Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 213
Filtrar
1.
ACS Omega ; 7(16): 14211-14221, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35559200

RESUMO

The current global pandemic of new coronary pneumonia clearly reveals the importance of developing highly efficient filtration and fast germicidal performance of multifunctional air filters. In this study, a novel air filter with a controllable morphology based on the rod-like to flower-like zinc oxide/graphene-based photocatalytic composite particles loaded on glass microfiber was prepared by one-step microwave rapid synthesis. The multifunctional air filter shows the following special functions: the 10 mg·L-1 organic pollutant solution RhB was completely degraded within 2 h under a 500 W xenon lamp, and also 99% of Escherichia coli and Staphylococcus aureus were inactivated under a 60 W light-emitting diode lamp. Furthermore, after introducing the controllable morphology zinc oxide/graphene-based photocatalytic composite particles, the filtration efficiency of the multifunctional air filter was also kept at the same level (99.8%) as the one without any addition, indicating no loss of high-efficiency filtration while obtaining the rapid bactericidal function. The rapid antibacterial principle of the multifunctional air filter has also been proposed through the UV-vis spectroscopies, photoluminescence, and electron-spin resonance spectrum. The zinc oxide/graphene-based photocatalytic composite particles tightly coated on the glass microfiber surface could increase the active sites by changing the morphology of zinc oxide and, in the meantime, promote the separation of zinc oxide photo-generated electron-hole pairs to improve the rapid sterilization ability of the multifunctional air filters. In addition, an empirical formula to evaluate the relationship between the composition, viscosity, and viscosity modulus of glass microfiber was proposed by testing the viscosity of glass microfiber composed of 14 different compositions at 1300 and 1400 °C, which can be used as a criterion to evaluate the production technology of glass microfiber filters.

2.
Front Cell Dev Biol ; 10: 898652, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35573676

RESUMO

Retinal inflammation underlies multiple prevalent retinal diseases. While microglia are one of the most studied cell types regarding retinal inflammation, growing evidence shows that Müller glia play critical roles in the regulation of retinal inflammation. Müller glia express various receptors for cytokines and release cytokines to regulate inflammation. Müller glia are part of the blood-retinal barrier and interact with microglia in the inflammatory responses. The unique metabolic features of Müller glia in the retina makes them vital for retinal homeostasis maintenance, regulating retinal inflammation by lipid metabolism, purine metabolism, iron metabolism, trophic factors, and antioxidants. miRNAs in Müller glia regulate inflammatory responses via different mechanisms and potentially regulate retinal regeneration. Novel therapies are explored targeting Müller glia for inflammatory retinal diseases treatment. Here we review new findings regarding the roles of Müller glia in retinal inflammation and discuss the related novel therapies for retinal diseases.

3.
mSystems ; : e0150721, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35491818

RESUMO

Acute pancreatitis (AP) is usually accompanied by intestinal failure, but its mechanism is still unclear. In AP patients, the functions of Paneth cells (lysozyme, HD5, Reg3γ, and Wnt3a) decreased. Compared with AP mice, injuries and inflammation of the pancreas and ileum were aggravated in AP mice treated with dithizone (Dith) (Dith+AP mice). Intestinal permeability and bacterial translocation were also increased. 16S rRNA sequencing showed that the gut microbiota of Dith mice and Dith+AP mice exhibited a marked increase in the pathogenic bacterium Helicobacter and a significant decrease in the probiotic bacterium Blautia. Lysozyme gavage in Dith+AP mice effectively alleviated injuries of the pancreas and small intestine. The beneficial effect of lysozyme was associated with a significant increase in the probiotic bacterium Blautia and a virtual absence of the pathogenic bacterium Helicobacter. The severity of AP in antibiotic-treated mice (ABX mice) was significantly aggravated when receiving feces from Dith mice and was markedly alleviated when receiving feces from lysozyme-gavaged mice. In vitro, lysozyme increased the proliferation of enteroids by promoting the activation of the Wnt pathway and Lgr5 expression in intestinal stem cells. IMPORTANCE We demonstrate that AP patients and experimental AP mice exhibited a dysfunction of Paneth cells. Our in vivo research showed that the severity of AP was exacerbated by the long-term dysfunction of Paneth cells, which was associated with gut microbiota disorder. Restoring part of Paneth cell functions through lysozyme supplementation alleviated the severity of AP and gut microbiota dysbiosis. This study provides novel insight into the link of pancreas-gut interactions in the pathogenesis of AP, providing a new direction for the clinical treatment of intestinal complications during AP.

