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1.
EMBO J ; 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811853

RESUMO

It has remained unknown how cells reduce cystine taken up from the extracellular space, which is a required step for further utilization of cysteine in key processes such as protein or glutathione synthesis. Here, we show that the thioredoxin-related protein of 14 kDa (TRP14, encoded by TXNDC17) is the rate-limiting enzyme for intracellular cystine reduction. When TRP14 is genetically knocked out, cysteine synthesis through the transsulfuration pathway becomes the major source of cysteine in human cells, and knockout of both pathways becomes lethal in C. elegans subjected to proteotoxic stress. TRP14 can also reduce cysteinyl moieties on proteins, rescuing their activities as here shown with cysteinylated peroxiredoxin 2. Txndc17 knockout mice were, surprisingly, protected in an acute pancreatitis model, concomitant with activation of Nrf2-driven antioxidant pathways and upregulation of transsulfuration. We conclude that TRP14 is the evolutionarily conserved enzyme principally responsible for intracellular cystine reduction in C. elegans, mice, and humans.

2.
Bone Joint J ; 106-B(5 Supple B): 98-104, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38688511

RESUMO

Aims: Dual-mobility (DM) components are increasingly used to prevent and treat dislocation after total hip arthroplasty (THA). Intraprosthetic dissociation (IPD) is a rare complication of DM that is believed to have decreased with contemporary implants. This study aimed to report incidence, treatment, and outcomes of contemporary DM IPD. Methods: A total of 1,453 DM components were implanted at a single academic institution between January 2010 and December 2021: 695 in primary and 758 in revision THA. Of these, 49 presented with a dislocation of the large DM head and five presented with an IPD. At the time of closed reduction of the large DM dislocation, six additional IPDs occurred. The mean age was 64 years (SD 9.6), 54.5% were female (n = 6), and mean follow-up was 4.2 years (SD 1.8). Of the 11 IPDs, seven had a history of instability, five had abductor insufficiency, four had prior lumbar fusion, and two were conversions for failed fracture management. Results: The incidence of IPD was 0.76%. Of the 11 IPDs, ten were missed either at presentation or after attempted reduction. All ten patients with a missed IPD were discharged with a presumed reduction. The mean time from IPD to surgical treatment was three weeks (0 to 23). One patient died after IPD prior to revision. Of the ten remaining hips with IPD, the DM head was exchanged in two, four underwent acetabular revision with DM exchange, and four were revised to a constrained liner. Of these, five (50%) underwent reoperation at a mean 1.8 years (SD 0.73), including one additional acetabular revision. No patients who underwent initial acetabular revision for IPD treatment required subsequent reoperation. Conclusion: The overall rate of IPD was low at 0.76%. It is essential to identify an IPD on radiographs as the majority were missed at presentation or after iatrogenic dissociation. Surgeons should consider acetabular revision for IPD to allow conversion to a larger DM head, and take care to remove impinging structures that may increase the risk of subsequent failure.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Falha de Prótese , Reoperação , Humanos , Feminino , Pessoa de Meia-Idade , Artroplastia de Quadril/métodos , Masculino , Incidência , Reoperação/estatística & dados numéricos , Idoso , Desenho de Prótese , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Luxação do Quadril/cirurgia , Luxação do Quadril/etiologia , Resultado do Tratamento
3.
J Gastrointest Surg ; 28(5): 725-730, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38480039

RESUMO

BACKGROUND: Iatrogenic bile duct injury (BDI) during cholecystectomy is associated with a complex and heterogeneous management owing to the burden of morbidity until their definitive treatment. This study aimed to define the textbook outcomes (TOs) after BDI with the purpose to indicate the ideal treatment and to improve it management. METHODS: We collected data from patients with an BDI between 1990 and 2022 from 27 hospitals. TO was defined as a successful conservative treatment of the iatrogenic BDI or only minor complications after BDI or patients in whom the first repair resolves the iatrogenic BDI without complications or with minor complications. RESULTS: We included 808 patients and a total of 394 patients (46.9%) achieved TO. Overall complications in TO and non-TO groups were 11.9% and 86%, respectively (P < .001). Major complications and mortality in the non-TO group were 57.4% and 9.2%, respectively. The use of end-to-end bile duct anastomosis repair was higher in the non-TO group (23.1 vs 7.8, P < .001). Factors associated with achieving a TO were injury in a specialized center (adjusted odds ratio [aOR], 4.01; 95% CI, 2.68-5.99; P < .001), transfer for a first repair (aOR, 5.72; 95% CI, 3.51-9.34; P < .001), conservative management (aOR, 5.00; 95% CI, 1.63-15.36; P = .005), or surgical management (aOR, 2.45; 95% CI, 1.50-4.00; P < .001). CONCLUSION: TO largely depends on where the BDI is managed and the type of injury. It allows hepatobiliary centers to identify domains of improvement of perioperative management of patients with BDI.


