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BACKGROUND: The Catfish stent retriever is a newly developed mechanical thrombectomy device for rapid recanalisation in emergent large vessel occlusion (ELVO) stroke. The current trial aimed to assess whether the Catfish stent retriever is non-inferior to the Solitaire stent retriever in terms of outcomes in ELVO stroke. METHODS: This was a randomised, prospective, parallel-group, multicentre, open-label, non-inferiority study conducted at 18 sites in China. The primary outcome was the proportion of cases with successful recanalisation (modified thrombolysis in cerebral infarction score of 2b or 3) following the procedure. Secondary efficacy outcomes included the National Institutes of Health Stroke Scale scores at 24 hours and 7 days or discharge if earlier, time from artery puncture to successful recanalisation and good clinical outcome (modified Rankin scale score ≤2) at 90 days. Safety outcomes included symptomatic intracranial haemorrhage, all cause-death and severe adverse events at 90 days. RESULTS: Between 3 March 2019 and 5 June 2021, 118 and 120 patients were randomly allocated to the Catfish and Solitaire groups, respectively. The primary endpoint after all endovascular procedures was non-inferior in the Catfish group (88.5%, 100/113) than in the Solitaire group (87.7%, 100/114), with a rate difference (RD) of 0.78% (95% CI -7.64 to -9.20; p=0.001). Sensitivity analysis only considering the per-protocol set also yielded similar results, with an RD of 0.83% (95% CI -7.03 to -8.70; p<0.001). Additionally, the proportions of cases with good clinical outcomes (47.8% vs 50.0%, p=0.739) and all-cause death rates (17.7% vs 18.8%, p=0.700) were similar in both groups at 90 days. CONCLUSIONS: The Catfish stent retriever is an effective and safe device for endovascular recanalisation in ELVO stroke. TRIAL REGISTRATION NUMBER: NCT03820882.
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Arteriopatías Oclusivas , Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Estados Unidos , Humanos , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/cirugía , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/complicaciones , Estudios Prospectivos , Resultado del Tratamiento , Trombectomía , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/terapia , Accidente Cerebrovascular Isquémico/complicaciones , Stents/efectos adversosRESUMEN
OBJECTIVE: The effectiveness of MRI-guided intravenous recombinant tissue-type plasminogen activator (r-tPA) for acute ischaemic stroke (AIS) with an unknown time of onset has been demonstrated by the WAKE-UP Trial. We aim to evaluate its long-term cost-effectiveness from the perspective of Chinese and US healthcare payers. METHODS: A combination of decision tree and Markov model was built to project lifetime costs and quality-adjusted life-years (QALYs) associated with intravenous r-tPA or placebo treatment. Model inputs including the transition probabilities, costs and utilities were derived from the WAKE-UP Trial, similar cost-effectiveness studies and other published sources. To compare intravenous r-tPA to placebo, we calculated incremental costs, incremental QALYs and incremental cost-effectiveness ratio (ICER). One-way sensitivity, probabilistic sensitivity and subgroup analyses were performed to evaluate uncertainty in the results. RESULTS: In China, intravenous r-tPA gained an additional lifetime QALY of 0.293 with an additional cost of the Chinese Yuan (¥) of 7871 when compared with placebo, resulting in an ICER of ¥26 870 (US$3894)/QALY. In the USA, intravenous r-tPA yielded a higher QALY (difference: 0.430) and lower cost (difference: ¥-4563) when compared with placebo. In probabilistic sensitivity analyses, intravenous r-tPA had a 97.8% and 99.8% probability of being cost-effective or cost-saving in China and the USA, respectively. These findings remained robust under one-way sensitivity and subgroup analysis except for patients with a National Institute of Health Stroke Scale Score of less than 4, between 11 and 16, and over 16. CONCLUSIONS: MRI-guided intravenous r-tPA for patients with AIS with an unknown time of onset is cost-effective in China and cost-saving in the USA.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Activador de Tejido Plasminógeno/uso terapéutico , Análisis Costo-Beneficio , Isquemia Encefálica/tratamiento farmacológico , Accidente Cerebrovascular/terapia , Años de Vida Ajustados por Calidad de VidaRESUMEN
