Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 95
Filtrar
1.
J Colloid Interface Sci ; 605: 110-119, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34311305

RESUMO

Synthetic plastic oligomers can interact with the cells of living organisms by different ways. They can be intentionally administered to the human body as part of nanosized biomedical devices. They can be inhaled by exposed workers, during the production of multicomponent, polymer-based nanocomposites. They can leak out of food packaging. Most importantly, they can result from the degradation of plastic waste, and enter the food chain. A physicochemical characterization of the effects of synthetic polymers on the structure and dynamics of cell components is still lacking. Here, we combine a wide spectrum of experimental techniques (calorimetry, x-ray, and neutron scattering) with atomistic Molecular Dynamics simulations to study the interactions between short chains of polystyrene (25 monomers) and model lipid membranes (DPPC, in both gel and fluid phase). We find that doping doses of polystyrene oligomers alter the thermal properties of DPPC, stabilizing the fluid lipid phase. They perturb the membrane structure and dynamics, in a concentration-dependent fashion. Eventually, they modify the mechanical properties of DPPC, reducing its bending modulus in the fluid phase. Our results call for a systematic, interdisciplinary assessment of the mechanisms of interaction of synthetic, everyday use polymers with cell membranes.


Assuntos
1,2-Dipalmitoilfosfatidilcolina , Bicamadas Lipídicas , Varredura Diferencial de Calorimetria , Membrana Celular , Humanos , Simulação de Dinâmica Molecular , Poliestirenos
2.
Curr Oncol Rep ; 23(11): 134, 2021 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-34677721

RESUMO

PURPOSE OF REVIEW: Since the past year, the fast spread of coronavirus disease 2019 (COVID-19) has represented a global health threat, especially for cancer patients, that has required an urgent reorganization of clinical activities. Here, we will critically revise the profound impact that the pandemic has generated in lung cancer patients, as well the most significant challenges that oncologists have to face to maintain the highest possible standards in the management of lung cancer patients in the pandemic era. RECENT FINDINGS: Evidences suggested a higher susceptibility and mortality of lung cancer patients due to COVID-19. The hard management of this patient population has been also due to the potential cross interference of anti-tumor drugs on SARS-Cov-2 infection and to the differential diagnosis between COVID-19 pneumonitis and drug-related pneumonitis. COVID-19 pandemic has generated a profound reshaping of oncological activities and the development of recommendations by the oncology scientific community to prioritize anti-tumor treatments for lung cancer patients.


Assuntos
COVID-19/complicações , COVID-19/mortalidade , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/mortalidade , Pneumonia/diagnóstico , Antineoplásicos/farmacologia , Vacinas contra COVID-19 , Comorbidade , Diagnóstico Diferencial , Humanos , Oncologia/métodos , Pandemias , Fatores de Risco , SARS-CoV-2 , Tomografia Computadorizada por Raios X
3.
Biol Lett ; 17(9): 20210329, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34520682

RESUMO

In fish, vision may be impaired when eye tissue is in direct contact with environmental conditions that limit aerobic ATP production. We hypothesized that the visual acuity of fishes exposed to hydrogen sulfide (H2S)-rich water would be altered owing to changes in cytochrome c oxidase (COX) activity. Using the H2S-tolerant mangrove rivulus (Kryptolebias marmoratus), we showed that a 10 min exposure to greater than or equal to 200 µM of H2S impaired visual acuity and COX activity in the eye. Visual acuity and COX activity were restored in fish allowed to recover in H2S-free water for up to 1 h. Since K. marmoratus are found in mangrove pools with H2S concentrations exceeding 1000 µM, visual impairment may impact predator avoidance, navigation and foraging behaviour in the wild.


Assuntos
Ciprinodontiformes , Sulfeto de Hidrogênio , Animais , Sulfetos , Acuidade Visual , Áreas Alagadas
4.
J Phys Chem Lett ; 12(35): 8583-8590, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34468146

RESUMO

Plasma membranes represent pharmacokinetic barriers for the passive transport of site-specific drugs within cells. When engineered nanoparticles (NPs) are considered as transmembrane drug carriers, the plasma membrane composition can affect passive NP internalization in many ways. Among these, cholesterol-regulated membrane fluidity is probably one of the most biologically relevant. Herein, we consider small (2-5 nm in core diameter) amphiphilic gold NPs capable of spontaneously and nondisruptively entering the lipid bilayer of plasma membranes. We study their incorporation into model 1,2-dioleoyl-sn-glycero-3-phosphocholine membranes with increasing cholesterol content. We combine dissipative quartz crystal microbalance experiments, atomic force microscopy, and molecular dynamics simulations to show that membrane cholesterol, at biologically relevant concentrations, hinders the molecular mechanism for passive NP penetration within fluid bilayers, resulting in a dramatic reduction in the amount of NP incorporated.

