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1.
Blood Purif ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38934142

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic represented a global public health problem with devastating consequences. Continuous renal replacement therapy (CRRT) can modify cytokine storms and improve the clearance of inflammatory factors. Severe COVID-19 can lead to acute kidney injury (AKI) requiring RRT. This is due to complications that lead to organ dysfunction. The aim of our study was to assess renal recovery and survival while use of the oXiris membrane, as well as a decrease in vasopressors and hemodynamic parameters. This was a retrospective, observational study. The population included adult patients with a real-time PCR COVID-19 positive test, admitted to the intensive care unit (ICU) with acute kidney injury KDIGO 3, which required CRRT, in a hospital in northern Mexico. The primary outcomes were renal recovery and survival, and the secondary outcomes were a decrease in the vasopressor requirements and changes in the hemodynamic parameters. Thirteen patients were included. oXiris, was used for blood purification and cytokine storm control in all the patients. The primary outcome, renal recovery, and survival was observed in 23% of the patients. The secondary outcome was a decrease of 12% in the use of noradrenaline in the first 24 h of CRRT initiation with oXiris, in addition to a decrease in creatinine and C- reactive protein levels in all patients. The use of the oXiris membrane in patients with severe COVID-19 improved hemodynamic parameters, with 23% of the patients achieving renal recovery. The decrease on the requirement of vasopressors in the overall patients in the first 24 hours of CRRT with oXiris was achieved. The mean decrease was of 12%, accompanied by a decrease in inflammatory markers. There is literature on the benefit of CRRT with a modified AN69 membrane in Mexico; however, studies in this regard are scarce, and our research provides valuable information on our experience in this field.

2.
Neoplasia ; 53: 101003, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38759377

RESUMO

Dynamic changes in the endoplasmic reticulum (ER) morphology are central to maintaining cellular homeostasis. Microtubules (MT) facilitate the continuous remodeling of the ER network into sheets and tubules by coordinating with many ER-shaping protein complexes, although how this process is controlled by extracellular signals remains unknown. Here we report that TAK1, a kinase responsive to various growth factors and cytokines including TGF-ß and TNF-α, triggers ER tubulation by activating αTAT1, an MT-acetylating enzyme that enhances ER-sliding. We show that this TAK1/αTAT1-dependent ER remodeling promotes cell survival by actively downregulating BOK, an ER membrane-associated proapoptotic effector. While BOK is normally protected from degradation when complexed with IP3R, it is rapidly degraded upon their dissociation during the ER sheets-to-tubules conversion. These findings demonstrate a distinct mechanism of ligand-induced ER remodeling and suggest that the TAK1/αTAT1 pathway may be a key target in ER stress and dysfunction.


Assuntos
Retículo Endoplasmático , MAP Quinase Quinase Quinases , Microtúbulos , Transdução de Sinais , Microtúbulos/metabolismo , Retículo Endoplasmático/metabolismo , Humanos , MAP Quinase Quinase Quinases/metabolismo , MAP Quinase Quinase Quinases/genética , Acetilação , Animais , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Acetiltransferases/metabolismo , Acetiltransferases/genética , Estresse do Retículo Endoplasmático , Camundongos , Proteínas dos Microtúbulos
3.
Biochem Biophys Res Commun ; 711: 149916, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38613866

RESUMO

ßIV-spectrin is a membrane-associated cytoskeletal protein that maintains the structural stability of cell membranes and integral proteins such as ion channels and transporters. Its biological functions are best characterized in the brain and heart, although recently we discovered a fundamental new role in the vascular system. Using cellular and genetic mouse models, we reported that ßIV-spectrin acts as a critical regulator of developmental and tumor-associated angiogenesis. ßIV-spectrin was shown to selectively express in proliferating endothelial cells (EC) and suppress VEGF/VEGFR2 signaling by enhancing receptor internalization and degradation. Here we examined how these events impact the downstream kinase signaling cascades and target substrates. Based on quantitative phosphoproteomics, we found that ßIV-spectrin significantly affects the phosphorylation of epigenetic regulatory enzymes in the nucleus, among which DNA methyltransferase 1 (DNMT1) was determined as a top substrate. Biochemical and immunofluorescence results showed that ßIV-spectrin inhibits DNMT1 function by activating ERK/MAPK, which in turn phosphorylates DNMT1 at S717 to impede its nuclear localization. Given that DNMT1 controls the DNA methylation patterns genome-wide, and is crucial for vascular development, our findings suggest that epigenetic regulation is a key mechanism by which ßIV-spectrin suppresses angiogenesis.