BACKGROUND: Being physically active is important for cardiovascular health. This study aimed to examine the trend in adherence to the physical activity guidelines (PAG) for aerobic activity among US adults with a history of cardiovascular disease (CVD) and evaluated its association with cardiovascular risk factors. METHODS: We studied participants from the national health and nutrition examination survey 2007-08 to 2017-18. Regression models were used to evaluate the significance of the trend and the association between adherence to the PAG with cardiovascular risk factors. RESULTS: A total of 3638 participants were reported to have a history of CVD. The proportion of adherence to PAG significantly increased from 41.5% in 2007-08 to 54.3% in 2017-18. Males had a higher proportion of adherence compared to the females, while the trend in adherence was only significant in females. Adherence to the PAG was significantly associated with decreased levels of waist circumference, body mass index, hemoglobin A1c, and triglycerides. CONCLUSIONS: There is a significant increase in the proportion of adherence to the PAG among US adults with a history of CVD from 2007-08 to 2017-18, and adherence to the PAG was associated with improvement in cardiovascular risk factors.
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Enfermedades Cardiovasculares , Adulto , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Estudios Transversales , Ejercicio Físico , Femenino , Hemoglobina Glucada , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Masculino , Encuestas Nutricionales , Factores de Riesgo , TriglicéridosRESUMEN
Perovskite quantum dots (PQDs) are applicable in light-emitting diodes (LEDs) owing to their color tunability, high color purity, and excellent photoluminescence quantum yield (PLQY) in the solution state. However, a PQD film obtained through nonradiative recombination by concentration quenching and the formation of surface defects exhibited a low PLQY. In this study, we focused on the energy transfer between PQDs with different energy gaps (Eg) to reduce nonradiative recombination in the film state and consequently achieve high device performance. We prepared size-controlled PQDs measuring 10.7 nm (large-size QD; LQD) and 7.9 nm (small-size QD; SQD) with different Eg values and observed a spectral overlap between SQD emission and LQD absorption. To investigate the Förster resonance energy transfer (FRET) from SQDs to LQDs, we prepared SQD-LQD mixed QDs (MQDs). The MQD film enhanced LQD emission and exhibited a higher PLQY (52%) with a longer PL decay time (7.4 ns) than those exhibited by the neat LQD film (38% and 6.2 ns). This energy transfer was determined to be FRET by photoluminescence excitation and PL decay times. Moreover, the external quantum efficiency of an MQD-based LED increased to 15%, indicating that the FRET process can enhance the PLQY of the film and LED efficiency.
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The emergence of green materials has attracted considerable attention in the field of optoelectronics. Copper-based lead-free metal halide (with a near-unity quantum yield) obtained from Cs3Cu2I5 nanocrystals (NCs) can exhibit blue emission with a wavelength of 440 nm and provide outstanding stability for various applications. However, in practical applications, colloidal dispersion purity and film quality are inadequate toward a high-performance device. In this study, antisolvent-free gel permeation chromatography is used to purify Cs3Cu2I5 NCs. The purified Cs3Cu2I5 NCs exhibit a high photoluminescent quantum yield and provide a highly oriented single-crystal film. Density functional theory calculation results indicate that the iodide-rich surface in the NCs makes them highly stable. In addition, it has been demonstrated for the first time that the mixture of polymethyl methacrylate (PMMA) and Cs3Cu2I5 NCs has waterproofing capabilities. The composite film consisting of Cs3Cu2I5 NCs and PMMA can survive in water for several days. This result opens up more possibilities for the application of these green material.