Assuntos
Ductos Biliares , Doença Iatrogênica , Complicações Intraoperatórias , Humanos , Masculino , Feminino , Ductos Biliares/lesões , Ductos Biliares/cirurgia , Pessoa de Meia-Idade , Complicações Intraoperatórias/etiologia , Idoso , Estudos Retrospectivos , Colecistectomia/efeitos adversos , Adulto , Anastomose Cirúrgica , Colecistectomia Laparoscópica/efeitos adversos , Resultado do Tratamento , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Tratamento Conservador
4.
Free Radic Biol Med ; 207: 183-193, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37481144

RESUMO

p53 is a redox-sensitive transcription factor that can regulate multiple cell death programs through different signaling pathways. In this review, we assess the role of p53 in the regulation of necroptosis, a programmed form of lytic cell death highly involved in the pathophysiology of multiple diseases. In particular, we focus on the role of mitochondrial reactive oxygen species (mtROS) as essential contributors to modulate necroptosis execution through p53. The enhanced generation of mtROS during necroptosis is critical for the correct interaction between receptor-interacting serine/threonine-protein kinase 1 (RIPK1) and 3 (RIPK3), two key components of the functional necrosome. p53 controls the occurrence of necroptosis by modulating the levels of mitochondrial H2O2 via peroxiredoxin 3 and sulfiredoxin. Furthermore, in response to increased levels of H2O2, p53 upregulates the long non-coding RNA necrosis-related factor, favoring the translation of RIPK1 and RIPK3. In parallel, a fraction of cytosolic p53 migrates into mitochondria, a process notably involved in necroptosis execution via its interaction with the mitochondrial permeability transition pore. In conclusion, p53 is located at the intersection between mtROS and the necroptosis machinery, making it a key protein to orchestrate redox signaling during necroptosis.


Assuntos
Mitocôndrias , Necroptose , Proteína Supressora de Tumor p53 , Apoptose/genética , Peróxido de Hidrogênio/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Necroptose/genética , Espécies Reativas de Oxigênio/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Humanos
5.
Polymers (Basel) ; 15(23)2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-38231935

RESUMO

The aim of this work is to investigate the influence of the ethanol content of adducts on the catalytic behavior of related Ziegler-Natta (ZN) catalysts in propylene homo- and copolymerizations (with 1-hexene comonomer) in terms of activity, isotacticity, H2 response, and comonomer incorporation. For this purpose, three MgCl2.nEtOH adducts with n values of 0.7, 1.2, and 2.8 were synthesized and used in the synthesis of related ZN catalysts. The catalysts were thoroughly characterized using XRD, BET, SEM, EDX, N2 adsorption-desorption, and DFT techniques. Additionally, the microstructure of the synthesized (co)polymers was distinguished via DSC, SSA, and TREF techniques. Their activity was found to enhance with the adduct's ethanol content in both homo- and copolymerization experiments, and the increase was more pronounced in homopolymerization reactions in the absence of H2. Furthermore, the catalyst with the highest ethanol content provided a copolymer with a lower isotacticity index, a shorter meso sequence length, and a more uniform distribution of comonomer within the chains. These results were attributed to the higher total surface area and Ti content of the corresponding catalyst, as well as its lower average pore diameter, a larger proportion of large pores compared to the other two catalysts, and its spherical open bud morphology. It affirms the importance of catalyst/support ethanol-content control during the preparation process. Then, molecular simulation was employed to shed light on the iso-specificity of the polypropylene produced via synthesized catalysts.

6.
Syst Rev ; 11(1): 239, 2022 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-36371235

RESUMO

BACKGROUND: Depression is common among patients with cancer and is associated with lower treatment participation, lower satisfaction with care, poorer quality of life, greater symptom burden and higher healthcare costs. Various types of interventions (e.g. pharmacological, psychotherapy) are used for the treatment of depression. However, evidence for these among patients with cancer is limited. Furthermore, the relative effectiveness and acceptability of different approaches are unknown because a direct comparison between all available treatments has not been carried out. We will address this by conducting a network meta-analysis (NMA) of interventions for depression among people with cancer using a hybrid overview of reviews and systematic review methodology. METHODS: We will search for and extract data from systematic reviews of randomised controlled trials (RCTs) of depression interventions for patients with cancer from inception, before performing a supplemental search for more recent RCTs. We will include RCTs comparing pharmacological, psychotherapy, exercise, combination therapy, collaborative care or complementary and alternative medicine interventions with pill placebo, no treatment, waitlist, treatment as usual or minimal treatment control groups, or directly in head-to-head trials, among adults who currently have cancer or have a history of any cancer and elevated depressive symptoms (scores above a cut-off on validated scales or meeting diagnostic criteria). Our primary outcomes will be change in depressive symptoms (standardised mean difference) and intervention acceptability (% who withdrew). Our secondary outcomes will be 6-month change in depressive symptoms, health-related quality of life, adverse events and mortality. We will independently screen for eligibility, extract data and assess risk of bias using the RoB 2 tool. We will use frequentist random-effects multivariate NMA in Stata, rankograms and surface under the cumulative ranking curves to synthesise evidence and obtain a ranking of intervention groups. We will explore heterogeneity and inconsistency using local and global measures and evaluate the credibility of results using the Confidence in NEtwork Meta-Analysis (CINeMA) framework. DISCUSSION: Our findings will provide the best available evidence for managing depression among patients with cancer. Such information will help to inform clinical guidelines, evidence-based treatment decisions and future research by identifying gaps in the current literature. SYSTEMATIC REVIEW REGISTRATION: Submitted to PROSPERO (record number: 290145), awaiting registration.


