RESUMO
Lung transplantation (LTx) continues to have lower rates of long-term graft survival compared with other organs. Additionally, lung utilization rates from brain-dead donors remain substantially lower compared with other solid organs, despite a growing need for LTx and the significant risk of waitlist mortality. This study aims to examine the effects of using a combination of the recently described novel lung donor (LUNDON) acceptability score and the newly adopted recipient lung Composite Allocation Score (CAS) to guide transplantation. We performed a review of nearly 18 000 adult primary lung transplants from 2015-2022 across the US with retroactive calculations of the CAS value. The medium-CAS group (29.6-34.5) had superior 1-year posttransplant survival. Importantly, the combination of high-CAS (> 34.5) recipients with low LUNDON score (≤ 40) donors had the worst survival at 1 year compared with any other combination. Additionally, we constructed a model that predicts 1-year and 3-year survival using the LUNDON acceptability score and CAS values. These results suggest that caution should be exercised when using marginally acceptable donor lungs in high-priority recipients. The use of the LUNDON score with CAS value can potentially guide clinical decision-making for optimal donor-recipient matches for LTx.
Assuntos
Sobrevivência de Enxerto , Transplante de Pulmão , Doadores de Tecidos , Obtenção de Tecidos e Órgãos , Listas de Espera , Humanos , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Seguimentos , Taxa de Sobrevida , Prognóstico , Adulto , Fatores de Risco , Transplantados/estatística & dados numéricos , Seleção do Doador , Estudos RetrospectivosRESUMO
There is a chronic shortage of donor lungs for pulmonary transplantation due, in part, to low lung utilization rates in the United States. We performed a retrospective cohort study using data from the Scientific Registry of Transplant Recipients database (2006-2019) and developed the lung donor (LUNDON) acceptability score. A total of 83 219 brain-dead donors were included and were randomly divided into derivation (n = 58 314, 70%) and validation (n = 24 905, 30%) cohorts. The overall lung acceptance was 27.3% (n = 22 767). Donor factors associated with the lung acceptance were age, maximum creatinine, ratio of arterial partial pressure of oxygen to fraction of inspired oxygen, mechanism of death by asphyxiation or drowning, history of cigarette use (≥20 pack-years), history of myocardial infarction, chest x-ray appearance, bloodstream infection, and the occurrence of cardiac arrest after brain death. The prediction model had high discriminatory power (C statistic, 0.891; 95% confidence interval, 0.886-0.895) in the validation cohort. We developed a web-based, user-friendly tool (available at https://sites.wustl.edu/lundon) that provides the predicted probability of donor lung acceptance. LUNDON score was also associated with recipient survival in patients with high lung allocation scores. In conclusion, the multivariable LUNDON score uses readily available donor characteristics to reliably predict lung acceptability. Widespread adoption of this model may standardize lung donor evaluation and improve lung utilization rates.
Assuntos
Transplante de Pulmão , Obtenção de Tecidos e Órgãos , Humanos , Adulto Jovem , Adulto , Estudos Retrospectivos , Doadores de Tecidos , Pulmão , Morte EncefálicaRESUMO
PURPOSE: To construct a novel nomogram model that can predict DVT and avoid unnecessary examination. METHODS: Patients admitted to the hospital with pelvis/acetabular fractures were included between July 2014 and July 2018. The potential predictors associated with DVT were analyzed using Univariate and multivariable logistic regression analysis. The predictive nomogram was constructed and internally validated. RESULTS: 230 patients were finally enrolled. There were 149 individuals in the non-DVT group and 81 in the DVT group. Following analysis, we obtained the final nomogram model. The risk factors included age (OR, 1.037; 95% CI, 1.013-1.062; P = 0.002), body mass index (BMI) (OR, 1.253; 95% CI, 1.120-1.403; P < 0.001); instant application of anticoagulant after admission (IAA) (OR, 2.734; 95% CI, 0.847-8.829; P = 0.093), hemoglobin (HGB) (OR, 0.970; 95% CI, 0.954-0.986; P < 0.001), D-Dimer(OR, 1.154; 95% CI, 1.016-1.310; P = 0.027) and fibrinogen (FIB) (OR, 1.286; 95% CI, 1.024-1.616; P = 0.002). The apparent C-statistic was 0.811, and the adjusted C-statistic was 0.777 after internal validations, demonstrating good discrimination. Hosmer and Lemeshow's goodness of fit (GOF) test of the predictive model showed a good calibration for the probability of prediction and observation (χ2 = 3.285, P = 0.915; P > 0.05). The decision curve analysis (DCA) and Clinical impact plot (CIC) demonstrated superior clinical use of the nomogram. CONCLUSIONS: An easy-to-calculate nomogram model for predicting DVT in patients with pelvic-acetabular fractures were developed. It could help clinicians to reduce DVT and avoid unnecessary examinations.