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Metal halide perovskites attract significant attention because of their excellent optoelectronic and semiconducting properties. However, there are environmental concerns related to the toxicity of the lead metal that is mainly used in these perovskites. PEA2SnI4 perovskite is a potential candidate for lead-free perovskites because of its pure red emission. Although, undesired Sn4+ oxidation results in the deterioration of PEA2SnI4 perovskite. We demonstrate the two-step crystallization of PEA2SnI4 through the (i) reprecipitation and (ii) recrystallization processes. A film prepared using this method exhibits narrowed emission, with a full width at half-maximum from 30.0 to 26.1 nm, because of its homogeneous emission. Moreover, the Sn4+ content of two-step-crystallized PEA2SnI4 films is five times lower than that of a control film. Diffusion-ordered spectroscopy analysis indicates that the two-step precursor exhibits a smaller hydrodynamic radius crystal seed, which enhances crystallization during spin coating. The resulting two-step crystallized PEA2SnI4-based light-emitting diode (LED) exhibits a maximum external quantum efficiency (EQE) of 0.4% with an average of 0.2%, which is two times greater than that of the control device. This two-step approach may be generalized to synthesize other lead-free materials.
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An increasing amount of evidence has proven that serum metabolites can instantly reflect disease states. Therefore, sensitive and reproducible detection of serum metabolites in a high-throughput manner is urgently needed for clinical diagnosis. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a high-throughput platform for metabolite detection, but it is hindered by significant signal fluctuations because of the "sweet spot" effect of organic matrices. Here, by screening two transformation methods and four normalization techniques to reduce the significant signal fluctuations of the DHB matrix, an integrated MALDI-MS data processing approach combined with machine learning methods was established to reveal metabolic biomarkers of lung cancer. In our study, 13 distinctive features with statistically significant differences (p < 0.001) between 34 lung cancer patients and 26 healthy controls were selected as significant potential biomarkers of lung cancer. 6 out of the 13 distinctive features were identified as intact metabolites. Our results demonstrate the potential for clinical application of MALDI-MS in serum metabolomics for biomarker screening in lung cancer.
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Neoplasias Pulmonares , Metabolómica , Humanos , Neoplasias Pulmonares/diagnóstico , Aprendizaje Automático , Metabolómica/métodos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodosRESUMEN
AIM: To compare the differences and consistency of IOL-Master 700 biometers applying swept optical coherence tomography with the conventional IOL-Master 500 applying partial coherence interference in terms of the ocular biological parameters in adolescents with ametropia. METHODS: A total of 110 adolescents (110 eyes) with ametropia were collected, including 55 males and 55 females; age 10.69±2.81y. Ocular biological measurements were taken by IOL-Master 700 and IOL-Master 500 respectively to obtain biological parameters including axial length (AL), mean corneal anterior surface keratometry (Km), anterior chamber depth (ACD), and horizontal corneal diameter (WTW). Paired t-test was used to compare the differences between the two instruments. The intra-group correlation coefficient (ICC) and the Bland-Altman analysis were used to evaluate the consistency of parameter measurements between the two instruments for the four biological parameters. RESULTS: Statistical analysis showed that there was no significant difference in the Km value measured by IOL-Master 700 and IOL-Master 500 (t=-1.644, P=0.116). The average differences of the AL, ACD, and WTW distances between the two instruments are 0.028, 0.101 and 0.064 mm respectively, and the differences are statistically significant (t=2.644, 12.505, 3.911, P<0.001). The consistency study results indicated high correlation in the measurement of AL, Km, ACD and WTW between the two instruments (ICC=0.994, 0.873, 0.927, 0.912). CONCLUSION: The novel biometric instrument IOL-Master 700 makes no difference with IOL-Master 500 in the measurement of Km. There are some differences in the values of AL, ACD, and WTW. However, the two instruments show good consistency in these four biological measurements. The measured values of Km are interchangeable between the instruments. These two types of biometrics can be used as mutual reference in consideration of that the differences in AL, ACD, and WTW measurements are not sufficient to produce clinically meaningful differences.