Assuntos
Depressão , Neoplasias , Adulto , Humanos , Metanálise em Rede , Depressão/etiologia , Psicoterapia/métodos , Qualidade de Vida , Neoplasias/complicações , Neoplasias/terapia , Metanálise como Assunto , Revisões Sistemáticas como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Redox Biol ; 56: 102423, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36029648

RESUMO

Mitochondrial dysfunction is a key contributor to necroptosis. We have investigated the contribution of p53, sulfiredoxin, and mitochondrial peroxiredoxin 3 to necroptosis in acute pancreatitis. Late during the course of pancreatitis, p53 was localized in mitochondria of pancreatic cells undergoing necroptosis. In mice lacking p53, necroptosis was absent, and levels of PGC-1α, peroxiredoxin 3 and sulfiredoxin were upregulated. During the early stage of pancreatitis, prior to necroptosis, sulfiredoxin was upregulated and localized into mitochondria. In mice lacking sulfiredoxin with pancreatitis, peroxiredoxin 3 was hyperoxidized, p53 localized in mitochondria, and necroptosis occurred faster; which was prevented by Mito-TEMPO. In obese mice, necroptosis occurred in pancreas and adipose tissue. The lack of p53 up-regulated sulfiredoxin and abrogated necroptosis in pancreas and adipose tissue from obese mice. We describe here a positive feedback between mitochondrial H2O2 and p53 that downregulates sulfiredoxin and peroxiredoxin 3 leading to necroptosis in inflammation and obesity.


Assuntos
Pancreatite , Peroxirredoxina III , Doença Aguda , Animais , Regulação para Baixo , Peróxido de Hidrogênio/metabolismo , Camundongos , Camundongos Obesos , Necroptose , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/genética , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/metabolismo , Peroxirredoxina III/genética , Peroxirredoxina III/metabolismo , Proteína Supressora de Tumor p53/genética
8.
Nat Commun ; 13(1): 4934, 2022 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-35995795

RESUMO

Nonaqueous sodium-based batteries are ideal candidates for the next generation of electrochemical energy storage devices. However, despite the promising performance at ambient temperature, their low-temperature (e.g., < 0 °C) operation is detrimentally affected by the increase in the electrolyte resistance and solid electrolyte interphase (SEI) instability. Here, to circumvent these issues, we propose specific electrolyte formulations comprising linear and cyclic ether-based solvents and sodium trifluoromethanesulfonate salt that are thermally stable down to -150 °C and enable the formation of a stable SEI at low temperatures. When tested in the Na||Na coin cell configuration, the low-temperature electrolytes enable long-term cycling down to -80 °C. Via ex situ physicochemical (e.g., X-ray photoelectron spectroscopy, cryogenic transmission electron microscopy and atomic force microscopy) electrode measurements and density functional theory calculations, we investigate the mechanisms responsible for efficient low-temperature electrochemical performance. We also report the assembly and testing between -20 °C and -60 °C of full Na||Na3V2(PO4)3 coin cells. The cell tested at -40 °C shows an initial discharge capacity of 68 mAh g-1 with a capacity retention of approximately 94% after 100 cycles at 22 mA g-1.

9.
Surgery ; 172(4): 1067-1075, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35965144

RESUMO

BACKGROUND: The management of a vascular injury during cholecystectomy is still very complicated, especially in centers not specialized in complex hepatobiliary surgery. METHODS: This was a multi-institutional retrospective study in patients with vascular injuries during cholecystectomy from 18 centers in 4 countries. The aim of the study was to analyze the management of vascular injuries focusing on referral, time to perform the repair, and different treatments options outcomes. RESULTS: A total of 104 patients were included. Twenty-nine patients underwent vascular repair (27.9%), 13 (12.5%) liver resection, and 1 liver transplant as a first treatment. Eighty-four (80.4%) vascular and biliary injuries occurred in nonspecialized centers and 45 (53.6%) were immediately transferred. Intraoperative diagnosed injuries were rare in referred patients (18% vs 84%, P = .001). The patients managed at the hospital where the injury occurred had a higher number of reoperations (64% vs 20%, P ˂ .001). The need for vascular reconstruction was associated with higher mortality (P = .04). Two of the 4 patients transplanted died. CONCLUSION: Vascular lesions during cholecystectomy are a potentially life-threatening complication. Management of referral to specialized centers to perform multiple complex multidisciplinary procedures should be mandatory. Late vascular repair has not shown to be associated with worse results.


Assuntos
Colecistectomia Laparoscópica , Lesões do Sistema Vascular , Ductos Biliares/cirurgia , Colecistectomia/efeitos adversos , Humanos , Complicações Intraoperatórias/diagnóstico , Complicações Intraoperatórias/epidemiologia , Complicações Intraoperatórias/etiologia , Reoperação , Estudos Retrospectivos , Lesões do Sistema Vascular/diagnóstico , Lesões do Sistema Vascular/etiologia , Lesões do Sistema Vascular/cirurgia
10.
Antioxidants (Basel) ; 11(7)2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35883885