Assuntos
DNA (Citosina-5-)-Metiltransferase 1 , Sistema de Sinalização das MAP Quinases , Proteômica , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , DNA (Citosina-5-)-Metiltransferase 1/genética , Animais , Proteômica/métodos , Camundongos , Fosforilação , Humanos , Neovascularização Fisiológica , Espectrina/metabolismo , Espectrina/genética , Fosfoproteínas/metabolismo , Neovascularização Patológica/metabolismo , Neovascularização Patológica/genética , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais/metabolismo , Angiogênese
4.
BMJ Open ; 13(11): e076774, 2023 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-37993168

RESUMO

INTRODUCTION: Stroke is a significant worldwide cause of death and a prevalent contributor to long-term disability among adults. Survivors commonly encounter a wide array of motor, sensory and cognitive impairments. Rehabilitation interventions, mainly targeting the upper extremities, include a wide array of components, although the evidence indicates that the intensity of practice and task-specific training play crucial roles in facilitating effective results. Assisted therapy with electronic devices designed for the affected upper extremity could be employed to enable partial or total control of this limb, while simultaneously incorporating the aforementioned characteristics in the rehabilitation process. METHODS AND ANALYSIS: 32 adults who had a subacute or chronic stroke, aged over 18 years old, will be included for this randomised controlled trial aiming to determine the non-inferiority effect of the inclusion of a robotic device (ALBA) to regular treatment against only regular rehabilitation. Participants will be assessed before and after 4 weeks of intervention and at 3 months of follow-up. The primary outcome will be the Fugl-Meyer assessment for upper extremities; secondary outcomes will include the questionnaires Functional Independence Measure, Medical Outcomes Study 36-item Short-Form Health Survey as well as the System Usability Scale. ETHICS AND DISSEMINATION: Full ethical approval was obtained for this study from the scientific and ethical review board Servicio de Salud Metropolitano Oriente of Santiago (approval number: SSMOriente030522), and the recommendations of the Chilean law no 20120 of 7 September 2006, concerning scientific research in the human being, its genome and human cloning, will be followed. Ahead of inclusion, potential participants will read and sign a written informed consent form. Future findings will be presented and published in conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: International ClinicalTrials.gov Registry (NCT05824416; https://clinicaltrials.gov/ct2/show/NCT05824416?term=uMOV&draw=2&rank=1).


Assuntos
Lesões Encefálicas , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Adulto , Humanos , Lesões Encefálicas/complicações , Chile , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/complicações , Reabilitação do Acidente Vascular Cerebral/métodos , Resultado do Tratamento , Extremidade Superior
5.
Front Glob Womens Health ; 4: 1232662, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37811534

RESUMO

Progress in maternal child health has been hampered by poor rates of outpatient follow up for postpartum individuals. Primary care after delivery can effectively detect and treat several pregnancy-related complications and comorbidities, but postpartum linkage to primary care remains low. In this manuscript, we share the experience of implementing a novel mother-infant dyad program, the Multimodal Maternal Infant Perinatal Outpatient Delivery System (MOMI PODS), to improve primary care linkage and community resource access postpartum via integration into pediatric care structures. With a focus on providing care for people who are publicly insured, we designed a program to mitigate maternal morbidity risk factors in postpartum individuals with chronic disease or pregnancy complications. We discuss the systematic process of designing, executing, and evaluating a collaborative clinical program with involvement of internal medicine/pediatric, family medicine, and obstetric clinicians via establishing stakeholders, identifying best practices, drawing from the evidence base, designing training and promotional materials, training partners and providers, and evaluating clinic enrollment. We share the challenges encountered such as in achieving sufficient provider capacity, consistent provision of care, scheduling, and data tracking, as well as mitigation strategies to overcome these barriers. Overall, MOMI PODS is an innovative approach that integrates outpatient postpartum care into traditional pediatric structures to increase access, showing significant promise to improve healthcare utilization and promote postpartum health.

6.
Artigo em Inglês | MEDLINE | ID: mdl-37704815

RESUMO

In the present research, the presence of water hyacinth (Eichhornia crassipes) on the surface of the San Jose Dam located in the city of San Luis Potosi, S.L.P, Mexico, was monitored and mapped. The monitoring was conducted for 2 years (2018-2020) with remote sensing data from OLI Landsat 8 sensors, based on the normalized difference vegetation index (NDVI). The results demonstrated the capability and accuracy of this method, where it was observed that the aboveground cover area, proliferation, and distribution of water hyacinth are influenced by climatic and anthropogenic factors during the four seasons of the year. As part of a sustainable environmental control of this invasive species, the use of water hyacinth (WH) root (RO), stem (ST), and leaf (LE) components as adsorbent material for Pb(II) present in aqueous solution was proposed. The maximum adsorption capacity was observed at pH 5 and 25 °C and was 107.3, 136.8, and 120.8 mg g-1 for RO, ST, and LE, respectively. The physicochemical characterization of WH consisted of scanning electron microscopy (SEM), N2 physisorption, infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), charge distribution, and zero charge point (pHPZC). Due to the chemical nature of WH, several Pb(II) adsorption mechanisms were proposed such as electrostatic attractions, ion exchange, microprecipitation, and π-cation.