5.
J Chem Theory Comput ; 17(10): 6597-6609, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34491056

RESUMO

Citrate capping is one of the most common strategies to achieve the colloidal stability of Au nanoparticles (NPs) with diameters ranging from a few to hundreds of nanometers. Citrate-capped Au nanoparticles (CNPs) represent a step of the synthesis of Au NPs with specific functionalities, as CNPs can be further functionalized via ligand-exchange reactions, leading to the replacement of citrate with other organic ligands. In vitro, CNPs are also used to address the fundamental aspects of NP-membrane interactions, as they can directly interact with cells or model cell membranes. Their affinity for the bilayer is again mediated by the exchange of citrate with lipid molecules. Here, we propose a new computational model of CNPs compatible with the coarse grained Martini force field. The model, which we develop and validate through an extensive comparison with new all-atom molecular dynamics (MD) simulations and UV-vis and Fourier transform infrared spectroscopy data, is aimed at the MD simulation of the interaction between citrate-capped NPs and model phosphatidylcholine lipid membranes. As a test application we show that, during the interaction between a single CNP and a flat planar 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayer, the citrate coating is spontaneously replaced by lipids on the surface of Au NPs, while the NP size and shape determine the final structural configuration of the NP-bilayer complex.

6.
Immunity ; 54(9): 1989-2004.e9, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34363750

RESUMO

The migration of neutrophils from the blood circulation to sites of infection or injury is a key immune response and requires the breaching of endothelial cells (ECs) that line the inner aspect of blood vessels. Unregulated neutrophil transendothelial cell migration (TEM) is pathogenic, but the molecular basis of its physiological termination remains unknown. Here, we demonstrated that ECs of venules in inflamed tissues exhibited a robust autophagic response that was aligned temporally with the peak of neutrophil trafficking and was strictly localized to EC contacts. Genetic ablation of EC autophagy led to excessive neutrophil TEM and uncontrolled leukocyte migration in murine inflammatory models, while pharmacological induction of autophagy suppressed neutrophil infiltration into tissues. Mechanistically, autophagy regulated the remodeling of EC junctions and expression of key EC adhesion molecules, facilitating their intracellular trafficking and degradation. Collectively, we have identified autophagy as a modulator of EC leukocyte trafficking machinery aimed at terminating physiological inflammation.


Assuntos
Autofagia/fisiologia , Células Endoteliais/fisiologia , Infiltração de Neutrófilos/fisiologia , Migração Transendotelial e Transepitelial/fisiologia , Animais , Quimiotaxia de Leucócito/fisiologia , Células Endoteliais/patologia , Células Endoteliais da Veia Umbilical Humana/imunologia , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Inflamação/imunologia , Inflamação/patologia , Junções Intercelulares/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/fisiologia
7.
J Endocrinol ; 251(2): R1-R9, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34448729

RESUMO

Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder in women in their reproductive age. In recent years, the role of advanced glycation end products (AGEs) in PCOS has gained great attention. AGEs are highly reactive molecules that can be assumed by diet or endogenously synthesized as by-products of metabolic processes. AGE deposition increases with aging, hyperglycemia, insulin resistance, and glycotoxin-rich diet. Therefore, it has become imperative to understand the underlying mechanism of AGEs actions and its downstream effects in PCOS pathophysiology. By integrating evidence from human studies and experimental models, the present review points out that altered AGE deposition is a common feature in all PCOS phenotypes. Searching for possible mechanisms involved in the adaptive response against glycation injury in oocytes and ovaries, the role of SIRT1, the main member of the mammalian sirtuin family, has also recently emerged. Therefore, further studies based on anti-AGE interventions could be helpful in creating innovative strategies for counteracting PCOS and its effects on fertility.

8.
Physiology (Bethesda) ; 36(5): 307-314, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34431416

RESUMO

Amphibious and aquatic air-breathing fishes both exchange respiratory gasses with the atmosphere, but these fishes differ in physiology, ecology, and possibly evolutionary origins. We introduce a scoring system to characterize interspecific variation in amphibiousness and use this system to highlight important unanswered questions about the evolutionary physiology of amphibious fishes.


