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1.
Crit Rev Immunol ; 44(4): 51-60, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505921

RESUMO

This study aimed to elucidate the role of microRNA-503 (miR-503) in pancreatic cancer (PC) progression and the underlying regulatory mechanisms. We acquired miR-503-3p and miR-503-5p expression data along with survival times of PC and normal samples from the UCSC Xena database. Using the t-test, we compared the expression of miR-503-3p and miR-503-5p between PC and normal samples, and evaluated their prognostic significance via Kaplan-Meier survival analysis. The expression of miR-503-5p in PC cells was detected by quantitative PCR. We subsequently overexpressed miR-503-5p in PC cells and examined cell viability, apoptosis, and migration through CCK8 assay, flow cytometry, and Transwell assay, respectively. Potential functional targets were identified using miRTarBase and validated by dual-luciferase reporter assay. Both miR-503-3p and miR-503-5p expression were found to be downregulated in PC; however, only miR-503-5p was linked to cancer prognosis based on public data. In vitro experiments demonstrated that overexpression of miR-503-5p substantially decreased cell viability, induced apoptosis, caused G0/G1 arrest, and inhibited cell migration. miR-503-5p was found to target cyclin E2 (CCNE2), and overexpression of CCNE2 could counteract the effects of miR-503-5p on PC cells. Conclusion: The downregulation of miR-503-5p enhances the progression of PC by targeting CCNE2. The detection of miR-503-5p expression may provide valuable insights for the prevention and prognostic evaluation of PC.


Assuntos
MicroRNAs , Neoplasias Pancreáticas , Humanos , MicroRNAs/genética , Regulação para Baixo , Linhagem Celular Tumoral , Proliferação de Células/genética , Ciclinas/metabolismo , Neoplasias Pancreáticas/genética , Regulação Neoplásica da Expressão Gênica
2.
Mol Cancer ; 23(1): 91, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38715012

RESUMO

BACKGROUND: Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are involved in the occurrence and development of a variety of tumors. The aim of this study was to investigate the effects of circ_PPAPDC1A in Osimertinib resistance in NSCLC. METHODS: Human circRNAs microarray analysis was conducted to identify differentially expressed (DE) circRNAs in Osimertinib-acquired resistance tissues of NSCLC. The effect of circ_PPAPDC1A on cell proliferation, invasion, migration, and apoptosis was assessed in both in vitro and in vivo. Dual-luciferase reporter assay, RT-qPCR, Western-blot, and rescue assay were employed to confirm the interaction between circ_PPAPDC1A/miR-30a-3p/IGF1R axis. RESULTS: The results revealed that circ_PPAPDC1A was significantly upregulated in Osimertinib acquired resistance tissues of NSCLC. circ_PPAPDC1A reduced the sensitivity of PC9 and HCC827 cells to Osimertinib and promoted cell proliferation, invasion, migration, while inhibiting apoptosis in Osimertinib-resistant PC9/OR and HCC829/OR cells, both in vitro and in vivo. Silencing circ_PPAPDC1A partially reversed Osimertinib resistance. Additionally, circ_PPAPDC1A acted as a competing endogenous RNA (ceRNA) by targeting miR-30a-3p, and Insulin-like Growth Factor 1 Receptor (IGF1R) was identified as a functional gene for miR-30a-3p in NSCLC. Furthermore, the results confirmed that circ_PPAPDC1A/miR-30a-3p/IGF1R axis plays a role in activating the PI3K/AKT/mTOR signaling pathway in NSCLC with Osimertinib resistance. CONCLUSIONS: Therefore, for the first time we identified that circ_PPAPDC1A was significantly upregulated and exerts an oncogenic role in NSCLC with Osimertinib resistance by sponging miR-30a-3p to active IGF1R/PI3K/AKT/mTOR pathway. circ_PPAPDC1A may serve as a novel diagnostic biomarker and therapeutic target for NSCLC patients with Osimertinib resistance.


