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ABSTRACT Purpose: We reported, as a referral center in prostate cancer, our perspectives and experience performing Telesurgery using robotic surgery and 5G network. Material and methods: We described and illustrated the Telesurgery applications and outcomes to treat a patient with prostate cancer located 1300 kilometers away from the surgeon (Beijing-Harbin) in China. We used the Edge Medical Robot (MP1000) in November 2023 in a 71-year-old patient with Gleason 6 (ISUP 1) in 8 cores from 13, PSA of 14 ng/dL, and clinical stage cT2a. MRI described a PIRADS 5 nodule on the left peripheral zone at the base, and 20gr prostate. We described details about the connection between centers, perioperative outcomes, and our perspectives as a referral center in prostate cancer. Results: We had no delays, or problems with network connection between the centers. The procedure was performed in 60 minutes, with no intra- or postoperative complications. Estimated blood loss was 100 mL. The patient was ambulating soon after anesthesia recovery. Final pathology described a Gleason 6 (ISUP 1) involving the left base and left seminal vesicle, negative surgical margins, and no lymph node involvement (pT3bN0). The patient was continent soon after catheter removal (7 days). Conclusion: As technological progress introduced novel robotic platforms and high-speed networks, the concept of Telesurgery became a tangible reality while 5G technology solved latency and transmission concerns. However, with these advancements, ethical considerations and regulatory frameworks should underline the importance of transparency and patient safety with responsible innovation in the field.
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PURPOSE: We reported, as a referral center in prostate cancer, our perspectives and experience performing Telesurgery using robotic surgery and 5G network. MATERIAL AND METHODS: We described and illustrated the Telesurgery applications and outcomes to treat a patient with prostate cancer located 1300 kilometers away from the surgeon (Beijing-Harbin) in China. We used the Edge Medical Robot (MP1000) in November 2023 in a 71-year-old patient with Gleason 6 (ISUP 1) in 8 cores from 13, PSA of 14 ng/dL, and clinical stage cT2a. MRI described a PIRADS 5 nodule on the left peripheral zone at the base, and 20gr prostate. We described details about the connection between centers, perioperative outcomes, and our perspectives as a referral center in prostate cancer. RESULTS: We had no delays, or problems with network connection between the centers. The procedure was performed in 60 minutes, with no intra- or postoperative complications. Estimated blood loss was 100 mL. The patient was ambulating soon after anesthesia recovery. Final pathology described a Gleason 6 (ISUP 1) involving the left base and left seminal vesicle, negative surgical margins, and no lymph node involvement (pT3bN0). The patient was continent soon after catheter removal (7 days). CONCLUSION: As technological progress introduced novel robotic platforms and high-speed networks, the concept of Telesurgery became a tangible reality while 5G technology solved latency and transmission concerns. However, with these advancements, ethical considerations and regulatory frameworks should underline the importance of transparency and patient safety with responsible innovation in the field.
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Prostatectomia , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Humanos , Masculino , Prostatectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Idoso , Telemedicina , Resultado do TratamentoRESUMO
ABSTRACT Background: Adriamycin (ADM) resistance remains an obstacle to gastric cancer chemotherapy treatment. Objective: The objective of this study was to study the role and mechanism of transcription factor E2F7 in sensitivity to ADM chemotherapeutic agents in gastric cancer. Methods: Cell viability and cell sensitivity were assessed by CCK-8 and IC50 values of ADM were calculated. The impact of ADM on cellular proliferative capacity was assessed through colony formation assay. The binding relationship between E2F7 and PKMYT1 was then verified by dual luciferase assay and chromatin immunoprecipitation assay. ERK1/ERK2 and p-ERK1/p-ERK2 protein expression levels were detected by western blot. Results: In both gastric cancer tissue and ADM-resistant cells, a conspicuous upregulation of E2F7 and PKMYT1 was observed. Upregulated PKMYT1 was notably enriched in the MAPK signaling pathway. Enhanced levels of E2F7 were shown to not only drive gastric cancer cell proliferation but also engender a reduction in the sensitivity of these cells to ADM. Furthermore, PKMYT1 emerged as a downstream target of E2F7. Activation of E2F7 culminated in the transcriptional upregulation of PKMYT1, and silencing E2F7 reversed the inhibitory impact of PKMYT1 overexpression on ADM sensitivity in gastric cancer cells. Conclusion: E2F7/PKMYT1 axis might promote the proliferation and partially inhibit ADM sensitivity of gastric cancer cells by activating the MAPK pathway.