RESUMO

Macrophage polarization refers to the process by which macrophages can produce two distinct functional phenotypes: M1 or M2. The balance between both strongly affects the progression of inflammatory disorders. Here, we review how redox signals regulate macrophage polarization and reprogramming during acute inflammation. In M1, macrophages augment NADPH oxidase isoform 2 (NOX2), inducible nitric oxide synthase (iNOS), synaptotagmin-binding cytoplasmic RNA interacting protein (SYNCRIP), and tumor necrosis factor receptor-associated factor 6 increase oxygen and nitrogen reactive species, which triggers inflammatory response, phagocytosis, and cytotoxicity. In M2, macrophages down-regulate NOX2, iNOS, SYNCRIP, and/or up-regulate arginase and superoxide dismutase type 1, counteract oxidative and nitrosative stress, and favor anti-inflammatory and tissue repair responses. M1 and M2 macrophages exhibit different metabolic profiles, which are tightly regulated by redox mechanisms. Oxidative and nitrosative stress sustain the M1 phenotype by activating glycolysis and lipid biosynthesis, but by inhibiting tricarboxylic acid cycle and oxidative phosphorylation. This metabolic profile is reversed in M2 macrophages because of changes in the redox state. Therefore, new therapies based on redox mechanisms have emerged to treat acute inflammation with positive results, which highlights the relevance of redox signaling as a master regulator of macrophage reprogramming.

11.
J Card Surg ; 37(10): 2991-2996, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35900290

RESUMO

BACKGROUND: Sequential synchronized atrioventricular (AV) pacing provides enhanced electrophysiologic parameters which contribute to improved hemodynamic parameters and increased cardiac performance to subsequently confer a clinical advantage over traditional ventricular pacing. Current temporary transvenous pacemaker catheters are limited to only one electrode which paces solely the right ventricle, thus lacking the capability to provide the optimal pacing mode. A new multilead pacemaker device was developed in response to the need for improved temporary pacing through the utilization of sequential synchronized atrioventricular pacing (TAVSP). It consists of seven preformed, preshaped nitinol wires electrodes, of which four are for intra-atrial and three for intraventricular positioning and endocardial contact, respectively. Each wire carries a ball tip designed to minimize tissue trauma and provide a high current density for adequate myocardial capture. The device is not yet Food and Drug Administration approved. OBJECTIVE: To present the unique structural components and mechanical properties of a novel sequential synchronized AV pacing device for temporary insertion and to report its first-in-human application with an analysis of the early clinical experience. METHODS: Following a process of development and proof of concept of the novel pacing modality in an animal model which demonstrated feasibility and safety, a series of patients who were candidates for the device application was identified. During left and right heart catheterization, the novel temporary pacing catheter was inserted transvenously and delivered in most patients under fluoroscopy or echocardiography. The catheter was deployed to its target right heart anatomic sites and then activated in an AV sequential mode. The technical aspects, the corresponding clinical utilization, and device performance were documented and analyzed. RESULTS: The series included 10 enrolled subjects. During planned left and right heart catheterization, the novel TAVSP device was inserted transvenously and then delivered and deployed successfully in a timely fashion in all patients. The pacing catheter achieved proper threshold and impedance in all (100%) patients. The performance of all ventricular leads was adequate; however, in 1 (10%) patient poor performance of the atrial leads was detected. The device was successfully retrieved in all patients. No adverse arrhythmia, impaired hemodynamics, or clinical adverse events occurred. No technical difficulties, component failure, or wires thrombosis were detected. All patients sustained the device application without sequala and were discharged home. CONCLUSION: Initial clinical experience with the utilization of a novel TAVSP demonstrates feasibility and safety in humans. The TAVSP modality potentially offers improved pacing capability and subsequent hemodynamic benefits over the current temporary pacing catheters. Further experience with the clinical application of this pacing catheter is warranted.


Assuntos
Estimulação Cardíaca Artificial , Marca-Passo Artificial , Animais , Arritmias Cardíacas/terapia , Catéteres , Ventrículos do Coração , Humanos
12.
J Gastrointest Surg ; 26(8): 1713-1723, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35790677

RESUMO

BACKGROUND: Iatrogenic bile duct injury (IBDI) is a challenging surgical complication. IBDI management can be guided by artificial intelligence models. Our study identified the factors associated with successful initial repair of IBDI and predicted the success of definitive repair based on patient risk levels. METHODS: This is a retrospective multi-institution cohort of patients with IBDI after cholecystectomy conducted between 1990 and 2020. We implemented a decision tree analysis to determine the factors that contribute to successful initial repair and developed a risk-scoring model based on the Comprehensive Complication Index. RESULTS: We analyzed 748 patients across 22 hospitals. Our decision tree model was 82.8% accurate in predicting the success of the initial repair. Non-type E (p < 0.01), treatment in specialized centers (p < 0.01), and surgical repair (p < 0.001) were associated with better prognosis. The risk-scoring model was 82.3% (79.0-85.3%, 95% confidence interval [CI]) and 71.7% (63.8-78.7%, 95% CI) accurate in predicting success in the development and validation cohorts, respectively. Surgical repair, successful initial repair, and repair between 2 and 6 weeks were associated with better outcomes. DISCUSSION: Machine learning algorithms for IBDI are a novel tool may help to improve the decision-making process and guide management of these patients.