Assuntos
Fraturas do Quadril , Lesões do Pescoço , Fraturas da Coluna Vertebral , Trombose Venosa , Humanos , Nomogramas , Estudos Retrospectivos , Anticoagulantes , Fraturas do Quadril/epidemiologia , Pelve , Trombose Venosa/diagnóstico , Trombose Venosa/epidemiologia , Trombose Venosa/etiologiaRESUMO
Previous data have reported the high expression of circRNA paralemmin 2 (circPALM2) in mice with acute lung injury (ALI). However, the role of circPALM2 in ALI pathogenesis remains unclear. The study aims to reveal the function of circPALM2 in ALI and the underlying mechanism. C57BL/6 J mice and murine lung epithelial-12 (MLE-12) cells were treated with lipopolysaccharide (LPS) to simulate ALI mouse and ALI cell models, respectively. Lung injury score and lung wet-to-dry ratio assays were used to evaluate the ALI mouse model. Quantitative real-time polymerase chain reaction and Western blot assays were implemented to analyze the expressions of circPALM2, microRNA-330-5p (miR-330-5p), rho-associated coiled-coil containing protein kinase 2 (ROCK2), and apoptosis-related markers. Cell viability, apoptosis, and the production of inflammatory cytokines were investigated by cell counting kit-8, flow cytometry, and enzyme-linked immunosorbent assays. The expressions of circPALM2 and ROCK2 were significantly increased, while miR-330-5p was decreased in ALI mice and LPS-induced MLE-12 cells compared with controls. LPS treatment inhibited cell viability but induced apoptosis, inflammatory cytokine production, and oxidative stress; however, these effects were attenuated after the combination of circPALM2 knockdown and LPS. CircPALM2 regulated LPS-caused MLE-12 cell damage by targeting miR-330-5p. Additionally, ROCK2, a target gene of miR-330-5p, participated in LPS-induced MLE-12 cell injury. Further, circPALM2 activated ROCK2 by associating with miR-330-5p. CircPALM2 modulated LPS-caused murine lung epithelial cell injury by the miR-330-5p/ROCK2 pathway, providing a therapeutic target for ALI.
Assuntos
Lesão Pulmonar Aguda , MicroRNAs , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/genética , Animais , Apoptose , Células Epiteliais/metabolismo , Lipopolissacarídeos/farmacologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , Quinases Associadas a rho/genética , Quinases Associadas a rho/metabolismo , Quinases Associadas a rho/farmacologiaRESUMO
Paraquat (PQ) poisoning often leads to severe lung injuries, in which the mitochondria damage plays a critical role. Mitoquinone (MitoQ), a newly designed mitochondria-targeted antioxidant, has been proved for its benefit in mitochondria protection. However, the role of MitoQ in PQ-induced lung injury remains unclear. Thus, this study was performed to investigate the effect of MitoQ on PQ-induced lung injury and its underlying mechanisms. Our work showed that PQ caused the inhibition of A549 lung epithelial cell viability in a dose-dependent manner, while MitoQ remarkably mitigated the PQ-induced cell viability suppression. Besides this, PQ-mediated apoptosis of A549 cells was significantly attenuated by MitoQ, as indicated by the TUNEL assay and mitochondria membrane potential assay. Moreover, the intracellular reactive oxygen species (ROS) production was also dramatically suppressed when cotreated MitoQ with PQ. This could be ascribed to enhanced mitochondrial fusion mediated by Mitofusin 1 (MFN1)/Mitofusin 2 (MFN2), because MitoQ preserved mitochondrial network integrity, as reflected by MitoTracker staining, and MitoQ also increased the expression of MFN1/MFN2 in A549 cells after PQ treatment. Our data suggested MitoQ mitigated PQ-induced lung epithelial cell injury by promoting MFN1/MFN2-mediated mitochondrial fusion, and MitoQ might be a potential candidate drug for the treatment of PQ-induced lung injury.