Assuntos
Evolução Biológica , Peixes , Animais , Humanos , Estilo de Vida
9.
Proc Biol Sci ; 288(1953): 20210603, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34130503

RESUMO

Amphibious fishes transition between aquatic and terrestrial habitats, and must therefore learn to navigate two dramatically different environments. We used the amphibious killifish Kryptolebias marmoratus to test the hypothesis that the spatial learning ability of amphibious fishes would be altered by exposure to terrestrial environments because of neural plasticity in the brain region linked to spatial cognition (dorsolateral pallium). We subjected fish to eight weeks of fluctuating air-water conditions or terrestrial exercise before assessing spatial learning using a bifurcating T-maze, and neurogenesis in the dorsolateral pallium by immunostaining for proliferating cell nuclear antigen. In support of our hypothesis, we found that air-water fluctuations and terrestrial exercise improved some markers of spatial learning. Moreover, air-water and exercised fish had 39% and 46% more proliferating cells in their dorsolateral pallium relative to control fish, respectively. Overall, our findings suggest that fish with more terrestrial tendencies may have a cognitive advantage over those that remain in water, which ultimately may influence their fitness in both aquatic and terrestrial settings. More broadly, understanding the factors that promote neural and behavioural plasticity in extant amphibious fishes may provide insights into how ancestral fishes successfully colonized novel terrestrial environments before giving rise to land-dwelling tetrapods.


Assuntos
Fundulidae , Peixes Listrados , Animais , Ecossistema , Aprendizagem Espacial , Água
10.
Acta Biomed ; 92(2): e2021046, 2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-33988179

RESUMO

Objectives Type Ia endoleak (EL) after endovascular abdominal aortic repair (EVAR) may be misdiagnosed at completion angiography. Intraoperative contrast-enhanced ultrasound (CEUS) may play a role in early detection and immediate treatment of type Ia EL. Methods From January 2017 to April 2018, patients treated with EVAR underwent intraoperative CEUS. After endograft deployment and ballooning, digital subtraction angiography (DSA) and intraoperative CEUS were performed in a blinded fashion. All cases of type Ia EL at DSA or CEUS were considered. Results Type Ia EL detected at intraoperative CEUS and undetected at DSA was defined in 2 patients. The former was solved with intraoperative re-ballooning; in the latter case, a Palmaz stent deployment was required. The resolution of type Ia EL was detected at intraoperative CEUS control and post-operative computed tomography angiography (CTA). In another patient, the DSA detected a type Ia EL, but intraoperative CEUS reveal a type II EL from lumbar arteries. Post-operative CTA confirm the type II EL. Conclusions The reported cases prove the clinical utility of the intraoperative CEUS, permitting the early identification of 2 type Ia EL. In addition, the intraoperative CEUS is useful in case of dubious type Ia EL at DSA, avoiding unnecessary intraoperative adjunctive procedure or post-operative CTA.


Assuntos
Aneurisma da Aorta Abdominal , Procedimentos Endovasculares , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Meios de Contraste , Endoleak/diagnóstico por imagem , Endoleak/etiologia , Humanos , Resultado do Tratamento
11.
Primates ; 62(4): 555-562, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33950405

RESUMO

Predation is a major cause of mortality in non-human primates, and considered a selective force in the evolution of primate societies. Although larger body size is considered as protection against predation, evidence for predation on great apes by carnivores comes from chimpanzees (Pan troglodytes), gorillas (Gorilla gorilla), and orangutans (Pongo spp.). Here, we describe the first encounter between wild bonobos (Pan paniscus) and a leopard (Panthera pardus). A single leopard was confronted by a group of habituated bonobos for three hours. Two adult males and one adolescent female bonobo actively harassed the leopard, which remained still for most of the encounter and reacted only to close approaches by bonobos. While no predation was observed, their behaviours confirm that bonobos perceive leopards as potential predators. Our report adds novel information to descriptions from other African ape species, and sheds light on the behavioural repertoire of bonobos' anti-predation strategies. For future investigations, we suggest tagging leopards to remotely monitor their movements and allow assessment of encounter rates as one of several factors influencing predation pressure.