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The characterization of photoexcited electrons on the surface of nanomaterial remains challenging. Herein, laser excitation mass spectrometry combined with a chemical thermometer and electron acceptor has been developed to characterize the energetics and population density of photoexcited electrons transferred from gold nanoparticles (AuNPs). In contrast to laser fluence and bias voltage, the hot spots of closely packed AuNPs play a more significant role in enhancing the average energetics of photoexcited electrons, which can be harvested effectively by the electron acceptor. By harvesting more energetic photoexcited electrons for the desorption and ionization process, it is anticipated that the sensitive detection of biomarkers can be achieved, which is beneficial to metabolomic studies and early disease diagnosis.
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The ability to recognize mRNA with high efficiency in cells would greatly facilitate the elucidation of mRNA-mediated cellular cascades and their disease associations. However, most traditional electrochemical strategies targeting nucleotides are always confronted with cumbersome interface operation and washing procedures, as well as the high cost of labeling and the strict reaction conditions of tool enzymes, limiting their potential applications. To address these issues, herein we reported, for the first time, a simple label-free, isothermal, non-enzymatic, and ultrasensitive homogeneous electrochemical biosensor based on autonomous proximity-dependent surface hybridization chain reaction (HCR), for sensitive signal amplification and highly specific detection of target survivin mRNA with a detection limit of 3 fM. The target triggers hybridization chain reaction and mRNA-fueled surface hybridization of ferrocene-tagged metastable DNA hairpin probes on proximity-dependent surface hybridization, resulting in the formation of multiple long-range duplex DNA chains which are immobilized onto the gold electrodes with a substantially stable ferrocene-mediated redox current. Thus, a significant electrochemical signal increase is observed dependent on the concentration of the target RNA, with a very low detection limit. Mo-reover, this molecular biosensor also exhibits excellent specificity to distinguish even single base mismatched, with strong reliability. The developed biosensor provides a novel promising tool for ultra-sensitive and selective detection, and it has great potential to be applied in mRNA-related biochemical research and clinical cancer diagnostics in more detail.
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Técnicas Biosensibles , Técnicas Electroquímicas , Límite de Detección , Técnicas de Amplificación de Ácido Nucleico , Hibridación de Ácido Nucleico , ARN Mensajero/genética , Reproducibilidad de los ResultadosRESUMEN
AIM: To assess the efficacy and safety of parafoveal retinal massage combined with autologous whole blood cover in the treatment of refractory macular holes (MHs) and present the surgical procedure. METHODS: Patients with giant (minimum diameter ≥800 µm), recurrent or persistent MHs who underwent PPV combined with parafoveal retinal massage and autologous whole blood cover using C3F8 as tamponade agent from February 2018 to May 2019 were enrolled in this retrospective study. After surgery, all patients were informed to maintain a prone position for at least 7d. Preoperative and postoperative best-corrected visual acuities (BCVAs) were compared and MH closure rate was measured as the main outcome. RESULTS: A total of 13 MH patients consisted of 6 giant MHs, 4 persistent holes and 3 recurrent holes (5 men and 8 women; average age was 56.40±11.72y) were enrolled in this study. MH closure was achieved in 11 eyes by this modified surgical technique while 2 eyes failed. Revitrectomy with autologous neurosensory retinal patch transplantations was applied for those 2 patients and then both holes were closed. No intraoperative complications were observed. BCVA improved from 1.73 logMAR to 0.74 logMAR at 6mo postoperation. There was significant difference in BCVA before versus after the surgery (P<0.05). There were no adverse events occurred during the follow-up period. CONCLUSION: With easier surgical procedure, parafoveal retinal massage combined with autologous whole blood cover is an effective addition to the surgical options for the management of refractory MHs.