4.
Front Pharmacol ; 13: 838247, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35462930

RESUMO

The acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is inevitable and heterogeneous. The strategies to overcome acquired resistance are significant. For patients with secondary T790M-positive after early generation EGFR-TKIs, osimertinib is the standard second-line therapy. In patients resistant to prior early generation EGFR-TKIs, the acquired T790M mutation overlaps with other driver gene resistance, such as HER2-and MET amplification, accounting for 4-8%. The efficacy of osimertinib is unclear in patients with concurrent multiple driver gene resistance. We here report a patient who acquired EGFR T790M, STRN-ALK fusion, and EGFR amplification after gefitinib progression and subsequent MET amplification acquired from osimertinib. The other patient acquired EGFR T790M and MET amplification post-dacomitinib and acquired CCDC6-RET fusion after osimertinib treatment. Besides, subsequent new bypass activations were the possible resistance mechanisms to second-line osimertinib. Both patients had progression-free survival (PFS) less than 4 months and limited benefits from osimertinib second-line therapy. The T790M accompanying driver gene resistance will be a new subtype after EGFR-TKIs progression, needing effective treatment options.

5.
Cutan Ocul Toxicol ; 41(1): 98-104, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35373690

RESUMO

PURPOSE: The inhibitory effect of conbercept on corneal neovascularization (CNV) after penetrating keratoplasty (PKP) and its effect on postoperative wound healing and corneal strength recovery was investigated. METHODS: New Zealand white rabbits were randomly divided into 3 groups, two experimental arms A and B and one control arm C. Topical conbercept and subconjunctival injection were carried out respectively after PKP. Slit lamp microscope was used to observe the growth of CNV. The expression of vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and vimentin (Vim) were determined via real-time quantitative polymerase chain reaction (RT-qPCR). The placenta growth factor and vimentin, determination of corneal biomechanical machine strength changed. To measure the maximal strength of the corneal, uniaxial tensile test was carried out on the electroforce 3220-AT biomechanics machine. RESULTS: Two weeks after PKP, CNV appeared, inflammatory cell infiltration and new blood vessel formation were observed in the corneal stroma and superficial stroma layer. Compared with the control arm, the expression levels of VEGF and PlGF in the experimental arms were significantly decreased after using conbercept (P < 0.05), and the expression levels reached the maximum at the 4th week and then decreased gradually. The expression level of Vimentin and corneal intensity increased gradually over time. CONCLUSION: Conbercept effectively inhibited the formation of CNV after PKP in rabbits, and did not affect postoperative wound healing, nor did it affect postoperative corneal strength recovery.

6.
Research (Wash D C) ; 2022: 9834093, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35402922

RESUMO

Photosynthetic biohybrid systems exhibit promising performance in biosynthesis; however, these systems can only produce a single metabolite and cannot further transform carbon sources into highly valuable chemical production. Herein, a photosynthetic biohybrid system integrating biological and chemical cascade synthesis was developed for solar-driven conversion of glucose to value-added chemicals. A new ternary cooperative biohybrid system, namely bacterial factory, was constructed by self-assembling of enzyme-modified light-harvesting donor-acceptor conjugated polymer nanoparticles (D-A CPNs) and genetically engineered Escherichia coli (E. coli). The D-A CPNs coating on E. coli could effectively generate electrons under light irradiation, which were transferred into E. coli to promote the 37% increment of threonine production by increasing the ratio of nicotinamide adenine dinucleotide phosphate (NADPH). Subsequently, the metabolized threonine was catalyzed by threonine deaminase covalently linking with D-A CPNs to obtain 2-oxobutyrate, which is an important precursor of drugs and chemicals. The 2-oxobutyrate yield under light irradiation is increased by 58% in comparison to that in dark. This work provides a new organic semiconductor-microorganism photosynthetic biohybrid system for biological and chemical cascade synthesis of highly valuable chemicals by taking advantage of renewable carbon sources and solar energy.