Assuntos
Pan paniscus , Panthera/fisiologia , Comportamento Predatório , Animais , República Democrática do Congo , Feminino , Masculino
12.
Lancet Respir Med ; 9(9): 969-976, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33844995

RESUMO

BACKGROUND: The NIBIT-MESO-1 study demonstrated the efficacy and safety of tremelimumab combined with durvalumab in patient with unresectable mesothelioma followed up for a median of 52 months [IQR 49-53]. Here, we report 4-year survival and outcomes after retreatment, and the role of tumour mutational burden (TMB) in identifying patients who might have a better outcome in response to combined therapy. METHODS: NIBIT-MESO-1 was an open-label, non-randomised, phase 2 trial of patients with unresectable pleural or peritoneal mesothelioma who received intravenous tremelimumab (1 mg/kg bodyweight) and durvalumab (20 mg/kg bodyweight) every 4 weeks for four doses, followed by maintenance intravenous durvalumab at the same dose and schedule for nine doses. In this follow-up study, patients with disease progression following initial clinical benefit-ie, a partial repsonse or stable disease-were eligible for retreatment and with the same doses and schedules for tremelimumab and durvalumab as used in the NIBIT-MESO-1 trial. The primary endpoint, immune-related objective response rate, was evaluated per immune-related modified Response Evaluation Criteria in Solid Tumors (RECIST) or immune-related RECIST 1.1 criteria for patients with pleural or peritoneal malignant mesothelioma, respectively. Key secondary endpoints were overall survival and safety, and TMB was also evaluated post hoc in patients who had tumour tissue available before treatment. The intention-to-treat population was used for analysis of all efficacy endpoints. This study is registered with ClinicalTrials.gov, number NCT02588131. FINDINGS: 40 patients were enrolled in the NIBIT-MESO-1 study between Oct 30, 2015, and Oct 12, 2016. At data cut-off, April 30, 2020, five (13%) of 40 patients were alive, and 35 (88%) patients had died of progressive disease. At a median follow-up of 52 months (IQR 49-53), median overall survival was 16·5 months (95% CI 13·7-19·2). Survival was 20% (eight of 40 patients) at 36 months and 15% (six of 40 patients) and 48 months. 17 (43%) of 40 patients met the criteria for enrolment in the retreatment study and were retreated with at least one dose of tremelimumab and durvalumab. No immune-related objective responses were observed in the 17 retreated patients. Seven (41%) of 17 patients achieved immune-related stable disease. From the start of retreatment to a median follow-up of 24 months (22·0-25·0), median overall survival was 12·5 months (95% CI 0·0-25·8), and survival at 12 months was 52·9%, at 18 months was 35·3%, and at 24 months was 23·5%. There were no grade 3-4 immune-related adverse events in the retreatment cohort. In a post-hoc analysis of 28 patients for whom tumour tissue before treatment was available, patients with a TMB higher than the median value of 8·3 mutations per Mb had a higher median overall survival compared with patients with TMB below the median value, but this difference was non-significant. Moreover, when patients were additionally stratified for ICI retreatment (n=13), there was a significant difference in survival between those with a TMB higher than the median of 8·3 mutations per Mb and those with TMB lower than the median in the retreated cohort (41·3 months vs 17·4 months; p=0·02). INTERPRETATION: Tremelimumab combined with durvalumab was associated with long-term survival in patients with mesothelioma. Retreatment was safe and resulted in clinically meaningful outcomes, thus suggesting its potential application in the clinical practice of mesothalioma patients. FUNDING: NIBIT Foundation, Fondazione AIRC, AstraZeneca.


Assuntos
Neoplasias Pulmonares , Mesotelioma , Anticorpos Monoclonais , Anticorpos Monoclonais Humanizados , Seguimentos , Humanos , Mesotelioma/tratamento farmacológico , Retratamento
13.
Molecules ; 26(6)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33802807

RESUMO

Infertility is a potential side effect of radiotherapy and significantly affects the quality of life for adolescent cancer survivors. Very few studies have addressed in pubertal models the mechanistic events that could be targeted to provide protection from gonadotoxicity and data on potential radioprotective treatments in this peculiar period of life are elusive. In this study, we utilized an in vitro model of the mouse pubertal testis to investigate the efficacy of crocetin to counteract ionizing radiation (IR)-induced injury and potential underlying mechanisms. Present experiments provide evidence that exposure of testis fragments from pubertal mice to 2 Gy X-rays induced extensive structural and cellular damage associated with overexpression of PARP1, PCNA, SOD2 and HuR and decreased levels of SIRT1 and catalase. A twenty-four hr exposure to 50 µM crocetin pre- and post-IR significantly reduced testis injury and modulated the response to DNA damage and oxidative stress. Nevertheless, crocetin treatment did not counteract the radiation-induced changes in the expression of SIRT1, p62 and LC3II. These results increase the knowledge of mechanisms underlying radiation damage in pubertal testis and establish the use of crocetin as a fertoprotective agent against IR deleterious effects in pubertal period.


