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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 285: 121914, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36183538

RESUMO

Lithium perchlorate (LiClO4), as one of the new high-energy oxidizers, is chosen for high pressure Raman research to gain a better understanding of the structure and stability, which is very important for the performance of an explosive. Raman spectra of LiClO4 crystal have been measured from ambient to 25.07 GPa with diamond anvil cells (DACs) at room temperature to investigate the structural stability of this system. Raman vibrational modes of LiClO4 crystal at ambient pressure were resolved comprehensively on the basis of our experimental and calculated results. Upon increase of pressure on LiClO4 crystal sample to 1.96 GPa, it was found that the LiClO4 crystal exhibited a pressure-induced first-order phase transformation behavior. The occurrence of a second phase transformation of LiClO4 crystal induced by pressure was observed at about 5.09 GPa. Both phase transformations were demonstrated based on the detailed spectroscopic analysis of the variations in the number of lattice modes, splitting of Raman bands and frequency jumps of the Raman vibrational modes of LiClO4 crystal.

2.
Diabetes Metab Syndr Obes ; 15: 3705-3715, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36465992

RESUMO

Purpose: To evaluate the relationships of the triglyceride-glucose (TyG) index with pregnancy-related complications (PRCs) and to clarify the predictability of the TyG index for PRCs. Patients and Methods: Totally of 11,387 women with a singleton pregnancy were prospectively followed until after delivery. Maternal fasting lipids and glucose concentration were measured in the first trimester (11 weeks gestation on average). The TyG index was calculated as ln [triglyceride (mg/dL) × fasting plasma glucose (mg/dL)/2]. We used generalized linear models to calculate the relative risks and 95% confidence intervals. Receiver-operating characteristic curve analysis was employed to assess the ability of the TyG index to predict the risks of PRCs. Results: Smooth spline reveals that the probability of gestational diabetes mellitus (GDM) is intensified with the increasing TyG index. Multivariate logistic regression adjusted for risk factors demonstrates a 1-unit and a 1-SD increment in the TyG index raises the risk of GDM by 3.63 and 1.57 times, respectively. Identically, the risk of GDM maximizes in the TyG quintile 5 (OR: 3.14; 95% CI: 2.55~3.85) relative to the lowest TyG index group. However, no association between TyG index and the risk of other PRCs was observed after full adjustment. The area under receiver operating characteristic curves is 0.647 (95% CI: 0.632-0.66) for GDM, and the optimal predictive cut-off is 8.55, with a specificity of 0.679 and sensitivity of 0.535. Conclusion: The first-trimester TyG index is significantly associated with the risk of incident GDM, while the relationships between the TyG index and other PRCs need further exploration.

3.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 39(12): 1375-1378, 2022 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-36453962

RESUMO

OBJECTIVE: To explore the clinical phenotype and genetic basis for a fetus suspected for Coffin-Siris syndrome. METHODS: Chromosomal microarray analysis (CMA) and whole exome sequencing (WES) were carried out for the fetus. Candidate variant was verified by Sanger sequencing. RESULTS: Prenatal ultrasound at 23rd gestational week has revealed fetal ventriculomegaly. No abnormality was found by CMA, while WES revealed that the fetus has harbored a de novo heterozygous c.2851G>A (p.G951R) variant of the SMARCA4 gene, which was predicted to be pathogenic. CONCLUSION: Genetic testing should be considered for fetuses featuring progressive widening of lateral cerebral ventricles.