7.
Rev Sci Instrum ; 93(3): 033507, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35364986

RESUMO

A practical procedure of determining the best choice of particle tracking velocimetry (PTV) methods for the analysis of two-dimensional (2D) dusty plasmas is provided. Using the measured particle positions with errors, the algorithm of PTV introduces further systematic errors while calculating particle velocities. To better quantify the errors, computer simulations of 2D Yukawa liquids are performed so that the true particle positions and velocities are precisely known. Synthetic data are achieved by varying the time interval between frames and adding the uncertainty with the different magnitude to the particle position data. Various PTV methods are used to calculate the velocity data from the achieved synthetic data, and the obtained velocity data from these PTV methods are compared with the true velocity data using two diagnostics to determine the best PTV method for various conditions. The results of various PTV methods with the simulation data are further confirmed by the demonstration using the 2D dusty plasma experimental data. This practical procedure is also applicable to determine the best PTV method for dusty plasmas in different conditions, such as those in Tokamaks, and for other physical systems, including colloids, granular materials, and fluid mechanics.

9.
Zhongguo Fei Ai Za Zhi ; 25(3): 201-206, 2022 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-35340163

RESUMO

Lung cancer is the most lethal malignancy around the world and non-small cell lung cancer (NSCLC) accounts for 80% of all cases. Most of the NSCLC patients has "driver gene mutations" and targeted therapy achieved a relatively good efficacy, but some patients progressed or relapsed after treatment. Previous studies demonstrated that immune checkpoint inhibitor could improve the prognosis of advanced-stage NSCLC and prolong the survival time. However, the efficacy of immune therapy varies in NSCLC patients with different immune and molecular features. The efficacy of immune therapy was controversial in NSCLC patients with driver gene mutation. The present review will summarize the immune characteristics of NSCLC patients with driver mutation and the directions of immunotherapy for patients with driver mutation.
.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/terapia , Terapia de Alvo Molecular , Mutação
10.
Biomark Res ; 10(1): 9, 2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35255999

RESUMO

Immunotherapy has become the standard of care for non-small cell lung cancer (NSCLC), either in combination or monotherapy. However, there are still some patients who cannot benefit from it. Immunization strategies for NSCLC are based on the expression of PD-L1 on tumor cells and TMB, and although these indicators have a certain predictive effect, their predictive performance is not good. Therefore, clinicians must make adjustments to recognize markers. This is a review article that summarized immunotherapeutic biomarkers according to the "seed-soil-environment", generalizes primary resistance to immunotherapy, and summarizes the integration of markers.

11.
Front Cell Dev Biol ; 10: 865043, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35317388

RESUMO

[This corrects the article DOI: 10.3389/fcell.2021.777018.].

12.
Front Med (Lausanne) ; 9: 802036, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35308529

RESUMO

Background: Atopic dermatitis (AD) is one of the most common chronic inflammatory skin disorders. Dupilumab, the first targeted biological drug approved for the treatment of AD, has been widely used, along with increasing ocular adverse effects (AEs). Objective: To perform a bibliometric analysis of all the qualified literature involving ocular AEs during the treatment of AD with dupilumab. Methods: Relevant studies were extracted from the Web of Science database and screened by researchers. The bibliographic analysis was performed using the VOSviewer. Results: A total of 138 articles were enrolled in this study. The first study was published in 2016 by Oregon Health and Science University from the United States. The majority of publications were published in the past 3 years. British Journal of Dermatology published the highest number of articles. The United States was the country with the most publications. Sanofi (France) and Regeneron Pharmaceuticals (USA) were the leading organizations with the most contributions. Conjunctivitis was the most common ocular AE. The management of AD will continue to be the research hotspot and development trend in this area. The milestone research is the first article "Two Phase 3 Trials of Dupilumab vs. Placebo in Atopic Dermatitis" published in the New England Journal of Medicine. Most of the top 10 papers were mainly randomized, placebo-controlled phase 2 and phase 3 clinical trials and real-life large cohort studies. Conclusions: This study may help better understand ocular AEs in the dupilumab treatment of AD, and grasp the research trends and most influential topics in this field.