Assuntos
Carotenoides/farmacologia , Fertilidade/efeitos dos fármacos , Puberdade/efeitos dos fármacos , Lesões por Radiação/tratamento farmacológico , Testículo/efeitos dos fármacos , Vitamina A/análogos & derivados , Animais , Autofagia/efeitos dos fármacos , Autofagia/efeitos da radiação , Carotenoides/uso terapêutico , Catalase/metabolismo , Células Cultivadas , Regulação para Baixo , Proteína Semelhante a ELAV 1/metabolismo , Fertilidade/efeitos da radiação , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos da radiação , Imuno-Histoquímica , Técnicas In Vitro , Masculino , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Poli(ADP-Ribose) Polimerase-1/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Puberdade/efeitos da radiação , Túbulos Seminíferos/citologia , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/efeitos da radiação , Sirtuína 1/metabolismo , Superóxido Dismutase/metabolismo , Testículo/efeitos da radiação , Regulação para Cima , Vitamina A/farmacologia , Vitamina A/uso terapêutico , Raios X
14.
J Cardiovasc Magn Reson ; 23(1): 33, 2021 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-33775246

RESUMO

BACKGROUND: Radial self-navigated (RSN) whole-heart coronary cardiovascular magnetic resonance angiography (CCMRA) is a free-breathing technique that estimates and corrects for respiratory motion. However, RSN has been limited to a 1D rigid correction which is often insufficient for patients with complex respiratory patterns. The goal of this work is therefore to improve the robustness and quality of 3D radial CCMRA by incorporating both 3D motion information and nonrigid intra-acquisition correction of the data into a framework called focused navigation (fNAV). METHODS: We applied fNAV to 500 data sets from a numerical simulation, 22 healthy subjects, and 549 cardiac patients. In each of these cohorts we compared fNAV to RSN and respiratory resolved extradimensional golden-angle radial sparse parallel (XD-GRASP) reconstructions of the same data. Reconstruction times for each method were recorded. Motion estimate accuracy was measured as the correlation between fNAV and ground truth for simulations, and fNAV and image registration for in vivo data. Percent vessel sharpness was measured in all simulated data sets and healthy subjects, and a subset of patients. Finally, subjective image quality analysis was performed by a blinded expert reviewer who chose the best image for each in vivo data set and scored on a Likert scale 0-4 in a subset of patients by two reviewers in consensus. RESULTS: The reconstruction time for fNAV images was significantly higher than RSN (6.1 ± 2.1 min vs 1.4 ± 0.3, min, p < 0.025) but significantly lower than XD-GRASP (25.6 ± 7.1, min, p < 0.025). Overall, there is high correlation between the fNAV and reference displacement estimates across all data sets (0.73 ± 0.29). For simulated data, healthy subjects, and patients, fNAV lead to significantly sharper coronary arteries than all other reconstruction methods (p < 0.01). Finally, in a blinded evaluation by an expert reviewer fNAV was chosen as the best image in 444 out of 571 data sets (78%; p < 0.001) and consensus grades of fNAV images (2.6 ± 0.6) were significantly higher (p < 0.05) than uncorrected (1.7 ± 0.7), RSN (1.9 ± 0.6), and XD-GRASP (1.8 ± 0.8). CONCLUSION: fNAV is a promising technique for improving the quality of RSN free-breathing 3D whole-heart CCMRA. This novel approach to respiratory self-navigation can derive 3D nonrigid motion estimations from an acquired 1D signal yielding statistically significant improvement in image sharpness relative to 1D translational correction as well as XD-GRASP reconstructions. Further study of the diagnostic impact of this technique is therefore warranted to evaluate its full clinical utility.