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Diabetic retinopathy (DR) is one of the common complications of diabetes mellitus. C1q/TNF-related protein 9 (CTRP9) has been demonstrated to be associated with the progression of diabetes and relative complications. However, its role in DR and underlying action of mechanism are not yet well understood. In the present study, human retinal pigment epithelial ARPE-19 cells were cultured under high concentration of glucose to simulate hyperglycemia condition in vitro. Our results showed that the expression of CTRP9 was significantly decreased in high glucose (HG)-stimulated ARPE-19 cells. CTRP9 overexpression improved HG-caused reduction in cell viability of ARPE-19 cells. CTRP9 overexpression significantly attenuated HG-induced oxidative stress, as proved by decreased levels of reactive oxygen species and malondialdehyde, and increased superoxide dismutase activity. Moreover, CTRP9 also prevented apoptosis in ARPE-19 cells in response to HG stimulation with decreased caspse-3 activity and bax expression, as well as increased bcl-2 expression. In contrast, knockdown of CTRP9 aggravated HG-induced oxidative stress and apoptosis. Furthermore, CTRP9 significantly induced the activation of AMPK/Nrf2 pathway in HG-induced ARPE-19 cells. Notably, inhibiting AMPK or Nrf2 blocked the protective effect of CTRP9 on ARPE-19 cells exposed to HG stimulation. Taken together, our findings suggested a protective effect of CTRP9 on HG-induced ARPE-19 cells and a putative mechanism involving the activation of AMPK/Nrf2 signaling pathway.
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Proteínas Quinasas Activadas por AMP/metabolismo , Adiponectina/metabolismo , Apoptosis/efectos de los fármacos , Glucosa/toxicidad , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/efectos de los fármacos , Epitelio Pigmentado de la Retina/patología , Transducción de Señal , Proteínas Quinasas Activadas por AMP/antagonistas & inhibidores , Línea Celular , Supervivencia Celular/efectos de los fármacos , Activación Enzimática/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Hemo-Oxigenasa 1/metabolismo , Humanos , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , Fármacos Neuroprotectores/farmacología , Pirazoles/farmacología , Pirimidinas/farmacología , Transducción de Señal/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacosRESUMEN
AIM: To observe the efficacy and safety of pars plana vitrectomy (PPV) with eye position guided fluid-air exchange (FAX) and air tamponade in the treatment of rhegmatogenous retinal detachment (RRD). METHODS: RRD patients without severe proliferative vitreoretinopathy (PVR) C1 or more were enrolled. All patients underwent PPV combining with air tamponade. During operation, the primary retinal break(s) were placed at lower site and subretinal fluid was aspirated through the break(s) at the same time when eye position guided FAX was proceeding. Sufficient laser spots were made to seal the retinal break(s) after FAX, and filtered air was left in vitreous cavity as tamponade agent finally. The main outcomes were primary and final success rates, best corrected visual acuity (BCVA), and the secondary outcomes were rate of postoperative cataract surgery and high intraocular pressure. RESULTS: A total of 37 eyes (20 males and 17 females) with a follow-up time of ≥6mo were included. The range of RRD was 5.6±1.8h, and the number of retinal breaks was 1.9±1.2. The breaks located at inferior quadrants (between 3:00 and 9:00) in 5 cases (13.5%), and both superior and inferior breaks were found in 3 cases (8.1%). A total of 25 cases (67.6%) with macular detached involvement, 9 cases (24.3%) with intraocular lens, and 8 patients (21.6%) were treated with phacoemulsification and intraocular lens implantation together. The success rate of primary retinal reattachment was 100% (37/37). At 6mo postoperatively, BCVA (logMAR) was increased from 1.13±1.07 to 0.23±0.15 (P<0.001). Phacoemulsification combined with intraocular lens implantation was performed in 2 patients (5.4%), and one of them underwent macular epiretinal membrane peeling in addition (2.7%). Furthermore, high intraocular pressure was found in 4 cases (10.8%). CONCLUSION: PPV with air tamponade by eye position guided FAX can achieve a high reattachment success rate in the management of patients with RRD, and it has the advantages of short postoperative prone time and fewer operative complications.
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HPV-induced cervical cancer is one of the most lethal cancers. Therefore, the development of a reliable and accurate method for the early diagnosis of HPV infections is highly important. Here, gold nanoparticles (AuNPs) were utilized as mass tags in an immuno-capture LI-MS assay for the detection of HPV marker proteins. Through the optimization of the amount of antibodies and surface charges on AuNPs, high antigen detection efficiency with minimal non-specific binding was achieved. With optimized antibody-conjugated AuNPs, low attomole amount of HPV proteins in HeLa cell lysate was quantified.