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Background: Adriamycin resistance remains an obstacle to gastric cancer chemotherapy treatment. Objective: The objective of this study was to study the role and mechanism of transcription factor E2F7 in sensitivity to ADM chemotherapeutic agents in gastric cancer. Methods: Cell viability and cell sensitivity were assessed by CCK-8 and IC50 values of ADM were calculated. The impact of ADM on cellular proliferative capacity was assessed through colony formation assay. The binding relationship between E2F7 and PKMYT1 was then verified by dual luciferase assay and chromatin immunoprecipitation assay. ERK1/ERK2 and p-ERK1/p-ERK2 protein expression levels were detected by western blot. Results: In both gastric cancer tissue and ADM-resistant cells, a conspicuous upregulation of E2F7 and PKMYT1 was observed. Upregulated PKMYT1 was notably enriched in the MAPK signaling pathway. Enhanced levels of E2F7 were shown to not only drive gastric cancer cell proliferation but also engender a reduction in the sensitivity of these cells to ADM. Furthermore, PKMYT1 emerged as a downstream target of E2F7. Activation of E2F7 culminated in the transcriptional upregulation of PKMYT1, and silencing E2F7 reversed the inhibitory impact of PKMYT1 overexpression on ADM sensitivity in gastric cancer cells. Conclusion: E2F7/PKMYT1 axis might promote the proliferation and partially inhibit ADM sensitivity of gastric cancer cells by activating the MAPK pathway.
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MicroRNAs , Neoplasias Gástricas , Humanos , Doxorrubicina/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Fatores de Transcrição/metabolismo , Linhagem Celular Tumoral , Transdução de Sinais , MicroRNAs/metabolismo , Regulação Neoplásica da Expressão Gênica , Fator de Transcrição E2F7/genética , Fator de Transcrição E2F7/metabolismo , Proteínas de Membrana/genética , Proteínas Tirosina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismoRESUMO
The gut microbiome plays a critical role to all animals and humans health. Methods based on ex vivo cultures are time and cost-effective solutions for rapid evaluation of probiotic effects on microbiomes. In this study, we assessed whether the protein secretome from the potential probiotic Enterococcus durans LAB18S grown on fructoligosaccharides (FOS) and galactoligosaccharides (GOS) had specific effects on ex vivo cultured intestinal microbiome obtained from a healthy individual. Metaproteomics was used to evaluate changes in microbial communities of the human intestinal microbiome. Hierarchical clustering analysis revealed 654 differentially abundant proteins from the metaproteome samples, showing that gut microbial protein expression varied on the presence of different E. durans secretomes. Increased amount of Bacteroidetes phylum was observed in treatments with secretomes from E. durans cultures on FOS, GOS and albumin, resulting in a decrease of the Firmicutes to Bacteroidetes (F/B) ratio. The most functionally abundant bacterial taxa were Roseburia, Bacteroides, Alistipes and Faecalibacterium. The results suggest that the secretome of E. durans may have favorable effects on the intestinal microbial composition, stimulating growth and different protein expression of beneficial bacteria. These findings suggest that proteins secreted by E. durans growing on FOS and GOS have different effects on the modulation of gut microbiota functional activities during cultivation.
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Metabolomics studies in sickle cell disease (SCD) have been so far limited to tens of samples, owing to technical and experimental limitations. To overcome these limitations, we performed plasma metabolomics analyses on 596 samples from patients with SCD enrolled in the WALK-PHaSST study (clinicaltrials gov. Identifier: NCT00492531). Clinical covariates informed the biological interpretation of metabolomics data, including genotypes (hemoglobin [Hb] SS, hemoglobin SC), history of recent transfusion (HbA%), response to hydroxyurea treatment (fetal Hb%). We investigated metabolic correlates to the degree of intravascular hemolysis, cardiorenal function, as determined by tricuspid regurgitation velocity (TRV), estimated glomerular filtration rate (eGFR), and overall hazard ratio (unadjusted or adjusted by age). Recent transfusion events or hydroxyurea treatment were associated with elevation in plasma-free fatty acids and decreases in acyl-carnitines, urate, kynurenine, indoles, carboxylic acids, and glycine- or taurine-conjugated bile acids. High levels of these metabolites, along with low levels of plasma S1P and L-arginine were identified as top markers of hemolysis, cardiorenal function (TRV, eGFR), and overall hazard ratio. We thus uploaded all omics and clinical data on a novel online portal that we used to identify a potential mechanism of dysregulated red cell S1P synthesis and export as a contributor to the more severe clinical manifestations in patients with the SS genotype compared to SC. In conclusion, plasma metabolic signatures - including low S1P, arginine and elevated kynurenine, acyl-carnitines and bile acids - are associated with clinical manifestation and therapeutic efficacy in SCD patients, suggesting new avenues for metabolic interventions in this patient population.