Assuntos
Traumatismos Abdominais , Doenças dos Ductos Biliares , Colecistectomia Laparoscópica , Traumatismos Abdominais/cirurgia , Inteligência Artificial , Ductos Biliares/lesões , Ductos Biliares/cirurgia , Colecistectomia/efeitos adversos , Colecistectomia Laparoscópica/efeitos adversos , Humanos , Doença Iatrogênica , Complicações Intraoperatórias/cirurgia , Aprendizado de Máquina , Estudos Retrospectivos
13.
Rev. colomb. cir ; 37(3): 499-504, junio 14, 2022. fig
Artigo em Espanhol | LILACS | ID: biblio-1378846

RESUMO

Introducción. El trauma penetrante de cuello representa un evento desafortunado de baja incidencia y alta complejidad diagnóstica y terapéutica, lo que supone un reto para el cirujano general.Caso clínico. Paciente femenina de 20 años de edad, quien sufrió una herida cervical por proyectil de arma de fuego, desarrollando de forma secundaria una lesión aerodigestiva. Se realizó un tratamiento expectante en un hospital de alta complejidad, con una evolución favorable. Discusión. En la literatura existe un claro debate en cuanto al manejo de las lesiones penetrantes en cuello y la sospecha de lesión orgánica oculta. En nuestro paciente la lesión aerodigestiva fue tratada mediante observación y seguimiento clínico. Conclusiones. El manejo de un paciente con lesión aerodigestiva se puede corroborar mediante las imágenes diagnósticas y se puede tratar de forma expectante con un resultado exitoso, sin agregar morbilidad y con un impacto adecuado en el buen uso de los recursos disponibles


Introduction. Penetrating neck trauma represents an unfortunate event with a low incidence and high diagnostic and therapeutic complexity, which represents a challenge for the general surgeon. Clinical case. A 20-year-old female patient, who suffered a cervical wound from a firearm projectile, secondarily developing an aerodigestive lesion. An expectant treatment was carried out in a high complexity hospital, with a favorable evolution.Discussion. In the literature there is a clear debate regarding the management of penetrating neck injuries and suspected occult organic injury. In our patient, the aerodigestive injury was treated by observation and clinical follow-up.Conclusions. The management of a patient with aerodigestive injury can be corroborated by diagnostic images and can be treated expectantly with a successful result, without adding morbidity and with an adequate impact on the proper use of available resources


Assuntos
Humanos , Ferimentos por Arma de Fogo , Pescoço , Terapêutica , Ferimentos e Lesões , Observação , Diagnóstico
14.
Front Immunol ; 13: 789349, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35529852

RESUMO

SOX4 belongs to the group C of the SOX transcription factor family. It is a critical mediator of tumor necrosis factor alpha (TNF)-induced transformation of fibroblast-like s-ynoviocytes (FLS) in arthritis. In this study we investigated the genome wide association between the DNA binding and transcriptional activities of SOX4 and the NF-kappaB signaling transcription factor RELA/p65 downstream of TNF signaling. We used ChIP-seq assays in mouse FLS to compare the global DNA binding profiles of SOX4 and RELA. RNA-seq of TNF-induced wildtype and SoxC-knockout FLS was used to identify the SOX4-dependent and independent aspects of the TNF-regulated transcriptome. We found that SOX4 and RELA physically interact with each other on the chromatin. Interestingly, ChIP-seq assays revealed that 70.4% of SOX4 peak summits were within 50bp of the RELA peak summits suggesting that both proteins bind in close-proximity on regulatory sequences, enabling them to co-operatively regulate gene expression. By integrating the ChIP-seq results with RNA-seq from SoxC-knockout FLS we identified a set of TNF-responsive genes that are targets of the RELA-SOX4 transcriptional complex. These TNF-responsive and RELA-SOX4-depenedent genes included inflammation mediators, histone remodeling enzymes and components of the AP-1 signaling pathway. We also identified an autoregulatory mode of SoxC gene expression that involves a TNF-mediated switch from RELA binding to SOX4 binding in the 3' UTR of Sox4 and Sox11 genes. In conclusion, our results show that SOX4 and RELA together orchestrate a multimodal regulation of gene expression downstream of TNF signaling. Their interdependent activities play a pivotal role in the transformation of FLS in arthritis and in the inflammatory pathology of diverse tissues where RELA and SOX4 are co-expressed.


Assuntos
Artrite Reumatoide , Sinoviócitos , Animais , Artrite Reumatoide/metabolismo , DNA/metabolismo , Fibroblastos/metabolismo , Estudo de Associação Genômica Ampla , Camundongos , Membrana Sinovial/patologia , Sinoviócitos/metabolismo , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
15.
Rev. colomb. ortop. traumatol ; 36(3): 1-6, 2022. ilus
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1532626

RESUMO

Introducción: El entendimiento de la anatomía del nervio mediano en su curso por el codo permite comprender el origen de diversas patologías en este sitio, además identificar la distribución y las variantes de las ramas nerviosas es útil para definir las vías de abordaje en las cirugías del nervio mediano. Materiales y Métodos: Disección de especímenes cadavéricos, muestra por conveniencia, previa aprobación del comité de ética y siguiendo un protocolo de disección identificando el nervio mediano, las ramificaciones en el codo y su relación con estructuras vasculares y miotendinosas. Resultados: Se disecaron 20 codos con edad promedio 60,8 años, explorando el nervio mediano, sus ramificaciones y estructuras anatómicas adyacentes en la fosa antecubital. En ningún caso se encontró ligamento de Struthers, la distancia a la arcada del pronator teres (PT) desde la línea interepicondílea fue de 51,3 mm y a la arcada del flexor digitorum superficialis (FDS) 74,1 mm. El patrón más frecuente fue un tronco para el PT, una rama trasversa proximal con divisiones para el FDS, flexor carpi radialis (FCR) y palmaris longus (PL). La inervación del FCR provenía en su mayoría del tronco del PT. Discusión: Se muestra la gran variabilidad de origen y distribución de las ramas originadas del nervio mediano en el codo, se cuantifican las distancias y características morfológicas en los sitios de compresión conocidos. La rama para el FCR se pone en riesgo en la exploración de las arcadas tendinosas del PT y el FDS.