Assuntos
Acrilamidas , Compostos de Anilina , Carcinoma Pulmonar de Células não Pequenas , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , MicroRNAs , RNA Circular , Receptor IGF Tipo 1 , Transdução de Sinais , Humanos , MicroRNAs/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Acrilamidas/farmacologia , RNA Circular/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Compostos de Anilina/farmacologia , Linhagem Celular Tumoral , Animais , Camundongos , Apoptose , Movimento Celular/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Masculino , Feminino , Indóis , Pirimidinas
3.
BMC Plant Biol ; 24(1): 492, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831289

RESUMO

Non-hydraulic root source signaling (nHRS) is a unique positive response to soil drying in the regulation of plant growth and development. However, it is unclear how the nHRS mediates the tradeoff between source and sink at the late growth stages and its adaptive mechanisms in primitive wheat. To address this issue, a root-splitting design was made by inserting solid partition in the middle of the pot culture to induce the occurrence of nHRS using four wheat cultivars (MO1 and MO4, diploid; DM22 and DM31, tetraploid) as materials. Three water treatments were designed as 1) both halves watered (CK), 2) holistic root system watered then droughted (FS), 3) one-half of the root system watered and half droughted (PS). FS and PS were designed to compare the role of the full root system and split root system to induce nHRS. Leaves samples were collected during booting and anthesis to compare the role of nHRS at both growth stages. The data indicated that under PS treatment, ABA concentration was significantly higher than FS and CK, demonstrating the induction of nHRS in split root design and nHRS decreased cytokinin (ZR) levels, particularly in the PS treatment. Soluble sugar and proline accumulation were higher in the anthesis stage as compared to the booting stage. POD activity was higher at anthesis, while CAT was higher at the booting stage. Increased ABA (nHRS) correlated with source-sink relationships and metabolic rate (i.e., leaf) connecting other stress signals. Biomass density showed superior resource acquisition and utilization capabilities in both FS and PS treatment as compared to CK in all plants. Our findings indicate that nHRS-induced alterations in phytohormones and their effect on source-sink relations were allied with the growth stages in primitive wheat.


Assuntos
Diploide , Raízes de Plantas , Transdução de Sinais , Tetraploidia , Triticum , Triticum/genética , Triticum/crescimento & desenvolvimento , Triticum/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Raízes de Plantas/genética , Brotos de Planta/crescimento & desenvolvimento , Brotos de Planta/metabolismo , Brotos de Planta/genética , Reguladores de Crescimento de Plantas/metabolismo , Ácido Abscísico/metabolismo , Citocininas/metabolismo , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Folhas de Planta/genética
4.
Proc Natl Acad Sci U S A ; 118(42)2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34649989

RESUMO

Deserts exert strong selection pressures on plants, but the underlying genomic drivers of ecological adaptation and subsequent speciation remain largely unknown. Here, we generated de novo genome assemblies and conducted population genomic analyses of the psammophytic genus Pugionium (Brassicaceae). Our results indicated that this bispecific genus had undergone an allopolyploid event, and the two parental genomes were derived from two ancestral lineages with different chromosome numbers and structures. The postpolyploid expansion of gene families related to abiotic stress responses and lignin biosynthesis facilitated environmental adaptations of the genus to desert habitats. Population genomic analyses of both species further revealed their recent divergence with continuous gene flow, and the most divergent regions were found to be centered on three highly structurally reshuffled chromosomes. Genes under selection in these regions, which were mainly located in one of the two subgenomes, contributed greatly to the interspecific divergence in microhabitat adaptation.


Assuntos
Adaptação Fisiológica/genética , Brassicaceae/genética , Ecossistema , Especiação Genética , Genoma de Planta , Brassicaceae/classificação , Brassicaceae/fisiologia , Filogenia , Poliploidia
5.
Pediatr Cardiol ; 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38217691

RESUMO

Acute kidney injury (AKI) is a common complication after cardiac surgery and associated with adverse outcomes. The purpose of this study is to construct a nomogram to predict the probability of postoperative AKI in pediatric patients undergoing cardiac surgery. We conducted a single-center retrospective cohort study of 1137 children having cardiac surgery under cardiopulmonary bypass. We randomly divided the included patients into development and validation cohorts at a ratio of 7:3. The least absolute shrinkage and selection operator regression model was used for feature selection. We constructed a multivariable logistic regression model to select predictors and develop a nomogram to predict AKI risk. Discrimination, calibration and clinical benefit of the final prediction model were evaluated in the development and validation cohorts. A simple nomogram was developed to predict risk of postoperative AKI using six predictors including age at operation, cyanosis, CPB duration longer than 120 min, cross-clamp time, baseline albumin and baseline creatinine levels. The area under the receiver operator characteristic curve of the nomogram was 0.739 (95% CI 0.693-0.786) and 0.755 (95% CI 0.694-0.816) for the development and validation cohort, respectively. The calibration curve showed a good correlation between predicted and observed risk of postoperative AKI. Decision curve analysis presented great clinical benefit of the nomogram. This novel nomogram for predicting AKI after pediatric cardiac surgery showed good discrimination, calibration and clinical practicability.