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Anemia Falciforme , Doença da Hemoglobina SC , Humanos , Hidroxiureia/uso terapêutico , Cinurenina/uso terapêutico , Anemia Falciforme/complicações , Anemia Falciforme/tratamento farmacológico , Doença da Hemoglobina SC/complicações , Hemólise , Hemoglobina Falciforme , Ácidos e Sais Biliares/uso terapêuticoRESUMO
Ischaemic stroke is a common complication of sickle cell disease (SCD) and without intervention can affect 11% of children with SCD before the age of 20. Within the Trans-Omics for Precision Medicine (TOPMed), a genome-wide association study (GWAS) of ischaemic stroke was performed on 1333 individuals with SCD from Brazil (178 cases, 1155 controls). Via a novel Cox proportional-hazards analysis, we searched for variants associated with ischaemic stroke occurring at younger ages. Variants at genome-wide significance (p < 5 × 10-8 ) include two near genes previously linked to non-SCD early-onset stroke (<65 years): ADAMTS2 (rs147625068, p = 3.70 × 10-9 ) and CDK18 (rs12144136, p = 2.38 × 10-9 ). Meta-analysis, which included the independent SCD cohorts Walk-PHaSST and PUSH, exhibited consistent association for variants rs1209987 near gene TBC1D32 (p = 3.36 × 10-10 ), rs188599171 near CUX1 (p = 5.89 × 10-11 ), rs77900855 near BTG1 (p = 4.66 × 10-8 ), and rs141674494 near VPS13C (1.68 × 10-9 ). Findings from this study support a multivariant model of early ischaemic stroke risk and possibly a shared genetic architecture between SCD individuals and non-SCD individuals younger than 65 years.
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Anemia Falciforme , Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Adolescente , Adulto , Criança , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Proteínas ADAMTS/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Anemia Falciforme/complicações , Anemia Falciforme/genética , Isquemia Encefálica/genética , Brasil/epidemiologia , Estudo de Associação Genômica Ampla , Acidente Vascular Cerebral/genéticaRESUMO
Aging is a major risk factor to develop neurodegenerative diseases and is associated with decreased buffering capacity of the proteostasis network. We investigated the significance of the unfolded protein response (UPR), a major signaling pathway activated to cope with endoplasmic reticulum (ER) stress, in the functional deterioration of the mammalian brain during aging. We report that genetic disruption of the ER stress sensor IRE1 accelerated age-related cognitive decline. In mouse models, overexpressing an active form of the UPR transcription factor XBP1 restored synaptic and cognitive function, in addition to reducing cell senescence. Proteomic profiling of hippocampal tissue showed that XBP1 expression significantly restore changes associated with aging, including factors involved in synaptic function and pathways linked to neurodegenerative diseases. The genes modified by XBP1 in the aged hippocampus where also altered. Collectively, our results demonstrate that strategies to manipulate the UPR in mammals may help sustain healthy brain aging.