Assuntos
Lesão Pulmonar , Paraquat , Células A549 , Antioxidantes/farmacologia , GTP Fosfo-Hidrolases/farmacologia , Humanos , Pulmão/metabolismo , Dinâmica Mitocondrial , Proteínas de Transporte da Membrana Mitocondrial , Proteínas Mitocondriais , Compostos Organofosforados , Paraquat/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Ubiquinona/análogos & derivadosRESUMO
Macrophages are a key in innate immune responses and play vital roles in homeostasis and inflammatory diseases. Phosphatidylserine-specific phospholipase A1 (PS-PLA1) is a specific phospholipase which hydrolyzes fatty acid from the sn-1 position of phosphatidylserine (PS) to produce lysophosphatidylserine (lysoPS). Both PS and lysoPS are associated with activation of immune cells including macrophages. However, the effect of PS-PLA1 on macrophage inflammation remains unclear. The purpose of this study is to evaluate the role of PS-PLA1 in lipopolysaccharide (LPS)-induced macrophage inflammation. Alterations of PS-PLA1 expression in LPS-stimulated RAW264.7 macrophages were investigated via Western blot. PS-PLA1 stable knockdown and overexpression RAW264.7 cell lines were generated by infecting cells with appropriate lentiviral vectors, respectively. PS-PLA1 expression was found to be dramatically upregulated in RAW264.7 macrophages after LPS stimulation. PS-PLA1 knockdown promotes while PS-PLA1 overexpression ameliorates the release of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and nitric oxide from RAW264.7 cells and M1 macrophage polarization. Additionally, PS-PLA1 knockdown facilitates phosphorylation of p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), while PS-PLA1 overexpression attenuates their phosphorylation. Moreover, mitogen-activated protein kinase (MAPK) inhibitors block the release of TNF-α and IL-1ß in PS-PLA1 knockdown RAW264.7 cells after LPS stimulation. These findings suggest PS-PLA1 ameliorates LPS-induced macrophage inflammation by inhibiting MAPKs activation, and PS-PLA1 might be considered as a target for modulating macrophage inflammation.
Assuntos
Macrófagos , Proteínas Quinases Ativadas por Mitógeno , Fosfatidilserinas , Fosfolipases A1 , Animais , Inflamação/induzido quimicamente , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fosfatidilserinas/metabolismo , Fosfolipases A1/metabolismo , Células RAW 264.7 , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The new lung allocation policy has led to an increase in distant donors and consequently enhanced logistical burden of procuring organs. Though early single-center studies noted similar outcomes between same-team transplantation (ST, procuring team from transplanting center) and different-team transplantation (DT, procuring team from different center), the efficacy of DT in the contemporary era remains unclear. In this study, we evaluated the trend of DT, rate of transplanting both donor lungs, 1-year graft survival, and risk of Grade 3 primary graft dysfunction (PGD) using the Scientific Registry of Transplant Recipient (SRTR) database from 2006 to 2018. A total of 21619 patients (DT 2085, 9.7%) with 19837 donors were included. Utilization of DT decreased from 15.9% in 2006 to 8.5% in 2018. Proportions of two-lung donors were similar between the groups, and DT had similar 1-year graft survival as ST for both double (DT, HR 1.108, 95% CI 0.894-1.374) and single lung transplants (DT, HR 1.094, 95% CI 0.931-1.286). Risk of Grade 3 PGD was also similar between ST and DT. Given our results, expanding DT may be a feasible option for improving lung procurement efficiency in the current era, particularly in light of the COVID-19 pandemic.