6.
Ren Fail ; 46(1): 2318417, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38374700

RESUMO

BACKGROUND: Acute kidney injury (AKI) is a common complication after pediatric cardiac surgery and is associated with worse outcomes. Ibuprofen is widely used in the perioperative period and can affect kidney function in children. However, the association between ibuprofen exposure and AKI after pediatric cardiac surgery has not been determined yet. METHODS: In this retrospective cohort study, children undergoing cardiac surgery with cardiopulmonary bypass were studied. Exposure was defined as given ibuprofen in the first 7 days after surgery. Postoperative AKI was diagnosed using the KDIGO criteria. A multivariable Cox regression model was used to assess the association between ibuprofen exposure and postoperative AKI by taking ibuprofen as a time-varying covariate. RESULTS: Among 1,112 included children, 198 of them (17.8%) experienced AKI. In total, 396 children (35.6%) were exposed to ibuprofen. AKI occurred less frequently among children who were administered ibuprofen than among those who were not (46 of 396 [11.6%] vs. 152 of 716 [21.2%], p < 0.001). Using the Cox regression model accounting for time-varying exposures, ibuprofen treatment was not associated with AKI (adjusted HR, 0.99; 95% CI 0.70-1.39, p = 0.932). This insignificant association was consistent across the sensitivity and subgroup analyses. CONCLUSIONS: Postoperative ibuprofen exposure in pediatric patients undergoing cardiac surgery was not associated with an increased risk of AKI.


Assuntos
Injúria Renal Aguda , Procedimentos Cirúrgicos Cardíacos , Humanos , Criança , Ibuprofeno/efeitos adversos , Estudos Retrospectivos , Complicações Pós-Operatórias/induzido quimicamente , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Fatores de Risco
7.
J Nat Prod ; 86(1): 199-208, 2023 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-36635870

RESUMO

Fifteen compounds including nine new diterpenes were isolated from the roots of Croton yunnanensis. By HRESIMS, NMR, ECD data, and X-ray diffraction analysis, the new compounds were characterized as eight neo-clerodane diterpenes (compounds 1-8) and one 15,16-dinor-ent-pimarane diterpene (9). All diterpenes were assayed for their hypoglycemic activities. Compounds 1-4, 6, 7, and 10 promoted glucose uptake activity in insulin-resistant 3T3-L1 adipocytes. Compounds 1 and 6 showed insulin sensitizing activity, potentiating conspicuously their glucose uptake activity at a concentration of 20 µM when treated synergistically with low-concentration insulin at 1 nM.


Assuntos
Croton , Diterpenos Clerodânicos , Diterpenos , Insulinas , Croton/química , Hipoglicemiantes/farmacologia , Diterpenos/farmacologia , Diterpenos/química , Diterpenos Clerodânicos/química , Glucose , Estrutura Molecular
8.
Nucleic Acids Res ; 49(20): 11855-11867, 2021 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-34642752

RESUMO

Retroviral infection requires reverse transcription, and the reverse transcriptase (RT) uses cellular tRNA as its primer. In humans, the TRMT6-TRMT61A methyltransferase complex incorporates N1-methyladenosine modification at tRNA position 58 (m1A58); however, the role of m1A58 as an RT-stop site during retroviral infection has remained questionable. Here, we constructed TRMT6 mutant cells to determine the roles of m1A in HIV-1 infection. We confirmed that tRNA3Lys m1A58 was required for in vitro plus-strand strong-stop by RT. Accordingly, infectivity of VSV-G pseudotyped HIV-1 decreased when the virus contained m1A58-deficient tRNA3Lys instead of m1A58-modified tRNA3Lys. In TRMT6 mutant cells, the global protein synthesis rate was equivalent to that of wild-type cells. However, unexpectedly, plasmid-derived HIV-1 expression showed that TRMT6 mutant cells decreased accumulation of HIV-1 capsid, integrase, Tat, Gag, and GagPol proteins without reduction of HIV-1 RNAs in cells, and fewer viruses were produced. Moreover, the importance of 5,2'-O-dimethyluridine at U54 of tRNA3Lys as a second RT-stop site was supported by conservation of retroviral genome-tRNALys sequence-complementarity, and TRMT6 was required for efficient 5-methylation of U54. These findings illuminate the fundamental importance of tRNA m1A58 modification in both the early and late steps of HIV-1 replication, as well as in the cellular tRNA modification network.