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Envelhecimento , Encéfalo , Proteínas Serina-Treonina Quinases , Resposta a Proteínas não Dobradas , Proteína 1 de Ligação a X-Box , Animais , Camundongos , Envelhecimento/genética , Encéfalo/metabolismo , Estresse do Retículo Endoplasmático/genética , Proteínas Serina-Treonina Quinases/genética , Proteômica , Transdução de Sinais/fisiologia , Proteína 1 de Ligação a X-Box/genética , Proteína 1 de Ligação a X-Box/metabolismoRESUMO
PURPOSE: To investigate the protective effects of Shenkang injection (SKI) on adenine-induced chronic renal failure (CRF) in rat. METHODS: Sprague Dawley rats were randomly divided into five groups: control, model, and SKI groups (5, 10, 20 mL/kg). Rats in model and SKI groups were treated with adenine i.g. at a dose of 150 mg/kg every day for 12 weeks to induce CRF. Twelve weeks later, SKI was administered to the rat i.p. for four weeks. The effects of SKI on kidney injury and fibrosis were detected. RESULTS: SKI inhibited the elevation of the urine level of N-acetyl-b-D-glucosaminidase, kidney injury molecule-1, beta-2-microglobulin, urea protein in CRF rats. The serum levels of uric acid and serum creatinine increased and albumin decreased in the model group, which was prevented by SKI. SKI inhibited the release of inflammatory cytokines and increasing the activities of antioxidant enzymes in serum. SKI inhibited the expression of transforming growth factor-ß1, vascular cell adhesion molecule 1, intercellular adhesion molecule 1, collagen I, collagen III, endothelin-1, laminin in kidney of CRF rats. CONCLUSIONS: SKI protected against adenine-induced kidney injury and fibrosis and exerted anti-inflammatory, and antioxidant effects in CRF rats.
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Falência Renal Crônica , Insuficiência Renal Crônica , Adenina/metabolismo , Adenina/farmacologia , Adenina/uso terapêutico , Animais , Medicamentos de Ervas Chinesas , Fibrose , Rim , Falência Renal Crônica/induzido quimicamente , Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/prevenção & controle , Ratos , Ratos Sprague-Dawley , Insuficiência Renal Crônica/tratamento farmacológicoRESUMO
Purpose: To investigate the protective effects of Shenkang injection (SKI) on adenine-induced chronic renal failure (CRF) in rat. Methods: Sprague Dawley rats were randomly divided into five groups: control, model, and SKI groups (5, 10, 20 mL/kg). Rats in model and SKI groups were treated with adenine i.g. at a dose of 150 mg/kg every day for 12 weeks to induce CRF. Twelve weeks later, SKI was administered to the rat i.p. for four weeks. The effects of SKI on kidney injury and fibrosis were detected. Results: SKI inhibited the elevation of the urine level of N-acetyl-b-D-glucosaminidase, kidney injury molecule-1, beta-2-microglobulin, urea protein in CRF rats. The serum levels of uric acid and serum creatinine increased and albumin decreased in the model group, which was prevented by SKI. SKI inhibited the release of inflammatory cytokines and increasing the activities of antioxidant enzymes in serum. SKI inhibited the expression of transforming growth factor-β1, vascular cell adhesion molecule 1, intercellular adhesion molecule 1, collagen I, collagen III, endothelin-1, laminin in kidney of CRF rats. Conclusions: SKI protected against adenine-induced kidney injury and fibrosis and exerted anti-inflammatory, and antioxidant effects in CRF rats.
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Animais , Ratos , Fibrose , Ratos Sprague-Dawley , Falência Renal CrônicaRESUMO
SUMMARY: A comparative study of the morphology of suboccipital cavernous sinus (SCS) using MRI and cast specimens was performed. The present retrospective study analysed the craniocervical magnetic resonance venography (MRV) imaging data of 61 patients. Three-dimensional reconstruction was performed using Mimics 19.0. The SCS left-right diameter(d1), distance from the midline (d2), supero-inferior diameter(d3), anteroposterior diameter (d4), distance from posterior diameter to skin (d5), and diameter of the SCS at different parts (d6-d8) were measured. Comparison between MRV images and cast specimens, the SCS, marginal sinus, anterior condylar vein, and vertebral artery venous plexus were symmetrical and could be bilaterally displayed, whereas the presence of extra condylar vein and posterior condylar vein exhibited different types. The adjacency between the SCS and its communicating vessels and changes in its communicating vessels corresponded well with the MRV images and cast specimens. Many types of the presence of left and right lateral condylar and posterior condylar veins were found in the cast specimens, which could be divided into the bilateral presence of posterior condylar and lateral condylar veins, unilateral presence of posterior condylar veins, and unilateral presence of lateral condylar vein. A total of 61 cases analysed using MRV images revealed the bilateral presence of posterior condylar and lateral condylar veins (77.1 %), the unilateral presence of posterior condylar vein (18.0 %), and the unilateral presence of lateral condylar vein (9.8 %), of which the bilateral presence of posterior condylar and lateral condylar veins accounted for the largest proportion. MRV images and cast specimens of the SCS showed its normal morphological structure and adjacency, thus providing accurate and complete Three-dimensional imaging anatomical data of the SCS and its communicating vascular structures. This study enriches the Chinese SCS imaging anatomy data and may be valuable in clinical practice.