13.
Front Aging Neurosci ; 14: 824705, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35356297

RESUMO

Background and Objectives: The study aims to test the hypotheses that a higher burden of cerebral small vascular disease (CSVD) predicts major adverse cardiac and cerebrovascular events (MACCE) in patients with hypertension (HTN) and that abnormal blood pressure variability (BPV) pattern aggravates total CSVD burden. Methods: We retrospectively reviewed patients with HTN prospectively selected between February 2015 and February 2019 from three participating centers. Patients were included if they had HTN for over 1 year and had at least one MRI feature of CSVD. Independent predictors were found using multivariate logistic regression. Results: Among the 908 patients who finally enrolled in the study, the number of CSVD markers (OR = 1.940; 95% CI = 1.393-2.703; P < 0.001) independently predicted MACCE with acceptable predictive value (C-statistic = 0.730; 95% CI = 0.669-0.791; P < 0.001). An abnormal BPV pattern was identified as an independent risk factor for increased CSVD burden. Among them, reverse-dipper subtype demonstrated the most significant relationship (OR = 1.725; 95% CI = 1.129-2.633; P = 0.012). Conclusion: Total CSVD burden predicts an increased risk of composite MACCE independently. An abnormal BPV pattern is associated with a higher burden of CSVD.

14.
Bioengineered ; 13(3): 4702-4716, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35188876

RESUMO

Extracellular vesicles (EVs) are a promising new therapeutic platform. However, the low cargo-loading efficiency limits their clinical translation. In this study, we developed a high-yield EV cargo-loading device and explored its ability to encapsulate gene editing proteins. A series of fusion protein-based systems were constructed and their cargo loading efficiencies were compared by a NanoGlo luciferase assay. A myristoylated (Myr) peptide tag cloned from the N-terminal region of charged multivesicular body protein 6 (CHMP6), termed Myr(CHMP6), outcompeted CD9, ARRDC1, and other short polypeptides as an active packaging device. As determined by nanoparticle tracking analysis and transmission electron microscopy, the overexpression of Myr(CHMP6) increased small EV (sEV) production in Lenti-X 293T  cells without altering sEV morphology. The high passive packaging efficiency of Myr(CHMP6) was also elucidated for unmodified cargo loading. Western blotting revealed that Myr(CHMP6) facilitated the loading of Cre and Cas9 into sEVs without the generation of packaging device-cargo fusion proteins. Furthermore, Myr(CHMP6)-modified sEVs loaded with Cre or Cas9 promoted gene-editing in recipient cells, as observed using a fluorescence reporter system. Subsequent investigation demonstrated a dose-dependent effect of Myr(CHMP6) tag-induced cargo-loading. Mechanistically, N-myristoylation alone was necessary but not sufficient for the effective packaging of proteins into EVs. Thus, our results indicated that Myr(CHMP6) induces sEV production and may be effective in loading gene editing proteins into sEVs for therapeutic purposes.


Assuntos
Vesículas Extracelulares , Edição de Genes , Vesículas Extracelulares/metabolismo , Corpos Multivesiculares , Peptídeos/metabolismo
15.
Front Pharmacol ; 13: 759742, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35153772

RESUMO

Background: Retinopathy of prematurity (ROP) is a major cause of childhood blindness. Antenatal corticosteroids (ACS) exposure is known to ameliorate the risk of and mortality of neonatal morbidities. However, the effect of ACS on ROP development is currently unknown. We conducted a meta-analysis with up-to-date evidence to assess the association between ACS exposure and the development of ROP in at-risk preterm infants. Methods: PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library were systematically searched from inception to May 2021, supplemented with manual search from reference lists. Studies with a control group reporting ROP rate in ACS-exposed infants were included. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated utilizing a random-effects model. The Newcastle-Ottawa Scale was used for assessment of risk of bias in the included studies. Meta-regressions were performed to explore the predictive role of confounders for between-study variance. Results: A total of 63 studies, involving 196,264 infants, were included. Meta-analysis showed ACS exposure was not associated with ROP occurrence (uOR 0.92, 95% CI 0.80-1.07; aOR 0.87, 95% CI 0.7-1.08). Results from extremely immature subgroups revealed significant reduced risks of ROP occurrence in ACS-exposed infants. ACS exposure was associated with significantly lower odds of ROP progression in adjusted analysis (aOR 0.48, 95% CI 0.26-0.89) instead of unadjusted analysis (uOR 0.86, 95% CI 0.68-1.08). Meta-regression showed birth weight and patent ductus arteriosus of the cohort were associated with ROP occurrence, sample size and study design strongly associated with ROP progression in ACS-exposed infants. Conclusion: ACS treatment may decrease, but not prevent, the severity of ROP. Findings from severe ROP should be interpreted with caution owing to limited studies and the possibility of false-positive results. Considering the particular benefits in extremely immature infants, we recommend routine usage of ACS in mothers with threatened delivery to this particular birth cohort to prevent ROP occurrence. Future studies adjusting for major confounders are warranted to mitigate risk of bias in such observational evidence.