Introduction: Understanding the anatomy of the median nerve as it passes through the elbow allows us to understand the origin of various pathologies at this site. In addition, identifying the distribution and variants of the nerve branches is useful for defining the approach routes in surgeries of the elbow. median nerve. Materials and Methods: Dissection of cadaveric specimens, convenience sample, prior approval of the ethics committee and following a dissection protocol identifying the median nerve, the branches in the elbow and its relationship with vascular and myotendinous structures. Results: 20 elbows with an average age of 60.8 years were dissected, exploring the median nerve, its branches and adjacent anatomical structures in the antecubital fossa. In no case was Struthers' ligament found, the distance to the arch of the pronator teres (PT) from the interepicondylar line was 51.3 mm and to the arch of the flexor digitorum superficialis (FDS) 74.1 mm. The most frequent pattern was a trunk for the PT, a proximal transverse branch with divisions for the FDS, flexor carpi radialis (FCR) and palmaris longus (PL). The innervation of the FCR came mostly from the trunk of the PT. Discussion: The great variability of origin and distribution of the branches originating from the median nerve at the elbow is shown, the distances and morphological characteristics at the known compression sites are quantified. The branch for the FCR is put at risk in the exploration of the tendon arcades of the PT and the FDS.

16.
Pensar mov ; 19(2)dic. 2021.
Artigo em Espanhol | SaludCR, LILACS | ID: biblio-1386769

RESUMO

Resumen Ortega Muñoz, A., Fumero Pérez, S. y Solano López, A.L. (2021). Autoeficacia, percepción de barreras y beneficios de la actividad física en estudiantes universitarios costarricenses. PENSAR EN MOVIMIENTO: Revista de Ciencias del Ejercicio y la Salud, 19(2), 1-17. Según la Teoría de Promoción de la Salud, aspectos como autoeficacia, percepción de beneficios y barreras podrían estar influyendo en la actividad física. En Costa Rica, se ha investigado poco este fenómeno en estudiantes universitarios de enfermería, por lo que el objetivo del estudio fue determinar la relación entre autoeficacia y percepción beneficios y barreras de la actividad física en estudiantes de Enfermería de la Universidad de Costa Rica. Esta investigación es un estudio de caso grupal, correlacional descriptivo. La muestra estuvo conformada por 42 estudiantes de segundo año de Enfermería. Los instrumentos utilizados fueron la Escala de Beneficios/Barreras para el ejercicio y la Escala de Autoeficacia para la actividad física. El análisis de datos se realizó mediante estadística descriptiva y la correlación de Pearson. Dentro de los resultados resalta que caminar obtuvo mayor autoeficacia, seguido de actividades de la vida diaria y, por último, el ejercicio físico programado. El estudiantado identifica más los beneficios de la actividad física que las barreras. Existe una asociación entre la autoeficacia total para la actividad física y la percepción de beneficios del ejercicio y la autoeficacia para el ejercicio programado y las barreras del ejercicio. Se debe trabajar en potenciar los beneficios de la actividad física, así como en crear intervenciones que ayuden a la población estudiantil de enfermería a superar las barreras por medio del fortalecimiento de la autoeficacia para la actividad física independientemente de su intensidad.


Abstract Ortega Muñoz, A., Fumero Pérez, S. & Solano López, A.L. (2021). Self-effectiveness and perception of barriers and benefits of physical activity in Costa Rican university students. PENSAR EN MOVIMIENTO: Revista de Ciencias del Ejercicio y la Salud, 19(2), 1-17. According to Health Promotion Theory, factors such as self-effectiveness and the perception of benefits and barriers might be impacting physical activity. Since this phenomenon has been scarcely researched among nursing students, the purpose of this study has been to determine the relationship between self-effectiveness and perceived benefits and barriers of physical activity among nursing students at Universidad de Costa Rica. This research is a correlational, descriptive group case study. The sample was made up by 42 second-year students of the School of Nursing. The instruments used were the Scale of Benefits/Barriers for Exercise and the Self-Effectiveness Scale for Physical Activity. Data analysis was carried out through descriptive statistics and Pearson's correlation. The most outstanding result was that walking showed higher self-effectiveness, followed by daily life activities and finally scheduled physical exercise. The student community identifies the benefits of physical activities more easily than the barriers. An association exists between total self-effectiveness for physical activity and the perception of benefits of exercise and self-effectiveness for scheduled exercise and the barriers of exercise. Efforts must be made in enhancing the benefits of physical activity, as well as in creating interventions that will help nursing students to overcome barriers by strengthening self-effectiveness for physical activity, regardless of its intensity.