RESUMEN: Se realizó un estudio comparativo de la morfología del seno cavernoso suboccipital (SCS) mediante resonancia magnética y muestras de yeso. El presente estudio retrospectivo analizó los datos de imágenes de venografía por resonancia magnética (RNM) craneocervical de 61 pacientes. La reconstrucción tridimensional se realizó con Mimics 19.0. Se midió: el diámetro izquierdo-derecho del SCS (d1), la distancia desde la línea mediana (d2), el diámetro superoinferior (d3), el diámetro anteroposterior (d4), la distancia desde el diámetro posterior hasta la piel (d5) y el diámetro del SCS en diferentes partes (d6-d8). En la comparación entre las imágenes RNM y las muestras de yeso, el SCS, el seno marginal, la vena condilar anterior y el plexo venoso de la arteria vertebral eran simétricos y se observaron bilateralmente, mientras que la presencia de la vena extracondilar y la vena condilar posterior presentaba tipos diferentes. La proximidad del SCS y sus vasos comunicantes y los cambios en sus vasos comunicantes se correspondieron bien con las imágenes de RNM y los especímenes moldeados. Se encontraron muchos tipos de venas condilares laterales y condilares posteriores izquierda y derecha en las muestras de yeso, que podrían dividirse en presencia bilateral de venas condilares posteriores y condilares laterales, presencia unilateral de venas condilares posteriores y presencia unilateral de venas condilares laterales. Un total de 61 casos analizados mediante imágenes MRV revelaron la presencia bilateral de venas condilares posteriores y condilares laterales (77,1 %), la presencia unilateral de venas condilares posteriores (18,0 %) y la presencia unilateral de venas condilares laterales (9,8 %) de los cuales la presencia bilateral de las venas condilar posterior y condilar lateral representó la mayor proporción. Las imágenes de RNM y las muestras de yeso del SCS mostraron su estructura morfológica y adyacencia normales, lo que proporcionó datos anatómicos de imágenes tridimensionales precisos y completos del SCS y sus estructuras vasculares comunicantes. Este estudio enriquece los datos de anatomía de imágenes de SCS chino y puede ser valioso en la práctica clínica.
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Humanos , Seio Cavernoso/anatomia & histologia , Seio Cavernoso/diagnóstico por imagem , Sulfato de Cálcio , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Impressão TridimensionalAssuntos
Transtornos de Ansiedade , Radiação Ionizante , Ansiedade/etiologia , Humanos , Fatores de RiscoAssuntos
Humanos , Transtornos de Ansiedade , Radiação Ionizante , Ansiedade/etiologia , Fatores de RiscoRESUMO
Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic, which has reached 28 million cases worldwide in 1 year. The serological detection of antibodies against the virus will play a pivotal role in complementing molecular tests to improve diagnostic accuracy, contact tracing, vaccine efficacy testing, and seroprevalence surveillance. Here, we aimed first to evaluate a lateral flow assay's ability to identify specific IgM and IgG antibodies against SARS-CoV-2 and second, to report the seroprevalence estimates of these antibodies among health care workers and healthy volunteer blood donors in Panama. We recruited study participants between April 30th and July 7th, 2020. For the test validation and performance evaluation, we analyzed serum samples from participants with clinical symptoms and confirmed positive RT-PCR for SARS-CoV-2, and a set of pre-pandemic serum samples. We used two by two table analysis to determine the test positive and negative percentage agreement as well as the Kappa agreement value with a 95% confidence interval. Then, we used the lateral flow assay to determine seroprevalence among serum samples from COVID-19 patients, potentially exposed health care workers, and healthy volunteer donors. Our results show this assay reached a positive percent agreement of 97.2% (95% CI 84.2-100.0%) for detecting both IgM and IgG. The assay showed a Kappa of 0.898 (95%CI 0.811-0.985) and 0.918 (95% CI 0.839-0.997) for IgM and IgG, respectively. The evaluation of serum samples from hospitalized COVID-19 patients indicates a correlation between test sensitivity and the number of days since symptom onset; the highest positive percent agreement [87% (95% CI 67.0-96.3%)] was observed at ≥15 days post-symptom onset (PSO). We found an overall antibody seroprevalence of 11.6% (95% CI 8.5-15.8%) among both health care workers and healthy blood donors. Our findings suggest this lateral flow assay could contribute significantly to implementing seroprevalence testing in locations with active community transmission of SARS-CoV-2.