Assuntos
Feto , Testes Genéticos , Feminino , Gravidez , Humanos , Sequenciamento Completo do Exoma , Fenótipo , DNA Helicases/genética , Proteínas Nucleares/genética , Fatores de Transcrição/genética
4.
Phys Chem Chem Phys ; 24(44): 27184-27194, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36321469

RESUMO

Pillared MXenes with large interlayer spacing have shown great potential as an anode material for sodium-ion batteries (SIBs). To better understand the underlying mechanism of the pillar effect in enhancing the electrochemical performance, first-principles calculations were used to investigate the adsorption and diffusion of Na in MXenes (Ti2CO2 and Ti3C2O2), as well as the mechanical properties of the system under different MXenes layer spacings. The results showed that when the MXene layer spacing was ∼4 Å, the strongest adsorption of Na on MXenes was achieved due to the interlayer synergy effect. However, when the MXene layer spacing was greater than 5 Å, double Na-atomic layer adsorption would be formed, which increased the Na storage capacity. Interestingly, the diffusion of Na was not only affected by the interlayer spacing of MXenes, but also by the interlayer stacking mode of MXenes. Moreover, it was found that when the MXene layer spacing was more than 8 Å, the sodium storage properties basically did not change significantly. The optimal layer spacing for Ti2CO2 and Ti3C2O2 was predicted to be 7 and 6 Å, respectively. This work provides valuable theoretical guidance for developing high-performance anode materials for SIBs.

5.
BMC Cancer ; 22(1): 1127, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36324111

RESUMO

BACKGROUND: Acute myeloid leukemia (AML) is the main type of adult leukemia, and 60-day mortality is a vital clinical problem that doctors have to face at the begin with treatment. Studies on the association between serum albumin and 60-day mortality from AML (non-APL) are limited. METHODS: In this retrospective cohort study, ALB was measured after admission in all patients diagnosed with primary AML from Affiliated Ganzhou Hospital of Nanchang University between January 2013 and May 2021. The outcome was all-cause, 60-day mortality. Multivariable Cox regression analyses were performed to calculate the adjusted hazard ratio (HR) and its corresponding 95% confidence interval (CI). RESULTS: This study included 394 primary AML patients. The overall 60-day mortality was 28.9% (114/394); it was 43.1% (56/130), 27.5% (36/131), and 16.5% (22/133) for ALB quantile1 (Q, < 34.5 g/L), quantile 2 (Q2, 34.5-38.5 g/L), and quantile 3 (Q3, ≥ 38.6 g/L), respectively (P = 0.001). After adjusting for potential confounders, we found an association between a 6% decrease in 60-day mortality rate and a 1 g/L increase in ALB level (HR = 0.94, 95% CI: 0.89-0.99, P = 0.015), which was associated with 38 and 70% decreases in 60-day mortality rates in Q2 (HR = 0.50, 95% CI: 0.30-0.86, P = 0.012) and Q3 (HR = 0.47, 95% CI: 0.2 5-0.90, P = 0.022), respectively, compared with that in Q1. Similar results were obtained after subgrouping based on an ALB level of 35 g/L (HR = 0.55, 95% CI: 0.34-0.88, P = 0.013). CONCLUSIONS: Serum albumin was significantly associated with 60-day mortality of primary AML, which has important clinical significance. Further investigation is warranted.


Assuntos
Leucemia Mieloide Aguda , Albumina Sérica , Adulto , Humanos , Estudos Retrospectivos , Leucemia Mieloide Aguda/tratamento farmacológico , Modelos de Riscos Proporcionais , China/epidemiologia
6.
J Inflamm Res ; 15: 6021-6030, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36330168

RESUMO

Aim: The development of microsurgery has greatly advanced vascularized composite allotransplantation (VCA). However, like organ transplantation, VCA is also limited by acute rejection, and concerns regarding long-term survival and function of the transplanted graft. Therefore, it is necessary to elucidate the molecular mechanisms underlying acute rejection caused by VCA, in order to improve patient survival. Methods: Firstly, we used Brown Norway rats and Lewis rats to construct animal model of VCA. Regularly record the appearance changes of all subjects. Specimens were collected for histological examination, microRNAs (miRNAs) sequencing and RT-qPCR verification when acute immune rejection occurred. Then, bioinformatics analysis was employed to predict miRNA related molecules and pathway information. Finally, differentially expressed miRNAs were tested and verified. Results: MiRNAs are small non coding RNA transcripts that regulate gene expression at the post-transcriptional level. Studies have shown that miRNAs are involved in immune regulation and several miRNAs have been identified that are potential diagnostic and prognostic biomarkers of acute rejection. In this study, we found that the expression levels of rno-miR-21-5p, rno-miR-340-5p, rno-miR-1-3p and rno-miR-195-5p are significantly associated with acute rejection following VCA. Conclusion: This miRNA signature can potentially an auxiliary diagnostic indicator of rejection, which can help clinicians adjust the immunosuppressive program in time during acute rejection.