7.
Cancer Med ; 12(18): 18981-18987, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37680049

RESUMO

BACKGROUND: Tumor-associated angiogenesis mediates the growth and metastasis of most solid cancers. Targeted therapies of the VEGF pathways can effectively block these processes but often fail to provide lasting benefits due to acquired resistance and complications. RESULTS: Recently, we discovered ßIV -spectrin as a powerful regulator of angiogenesis and potential new target. We previously reported that ßIV -spectrin is dynamically expressed in endothelial cells (EC) to induce VEGFR2 protein turnover during development. Here, we explored how ßIV -spectrin influences the tumor vasculature using the murine B16 melanoma model and determined that loss of EC-specific ßIV -spectrin dramatically promotes tumor growth and metastasis. Intraperitoneally injected B16 cells formed larger tumors with increased tumor vessel density and greater propensity for metastatic spread particularly to the chest cavity and lung compared to control mice. These results support ßIV -spectrin as a key regulator of tumor angiogenesis and a viable vascular target in cancer.


Assuntos
Melanoma Experimental , Espectrina , Animais , Camundongos , Células Endoteliais/metabolismo , Melanoma Experimental/irrigação sanguínea , Neovascularização Patológica , Espectrina/metabolismo
8.
Cardiol Rev ; 2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37432017

RESUMO

Finerenone is a novel third-generation, selective nonsteroidal mineralocorticoid receptor antagonist (MRA) that was approved by the Food and Drug Administration in July of 2021 for its use in adults with chronic kidney disease and Type II diabetes mellitus. Randomized controlled trials The Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease and Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease showed decreased adverse kidney and cardiovascular outcomes, respectively, in this population. The incidence of hyperkalemia, while higher in the study versus placebo group, was lower than older generations of MRAs (spironolactone and eplerenone) and proved to be an infrequent cause for drug discontinuation. The incidences of other adverse effects such as gynecomastia and acute kidney injury were similar in both the study and the placebo groups. This is the first third-generation MRA authorized to use to reduce the burden of cardiorenal disease.

9.
Mol Biol Cell ; 34(7): ar72, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37126382

RESUMO

ßIV-Spectrin is a membrane cytoskeletal protein with specialized roles in the nervous system and heart. Recent evidence also indicates a fundamental role for ßIV-spectrin in angiogenesis as its endothelial-specific gene deletion in mice enhances embryonic lethality due to hypervascularization and hemorrhagic defects. During early vascular sprouting, ßIV-spectrin is believed to inhibit tip cell sprouting in favor of the stalk cell phenotype by mediating VEGFR2 internalization and degradation. Despite these essential roles, mechanisms governing ßIV-spectrin expression remain unknown. Here we identify bone morphogenetic protein 9 (BMP9) as a major inducer of ßIV-spectrin gene expression in the vascular system. We show that BMP9 signals through the ALK1/Smad1 pathway to induce ßIV-spectrin expression, which then recruits CaMKII to the cell membrane to induce phosphorylation-dependent VEGFR2 turnover. Although BMP9 signaling promotes stalk cell behavior through activation of hallmark stalk cell genes ID-1/3 and Hes-1 and Notch signaling cross-talk, we find that ßIV-spectrin acts upstream of these pathways as loss of ßIV-spectrin in neonate mice leads to retinal hypervascularization due to excessive VEGFR2 levels, increased tip cell populations, and strong Notch inhibition irrespective of BMP9 treatment. These findings demonstrate ßIV-spectrin as a BMP9 gene target critical for tip/stalk cell selection during nascent vessel sprouting.


Assuntos
Fator 2 de Diferenciação de Crescimento , Espectrina , Animais , Camundongos , Células Endoteliais/metabolismo , Fator 2 de Diferenciação de Crescimento/metabolismo , Neovascularização Fisiológica/fisiologia , Transdução de Sinais/fisiologia , Espectrina/metabolismo
10.
bioRxiv ; 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37131821

RESUMO

Dynamic changes in the endoplasmic reticulum (ER) morphology are central to maintaining cellular homeostasis. Microtubules (MT) facilitate the continuous remodeling of the ER network into sheets and tubules by coordinating with many ER-shaping protein complexes, although how this process is controlled by extracellular signals remains unknown. Here we report that TAK1, a kinase responsive to numerous growth factors and cytokines including TGF-ß and TNF-α, triggers ER tubulation by activating αTAT1, an MT-acetylating enzyme that enhances ER-sliding. We show that this TAK1/αTAT-dependent ER remodeling promotes cell survival by actively downregulating BOK, an ER membrane-associated proapoptotic effector. While BOK is normally protected from degradation when complexed with IP3R, it is rapidly degraded upon their dissociation during the ER sheets-to-tubules conversion. These findings demonstrate a distinct mechanism of ligand-induced ER remodeling and suggest that the TAK1/αTAT pathway may be a key target in ER stress and dysfunction.