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PURPOSE: To investigate the relationship between atherosclerotic abdominal aortic aneurysm (AAA) and CXC chemokine receptor type 2 (CXCR2). METHODS: Mouse AAA model was established by embedding angiotensin-II pump (1000 ng/kg/min) in ApoE-/- mice. Mice were received SB225002, a selective CXCR2 antagonist, for treatment. Blood pressure was recorded, and CXCR2+ macrophages were examined by flow cytometry analysis. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining was performed to detect cell apoptosis of abdominal aortic aneurysms. Macrophages were isolated from ApoE-/- mice and treated with Ang II and/or SB225002. Dihydroethidium staining was carried out to determine reactive oxygen species (ROS) activity. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the production of IL-1ß and TNF-α. The corresponding gene expressions were measured using real-time polymerase chain reaction (PCR), western blot, and immunohistochemistry staining. RESULTS: We found that Ang II activated the expression of CXCR2 in monocytes during the formation of AAA. Inhibition of CXCR2 significantly reduced the size of AAA, attenuated inflammation and phenotypic changes in blood vessels. Ang II-induced macrophages exhibited elevated ROS activity, and elevated levels of 1ß and TNF-α, which were then partly abolished by SB225002. CONCLUSIONS: CXCR2 plays an important role in AAA, suggesting that inhibiting CXCR2 may be a new treatment for AAA.
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Aneurisma da Aorta Abdominal , Angiotensina II , Animais , Aneurisma da Aorta Abdominal/tratamento farmacológico , Aneurisma da Aorta Abdominal/prevenção & controle , Apolipoproteínas E/genética , Modelos Animais de Doenças , Macrófagos , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Interleucina-8BRESUMO
Purpose To investigate the relationship between atherosclerotic abdominal aortic aneurysm (AAA) and CXC chemokine receptor type 2 (CXCR2). Methods Mouse AAA model was established by embedding angiotensin-II pump (1000 ng/kg/min) in ApoE-/- mice. Mice were received SB225002, a selective CXCR2 antagonist, for treatment. Blood pressure was recorded, and CXCR2+ macrophages were examined by flow cytometry analysis. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining was performed to detect cell apoptosis of abdominal aortic aneurysms. Macrophages were isolated from ApoE-/- mice and treated with Ang II and/or SB225002. Dihydroethidium staining was carried out to determine reactive oxygen species (ROS) activity. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the production of IL-1 and TNF-. The corresponding gene expressions were measured using real-time polymerase chain reaction (PCR), western blot, and immunohistochemistry staining. Results We found that Ang II activated the expression of CXCR2 in monocytes during the formation of AAA. Inhibition of CXCR2 significantly reduced the size of AAA, attenuated inflammation and phenotypic changes in blood vessels. Ang II-induced macrophages exhibited elevated ROS activity, and elevated levels of 1 and TNF-, which were then partly abolished by SB225002. Conclusions CXCR2 plays an important role in AAA, suggesting that inhibiting CXCR2 may be a new treatment for AAA.(AU)
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Animais , Camundongos , Receptores de Interleucina-8B/administração & dosagem , Aneurisma da Aorta Abdominal/veterinária , Aneurisma da Aorta Abdominal/terapia , Angiotensina IIRESUMO
ABSTRACT Purpose To investigate the relationship between atherosclerotic abdominal aortic aneurysm (AAA) and CXC chemokine receptor type 2 (CXCR2). Methods Mouse AAA model was established by embedding angiotensin-II pump (1000 ng/kg/min) in ApoE-/- mice. Mice were received SB225002, a selective CXCR2 antagonist, for treatment. Blood pressure was recorded, and CXCR2+ macrophages were examined by flow cytometry analysis. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining was performed to detect cell apoptosis of abdominal aortic aneurysms. Macrophages were isolated from ApoE-/- mice and treated with Ang II and/or SB225002. Dihydroethidium staining was carried out to determine reactive oxygen species (ROS) activity. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the production of IL-1β and TNF-α. The corresponding gene expressions were measured using real-time polymerase chain reaction (PCR), western blot, and immunohistochemistry staining. Results We found that Ang II activated the expression of CXCR2 in monocytes during the formation of AAA. Inhibition of CXCR2 significantly reduced the size of AAA, attenuated inflammation and phenotypic changes in blood vessels. Ang II-induced macrophages exhibited elevated ROS activity, and elevated levels of 1β and TNF-α, which were then partly abolished by SB225002. Conclusions CXCR2 plays an important role in AAA, suggesting that inhibiting CXCR2 may be a new treatment for AAA.