Assuntos
Técnicas de Imagem de Sincronização Cardíaca , Angiografia Coronária , Doença das Coronárias/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador , Angiografia por Ressonância Magnética , Adulto , Idoso , Estudos de Casos e Controles , Simulação por Computador , Doença das Coronárias/fisiopatologia , Vasos Coronários/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Cardiovasculares , Movimento , Análise Numérica Assistida por Computador , Valor Preditivo dos Testes , Respiração , Adulto Jovem
15.
Am J Respir Crit Care Med ; 204(3): 312-325, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33784491

RESUMO

Rationale: CD148/PTRJ (receptor-like protein tyrosine phosphatase η) exerts antifibrotic effects in experimental pulmonary fibrosis via interactions with its ligand syndecan-2; however, the role of CD148 in human pulmonary fibrosis remains incompletely characterized.Objectives: We investigated the role of CD148 in the profibrotic phenotype of fibroblasts in idiopathic pulmonary fibrosis (IPF).Methods: Conditional CD148 fibroblast-specific knockout mice were generated and exposed to bleomycin and then assessed for pulmonary fibrosis. Lung fibroblasts (mouse lung and human IPF lung), and precision-cut lung slices from human patients with IPF were isolated and subjected to experimental treatments. A CD148-activating 18-aa mimetic peptide (SDC2-pep) derived from syndecan-2 was evaluated for its therapeutic potential.Measurements and Main Results: CD148 expression was downregulated in IPF lungs and fibroblasts. In human IPF lung fibroblasts, silencing of CD148 increased extracellular matrix production and resistance to apoptosis, whereas overexpression of CD148 reversed the profibrotic phenotype. CD148 fibroblast-specific knockout mice displayed increased pulmonary fibrosis after bleomycin challenge compared with control mice. CD148-deficient fibroblasts exhibited hyperactivated PI3K/Akt/mTOR signaling, reduced autophagy, and increased p62 accumulation, which induced NF-κB activation and profibrotic gene expression. SDC2-pep reduced pulmonary fibrosis in vivo and inhibited IPF-derived fibroblast activation. In precision-cut lung slices from patients with IPF and control patients, SDC2-pep attenuated profibrotic gene expression in IPF and normal lungs stimulated with profibrotic stimuli.Conclusions: Lung fibroblast CD148 activation reduces p62 accumulation, which exerts antifibrotic effects by inhibiting NF-κB-mediated profibrotic gene expression. Targeting the CD148 phosphatase with activating ligands such as SDC2-pep may represent a potential therapeutic strategy in IPF.


Assuntos
Fibroblastos/metabolismo , Fibrose Pulmonar Idiopática/genética , Pulmão/metabolismo , Animais , Antibióticos Antineoplásicos/toxicidade , Autofagia/efeitos dos fármacos , Autofagia/genética , Bleomicina/toxicidade , Modelos Animais de Doenças , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Humanos , Fibrose Pulmonar Idiopática/metabolismo , Fibrose Pulmonar Idiopática/patologia , Técnicas In Vitro , Pulmão/efeitos dos fármacos , Pulmão/patologia , Camundongos , Camundongos Knockout , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Fragmentos de Peptídeos/farmacologia , Fenótipo , Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Tirosina Fosfatases Classe 3 Semelhantes a Receptores/genética , Proteínas Tirosina Fosfatases Classe 3 Semelhantes a Receptores/metabolismo , Transdução de Sinais , Sindecana-2/farmacologia , Serina-Treonina Quinases TOR/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo
16.
Arterioscler Thromb Vasc Biol ; 41(4): 1374-1389, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33596666
17.
Sci Rep ; 11(1): 1256, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441958

RESUMO

The potential toxicity of ligand-protected nanoparticles (NPs) on biological targets is crucial for their clinical translation. A number of studies are aimed at investigating the molecular mechanisms shaping the interactions between synthetic NPs and neutral plasma membranes. The role played by the NP surface charge is still widely debated. We compare, via liposome leakage assays, the perturbation induced by the penetration of sub-6 nm anionic and cationic Au NPs into model neutral lipid membranes composed of the zwitterionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). Our charged Au NPs are functionalized by a mixture of the apolar 1-octanethiol and a ω-charged thiol which is either the anionic 11-mercapto-1-undecanesulfonate or the cationic (11-mercaptoundecyl)-N,N,N-trimethylammonium. In both cases, the NP uptake in the bilayer is confirmed by quartz crystal microbalance investigations. Our leakage assays show that both negatively and positively charged Au NPs do not induce significant membrane damage on POPC liposomes when penetrating into the bilayer. By means of molecular dynamics simulations, we show that the energy barrier for membrane penetration is the same for both NPs. These results suggest that the sign of the NP surface charge, per se, does not imply different physicochemical mechanisms of interaction with zwitterionic lipid membranes.

