeneity in terms of genetic and transcriptional profiles between clones as well as marked phenotypic differences including distinctive motility patterns. Live single-cell tracking analysis of 3D migration and invasion assays showed that the single-cell-derived clones display a higher speed and longer travelled distance when in co-culture compared to mono-culture conditions. To determine the role of exosomes in PDHGG inter-clonal cross-talks, we isolated exosomes released by different clones and characterised them in terms of marker expression, size and concentration. We demonstrated that exosomes are actively internalized by the cells and that the inhibition of their biogenesis, using the phospholipase inhibitor GW4689, significantly reduced the cell motility in mono-culture and more prominently when the cells from the clones were in co-culture. Analysis of the exosomal miRNAs, performed with a miRNome PCR panel, identified clone-specific miRNAs and a set of miRNA target genes involved in the regulation of cell motility/invasion/migration. These genes were found differentially expressed in co-culture versus mono-culture conditions and their expression levels were significantly modulated upon inhibition of exosome biogenesis. CONCLUSIONS: In conclusion, our study highlights for the first time a key role for exosomes in the inter-clonal communication in PDHGG and suggests that interfering with the exosome biogenesis pathway may be a valuable strategy to inhibit cell motility and dissemination for these specific diseases.

19.
Biomedicines ; 11(1)2022 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-36672544

RESUMEN

Circular RNAs (circRNAs) are a class of single-stranded closed noncoding RNA molecules which are formed as a result of reverse splicing of mRNAs. Despite their relative abundance, only recently there appeared an increased interest in the understanding of their regulatory importance. Among their most relevant characteristics are high stability, abundance and evolutionary conservation among species. CircRNAs are implicated in several cellular functions, ranging from miRNA and protein sponges to transcriptional modulation and splicing. Additionally, circRNAs' aberrant expression in pathological conditions is bringing to light their possible use as diagnostic and prognostic biomarkers. Their use as indicator molecules of pathological changes is also supported by their peculiar covalent closed cyclic structure which bestows resistance to RNases. Their regulatory role in cancer pathogenesis and metastasis is supported by studies involving human tumors that have investigated different expression profiles of these molecules. As endogenous competitive RNA, circRNAs can regulate tumor proliferation and invasion and they arouse great consideration as potential therapeutic biomarkers and targets for cancer. In this review, we describe the most recent findings on circRNAs in the most common pediatric solid cancers (such as brain tumors, neuroblastomas, and sarcomas) and in more rare ones (such as Wilms tumors, hepatoblastomas, and retinoblastomas).

20.
Polymers (Basel) ; 14(20)2022 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-36298023

RESUMEN

An environmentally friendly hydrogel based on gelatin has been investigated as a gel polymer electrolyte in a symmetric carbon-based supercapacitor. To guarantee the complete sustainability of the devices, biomaterials from renewable resources (such as chitosan, casein and carboxymethyl cellulose) and activated carbon (from coconut shells) have been used as a binder and filler within the electrode, respectively. The electrochemical properties of the devices have been compared by using cyclic voltammetry, galvanostatic charge/discharge curves and impedance spectroscopy. Compared to the liquid electrolyte, the hydrogel supercapacitors show similar energy performance with an enhancement of stability up to 12,000 cycles (e.g., chitosan as a binder). The most performant device can deliver ca. 5.2 Wh/kg of energy at a high power density of 1256 W/kg. A correlation between the electrochemical performances and charge storage mechanisms (involving faradaic and non-faradaic processes) at the interface electrode/hydrogel has been discussed.

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