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Animais , Camundongos , Aneurisma da Aorta Abdominal/prevenção & controle , Aneurisma da Aorta Abdominal/tratamento farmacológico , Apolipoproteínas E/genética , Angiotensina II , Receptores de Interleucina-8B , Modelos Animais de Doenças , Macrófagos , Camundongos Endogâmicos C57BLRESUMO
During the first weeks of 2020, cases of SARS-CoV-2 began to be reported outside of China, with a rapid increase in cases and deaths worldwide. SARS-CoV-2 is a positive single-stranded RNA virus, encased in a lipid bilayer derived from the host cell membrane and consists of four structural proteins (S, M, E and N), plus a haemagglutinin-sterase. The binding of the S protein to the ECA2 receptor allows the entry of the virus into the host cell and is a potential therapeutic target. 81% of patients develop mild symptoms, 14% have severe symptoms and 5% require intensive care management. Fever is the most frequent symptom, followed by cough and dyspnea. Most patients do not present leukocytosis, but they do present lymphopenia with sputum cultures that do not show other pathogens. In lung biopsies of severe patients, the most noticeable finding is diffuse alveolar damage. Radiologically, ground glass and alveolar patterns are observed; the lesions being predominantly basal, subpleural, and posterior, with a multifocal peripheral distribution, more affecting the right lower lobe. There is a marked inflammatory response, up to the cytokine storm, in which anti-inflammatory treatment with pulse therapy with methylprednisolone would be indicated. Although there are no large-scale studies regarding the use of chloroquine / hydroxychloroquine, due to the global situation, its use has been authorized for its anti-SARS-CoV-2 and anti-inflammatory effect, which can be potentiated with the use of azithromycin.
Durante las primeras semanas de 2020 se comenzaron a informar casos de personas con SARS-CoV-2 fuera de China, con un rápido aumento de casos y muertes en todo el mundo. El SARS-CoV-2 es un virus ARN monocatenario positivo, envuelto en una bicapa lipídica derivada de la membrana celular del huésped y constituido por cuatro proteínas estructurales (S, M, E y N), además de una hemaglutinina-esterasa. La unión de la proteína S con el receptor de enzima convertidora de angiotensina 2 (ECA2) permite la entrada del virus a la célula huésped y es una potencial diana terapéutica. El 81% de los enfermos hace cuadro leve; el 14%, grave; y el 5% requiere cuidados intensivos. La fiebre es el síntoma más frecuente, seguido de tos y disnea. La mayoría de los pacientes no presentan leucocitosis pero sí linfopenia, con cultivos de esputo que no muestran otros patógenos. En las biopsias de pulmón de pacientes graves el hallazgo más llamativo es el daño alveolar difuso. Radiológicamente se aprecian patrones de vidrio esmerilado y alveolar, siendo las lesiones de predominio basal, subpleural y posterior, con una distribución periférica multifocal, afectando más el lóbulo inferior derecho. Hay una marcada respuesta inflamatoria, que llega hasta la tormenta de citoquinas, en la que el tratamiento antiinflamatorio con terapia de pulso con metilprednisolona estaría indicado. Aunque no existan estudios en gran escala respecto al uso de cloroquina/hidroxicloroquina, debido a la situación mundial se ha autorizado su uso por su efecto anti SARS-CoV-2 y anti-inflamatorio, el cual puede ser potenciado con el uso de azitromicina.