Assuntos
HIV-1/fisiologia , Processamento Pós-Transcricional do RNA , RNA de Transferência de Lisina/metabolismo , Replicação Viral , Animais , Células HEK293 , Células HeLa , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Metilação , Camundongos , Mutação , RNA de Transferência de Lisina/química
9.
Ren Fail ; 45(1): 2170244, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36728711

RESUMO

INTRODUCTION: Dysmagnesemia has been demonstrated to be involved in the pathophysiology of kidney diseases and is common in cardiac surgical patients. It remains unknown whether changes of serum magnesium after cardiac surgery affect AKI. We aimed to investigate the association of early postoperative magnesium with cardiac surgery-associated AKI in adults. METHODS: We conducted a multicenter retrospective cohort study involving patients who underwent cardiac surgery in the eICU Collaborative Research Database between 2014 and 2015. AKI within 7 days after surgery was defined using both serum creatinine and urine output criteria of Kidney Disease Improving Global Outcomes definition. Postoperative AKI was analyzed using multivariable logistic regression with early postoperative serum magnesium measured within the first 24 h after surgery as a continuous variable and categorically by quartiles. RESULTS: Postoperative AKI was identified in 3498 of 6124 (57.1%) patients receiving cardiac surgery. The median (25th-75th percentiles) early postoperative serum magnesium level of the study population was 2.3 (2.0-2.7) mg/dL. Higher serum magnesium level was associated with a higher risk of developing postoperative AKI (adjusted odds ratio (OR), 1.46 per 1 mg/dL increase; 95% confidence interval (CI), 1.31-1.62; p<.001). The multivariable-adjusted ORs (95% CIs) of postoperative AKI across increasing quartiles of serum magnesium were 1.00 (referent), 1.11 (0.95-1.29), 1.30 (1.12-1.52), and 1.72 (1.47-2.02) (p for trend <.001). CONCLUSIONS: These data demonstrate a significantly higher incidence of AKI in patients with higher early postoperative serum magnesium who underwent cardiac surgery.


Assuntos
Injúria Renal Aguda , Procedimentos Cirúrgicos Cardíacos , Adulto , Humanos , Magnésio , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Fatores de Risco
10.
Zhonghua Nan Ke Xue ; 29(9): 810-814, 2023 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-38639593

RESUMO

OBJECTIVE: To evaluate the therapeutic effects of Xuanju compound capsule combined with urofollitropin (uFSH) in the treatment of idiopathic oligoasthenozoospermia. METHODS: From June 2022 to June 2023, patients with idiopathic oligoastheospermia were enrolled in this study, and divided into trail group (Xuanju compound capsule combined with urofollitropin tablets, n=53) and control group (urofollitropin tablets, n=61) according to the difference in treatment. Treatment methods: Xuanju compound capsule, 3 pills, three times a day; Urofollitropin, 75IU, one times three day. The curses of treatments for control group and trail group is 12 weeks. In order to evaluate the therapeutic effects of control group and trial group, semen volume, sperm concentration, progressive sperm ratio (PR), peripheral serum sex hormone, liver functions were analyzed before and after treatment for two times. RESULTS: Compared with the baseline, the semen volume and liver function were not significantly changed after the treatment in control group and trial group. However, sperm concentration, PR, testosterone (T) levels, follicle stimulating hormone (FSH) levels, and luteinizing hormone (LH) levels were significantly unregulated after the treatment in control group and trial group. More importantly, compared to control group, sperm concentration, PR, T leves, FSH levels, LH levels, and T/E2 ratio of trial group were further enhanced after the treatment, which were statistically significant (P < 0.05). CONCLUSIONS: Xuanju compound capsule combined with urofollitropin tablets could significantly improve the semen quality, up-regulate the testosterone levels and T/E2 ratio in patients with idiopathic oligoasthenozoospermia.