11.
Artigo em Inglês | MEDLINE | ID: mdl-36767922

RESUMO

Sargassum algae has become a major environmental issue due to its abundance in the Pacific Ocean with hundreds of tons reaching the beaches of the Mexican Caribbean every year. This generates large quantities of decomposing organic matter that have a negative impact on the region's economy and ecosystems. Sargassum valorization has turned out to be a fundamental aspect to mitigate its environmental impact. This study proposes the use and application of untreated Sargassum biomass for the decontamination of waters polluted with lead (Pb) and cadmium (Cd) through single and binary adsorption tests. Physicochemical and textural properties examined by SEM, XRD, and FT-IR elucidated that Sargassum biomass is viable to be used as a potential environmental benign adsorbent, exhibiting Cd(II) and Pb(II) adsorption capacities as high as 240 mg g-1 and 350 mg g-1, respectively, outperforming conventionally used adsorbents. This is attributed to its morphology, favorable surface charge distribution, and the presence of -OH and -COH groups. A strong affinity between the biomass and metal pollutants was evidenced by a thermodynamics study, showing a spontaneous and endothermic process. This work sets a practical route for the utilization of the Sargassum biomass, demonstrating its applicability as a potential material for heavy-metal-polluted water remediation, making a substantial contribution to a circular economy system.


Assuntos
Metais Pesados , Sargassum , Poluentes Químicos da Água , Cádmio , Biomassa , Ecossistema , Espectroscopia de Infravermelho com Transformada de Fourier , Chumbo , Metais Pesados/química , Adsorção , Poluentes Químicos da Água/química
12.
Environ Sci Pollut Res Int ; 30(10): 25193-25204, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35015236

RESUMO

The importance of the textural and physicochemical characteristics upon the adsorption capacity of the commercial activated carbons (ACs) Coconut, Wood, Merck, Darco, and Norit towards ronidazole (RNZ) and diclofenac (DCF) from water solution was investigated thoroughly in this work. At pH = 7, Coconut AC and Wood AC presented the highest adsorption capacity towards RNZ (444 mg/g) and DCF (405 mg/g). The maximum mass of RNZ adsorbed onto Coconut AC was higher in this study than those outlined previously in other works. Besides, the maximum capacity of Wood AC for adsorbing DCF was comparable to those found for other ACs. The adsorption capacity of all the ACs was increased by surface area and was favored by incrementing the acidic site concentration. The π-π stacking interactions were the predominant adsorption mechanism for the RNZ and DCF adsorption on ACs, and the acidic sites favored the adsorption capacity by activating the π-π stacking. Electrostatic interactions did not influence the adsorption of RNZ on Coconut AC, but electrostatic repulsion decreased that of DCF on Wood AC. The adsorption of DCF on Wood AC was reversible but not that of RNZ on Coconut AC. Besides, the adsorption of RNZ and DCF on the Coconut and Wood ACs was endothermic in the range of 15-25 °C.


Assuntos
Carvão Vegetal , Poluentes Químicos da Água , Carvão Vegetal/química , Ronidazole , Diclofenaco/química , Adsorção , Água/química , Poluentes Químicos da Água/química , Concentração de Íons de Hidrogênio , Cinética
13.
Eur Cardiol ; 18: e63, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38213664

RESUMO

Left main coronary artery disease (LMCAD) is associated with high morbidity and mortality due to the large myocardial mass at risk. Although medical treatment may be an option in selected low-risk patients, revascularisation is recommended to improve survival in the majority of patients presenting with a significant left main stenosis. In the past decade, multiple randomised clinical trials and meta-analyses have compared coronary artery bypass grafting surgery (CABG) versus percutaneous coronary intervention (PCI), finding controversial results. The strategy for LMCAD revascularisation is still challenging. Coronary anatomy complexity, clinical features and patient preferences are key elements to be considered by the heart team. The current guidelines define CABG as standard therapy, but the continuous improvements in PCI techniques, the use of intracoronary imaging and functional assessment make PCI a feasible alternative in selected patients, particularly in those with comorbidities and contraindications to CABG. This review analyses the most important studies comparing CABG versus PCI in patients with LMCAD.