18.
Vasc Endovascular Surg ; 55(3): 254-264, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33353481

RESUMO

OBJECTIVES: The purpose of this paper is to report the different modalities for the treatment of isolated internal iliac artery aneurysms (IIIAA), as well as their outcomes. METHODS: We performed a systematic review of the literature (database searched: PubMed, Web of Science, Scopus, Cochrane Library; last search: April 2020). We included articles reporting on the outcomes for IIIAA interventions comprising at least 5 patients. Studies were included when presenting extractable outcome data regarding intraoperative and/or early results. We performed meta-analyses of proportions for different outcomes, using random effects model. RESULTS: Thirteen non-randomized studies were included (192 patients with 202 IIIAA). IIIAA were symptomatic in the 18.1% (95%CI 9.3-26.9; I2 54.46%, P = .019). Estimated mean IIIAA diameter was 46.28 mm (95%CI 39.72-52.85; I2 88.85%, P < .001). Open repair was performed in 21/202 cases. Endovascular treatments were: embolization (81/181), embolization and hypogastric artery coverage (79/181), hypogastric artery coverage by stent-grafting (15/181), stent-grafting in the hypogastric artery (6/181). Overall estimated technical success (TS) rate was 91.6% (95% CI 86.8-95.5; I2 45.82%, P = .031). TS rate was 94.5% for open surgery (95%CI 85.3-100; I2 0%, P = .907), and 89.7% for endovascular repair (95%CI 83.8-95.6; I2 55.43%, P = .006). Estimated overall 30-day mortality was 3.1% (95%CI 0.8-5.4; I2 0%, P = .969). Mortality rates after open surgery and endovascular repair were 8.2% (95%CI 3.4-19.8; I2 0%, P = .545) and 2.8% (95%CI 0.5-5.1; I2 0%, P = .994), respectively. Estimated mean follow-up was 32.63 months (95%CI 21.74-43.53; I2 94.45%, P < .001). During this timeframe, IIIAA exclusion was preserved in 92.8% of the patients (95%CI 89.3-96.2; I2 0%, P = .797). Buttock claudication occurred in 13.9% of the patients (95%CI 8.7-19.2; I2 0%, P = .622). CONCLUSIONS: IIIAA are frequently large, and symptomatic at presentation. Several treatments are proposed in literature, open and endovascular, both with good results. The endovascular treatment is the preferred method of treatment in literature, since it offers good short- to mid-term results and low early mortality. Buttock claudication after hypogastric artery exclusion is a common complication.


Assuntos
Implante de Prótese Vascular , Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Ilíaco/cirurgia , Idoso , Idoso de 80 Anos ou mais , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/mortalidade , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Aneurisma Ilíaco/diagnóstico por imagem , Aneurisma Ilíaco/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
19.
Rev. bras. educ. méd ; 45(3): e169, 2021. tab
Artigo em Português | LILACS | ID: biblio-1288301

RESUMO

Resumo: Introdução: A qualidade de aprendizado de estudantes de escolas médicas tem sido tema recorrente da literatura mundial nas últimas décadas, mas há escassez de estudos nacionais acerca do assunto. O ambiente de ensino deve favorecer o aprendizado profundo, por estar intimamente relacionado com uma aprendizagem significativa. Metodologias ativas de aprendizagem são vinculadas a maior qualidade de aprendizado, por propiciarem ambiente favorável ao aprendizado profundo. Objetivo: Este estudo teve como objetivos avaliar a qualidade do aprendizado de estudantes de Medicina de um curso que adota metodologias ativas de aprendizagem e correlacioná-la com as percepções dos alunos acerca do ambiente educacional e com dados sociodemográficos. Método: Trata-se de estudo descritivo transversal realizado com estudantes do curso de Medicina da Universidade Federal de São Carlos (UFSCar), do primeiro ao sexto ano. Foram utilizados os instrumentos R-SPQ-2F, DREEM e questionário sociodemográfico. Realizou-se análise descritiva, e compararam-se as frequências por meio do teste do qui-quadrado ou teste exato de Fisher. As diferenças entre médias foram avaliadas por meio de teste t de Student ou teste de Mann-Whitney, quando se compararam somente dois grupos, ou por meio de análise de variância (ANOVA) ou teste de Kruskal-Wallis, quando comparados mais de dois grupos. As associações entre as variáveis quantitativas foram verificadas por meio do coeficiente de correlação de Pearson ou de Spearman. A análise estatística foi realizada com auxílio do programa IBM SPSS Statistics versão 25.0, e adotou-se como parâmetro de significância um valor de p < 0,05. Resultado: Entrevistaram-se 226 alunos. A pontuação média para abordagem profunda foi de 33,52 e, para a abordagem superficial, 17,42. Em relação à percepção do ambiente educacional, a média foi de 129,77 pontos. As variáveis objetivas que demonstraram influência sobre o aprendizado foram: sexo, idade de início do curso, contato prévio com metodologias ativas, prática de idiomas, ter graduação ou pós-graduação prévia, receber auxílio financeiro de familiares e ano da graduação. Conclusão: As metodologias ativas de aprendizagem podem estimular a adoção de estratégias de aprendizado profundo. O estudo dos fatores que influenciam na abordagem de aprendizado é complexo e envolve questões individuais subjetivas.