Assuntos
Urofolitropina , Humanos , Masculino , Hormônio Foliculoestimulante , Sêmen , Análise do Sêmen , Contagem de Espermatozoides , Testosterona , Resultado do Tratamento , Urofolitropina/uso terapêutico
11.
Zhongguo Zhong Yao Za Zhi ; 48(3): 797-810, 2023 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-36872244

RESUMO

This study used bioinformatics analysis to screen out key genes involved in the transformation of idiopathic membranous nephropathy to end-stage renal disease and to predict targeted Chinese herbs and medicines and active ingredients with preventive and curative effects. The GSE108113 microarray of idiopathic membranous nephropathy and GSE37171 microarray of were downloaded from the comprehensive gene expression database, and 8 homozygous differentially expressed genes for the transformation of idiopathic membranous nephropathy into end-stage renal disease of were screened out by R software. GraphPad Prism was used to verify the expression of homozygous differentially expressed genes in GSE115857 microarray of idiopathic membranous nephropathy and GSE66494 microarray of chronic kidney disease, and 7 key genes(FOS, OGT, CLK1, TIA1, TTC14, CHORDC1, and ANKRD36B) were finally obtained. The Gene Ontology(GO) analysis was performed. There were 209 functions of encoded proteins, mainly involved in regulation of RNA splicing, cytoplasmic stress granule, poly(A) binding, etc. Thirteen traditional Chinese medicines with the effect of preventing the transformation of idiopathic membranous nephropathy to end-stage renal disease were screened out from Coremine Medical database, including Ginseng Radix et Rhizoma, Lycopi Herba, and Gardeniae Fructus, which were included in the Chinese Pharmacopoeia(2020 edition). The active ingredient quercetin mined from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) had ability to dock with the key gene FOS-encoded protein molecule, which provided targets and research ideas for the development of new traditional Chinese medicines.


Assuntos
Glomerulonefrite Membranosa , Falência Renal Crônica , Insuficiência Renal Crônica , Humanos , Medicina Tradicional Chinesa , Biologia Computacional
12.
BMC Cardiovasc Disord ; 22(1): 233, 2022 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-35596141

RESUMO

BACKGROUND: To evaluate the myocardial microcirculation perfusion of patients with acute ST-segment elevation myocardial infarction (STEMI) with a different index of microcirculatory resistance (IMR) after percutaneous coronary intervention (PCI) by myocardial contrast echocardiography (MCE) and analyse the value of MCE in predicting myocardial perfusion after PCI. METHODS: Fifty-six patients with acute STEMI who underwent an emergency PCI were selected from October 2018 to October 2019 in our hospital. According to the IMR values measured during PCI treatment, the patients were divided into three groups. Traditional ultrasound and MCE were performed one week after PCI. The left ventricular ejection fraction (LVEF), ventricular wall motion score index (WMSI), A value, ß value and A × ß value (which refers to the patient's myocardial blood flow) were measured. The receiver operating characteristic curve was drawn to evaluate the effectiveness of the MCE parameters in the diagnosis of myocardial microcirculation perfusion disorders. RESULTS: The results showed that there was no significant difference in the LVEF among the groups. The WMSI in Group 3 was statistically different from that in Groups 1 and 2 (P < 0.05), but there was no statistically significant difference in the WMSI between Groups 1 and 2. Among the three groups, the A value, ß value and A × ß value were significantly different (P < 0.05). According to Spearman's correlation analysis, the MCE quantitative parameters (i.e. the A value, ß value and A × ß value) were negatively correlated with the IMR value (r = -0.523, -0.471, -0.577, P < 0.01). CONCLUSIONS: The A value, ß value and A × ß value were negatively correlated with the IMR value. Furthermore, MCE could be used to observe the myocardial perfusion in patients with acute STEMI after PCI and may be one of the indicators used to accurately evaluate myocardial microcirculation.