14.
J Leukoc Biol ; 112(5): 1209-1221, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36164808

RESUMO

The rheumatoid arthritis (RA) inflammatory process occurs in the joints where immune cells are attracted into the synovium to promote remodeling and tissue damage. GPR15 is a G protein-coupled receptor (GPCR) located on chromosome 3 and has similarity in its sequence with chemokine receptors. Recent evidence indicates that GPR15 may be associated with modulation of the chronic inflammatory response. We evaluated the expression of GPR15 and GPR15L in blood and synovial tissue samples from RA patients, as well as to perform a functional migration assay in response to GPR15L. The expression of GPR15 and c10orf99/gpr15l mRNA was analyzed by RT-qPCR. Samples of synovial fluid and peripheral blood were analyzed for CD45+CD3+CD4+GPR15+ and CD45+CD3+CD8+GPR15+ T cell frequency comparing RA patients versus control subjects by flow cytometry. Migration assays were performed using PBMCs isolated from these individuals in response to the synthetic GPR15 ligand. Statistical analysis included Kruskal-Wallis test, T-test, or Mann-Whitney U test, according to data distribution. A higher expression in the mRNA for GPR15 was identified in early RA subjects. The frequencies of CD4+/CD8+ GPR15+ T lymphocytes are higher in RA patients comparing with healthy subjects. Also, the frequency CD4+/CD8+ GPR15+ T lymphocytes are higher in synovial fluid of established RA patients comparing with OA patients. GPR15 and GPR15L are present in the synovial tissue of RA patients and GPR15L promotes migration of PBMCs from RA patients and healthy subjects. Our results suggest that GPR15/GPR15L have a pathogenic role in RA and their antagonizing could be a therapeutic approach in RA.


Assuntos
Artrite Reumatoide , Membrana Sinovial , Humanos , Ligantes , Membrana Sinovial/patologia , Artrite Reumatoide/patologia , Líquido Sinovial/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Quimiocinas , Quimiotaxia de Leucócito , RNA Mensageiro/genética , Receptores de Peptídeos
15.
J Biol Chem ; 298(9): 102297, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35872017

RESUMO

Insulin signaling in blood vessels primarily functions to stimulate angiogenesis and maintain vascular homeostasis through the canonical PI3K and MAPK signaling pathways. However, angiogenesis is a complex process coordinated by multiple other signaling events. Here, we report a distinct crosstalk between the insulin receptor and endoglin/activin receptor-like kinase 1 (ALK1), an endothelial cell-specific TGF-ß receptor complex essential for angiogenesis. While the endoglin-ALK1 complex normally binds to TGF-ß or bone morphogenetic protein 9 (BMP9) to promote gene regulation via transcription factors Smad1/5, we show that insulin drives insulin receptor oligomerization with endoglin-ALK1 at the cell surface to trigger rapid Smad1/5 activation. Through quantitative proteomic analysis, we identify ependymin-related protein 1 (EPDR1) as a major Smad1/5 gene target induced by insulin but not by TGF-ß or BMP9. We found endothelial EPDR1 expression is minimal at the basal state but is markedly enhanced upon prolonged insulin treatment to promote cell migration and formation of capillary tubules. Conversely, we demonstrate EPDR1 depletion strongly abrogates these angiogenic effects, indicating that EPDR1 is a crucial mediator of insulin-induced angiogenesis. Taken together, these results suggest important therapeutic implications for EPDR1 and the TGF-ß pathways in pathologic angiogenesis during hyperinsulinemia and insulin resistance.


Assuntos
Endoglina , Fator 2 de Diferenciação de Crescimento , Insulina , Neovascularização Patológica , Proteínas do Tecido Nervoso , Receptores de Fatores de Crescimento Transformadores beta , Animais , Humanos , Camundongos , Receptores de Activinas Tipo II/metabolismo , Chlorocebus aethiops , Células COS , Endoglina/genética , Endoglina/metabolismo , Fator 2 de Diferenciação de Crescimento/genética , Insulina/metabolismo , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Fosfatidilinositol 3-Quinases , Proteômica , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Proteína Smad1/metabolismo , Proteína Smad5/metabolismo , Fator de Crescimento Transformador beta/metabolismo
16.
Nat Commun ; 13(1): 1326, 2022 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-35288568

RESUMO

Defective angiogenesis underlies over 50 malignant, ischemic and inflammatory disorders yet long-term therapeutic applications inevitably fail, thus highlighting the need for greater understanding of the vast crosstalk and compensatory mechanisms. Based on proteomic profiling of angiogenic endothelial components, here we report ßIV-spectrin, a non-erythrocytic cytoskeletal protein, as a critical regulator of sprouting angiogenesis. Early loss of endothelial-specific ßIV-spectrin promotes embryonic lethality in mice due to hypervascularization and hemorrhagic defects whereas neonatal depletion yields higher vascular density and tip cell populations in developing retina. During sprouting, ßIV-spectrin expresses in stalk cells to inhibit their tip cell potential by enhancing VEGFR2 turnover in a manner independent of most cell-fate determining mechanisms. Rather, ßIV-spectrin recruits CaMKII to the plasma membrane to directly phosphorylate VEGFR2 at Ser984, a previously undefined phosphoregulatory site that strongly induces VEGFR2 internalization and degradation. These findings support a distinct spectrin-based mechanism of tip-stalk cell specification during vascular development.