Abstract: Introduction: The quality of learning of medical students has been a recurring subject of research in recent decades, but there are scarce national studies on it. The learning environment should encourage deep learning, as it is intimately related to meaningful learning. Active learning methods are linked to better quality of learning, since they provide a favorable environment for deep learning. Objective: The aim of this study was to evaluate the quality of learning of students at a medical school that adopts active learning methods for all course years and correlate it to students' views on educational environment and sociodemographic data. Method: This is a cross-sectional descriptive study with 1st to 6th-year medical students from the Federal University of São Carlos. The R-SPQ-2f, DREEM and sociodemographic questionnaires were applied. Descriptive analysis was performed, and frequencies were compared using chi-square test or Fisher's exact test. Differences between means were evaluated with either Student's t-test or Mann-Whitney's test, when comparing only two groups, and with one-way analysis of variance (ANOVA) or Kruskal-Wallis' test, when comparing more than two groups. Associations between quantitative variables were verified with either Pearson's or Spearman's correlation coefficient. Statistical analysis was performed with IBM SPSS Statistics version 25.0. For significance, p-value<0.05 was adopted. Result: 226 students were interviewed. The average deep learning score was 33.52 points, and, for superficial learning, 17.42 points. As for how the environment was perceived, the average score was 129.77. The objective variables that showed influence in learning were sex, course start age, previous contact with active learning methods, language study, previous undergraduate training, or post-graduate degree, receiving financial help from family and current course year. Conclusion: Active learning methods may stimulate the adoption of deep learning strategies. The evaluation of factors that influence study approaches is complex, involving subjective individual parameters.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Adulto Jovem , Aprendizagem Baseada em Problemas/estatística & dados numéricos , Educação Médica/métodos , Aprendizado Profundo/estatística & dados numéricos , Faculdades de Medicina , Fatores Socioeconômicos , Estudos Transversais , Inquéritos e Questionários
20.
Rev Col Bras Cir ; 47: e20202460, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-33263650

RESUMO

OBJECTIVES: to analyze the survival in juvenile melanoma. METHODS: retrospective study conducted by hospital record review and cancer records of patients aged 0 to 19 years, with histologically proven melanoma and treated between 1997 and 2017 at the Erasto Gaertner Hospital in Curitiba-PR. RESULTS: the sample comprised 24 patients, female (62.5%), mean 14.14 ± 4.72 years old, with head and neck melanoma (37.5%), chest (25%) and extremities. (20.8%). Signs and symptoms at diagnosis were increased lesion size (25%), bleeding (20.8%) and pruritus (16.6%). There was a Breslow II and IV index and Clark IV level, with a statistical tendency between Breslow IV and death (p = 0.127), and significance between Clark V and death (p = 0.067). Nine (37.5%) patients had metastases, six (25%) with distant metastases died (p = 0.001), five were girls (20.8%). Surgery was the standard treatment and chemotherapy the most used adjuvant (37.5%). The average time between diagnosis and death was 1.3 ± 1.2 years and survival were 3.7 ± 3.2 years. CONCLUSION: there was a delay in diagnosis, high morbidity and mortality and average survival less than five years.


Assuntos
Melanoma/mortalidade , Neoplasias Cutâneas/mortalidade , Adolescente , Quimioterapia Adjuvante/efeitos adversos , Criança , Pré-Escolar , Feminino , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Lactente , Recém-Nascido , Masculino , Melanoma/patologia , Melanoma/terapia , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Linfonodo Sentinela , Análise de Sobrevida , Taxa de Sobrevida , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...