Assuntos
Infarto Miocárdico de Parede Anterior , Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Infarto Miocárdico de Parede Anterior/etiologia , Circulação Coronária , Ecocardiografia/métodos , Humanos , Microcirculação/fisiologia , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Perfusão , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Volume Sistólico , Resultado do Tratamento , Função Ventricular Esquerda/fisiologia
13.
J Nat Prod ; 85(2): 405-414, 2022 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-35080403

RESUMO

Thirty-five tigliane diterpenoids and two ent-kaurane diterpenoids were isolated from the leaves of Croton damayeshu, and, among them, compounds 1-10 were characterized as new tigliane diterpenoids. The structures of compounds 1-10 were determined by analysis of their HRESIMS, NMR, and ECD data and by chemical methods. The isolates were assayed for their larvicidal, antifungal, and α-glucosidase inhibitory activities, and compounds 8-10 were found to possess larvicidal activities against Plutella xylostella with LC50 values of 0.19, 0.16, and 0.26 µM, respectively, comparable to the LC50 of 0.14 µM for the positive control, flubendiamide.


Assuntos
Croton , Diterpenos do Tipo Caurano , Diterpenos , Forbóis , Antifúngicos/farmacologia , Croton/química , Diterpenos/química , Diterpenos do Tipo Caurano/farmacologia , Estrutura Molecular , alfa-Glucosidases
14.
Clin Infect Dis ; 72(11): 2035-2041, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32857836

RESUMO

WHO convened an Advisory Group (AG) to consider the feasibility, potential value, and limitations of establishing a closely-monitored challenge model of experimental severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) in healthy adult volunteers. The AG included experts in design, establishment, and performance of challenges. This report summarizes issues that render a COVID-19 model daunting to establish (the potential of SARS-CoV-2 to cause severe/fatal illness, its high transmissibility, and lack of a "rescue treatment" to prevent progression from mild/moderate to severe clinical illness) and it proffers prudent strategies for stepwise model development, challenge virus selection, guidelines for manufacturing challenge doses, and ways to contain SARS-CoV-2 and prevent transmission to household/community contacts. A COVID-19 model could demonstrate protection against virus shedding and/or illness induced by prior SARS-CoV-2 challenge or vaccination. A limitation of the model is that vaccine efficacy in experimentally challenged healthy young adults cannot per se be extrapolated to predict efficacy in elderly/high-risk adults.


Assuntos
COVID-19 , Idoso , Voluntários Saudáveis , Humanos , SARS-CoV-2 , Eliminação de Partículas Virais , Organização Mundial da Saúde , Adulto Jovem
15.
FASEB J ; 34(7): 8876-8886, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32510740

RESUMO

Autophagy, a macromolecular degradation process, plays a pivotal role in cell differentiation and survival. This study was designed to investigate the role of autophagy in the osteogenic differentiation in ligamentum fibroblasts. Rat ligamentum fibroblasts were isolated from the posterior longitudinal ligament and cultured in osteogenic induction medium. Ultrastructural analysis, immunofluorescence assay, western blot, flow cytometry, and lysosomal activity assessment were performed to determine the presence and activity of autophagy in the cells. The mineralization deposit and osteogenic gene expressions were evaluated to classify the association between autophagy activity and the bone formation ability of the spinal ligament cells. The influence of leptin and endothelin-1 on the autophagy activity was also evaluated. Our study demonstrated that autophagy was present and increased in the ligament cells under osteogenic induction. Inhibition of autophagy with either pharmacologic inhibitors (Bafilomycin A and 3-methyladenine) or Belcin1 (BECN1) knocking down weakened the mineralization capacity, decreased the gene expressions of COL1A1, osteocalcin (Ocn), and runt-related transcription factor 2 (Runx2) in the ligamentum fibroblasts and increased cell apoptosis. The Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-BECN1 autophagic pathway was activated in the osteogenic differentiating ligamentum fibroblasts. Leptin significantly increased the autophagy activity in the ligament cells under osteogenic induction. These discoveries might improve our understanding for the mechanism of ossification of the posterior longitudinal ligament (OPLL) and provide new approaches on the prevention and treatment of this not uncommon disease.