Assuntos
Política de Saúde , Transplante de Pulmão , Alocação de Recursos , Obtenção de Tecidos e Órgãos , COVID-19 , Sobrevivência de Enxerto , Humanos , Pulmão , Pandemias , Doadores de TecidosRESUMO
BACKGROUND: Previous studies in heart transplantation have shown an association between institutional case volume and outcomes. We aim to determine the case volume associated with optimal 1-year survival after transplantation. METHODS AND RESULTS: The United Network for Organ Sharing (UNOS) national database was analyzed for adult patients who underwent orthotopic heart transplantation between January 2013 and December 2017. A total of 11,196 cases at 128 transplant centers were included. Risk-adjusted restricted cubic splines revealed a non-linear association between institutional case volume and 1-year post-transplant survival. In the risk-adjusted, random-effect Cox model with segmented linear splines, higher heart transplant volume up to 24 cases per year was associated with better 1-year survival (HR = .978 every additional case, 95% CI .963-.993), and optimal survival was maintained between 24 and 38 cases per year. However, further increase in volume above 38 transplants per year was associated with mildly decreased 1-year survival (HR = 1.007 every additional case, 95% CI 1.002-1.013). CONCLUSIONS: The relationship between institutional case volume and heart transplant 1-year survival is non-linear, with optimal survival observed at institutional case volume of 24-38 cases per year.
Assuntos
Transplante de Coração , Adulto , Bases de Dados Factuais , Sobrevivência de Enxerto , Humanos , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Acute lung injury (ALI), as a life-threatening syndrome, is mainly characterized with diffuse alveolar injury, excessive pulmonary inflammation, edema and apoptosis of lung epithelial cells. This study investigated the effects of LncRNA Hsp4 (Hsp4, ENSMUST00000175718) on lipopolysaccharide (LPS)-induced apoptosis of MLE-12 cells. In our research, we found that LPS treatment remarkably induced apoptosis of MLE-12 cells and decreased the expression of Hsp4. Overexpression of Hsp4 significantly reversed LPS-induced cell apoptosis through inhibiting mTOR signaling, while suppression of Hsp4 presented opposite effects. Further results showed that Hsp4 positively regulated the expression of miR-466m-3p. Knockdown of miR-466m-3p reversed LPS-induced cell apoptosis via increasing the levels of DNAjb6 which was confirmed to be the target gene of miR-466m-3p. This finding will be helpful for further understanding the critical roles of Hsp4 in ALI and may provide potential targets for ALI diagnosis and treatment.
Assuntos
Lesão Pulmonar Aguda/genética , Proteínas de Choque Térmico HSP40/genética , Inflamação/genética , Chaperonas Moleculares/genética , RNA Longo não Codificante/genética , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/patologia , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Células Epiteliais , Humanos , Inflamação/induzido quimicamente , Inflamação/patologia , Lipopolissacarídeos/toxicidade , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Camundongos , Transdução de Sinais/genéticaRESUMO
Schisandra chinensis is widely used and effective in protecting liver. There are many mechanisms of drug-induced hepatocyte injury, among which endoplasmic reticulum (ER) stress-induced cell injury plays an important role. However, little is known about whether schisandra chinensis can inhibit rifampicin (RFP)-induced hepatocyte injury by affecting ER stress. In our study, firstly, L02 cells were treated with different concentrations of RFP for different time intervals, and the apoptosis, survival rate and endoplasmic reticulum stress gene and protein expressions of glucose-regulated protein 78 (GRP 78), PKR-like ER kinase (PERK), activating transcription factor (ATF)4, C/EBP-homologus protein (CHOP), ATF6, arginine-rich, mutated in early stage tumors (ARMET), p-inositol-requiring enzyme 1 (IRE1) and X-box binding protein 1 (XBP-1) were measured. We found that RFP increased apoptosis of L02 cells, decreased cell survival, and increased the gene and protein expression levels of GRP78, PERK, ATF4, CHOP, ATF6, ARMET, p-IRE1 and XBP-1, suggesting that RFP could induce hepatocyte injury, and the degree of injury was positively correlated with the dose and time of RFP. Next, we treated RFP-damaged hepatocytes with schizandrin B. We found that schizandrin B increased cell survival rate in dose-dependent and time-dependent manner, decreased cell apoptosis rate, and reduced protein and gene expression levels of GRP78, PERK, ATF4, CHOP, ATF6, ARMET and XBP-1. These results indicate that schizandrin B alleviates RFP-induced injury in L02 cells by inhibiting ER stress.