Assuntos
Espectrina , Fator A de Crescimento do Endotélio Vascular , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Camundongos , Neovascularização Fisiológica , Proteômica , Transdução de Sinais , Espectrina/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
17.
Mol Biol Cell ; 33(1): ar4, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34705526

RESUMO

Dynamin-related protein 1 (Drp1) is a key regulator of mitochondrial fission, a large cytoplasmic GTPase recruited to the mitochondrial surface via transmembrane adaptors to initiate scission. While Brownian motion likely accounts for the local interactions between Drp1 and the mitochondrial adaptors, how this essential enzyme is targeted from more distal regions like the cell periphery remains unknown. Based on proteomic interactome screening and cell-based studies, we report that GAIP/RGS19-interacting protein (GIPC) mediates the actin-based retrograde transport of Drp1 toward the perinuclear mitochondria to enhance fission. Drp1 interacts with GIPC through its atypical C-terminal PDZ-binding motif. Loss of this interaction abrogates Drp1 retrograde transport resulting in cytoplasmic mislocalization and reduced fission despite retaining normal intrinsic GTPase activity. Functionally, we demonstrate that GIPC potentiates the Drp1-driven proliferative and migratory capacity in cancer cells. Together, these findings establish a direct molecular link between altered GIPC expression and Drp1 function in cancer progression and metabolic disorders.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Dinaminas/metabolismo , Dinâmica Mitocondrial/fisiologia , Animais , Células COS , Linhagem Celular , Chlorocebus aethiops , Citoplasma/metabolismo , Citosol/metabolismo , Dinaminas/genética , GTP Fosfo-Hidrolases/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Microtúbulos/metabolismo , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Ligação Proteica , Proteômica
18.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1354918

RESUMO

Introducción: Investigaciones anteriores coinciden en que el enriquecimiento de alimentos es la mejor estrategia a largo plazo en la prevención de la deficiencia de hierro. Nuestro objetivo es evaluar el efecto de una mezcla láctea fortificada con hierro y zinc sobre los niveles de hemoglobina en niños de 2 a 10 años. Material y métodos: Se realizó un ensayo clínico aleatorizado, doble ciego, controlado en una comunidad ubicada a 2,590 metros sobre el nivel del mar. Se incluyeron niños con niveles en el límite inferior de los rangos de normalidad o anemia leve. Asignamos a los participantes de manera aleatoria que recibieran la mezcla láctea fortificada con hierro y zinc o una mezcla láctea no fortificada. La mezcla láctea se administró cinco días a la semana durante 24 semanas. Nuestro resultado principal fue el nivel de hemoglobina corregida tomando en cuenta la altura sobre el nivel del mar y los índices antropométricos se evaluaron como resultado secundario. La magnitud de la diferencia observada entre los grupos se estimó mediante la prueba t de Student. Todos los análisis se realizaron por intención de tratar. Resultados: Se asignaron al azar 67 niños, intervención: n=32 y control: n=35. La edad media fue de 5,8 años; 30 eran mujeres. La hemoglobina al final del seguimiento fue 13,1 gr/dL (0,9) en el grupo experimental mientras que, en el grupo control, fue de 12,1 gr/dL (0,8); p <0,001. Asimismo, se evidenció una diferencia positiva en los indicadores antropométricos en el grupo experimental. Conclusión: La mezcla láctea fortificada con hierro y zinc aumenta los niveles de hemoglobina y los índices antropométricos en niños de 2 a 10 años.


Objetive:Previous research agrees tha tfood fortification is the best long-term strategy for preventing iron deficiency. Our goal is to evaluate the effect of a dairy mixture fortified with iron and zinc on hemoglobin levels in children aged 2 to 10 years. Material and methods: A randomized, double-blind, controlled clinical trial was conducted in a community located 2,590 meters above sea level. Children with normal levels of hemoglobin or mild anemia were included. We assign participants to receive the iron-zinc-fortified dairy mixture or an unfortified dairy mixture. The supplement was administered five days a week for 24 weeks. Our main result was the corrected hemoglobin level taking into account the height above sea level and anthropometric indices were evaluated as a secondary result. The magnitude of the difference observed between the groups was estimated by the Student t-test. All analyzes were done with the intention to treat. Results: 67 children were randomly assigned, intervention: n=32 and control: n=35. The mean age was 5.8 years; 30 were women. Hemoglobin at the end of the follow-up was 13.1 g/dL(0.9) in the experimental group, while, in the control group, it was 12.1 g/dL(0.8); p <0.001. Likewise, a positive difference was evidenced in the anthropometric indicators in the experimental group. Conclusion: Dairy mixture fortified with iron and zinc increases hemoglobin levels and anthropometric indices in children from 2 to 10 years old.