Assuntos
Autofagia , Diferenciação Celular , Fibroblastos/citologia , Ligamentos Longitudinais/citologia , Ossificação do Ligamento Longitudinal Posterior/patologia , Osteogênese , Animais , Células Cultivadas , Fibroblastos/metabolismo , Ligamentos Longitudinais/metabolismo , Masculino , Ossificação do Ligamento Longitudinal Posterior/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
16.
RNA Biol ; 18(sup1): 478-495, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34382915

RESUMO

RNA contains a wide variety of posttranscriptional modifications covalently attached to its base or sugar group. These modified nucleosides are liberated from RNA molecules as the consequence of RNA catabolism and released into extracellular space, but the molecular mechanism of extracellular transport and its pathophysiological implications have been unclear. In the present study, we discovered that RNA-derived modified nucleosides are exported to extracellular space through equilibrative nucleoside transporters 1 and 2 (ENT1 and ENT2), with ENT1 showing higher preference for modified nucleosides than ENT2. Pharmacological inhibition or genetic deletion of ENT1 and ENT2 significantly attenuated export of modified nucleosides thereby resulting in their accumulation in cytosol. Using mutagenesis strategy, we identified an amino acid residue in ENT1 that is involved in the discrimination of unmodified and modified nucleosides. In ENTs-deficient cells, the elevated levels of intracellular modified nucleosides were closely associated with an induction of autophagy response as evidenced by increased LC3-II level. Importantly, we performed a screening of modified nucleosides capable of inducing autophagy and found that 1-methylguanosine (m1G) was sufficient to induce LC3-II levels. Pathophysiologically, defective export of modified nucleosides drastically induced Zika virus replication in an autophagy-dependent manner. In addition, we also found that pharmacological inhibition of ENTs by dilazep significantly induced Zika virus replication. Collectively, our findings highlight RNA-derived modified nucleosides as important signaling modulators that activate autophagy response and indicate that defective export of these modified nucleoside can have profound consequences for pathophysiology.


Assuntos
Autofagia , Transportador Equilibrativo 1 de Nucleosídeo/metabolismo , Transportador Equilibrativo 2 de Nucleosídeo/metabolismo , Nucleosídeos/metabolismo , RNA/metabolismo , Infecção por Zika virus/virologia , Zika virus/fisiologia , Transporte Ativo do Núcleo Celular , Transportador Equilibrativo 1 de Nucleosídeo/genética , Transportador Equilibrativo 2 de Nucleosídeo/genética , Humanos , Nucleosídeos/química , Nucleosídeos/genética , RNA/genética , Células Tumorais Cultivadas , Replicação Viral , Infecção por Zika virus/genética , Infecção por Zika virus/patologia
17.
BMC Pediatr ; 21(1): 461, 2021 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-34666729

RESUMO

BACKGROUND: Evidence for peritoneal dialysis catheter (PDC) usage in pediatric patients undergoing surgery for deteriorating cardiac dysfunction is lacking. This investigation explored factors associated with PDC usage and its effectiveness in children with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). METHODS: Eighty-four children undergoing left coronary artery transfer were retrospectively recruited. The primary endpoint was the postoperative ratio of the general ward/[intensive care unit (ICU)] length of stay. Univariable and multivariable analyses were fitted to assess factors related most strongly to PDC and the ratio of general ward/ICU length of stay. RESULTS: Of the 84 patients, 17 (20.2%) underwent postoperative PDC placement. Patients with extreme cardiac dysfunction [left ventricular ejection fraction (LVEF) ≤25%] were much more likely to require a PDC (OR, 9.88; 95% CI, 2.13-45.76; P = 0.003). Moreover, univariate analysis indicated that concomitant mitral repair significantly decreased the likelihood of PDC placement (OR, 0.25; 95% CI, 0.07-0.85; P = 0.026). In those with cardiac dysfunction (LVEF ≤50%), PDC use was associated with a reduced ratio of ward/ICU length of stay (B, - 1.62; 95% CI, - 2.77- -0.46; P = 0.008), as was age ≤ 12 months (B, - 1.57; 95% CI, - 2.88- -0.26; P = 0.02). At the 1-year follow-up, cardiac improvement was significantly greater in patients with PDC usage than in those without it (P <  0.001), and the number of mitral recoveries was comparable between the groups (64.2% vs. 53.3%, P = 0.434). CONCLUSION: In cohorts with ALCAPA, PDC placement following surgery may be necessary for patients with extreme cardiac compromise, while concomitant mitral repair can probably reduce their usage rate. PDC is beneficial in conferring an improvement in cardiac and mitral performance. Importantly, after patients are transferred from the ICU, recovery efficiency in the general ward can be enhanced by PDC placement, and hospital discharge can therefore be achieved early, especially for patients younger than 12 months or with LVEF ≤50%.