Assuntos
Apoptose/efeitos dos fármacos , Doença Hepática Crônica Induzida por Substâncias e Drogas/prevenção & controle , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Lignanas/farmacologia , Compostos Policíclicos/farmacologia , Substâncias Protetoras/farmacologia , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Ciclo-Octanos/isolamento & purificação , Ciclo-Octanos/farmacologia , Relação Dose-Resposta a Droga , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático/genética , Hepatócitos/metabolismo , Humanos , Lignanas/isolamento & purificação , Compostos Policíclicos/isolamento & purificação , Substâncias Protetoras/isolamento & purificação , Schisandra/químicaRESUMO
This paper aimed to study the protective effect of ginsenoside Rg_1 on endotoxin(LPS)-induced apoptosis of lung epithelial cells and its mechanism of action. Mouse lung epithelial cells(MLE-12) were first treated with LPS. The autophagy changes and apoptosis and the relationship with concentration and time of LPS were observed. Then,the level of autophagy in MLE-12 was regulated at a specific concentration and action time of LPS,and the changes of apoptosis were observed. Secondly,ginsenoside Rg_1 and autophagy inhibitor 3-MA were added respectively at the same concentration and action time of LPS. The lung epithelial cells were grouped to observe the effect of ginsenoside Rg_1 on LPS-induced apoptosis of lung epithelial cells and its mechanism. In the animal experiment,the mice were grouped and tested by apoptosis protein,lung injury score and HE staining section to verify whether ginsenoside Rg_1 has a protective effect on LPS-induced lung injury. The results showed that apoptosis and autophagy increased as the rise of concentration after treatment with LPS for 12 h. The apoptosis increased gradually,and the autophagy increased first and then decreased over time at the LPS concentration of 25 g·L-1. The apoptosis of LPS group was higher than that of control group,and LPS+3-MA group increased further,while apoptosis decreased significantly in LPS+RAM(rapamycin,autophagy promoter) group. The autophagy increased in LPS group,decreased in LPS+3-MA group and increased in LPS+RAM group. The apoptosis of LPS group was higher than that of control group,and the apoptosis of LPS+Rg_1 group decreased. The apoptosis of LPS+Rg_1+3-MA group increased again. The autophagy of LPS group further increased after administration of ginsenoside Rg_1,but decreased after administration of 3-MA. In the in vivo experiments in mice,the apoptosis of LPS group increased significantly compared with the control group,while LPS + ginsenoside Rg_1 group decreased. Lung injury score and HE staining also conformed to the above trend. LPS can induce the apoptosis of lung epithelial cells in a time-dependent and concentration-dependent manner. The autophagy of lung epithelial cells increases with the rise of LPS concentration. At the specific concentration of LPS,autophagy increases first and then decreases after 12-16 hours. Proper increase of autophagy in lung epithelial cells within a certain period of time can reduce the apoptosis induced by LPS,while inhibition of autophagy can increase apoptosis. Ginsenoside Rg_1 has a protective effect on lung cancer epithelial cell apoptosis induced by autophagy.
Assuntos
Apoptose , Autofagia , Células Epiteliais/efeitos dos fármacos , Ginsenosídeos/farmacologia , Pulmão/citologia , Animais , Células Cultivadas , Lipopolissacarídeos , CamundongosRESUMO
The rapid repair of gastric mucosa is critical upon exposure to injurious agents. Intestinal trefoil factor (ITF) is a member of the trefoil factor family domain peptides, which play an important role in the cytoprotection of gastric epithelium. However, the underlying molecular mechanisms that are responsible for ITF-induced gastric epithelial repair remain unclear. In the present study, we demonstrate that ITF enhances the proliferation and migration of GES-1 gastric endothelial cells in a dose- and time-dependent manner through the activation of extracellular signal-regulated kinase 1/2 (ERK1/2). Furthermore, the ITF-mediated protection of GES-1 cells from a NS398 (nonsteroidal anti-inflammatory drug) was dependent on the ERK1/2 signaling pathway. Taken together, the results provide a mechanistic explanation for ITF-mediated protection of gastric epithelial mucosa cells, suggesting that activation of the ERK1/2 signaling pathway may provide a new therapeutic strategy for repairing gastric injury.