19.
Vive (El Alto) ; 4(11)ago. 2021.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1390532

RESUMO

Resumen El bazo es el órgano que se lesiona con más frecuencia en el trauma abdominal cerrado, presentándose en 30 a 50% de los casos, principalmente por su fragilidad y localización, su tratamiento ha estado en constante cambio a lo largo del tiempo, siendo hoy en día más utilizado el manejo conservador por sobre el intervencionista, considerando sobre todo el mayor riesgo de mortalidad y las condiciones fisiológicas posteriores a la esplenectomía principalmente en niños y adolescentes. Objetivo. Realizar una revisión actual del diagnóstico, clasificación y tratamiento del trauma esplénico. Metodología . Se realizó una revisión bibliográfica incluyendo los descriptores relacionados con trauma esplénico y su tratamiento. Resultados. La identificación del trauma esplénico es de vital importancia para la supervivencia del paciente, el diagnostico se puede realizar mediante estudios de imagen eco-FAST o tomografía en dependencia del estado hemodinámico del paciente, la clasificación depende de las características anatómicas de las lesiones y orienta el tratamiento adecuado. Conclusiones. Actualmente el tratamiento conservador está recomendado para lesiones I-III; los estadios mayores (IV y V) o cualquier grado siempre y cuando exista compromiso hemodinámico implican tratamiento intervencionista o quirúrgico, no existe una diferencia significativa entre la utilización de técnica abierta vs laparoscópica.


Abstract The spleen is the organ that is most frequently injured in blunt abdominal trauma, occurring in 30 to 50% of cases, mainly due to its fragility and location, its treatment has been in constant change over time, today the conservative management is more widely used than interventionist, considering above all the greater risk of mortality and the physiological conditions after splenectomy, mainly in children and adolescents. Objective . To carry out a current review of the diagnosis, classification and treatment of splenic trauma. Methodology . A bibliographic review was carried out including the descriptors related to splenic trauma and its treatment. Results .The identification of splenic trauma is of vital importance for the survival of the patient, the diagnosis can be made by imaging studies, FAST ultrasound or tomography depending on the hemodynamic status of the patient, the classification depends on the anatomical characteristics of the lesions and guides the appropriate treatment. Conclusions . Conservative treatment is currently recommended for lesions I-III; the major stages (IV and V) or any grade whit hemodynamic compromise imply interventional or surgical treatment, there is no significant difference between the use of open versus laparoscopic technique.


Resumo O baço é o órgão mais frequentemente lesado no trauma abdominal fechado, ocorrendo em 30 a 50% dos casos, principalmente devido à sua fragilidade e localização, seu tratamento tem mudado constantemente ao longo do tempo, sendo hoje o manejo conservador mais utilizado que o intervencionista, considerando sobretudo o maior risco de mortalidade e as condições fisiológicas após a esplenectomia, principalmente em crianças e adolescentes. Objetivo . Fazer uma revisão atual do diagnóstico, classificação e tratamento do trauma esplênico. Metodologia . Foi realizada uma revisão bibliográfica incluindo os descritores relacionados ao trauma esplênico e seu tratamento. Resultados . A identificação do trauma esplênico é de vital importância para a sobrevida do paciente, o diagnóstico pode ser feito por exames de imagem echo-FAST ou tomografia dependendo do estado hemodinâmico do paciente, a classificação depende das características anatômicas das lesões e orienta o tratamento adequado. Conclusões . O tratamento conservador é atualmente recomendado para lesões I-III; os estágios principais (IV e V) ou em qualquer grau, desde que haja comprometimento hemodinâmico, implicam em tratamento intervencionista ou cirúrgico, não havendo diferença significativa entre o uso da técnica aberta e laparoscópica.