Resumo Ortega Muñoz, A., Fumero Pérez, S. e Solano López, A.L. (2021). Autoeficácia, percepção de barreiras e benefícios da atividade física entre universitários costarriquenhos. PENSAR EN MOVIMIENTO: Revista de Ciencias del Ejercicio y la Salud, 19(2), 1-17. De acordo com a Teoria de Promoção da Saúde, aspectos como autoeficácia, percepção de benefícios e barreiras podem estar influenciando a atividade física. Na Costa Rica, pouca pesquisa tem sido feita em estudantes universitários de enfermagem, portanto, o objetivo do estudo foi determinar a relação entre a autoeficácia e a percepção dos benefícios e das barreiras da atividade física entre estudantes de enfermagem da Universidade da Costa Rica. Esta pesquisa é um estudo de caso em grupo correlacional descritivo. A amostra foi composta por 42 estudantes de enfermagem do segundo ano. Os instrumentos utilizados foram a Escala de Benefícios/Barreiras para o Exercício e a Escala de Autoeficácia para Atividade Física. A análise dos dados foi realizada por meio de estatística descritiva e correlação de Pearson. Dentre os resultados, destaca-se que a caminhada alcançou maior autoeficácia, seguida das atividades da vida diária e, por fim, exercício físico programado. Os estudantes identificam mais os benefícios da atividade física do que as barreiras. Existe uma associação entre a autoeficácia total para a atividade física e a percepção de benefícios do exercício e a autoeficácia para o exercício programado e as barreiras do exercício. Deve-se potencializar os benefícios da atividade física, bem como criar intervenções que ajudem a população estudantil de enfermagem a superar barreiras, fortalecendo a autoeficácia para a atividade física, independentemente da intensidade.


Assuntos
Humanos , Estudantes de Enfermagem , Exercício Físico , Autoeficácia , Costa Rica
17.
Rev. chil. infectol ; 38(5): 678-687, oct. 2021. ilus, tab
Artigo em Espanhol | LILACS | ID: biblio-1388301

RESUMO

ANTECEDENTES: Los biomarcadores actuales para el diagnóstico de sepsis neonatal tienen una exactitud limitada. El desarrollo de la medicina de precisión basada en tecnologías ómicas ofrece una oportunidad para mejorar el diagnóstico de la sepsis neonatal. OBJETIVOS: Evaluar la sensibilidad y especificidad de las pruebas basadas en tecnologías ómicas (metabolómica, proteómica y genómica/transcriptómica) para el diagnóstico de sepsis neonatal. METODOLOGÍA: Se realizó una revisión sistemática en bases de datos electrónicas. Se incluyeron estudios observacionales y ensayos clínicos que evaluaran las pruebas basadas en tecnologías ómicas en neonatos comparado con el cultivo para el diagnóstico de sepsis neonatal. Dos revisores independientes realizaron la evaluación de la calidad de los estudios y la extracción de los datos. Para el metaanálisis se realizó un modelo de efectos aleatorios y se planeó una evaluación de la heterogeneidad a través de un análisis de subgrupos por prueba ómica, edad gestacional y tiempo de establecimiento de la sepsis. RESULTADOS: Se observa expresión diferencial del genoma, proteoma y metaboloma entre los neonatos con y sin sepsis, identificando diferentes biomarcadores. El metaanálisis mostró una medida de resumen combinada para la sensibilidad de 0,88 (IC 95% 0,72-0,96), especificidad de 0,76 (IC 95% 0,62-0,85). CONCLUSIÓN: Las pruebas basadas en ómicas tienen una alta sensibilidad, siendo las de mejor rendimiento las basadas en genómica/transcriptómica. Los estudios tienen alta heterogeneidad.


BACKGROUND: Current biomarkers for the diagnosis of neonatal sepsis llave limited accuracy. The development of precision medicine based on omic's technologies offer an opportunity to improve the diagnosis of neonatal sepsis. AIM: To evalúate the sensitivity and specificity of tests based on omic technologies (metabolomics, proteomics and genomics) for the diagnosis of neonatal sepsis. METHODS: A systematic review was carried out in electronic databases. Observational studies and clinical trials evaluating tests based on omic technologies in neonates compared to culture for the diagnosis of neonatal sepsis were included. For the meta-analysis, a random effects model and an evaluation of heterogeneity were proposed through a subgroup analysis by omic test, gestational age and time of establishment of sepsis. RESULTS: Differential expression of the genome, proteome and metabolome is observed between neonates with and without sepsis, identifying different biomarkers. The meta-analysis showed a pooled summary measure for sensitivity of0.88 (95% CI 0.72, 0.96), specificity of0.76 (95% CI 0.62, 0.85). CONCLUSION: Omics-based tests have a high sensitivity, with the best performing ones being those based on genomics / transcriptomics. The studies have high heterogeneity.


Assuntos
Humanos , Recém-Nascido , Sepse Neonatal/diagnóstico , Biomarcadores , Idade Gestacional , Sepse/diagnóstico , Medicina de Precisão
18.
Salud UNINORTE ; 37(2): 442-464, mayo-ago. 2021. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1377260

RESUMO

RESUMEN Objetivo: La incertidumbre de una posible transmisión posnatal por SARS-CoV-2 genera un desafío entre aplicar o evitar los cuidados esenciales del recién nacido para prevenir la transmisión. La revisión sistemática tiene como objetivo describir el impacto de los cuidados esenciales del neonato en la transmisión posnatal del SARS-CoV-2. Métodos: Se realizó una revisión sistemática en bases de datos electrónicas, se incluyeron estudios observacionales, serie de casos y reporte de casos. Dos investigadores de forma independiente evaluaron los criterios de inclusión, la calidad metodológica y la extracción de datos. Resultados: Se tamizaron 208 estudios para una inclusión final de 9 artículos relevantes. El reporte de transmisión del virus SARS-CoV-2 está centrado en la posibilidad de transferencia por la leche materna y ausencia de información acerca de la transmisión por otros cuidados esenciales, sin embargo, se observa un bajo uso en la práctica clínica de los cuidados esenciales del recién nacido hijo de madre con COVID- 19. Conclusiones: La información es limitada sobre la posible transmisión del SARS-CoV-2 a través de los cuidados esenciales del recién nacido, sin embargo, la pandemia ha impactado de forma importante los mismos. Según los hallazgos en la literatura, es mayor el beneficio de estas intervenciones y las recomendaciones científicas promueven su aplicación empleando las medidas de protección personal para la madre y el personal de salud.