Assuntos
Síndrome de Bland-White-Garland , Diálise Peritoneal , Catéteres , Criança , Estudos de Coortes , Humanos , Lactente , Estudos Retrospectivos , Volume Sistólico , Resultado do Tratamento , Função Ventricular Esquerda
18.
J Cardiothorac Vasc Anesth ; 35(8): 2330-2335, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33745835

RESUMO

OBJECTIVES: The study compared machine-learning models with traditional logistic regression to predicting liver outcomes after aortic arch surgery. DESIGN: Retrospective review from January 2013 to May 2017. SETTING: Fuwai Hospital. PARTICIPANTS: The study comprised 672 consecutive patients who had undergone aortic arch surgery. MEASUREMENTS AND MAIN RESULTS: Three machine-learning methods were compared with logistic regression with regard to the prediction of postoperative liver dysfunction (PLD) after aortic arch surgery. The perioperative characteristics, including the patients' baseline medical condition and intraoperative data, were analyzed. The performance of the models was assessed using the area under the receiver operating characteristic curve. Naïve Bayes had the best discriminative ability for the prediction of PLD (area under the receiver operating characteristic curve = 0.77) compared with random forest (0.76), support vector machine (0.73), and logistic regression (0.72). The primary endpoint of PLD was observed in 185 patients (27.5%). The cardiopulmonary bypass time, long surgery time, long aortic clamp time, high preoperative bilirubin value, and low rectal temperature were strongly associated with the development of PLD after aortic arch surgery. CONCLUSION: The machine-learning method of naïve Bayes predicts PLD after aortic arch surgery significantly better than traditional logistic regression.


Assuntos
Aorta Torácica , Hepatopatias , Aorta Torácica/cirurgia , Teorema de Bayes , Humanos , Aprendizado de Máquina , Estudos Retrospectivos
19.
J Transl Med ; 18(1): 211, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32456662

RESUMO

BACKGROUND: Lipid abnormality and obesity have been proposed to be associated with lumbar disc degeneration, but little is known about the effect of 'lipid healthy but obese' (LH-O) and 'lipid abnormal but not obese' (LA-NO) phenotypes on lumbar disc degeneration in Chinese. The study aims to determine the impact and distinction of LH-O and LA-NO phenotypes on lumbar disc degeneration in Chinese, and to identify the association of related factors with risk of lumbar disc degeneration. METHODS: A total of 678 individuals were included with lumbar magnetic resonance imaging, serum lipid levels and anthropometric measurements. Obesity was defined on the basis of body mass index or waist to hip ratio (WHR). Pfirrmann score and Weishaupt's scale were utilized to assess the degree of disc degeneration and facet joint degeneration. RESULTS: The incidence of the LH-O and LA-NO phenotypes were 11.4% and 18.1%, respectively. LA-NO phenotype demonstrates a high incidence for disc degeneration (P < 0.05), while LH-O phenotype confers a severe disc degeneration grade (P < 0.05). No statistical difference in the percentage of severe facet joint degeneration grade in each group (P > 0.05). Elevated triglycerides and greater WHR may be the risk factors for lumbar disc degeneration in Chinese. CONCLUSION: LH-O and LA-NO phenotypes are common with different status of disc degeneration in Chinese. Elevated triglycerides and abdominal obesity appear to play crucial roles in the development of lumbar disc degeneration.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , China , Humanos , Lipídeos , Vértebras Lombares , Imageamento por Ressonância Magnética , Obesidade/complicações , Fenótipo
20.
Opt Express ; 28(13): 19571-19573, 2020 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-32672231

RESUMO

This joint feature issue of Optics Express and Applied Optics highlights contributions from authors who presented their latest research at the OSA Optical Sensors and Sensing Congress, held in San Jose, California, USA from 25-27 June 2019. The joint feature issue comprises 6 contributed papers, which expand upon their respective conference proceedings. The published papers introduced here cover a range of timely research topics in optics and photonics for active open-path sensing, radiometry, and adaptive optics and fiber devices.

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