Assuntos
Epitélio/metabolismo , Mucosa Gástrica/metabolismo , Sistema de Sinalização das MAP Quinases/genética , Peptídeos/metabolismo , Linhagem Celular , Movimento Celular/genética , Proliferação de Células/genética , Epitélio/lesões , Mucosa Gástrica/lesões , Mucosa Gástrica/patologia , Humanos , Nitrobenzenos/administração & dosagem , Peptídeos/genética , Sulfonamidas/administração & dosagem , Fator Trefoil-2RESUMO
The impact of lubricants on pole-tip recession and surface morphology of hard disk drive heads in the precision lapping process was investigated with atomic force microscopy, scanning electron microscopy, and auger electron spectroscopy. In particular, the effects of deionized water, hydrocarbon oil, ethanediol, isopropanol, and ethanol lubricants were evaluated. The results reveal that proper selection of lubricant is critical for achieving optimal performance in the lapping process. A mixture of 68% hydrocarbon oil, 30% isopropanol, and 2% octadecenoic acid was found to yield the most favorable results, displaying a writer shield recession, first shield of reader recession, and surface roughness of 0.423, 0.581, and 0.242 nm, respectively.
RESUMO
Nanodiamonds, which are the main components of slurry in the precision lapping process of magnetic heads, play an important role in surface quality. This paper studies the mechanistic features of nanodiamond embedment into a Sn plate in the lapping process. This is the first study to develop mathematical models for nanodiamond embedment. Such models can predict the optimum parameters for particle embedment. From the modeling calculations, the embedded pressure satisfies p 0 = (3/2) · (W/πa (2)) and the indentation depth satisfies δ = k1âP/HV. Calculation results reveal that the largest embedded pressure is 731.48 GPa and the critical indentation depth δ is 7 nm. Atomic force microscopy (AFM), scanning electron microscopy (SEM), and Auger electron spectroscopy (AES) were used to carry out surface quality detection and analysis of the disk head. Both the formation of black spots on the surface and the removal rate have an important correlation with the size of nanodiamonds. The results demonstrate that an improved removal rate (21 nm · min(-1)) can be obtained with 100 nm diamonds embedded in the plate.
Assuntos
Magnetismo , Nanodiamantes/química , Nanodiamantes/ultraestrutura , Microscopia de Força Atômica , Microscopia Eletrônica de Varredura , Nanoestruturas/química , Nanoestruturas/ultraestruturaRESUMO
Nanozymes have recently become a research hotspot because of the advantages of good stability, excellent catalytic performance and easy storage in comparison to natural enzymes. Nanozymes with oxidase-like activity get special attention because they needn't the participation of hydrogen peroxide. In this paper, poly(N-isopropylacrylamide) nanogel with oxidase-like activity was synthesized for the first time. The catalytic mechanism was explored by EPR and UV spectroscopy after adding specific trapping agents of ROS, and the results showed that PNIPAM NG can catalyze O2 to 1O2. In the presence of PNIPAM NG, o-phenylenediamine (OPD) and ascorbic acid (AA) can be oxidized to 2,3-diaminophenazine (oxOPD) and dehydroascorbic acid (DHA), and DHA can further react with OPD to produce a fluorescence substance. The colorimetric and fluorescence detection platforms for AA were constructed based on the above principles. Both platforms have satisfactory results in real samples. The fluorescence platform has better sensitivity and selectivity than the colorimetric platform.
Assuntos
Resinas Acrílicas , Ácido Ascórbico , Ácido Ascórbico/química , Resinas Acrílicas/química , Nanogéis/química , Colorimetria/métodos , Oxirredutases/química , Polietilenoimina/química , Polietilenoglicóis/química , Fenilenodiaminas/química , Espectrometria de Fluorescência/métodos , CatáliseRESUMO
Antibacterial hydrogels as burn wound dressings are capable of efficaciously defending against bacterial infection and accelerating burn wound healing. Thus far, a large plethora of antibacterial hydrogels have adopted numerous components and intricate preparation processes, yet restricting their practical industrialization applications. Simple and effective preparation methods of antibacterial hydrogels are hence urgently needed. Herein, an easy but efficacious strategy with the employment of two natural products pullulan and ε-poly-l-lysine (ε-PL) was designed to fabricate composite antibacterial hydrogels for burn wound healing for the first time. The hydrogel crosslinking networks were formed through amidation reactions between carboxylated pullulan derivative (CP) and ε-poly-l-lysine hydrochloride (ε-PL·HCl). The resulting hydrogels possessed high transparency, porous structures, tunable gelation time and gel content, relatively low swelling ratios, appropriate self-degradability, proper mechanical properties, strong in vitro bacteriostatic activities, non-cytotoxicity, capacities of facilitating cell migration and excellent hemocompatibility. In the infected burn model of mice, the hydrogels were observed to display prominent in vivo antibacterial activities and enable the acceleration of burn wound healing. We opine the simply and effectively prepared antibacterial hydrogels as promising dressings for burn wound recovery have broad industrialization prospects.