20.
Vive (El Alto) ; 3(9): 158-165, dic. 2020. ilus
Artigo em Espanhol | LILACS | ID: biblio-1252334

RESUMO

INTRODUCCIÓN: desde la declaración de pandemia por la OMS el once de marzo de 2020, ha existido un descenso en los ingresos de pacientes quirúrgicos por la paralización de la cirugía electiva y la disminución de procedimientos quirúrgicos emergentes. OBJETIVO: analizar la incidencia y características de la patología quirúrgica emergente en un hospital de segundo nivel en Ecuador. MATERIAL Y MÉTODOS: estudio retrospectivo, descriptivo, que incluyó a todos los pacientes sometidos a cirugía general emergente en el Hospital General Riobamba IESS, desde el once de marzo hasta el once de agosto de 2020. RESULTADOS: en el estudio se incluyeron 63 pacientes, con una media de edad de 48,54 años; el 50,8% fueron hombres. El diagnóstico más frecuente fue apendicitis aguda en 61,9% casos. Se realizaron 66 cirugías, 36,5% fueron apendicectomías convencionales. El abordaje abierto se llevó a cabo en 68,2% de los pacientes. El 12,7% de pacientes presentaron COVID-19 en el perioperatorio de los cuales 25% fallecieron. La mortalidad general fue del 7,9% y todos los pacientes fallecidos fueron hombres. Discusión: La evidencia acerca del manejo quirúrgico durante la pandemia COVID-19 aún es limitada. La patología quirúrgica emergente no se puede diferir, se deben tener en cuenta el incremento en la mortalidad de pacientes infectados y el riesgo de exposición del equipo quirúrgico. CONCLUSIÓN: durante la pandemia se produjo un descenso en las cirugías realizadas en nuestro centro, la apendicitis aguda continúa siendo la principal patología quirúrgica emergente. La mortalidad se asoció al sexo masculino y diagnóstico de COVID-19.


INTRODUCTION: since the declaration of a pandemic by the WHO on March 11, 2020, there has been a decrease in the admissions of surgical patients due to the paralyzation of elective surgery and the decrease in emerging surgical procedures. OBJECTIVE: to analyze the incidence and characteristics of emerging surgical pathology in a second level hospital in Ecuador. MATERIAL AND METHODS: retrospective and descriptive study, which included all the patients undergoing emergency general surgery at Hospital General Riobamba IESS, from March 11 to August 11, 2020. RESULTS: 63 patients were included in the study, with a mean age of 48.54 years; 50.8% were men. The most frequent diagnosis was acute appendicitis in 61.9% cases. 66 surgeries were performed, 36.5% were conventional appendicectomies. The open approach was carried out in 68.2% of the patients. 12.7% of patients presented COVID-19 in the perioperative period, of which 25% died. Overall mortality was 7.9% and all deceased patients were men. DISCUSSION: the evidence about surgical management during the COVID-19 pandemic is still limited. Emerging surgical pathology cannot be deferred, the increased mortality of infected patients and the risk of exposure of the surgical team must be taken into account. CONCLUSION: during the pandemic there was a decrease in the surgeries performed in our center, acute appendicitis continues to be the main emerging surgical pathology. Mortality was associated with male sex and diagnosis of COVID-19.


INTRODUÇÃO: desde a declaração de uma pandemia pela OMS em 11 de março de 2020, houve uma diminuição nas admissões de pacientes cirúrgicos devido à paralisação das cirurgias eletivas e diminuição dos procedimentos cirúrgicos emergentes. OBJETIVO: analisar a incidência e as características da patologia cirúrgica emergente em um hospital de segundo nível no Equador. Material E Métodos: estudo retrospectivo, descritivo, que incluiu todos os pacientes submetidos à cirurgia geral de urgência no Hospital Geral de Riobamba IESS, no período de 11 de março a 11 de agosto de 2020. RESULTADOS: o estudo incluiu 63 pacientes, com média de idade de 48,54 anos; 50,8% eram homens. O diagnóstico mais frequente foi apendicite aguda em 61,9% dos casos. Foram realizadas 66 cirurgias, 36,5% foram apendicectomias convencionais. A abordagem aberta foi realizada em 68,2% dos pacientes. 12,7% dos pacientes apresentaram COVID-19 no período perioperatório, dos quais 25% morreram. A mortalidade geral foi de 7,9% e todos os pacientes falecidos eran homens. DISCUSSÃO: as evidências sobre o manejo cirúrgico durante a pandemia de COVID-19 ainda são limitadas. A patologia cirúrgica emergente não pode ser adiada, o aumento da mortalidade dos pacientes infectados e o risco de exposição da equipe cirúrgica devem ser levados em consideração. CONCLUSÃO: durante a pandemia houve diminuição das cirurgias realizadas em nosso centro, a apendicite aguda continua sendo a principal patologia cirúrgica emergente. A mortalidade foi associada ao sexo masculino e ao diagnóstico de COVID-19.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Patologia Cirúrgica , Cirurgia Geral , Pacientes , Procedimentos Cirúrgicos Operatórios , Mortalidade , COVID-19
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