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Oro , Nanopartículas del Metal , Biomarcadores , Células HeLa , Humanos , ProteínasRESUMEN
Charge separation lays the foundation for photocatalysis and photovoltaics, in which the catalytic/voltaic efficiency is primarily related to the amount of separated charges generated. Yet, direct experimental approaches for the quantification of separated charges are very limited, especially for nanostructures in small quantities. Here, by laser excitation mass spectrometry with tetrabutylammonium as a sensitive probe, the separated charges in gold-metal sulfide core-shell nanostructures are determined and correlated with the bandgap of the semiconductor shell. Moreover, the separated charges formed can already be detected unambiguously in only an attomole-level of nanoparticles (i.e., 1 × 108 NPs).
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Oxidative stress and inflammation have long been considered to be responsible for the development and progression of diabetic retinopathy. On the other hand, rhaponticin (RN) has received scientific attention due to its various pharmacological properties. Keeping all these in view, the present study was performed to investigate the potential protective effects of RN on the retina in diabetic rats. Rats were randomly divided into three groups: control group rats, diabetic group rats, diabetic + RN (20 mg/kg body weight for 28 days through oral route) group rats. RN supplementation to diabetic rats significantly prevent the reduction of final body weight loss, reduced weekly fasting blood glucose levels and HbA1c levels with a significant increase in serum insulin levels. quantitative polymerase chain reaction and immunohistochemical analysis found upregulation of Nrf2, NQO-1, HO-1 and upregulation of Keap1 genes and protein distribution along with significantly reduced levels of malondialdehyde and increased activity of superoxide dismutase, catalase and glutathione peroxidase in RN-treated diabetic rats as compared to diabetic rats. Furthermore, treatment of diabetic rats with RN showed downregulated expression of tumour necrosis factor-α, matrix metalloproteinase-2 and upregulated expression of interleukin-10 (IL-10) and TIMP-1 in the retina. RN treatment decreased nuclear factor kappa-light-chain-enhancer of activated B cells distribution and increased IL-10 protein distribution in the retinae of diabetic rats. In addition, RN treatment ameliorated morphological changes observed in retinae of diabetic rats. Altogether, these results provided clear evidence that treatment of diabetic rats with RN attenuated diabetic retinal changes through its hypoglycaemic, antioxidant and anti-inflammatory effects.
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Diabetes Mellitus Experimental/metabolismo , Hemo-Oxigenasa 1/metabolismo , Inflamación/prevención & control , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Retina/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Estilbenos/farmacología , Animales , Glucemia/metabolismo , Hemoglobina Glucada/metabolismo , Masculino , Ratas , Ratas WistarRESUMEN
Glucagon-like peptide-1 (GLP-1) is of particular interest for treating type 2 diabetes mellitus (T2DM), as it induces insulin secretion in a glucose-dependent fashion and has the potential to facilitate weight control. However, native GLP-1 is a short incretin peptide that is susceptible to fast proteolytic inactivation and rapid clearance from the circulation. Various GLP-1 analogs and bioconjugation of GLP-1 analogs have been developed to counter these issues, but these modifications are frequently accompanied by the sacrifice of potency and the induction of immunogenicity. Here, we demonstrated that with the conjugation of a zwitterionic polymer, poly(carboxybetaine) (pCB), the pharmacokinetic properties of native GLP-1 were greatly enhanced without serious negative effects on its potency and secondary structure. The pCB conjugated GLP-1 further provided glycemic control for up to 6 days in a mouse study. These results illustrate that the conjugation of pCB could realize the potential of using native GLP-1 for prolonged glycemic control in treating T2DM.