Assuntos
Antibacterianos , Queimaduras , Glucanos , Hidrogéis , Polilisina , Cicatrização , Hidrogéis/química , Hidrogéis/farmacologia , Glucanos/química , Glucanos/farmacologia , Polilisina/química , Polilisina/farmacologia , Cicatrização/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Animais , Queimaduras/tratamento farmacológico , Queimaduras/terapia , Camundongos , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Humanos , Testes de Sensibilidade MicrobianaRESUMO
The electrochemical performance of polyaniline-based all-gel-state supercapacitor (AGSSC) is significantly depended on the dispersity and mass loaded of polyaniline (PANI). In this manuscript, inspired by the properties of surfactant, sodium dodecylbenzene sulfonate (SDBS) was introduced to prepare various PANI-polyacrylamide/sodium alginate/SDBS (PANIy-PSSx) AGSSCs. With presence of SDBS, the electrochemical performance of PANIy-PSSx AGSSCs was greatly improved, displaying a trend of initial rise and then decrease with increasing concentration of SDBS from 0 to 0.75 wt%. As the content of SDBS was 0.5 wt%, the resulting PANI1.0-PSS0.5 AGSSC displayed the optimum electrochemical properties with area capacitance and energy density of 913.79 mF/cm2 and 81.23 µWh/cm2, respectively. The capacitance rate of PANI1.0-PSS0.5 AGSSC was still more than 93 % after 2000 cycles of sequential CV scans at the scan rate of 200 mV/s. These data were greatly higher than many reported PANI-based AGSSCs. Moreover, the resultant PANI1.0-PSS0.5 AGSSC could maintain high electrochemical performance even after various operations, such as compression, puncture, fluctuating temperature, bending situations and various voltage windows and series-parallel connections. The resultant PANI1.0-PSS0.5 AGSSC had the wide potentials to satisfy the real application requirements. This study offered a facile strategy for design and preparation of flexible supercapacitor with excellent electrochemical performance.
Assuntos
Resinas Acrílicas , Compostos de Anilina , Lipoproteínas , Tensoativos , Alginatos , HidrogéisRESUMO
BACKGROUND: Acute Respiratory Distress Syndrome (ARDS) is an acute life-threatening disease, and luteolin has the potential to become a therapeutic agent for ARDS. However, its mechanism of action has not yet been clarified. OBJECTIVE: The present study explored the potential effects and mechanisms of luteolin in the treatment of ARDS through network pharmacology analysis and verified them through biological experiments. METHODS: The potential targets of luteolin and ARDS were obtained from online databases. Functional enrichment and protein-protein interaction (PPI) analyses were performed to explore the underlying molecular mechanisms and to identify hub targets. Molecular docking was used to verify the relationship between luteolin and target proteins. Finally, the effects of luteolin on key signaling pathways and biological processes were verified by in vitro and in vivo experiments. RESULTS: A total of 146 luteolin- and 496 ARDS-related targets were extracted from public databases. The network pharmacological analysis suggested that luteolin could inhibit ARDS through the following potential therapeutic targets: AKT1, RELA, and NFKBIA. Inflammatory and oxidative stress responses were the main biological processes involved, with the AKT/NF-κB signaling pathway being the key signaling pathway targeted by luteolin for the treatment of ARDS. Molecular docking analysis indicated that luteolin had a good binding affinity to AKT1, RELA, and NFKBIA. The in vitro and in vivo experiments revealed that luteolin could regulate the inflammatory response and oxidative stress in the treatment of ARDS by inhibiting the AKT/NF- κB signaling pathway. CONCLUSION: Luteolin could reduce the production of reactive oxygen species and inflammatory factors by inhibiting the AKT/NF-κB signaling pathway, thus reducing apoptosis and attenuating ARDS.