16.
Eur J Pharmacol ; 920: 174846, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35202676

RESUMO

Oxidative stress plays a crucial role in the pathophysiology of diastolic dysfunction associated with diabetic cardiomyopathy. Novel oral edaravone (OED) alleviates oxidative stress by scavenging free radicals and may be suitable for the treatment of chronic diseases such as diabetic cardiomyopathy. Oral administration of OED to type 2 diabetic rats (induced by high-sugar/high-fat diet and intraperitoneal injection of streptozotocin) for 4 w decreased malondialdehyde and increased superoxide dismutase. Moreover, it significantly improved ratios of early to late diastolic peak velocity, myocardium hypertrophy accompanied by decreased cross-sectional areas of cardiomyocytes, the proportion of apoptotic cells, collagen volume fractions, and deposition of collagen I/III. In H9c2 cells, OED reduced reactive oxygen species, cell surface area, and numbers of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling-positive cells induced by glucolipotoxicity. OED remarkably upregulated expression of the nuclear factor E2-related factor (Nrf2) signaling pathway both in vivo and in vitro. In addition, OED promoted Nrf2 nuclear translocation and upregulated nicotinamide adenine dinucleotide phosphate quinone oxidoreductase and heme oxygenase. Silencing of Nrf2 abolished the protective effect of OED in H9c2 cells. Our findings demonstrate that OED has the therapeutic potential to ameliorate diastolic dysfunction associated with diabetic cardiomyopathy. Its effect was mainly achieved by attenuating hyperglycemia and hyperlipidemia-induced cardiomyocyte hypertrophy, apoptosis, and fibrosis by activating the Nrf2 signaling pathway.


Assuntos
Diabetes Mellitus Experimental , Cardiomiopatias Diabéticas , Animais , Apoptose , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Cardiomiopatias Diabéticas/tratamento farmacológico , Edaravone/farmacologia , Edaravone/uso terapêutico , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Ratos , Transdução de Sinais
17.
Int J Gen Med ; 15: 1319-1328, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35173470

RESUMO

BACKGROUND: In recent years, the cure rate of acute pancreatitis (AP) has increased gradually, but the morbidity of recurrent acute pancreatitis (RAP) has not decreased. Patients with RAP have a poor quality of life and are more likely to develop into chronic pancreatitis. To investigate the risk factors of RAP after first pancreatitis attack is very necessary. METHODS: Patients with first episode AP admitted to Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from January 2018 to May 2021 were included in this retrospective study, and follow-up was 3-45 months after discharge. The patients information were collected from medical records including laboratory tests and auxiliary inspection of their hospitalization. Univariate and multivariate Cox regression analysis were used to explore the risk factors of RAP. Cumulative risk of RAP was plotted using Kaplan-Meier curves. RESULTS: A total of 592 patients were enrolled in the study and 81 (13.7%) of the patients developed RAP. Among those RAP patients, the majority (67.9%) were men, with a median age of 43 years. The most common etiology of RAP was hypertriglyceridemia (38.3%). Multivariate Cox analysis showed that smoking history (p < 0.001), infected pancreatic necrosis occurred during first admission (p = 0.005), and high low-density lipoprotein cholesterol (LDLc) level (p < 0.001) were significant independent risk factors for RAP. Patients with the above independent risk factors had increased 3-year cumulative risk of recurrence (32.2%, 45.5%, 28.9%, respectively). CONCLUSION: Smoking history, infected pancreatic necrosis, and high LDLc level were the most decisive risk factors for RAP. Attention should be paid to the patients with the above factors.