ABSTRACT Objective: The uncertainty of a possible postnatal transmission by SARS-CoV-2 creates a challenge between applying or avoiding essential newborn care to prevent transmission. The objective of the systematic review is to describe the impact of essential neonate care on the postnatal transmission of SARS-CoV-2. Methods: A systematic review was carried out in electronic databases, observational studies, case series, and case reports. Two investigators independently assessed the inclusion criteria, methodological quality, and data extraction. Results: 208 studies were screened for a final inclusion of 9 relevant articles. The transmission report of the SARS-CoV-2 virus is focused on the possibility of transfer through breast milk and the absence of information about transmission by other essential care, however, a low use, in clinical practice, of essential care for the newborn child of a mother with COVID-19, is observed. Conclusions: Information is limited on the possible transmission of SARS-CoV-2 through essential newborn care; however, the pandemic has had a significant impact on them. According to the findings in the literature, the benefit of these interventions is greater, and the scientific recommendations promote their application, using personal protection measures for the mother and the healthcare personnel.

19.
Mol Neurobiol ; 58(1): 408-423, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32959172

RESUMO

Despite the promising neuroprotective effects of uric acid (UA) in acute ischemic stroke, the seemingly pleiotropic underlying mechanisms are not completely understood. Recent evidence points to transcription factors as UA targets. To gain insight into the UA mechanism of action, we investigated its effects on pertinent biomarkers for the most relevant features of ischemic stroke pathophysiology: (1) oxidative stress (antioxidant enzyme mRNAs and MDA), (2) neuroinflammation (cytokine and Socs3 mRNAs, STAT3, NF-κB p65, and reactive microglia), (3) brain swelling (Vegfa, Mmp9, and Timp1 mRNAs), and (4) apoptotic cell death (Bcl-2, Bax, caspase-3, and TUNEL-positive cells). Adult male Wistar rats underwent intraluminal filament transient middle cerebral artery occlusion (tMCAO) and received UA (16 mg/kg) or vehicle (Locke's buffer) i.v. at 20 min reperfusion. The outcome measures were neurofunctional deficit, infarct, and edema. UA treatment reduced cortical infarct and brain edema, as well as neurofunctional impairment. In brain cortex, increased UA: (1) reduced tMCAO-induced increases in Vegfa and Mmp9/Timp1 ratio expressions; (2) induced Sod2 and Cat expressions and reduced MDA levels; (3) induced Il6 expression, upregulated STAT3 and NF-κB p65 phosphorylation, induced Socs3 expression, and inhibited microglia activation; and (4) ameliorated the Bax/Bcl-2 ratio and induced a reduction in caspase-3 cleavage as well as in TUNEL-positive cell counts. In conclusion, the mechanism for morphological and functional neuroprotection by UA in ischemic stroke is multifaceted, since it is associated to activation of the IL-6/STAT3 pathway, attenuation of edematogenic VEGF-A/MMP-9 signaling, and modulation of relevant mediators of oxidative stress, neuroinflammation, and apoptotic cell death.


Assuntos
Interleucina-6/metabolismo , AVC Isquêmico/metabolismo , Neuroproteção/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Ácido Úrico/farmacologia , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Edema Encefálico/etiologia , Edema Encefálico/patologia , Edema Encefálico/fisiopatologia , Infarto Encefálico/etiologia , Infarto Encefálico/fisiopatologia , Citocinas/genética , Citocinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/fisiopatologia , AVC Isquêmico/etiologia , AVC Isquêmico/fisiopatologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Ácido Úrico/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/metabolismo
20.
Front Oncol ; 10: 605037, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33330106

RESUMO

Nanoparticles (NPs) are novel platforms that can carry both cancer-targeting molecules and drugs to avoid severe side effects due to nonspecific drug delivery in standard chemotherapy treatments. Cancer cells are characterized by abnormal membranes, metabolic changes, the presence of lectin receptors, glucose transporters (GLUT) overexpression, and glycosylation of immune receptors of programmed death on cell surfaces. These characteristics have led to the development of several strategies for cancer therapy, including a large number of carbohydrate-modified NPs, which have become desirable for use in cell-selective drug delivery systems because they increase nanoparticle-cell interactions and uptake of carried drugs. Currently, the potential of NP glycosylation to enhance the safety and efficacy of carried therapeutic antitumor agents has been widely acknowledged, and much information is accumulating in this field. This review seeks to highlight recent advances in NP stabilization, toxicity reduction, and pharmacokinetic improvement and the promising potential of NP glycosylation from the perspective of molecular mechanisms described for drug delivery systems for cancer therapy. From preclinical proof-of-concept to demonstration of therapeutic value in the clinic, the challenges and opportunities presented by glycosylated NPs, with a focus on their applicability in the development of nanodrugs, are discussed in this review.

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