Assuntos
Luteolina , Simulação de Acoplamento Molecular , Farmacologia em Rede , Síndrome do Desconforto Respiratório , Luteolina/farmacologia , Luteolina/química , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/metabolismo , Humanos , Animais , Camundongos , Masculino , Substâncias Protetoras/farmacologia , Substâncias Protetoras/química , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Estresse Oxidativo/efeitos dos fármacos , NF-kappa B/metabolismo , NF-kappa B/antagonistas & inibidoresRESUMO
Background: Large, node-negative but locally invasive non-small cell lung cancer (NSCLC) is associated with increased perioperative risk but improved survival if a complete resection is obtained. Factors associated with positive margins in this population are not well-studied. Methods: We performed a retrospective cohort study using National Cancer Database (NCDB) for adult patients with >5 cm, clinically node-negative NSCLC with evidence of invasion of nearby structures [2006-2015]. Patients were classified as having major structure involvement (azygous vein, pulmonary artery/vein, vena cava, carina/trachea, esophagus, recurrent laryngeal/vagus nerve, heart, aorta, vertebrae) or chest wall invasion (rib pleura, chest wall, diaphragm). Our primary outcome was to evaluate factors associated with incomplete resection (microscopic: R1, macroscopic: R2). Kaplan-Meier analysis and cox multivariable regression models were used to evaluate overall survival (OS), 90-day mortality, and factors associated with positive margins. Results: Among 2,368 patients identified, the median follow-up was 33.8 months [interquartile range (IQR), 12.6-66.5 months]. Most patients were white (86.9%) with squamous cell histology (47.3%). Major structures were involved in 26.4% of patients and chest wall invasion was seen in 73.6%. Four hundred and seventy-eight patients (20.2%) had an incomplete resection. Multivariable analysis revealed that black race [hazard ratio (HR) 1.568, 95% confidence interval (CI): 1.109-2.218] and major structure involvement (HR 1.412, 95% CI: 1.091-1.827) was associated with increased risk of incomplete resection and surgery at an academic hospitals (HR 0.773, 95% CI: 0.607-0.984), adenocarcinoma histology (HR 0.672, 95% CI: 0.514-0.878), and neoadjuvant chemotherapy (HR 0.431, 95% CI: 0.316-0.587) were associated with decreased risk of incomplete resection. The 5-year OS was 43.7% in the entire cohort and 28.8% in patients with positive margins and 47.5% in patients with an R0 resection. Positive margin was also associated with a significantly higher 90-day mortality rate (9.9% versus 6.7%). Conclusions: For patients with large, node-negative NSCLC invading nearby structures, R0 resection portends better survival. Treatment at academic centers, adenocarcinoma histology, and receipt of neoadjuvant chemotherapy are associated with R0 resection in this high-risk cohort.
RESUMO
With rapid urbanization and extreme rainstorm events associated with climate change, urban waterlogging has become one of the most frequent and severe disasters globally. In this study, a multi-dimensional and multi-process index system based on the Pressure-State-Response (PSR) framework was developed to measure the level of urban waterlogging resilience (UWR). The spatial distribution of UWR on a block scale was explored based on the entropy weight method with the natural breakpoint method (EWM-NBM) in the central district of Wuhan City, China. In addition, the effects of the runoff control facilities and early warning measures on UWR were also quantified. Further, the Geodetector was used to investigate the main driving factors of UWR and their interactions. Results showed that the constructed index system for UWR based on the PSR framework performed reasonably, and the EWM-NBM was validated to be effective in the integrated assessment. In terms of the validation results, 82.72 % of the recorded waterlogging points belonged to high and very-high risk levels. The spatial heterogeneity of UWR was significant in the study area where the higher-level UWR mainly appears in the areas near the undeveloped suburban and water bodies (lakes and rivers), and the lower-level UWR was concentrated in central urban areas with more impervious surfaces. There was a clear increasing trend in UWR after the implementation of runoff control facilities and early warning measures, but its spatial distribution remained almost invariant. Among all the indexes, the impervious surface percentage had the strongest (69.58 %) explanatory ability for the UWR, and mean annual precipitation (15.51 %), GDP (14.03 %), and population density (11.98 %) also demanded attention. Most driving factors of UWR showed nonlinear interactions. This research could provide a benchmark for urban planning to enhance UWR to mitigate the waterlogging within the main urban area.