18.
Brain Inj ; : 1-10, 2022 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-35133926

RESUMO

BACKGROUND: Untreated concussions are an important health concern. The number of concussions sustained each year is difficult to pinpoint due to diverse reporting routes and many people not reporting. A growing body of literature investigates the motivations for concussion under-reporting, proposing ties with knowledge of concussion outcomes and concussion culture. The present work employs machine learning to identify trends in knowledge and willingness to self-report concussions. METHODS: 2,204 cadets completed a survey addressing athletic and pilot status, concussion symptoms and outcome beliefs, ethical beliefs, demographics, and reporting willingness. RESULTS: Clustering and non-negative matrix analysis identified connections to self-report willingness within: knowledge of symptoms, ethical beliefs, reporting requirements, and belief of long-term concussion outcomes. Support vector machine classification of cadet reporting likelihood reveals symptom and outcome knowledge may be inversely related to reporting among those rating ethics considerations as low, while heightened ethics may predict higher reporting likeliness overall. CONCLUSIONS: Machine-learning analysis bolsters prior theories on the importance of concussion culture in reporting and indicate more symptom knowledge may decrease willingness to report. Uniquely, our analysis indicated importance of ethical behavior may be associated with general concussion reporting willingness, inviting further consideration from healthcare practitioners seeking increased reporting.

19.
Opt Express ; 30(2): 2610-2625, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35209397

RESUMO

Plasmonic nanocavities offer prospects for the amplification of inherently weak nonlinear responses at subwavelength scales. However, constructing these nanocavities with tunable modal volumes and reduced optical losses remains an open challenge in the development of nonlinear nanophotonics. Herein, we design and fabricate three-dimensional (3D) metal-dielectric-metal (MDM) plasmonic nanocavities that are capable of amplifying second-harmonic lights by up to three orders of magnitude with respect to dielectric-metal counterparts. In combination with experimental estimations of quantitative contributions of constituent parts in proposed 3D MDM designs, we further theoretically disclose the mechanism governing this signal amplification. We discover that this phenomenon can be attributed to the plasmon hybridization of both dipolar plasmon resonances and gap cavity resonances, such that an energy exchange channel can be attained and helps expand modal volumes while maintaining strong field localizations. Our results may advance the understanding of efficient nonlinear harmonic generations in 3D plasmonic nanostructures.

20.
Diabetes ; 71(4): 795-811, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35043173

RESUMO

Methazolamide (MTZ), a carbonic anhydrase inhibitor, has been shown to inhibit cardiomyocyte hypertrophy and exert a hypoglycemic effect in patients with type 2 diabetes and diabetic db/db mice. However, whether MTZ has a cardioprotective effect in the setting of diabetic cardiomyopathy is not clear. We investigated the effects of MTZ in a mouse model of streptozotocin-induced type 1 diabetes mellitus (T1DM). Diabetic mice received MTZ by intragastric gavage (10, 25, or 50 mg/kg, daily for 16 weeks). In the diabetic group, MTZ significantly reduced both random and fasting blood glucose levels and improved glucose tolerance in a dose-dependent manner. MTZ ameliorated T1DM-induced changes in cardiac morphology and dysfunction. Mechanistic analysis revealed that MTZ blunted T1DM-induced enhanced expression of ß-catenin. Similar results were observed in neonatal rat cardiomyocytes (NRCMs) and adult mouse cardiomyocytes treated with high glucose or Wnt3a (a ß-catenin activator). There was no significant change in ß-catenin mRNA levels in cardiac tissues or NRCMs. MTZ-mediated ß-catenin downregulation was recovered by MG132, a proteasome inhibitor. Immunoprecipitation and immunofluorescence analyses showed augmentation of AXIN1-ß-catenin interaction by MTZ in T1DM hearts and in NRCMs treated with Wnt3a; thus, MTZ may potentiate AXIN1-ß-catenin linkage to increase ß-catenin degradation. Overall, MTZ may alleviate cardiac hypertrophy by mediating AXIN1-ß-catenin interaction to promote degradation and inhibition of ß-catenin activity. These findings may help inform novel therapeutic strategy to prevent heart failure in patients with diabetes.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Cardiomiopatias Diabéticas , Animais , Proteína Axina/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/prevenção & controle , Glucose/metabolismo , Humanos , Metazolamida/metabolismo , Metazolamida/farmacologia , Metazolamida/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Ratos , beta Catenina/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...