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Diabetes Mellitus Tipo 2/sangre , Péptido 1 Similar al Glucagón/química , Control Glucémico/métodos , Hipoglucemiantes/uso terapéutico , Polímeros/química , Animales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Modelos Animales de Enfermedad , Péptido 1 Similar al Glucagón/farmacocinética , Péptido 1 Similar al Glucagón/uso terapéutico , Semivida , Hipoglucemiantes/farmacocinética , Ratones , Estructura Secundaria de ProteínaRESUMEN
We report a novel DNA-programmed plasmonic enzyme-linked immunosorbent assay (ELISA) for the ultrasensitive detection of protein biomarkers with the naked eye. The DNA-programmed plasmonic assay was based on two enzyme-free and isothermal nucleic acid amplification methods: hybridization chain reaction (HCR) and catalyzed hairpin assembly (CHA). In this study, a biotin-labeled DNA probe was utilized insteand of an enzyme-label probe in well-developed ELISA method. The biotin-labeled DNA probe was able to trigger the HCR and CHA processes, and the products could hybridize with DNA-modified gold nanoparticles (AuNPs) to induce the aggregation of the AuNPs and a color change in the solution. The developed method was able to detect as low as 1 pg mL-1 PSA target with the naked eye. Clinical serum samples demonstrated satisfactory results, indicating that the method is useful for early diagnostics and monitoring curative effects after a medical treatment. The developed method presents a simple and portable platform for ultrasensitive protein detection and has potential for point-of-care (POC) diagnostics in less developed areas.
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Oro , Nanopartículas del Metal , Biomarcadores , ADN/genética , Ensayo de Inmunoadsorción Enzimática , Hibridación de Ácido NucleicoRESUMEN
Diabetic retinopathy (DR) is the primary cause of blindness and visual impairment in diabetes patients worldwide. However, laser and surgical therapies at DR have short-term effectiveness and cause side effects. Treatment with natural products is a reasonable alternative treatment for DR. The main objective of this investigation is to explore the efficacy of a bioactive compound such as palbinone (PB) in DR. Experimental rats were injected intraperitoneally with streptozotocin (STZ, 65 mg/kg), and these established experimental rats were treated with PB (20 mg/kg/bw) for 42 days. The observed results showed that PB considerably reduced the proinflammatory cytokine (interleukin-18 [IL-18] and IL-1ß) production as well as improved the activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) particularly in the retinal region of STZ-induced DR rats. In addition, PB treatment improved nuclear factor erythroid 2-related factor 2 (Nrf2) accumulation and enhanced the heme oxygenase-1 expression, and major antioxidants downregulated Nrf2 in the damaged retina. Also, the expression levels of nod-like receptor family pyrin domain containing 3 (NLRP3), cleaved-caspase-1, IL-1ß, and apoptosis-associated speck-like protein containing CARD in the retinal region were notably upregulated in STZ-induced DR, which was eliminated by PB interference. PB administration exerted efficient antioxidant activities, Nrf2 pathway activation, and inhibition of NLRP3 inflammasome. This current investigation concluded that PB considerably reduced the retinal inflammation and oxidative stress stimulated via high glucose, and also activated the antioxidative Nrf2 pathway and inhibited the NLRP3 inflammasome formation in rats.
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Retinopatía Diabética/inducido químicamente , Retinopatía Diabética/tratamiento farmacológico , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Extractos Vegetales/administración & dosificación , Transducción de Señal/efectos de los fármacos , Estreptozocina/efectos adversos , Terpenos/administración & dosificación , Animales , Catalasa/metabolismo , Glutatión Peroxidasa/metabolismo , Inflamasomas/antagonistas & inhibidores , Inflamasomas/metabolismo , Inflamación/metabolismo , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Masculino , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Paeonia/química , Ratas , Ratas Sprague-Dawley , Superóxido Dismutasa/metabolismoRESUMEN
Photoexcited hot carriers have high impacts on various fields. However, in contrast to the attention attracted by the hot-electrons, the contributions of holes are seldom recognized. Yet, by simply removing the hot-electrons but retaining the holes on the surface of photoexcited plasmonic gold nanoparticles, a 60-fold ion intensity amplification could be achieved in laser desorption ionization mass spectrometry. A new desorption mechanism termed "charge-driven desorption" has been derived to rationalize the significant improvement.