7.
Front Biosci (Landmark Ed) ; 27(10): 279, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36336858

RESUMO

BACKGROUND: This study aimed to investigate the mechanisms of acute rejection for vascularized composite allotransplantation (VCA) using microRNAs (miRNAs) differential expression in a VCA animal model. METHODS: Brown Norway rats were used as transplant donors and Lewis rats as VCA receptors. The changes were divided into different stages before and after transplantation in Lewis rats, and all appearance changes were recorded. Also, histological evaluations were performed on all recipients, and the expression of microRNAs was analyzed when acute immune rejection occurred. Then, we used GO and KEGG Pathway enrichment analyses to predict miRNA targets. Finally, differentially expressed miRNAs were detected by RT-qPCR. RESULTS: Compared to pre-operation, 22 miRNAs were differentially expressed after operations. Among them, nine were upregulated, and 13 were downregulated in skin tissues. The RT-qPCR results revealed that rno-miR-340-5p and rno-miR-21-5p were significantly upregulated and enriched in the PI3K-Akt signaling pathway. Moreover, rno-miR-145-5p and rno-miR-195-5p were significantly downregulated, and most of their target genes were enriched in the Hippo signaling pathway. The histological evaluations showed that, after VCA, the skin tissue presented severe acute rejection. CONCLUSIONS: The miRNAs rno-miR-340-5p, rno-miR-21-5p, rno-miR-145-5p, and rno-miR-195-5p were significantly regulated during VCA acute rejection, when the four miRNAs analyses were done on skin biopsies. These miRNAs might be potential biomarkers for objective, early, and minimally invasive rejection diagnosis.


Assuntos
MicroRNAs , Alotransplante de Tecidos Compostos Vascularizados , Animais , Ratos , Fosfatidilinositol 3-Quinases , Ratos Endogâmicos Lew , MicroRNAs/genética , MicroRNAs/metabolismo , Biomarcadores
8.
Biomaterials ; 292: 121907, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36436305

RESUMO

The ongoing SARS-CoV-2 pandemic represents a brutal reminder of the continual threat of mucosal infectious diseases. Mucosal immunity may provide robust protection at the predominant sites of SARS-CoV-2 infection. However, it remains unclear whether respiratory mucosal administration of DNA vaccines could confer protective immune responses against SARS-CoV-2 challenge due to insurmountable barriers posed by the airway. Here, we applied self-assembled peptide-poloxamine nanoparticles with mucus-penetrating properties for pulmonary inoculation of a COVID-19 DNA vaccine (pSpike/PP-sNp). The pSpike/PP-sNp not only displays superior gene transfection and favorable biocompatibility in the mouse airway, but also promotes a tripartite immunity consisting of systemic, cellular, and mucosal immune responses that are characterized by mucosal IgA secretion, high levels of neutralizing antibodies, and resident memory phenotype T-cell responses in the lungs of mice. Most importantly, immunization with pSpike/PP-sNp completely eliminates SARS-CoV-2 infection in both upper and lower respiratory tracts and enables 100% survival rate of mice following lethal SARS-CoV-2 challenge. Our findings indicate PP-sNp is a promising platform in mediating DNA vaccines to elicit all-around mucosal immunity against SARS-CoV-2.

9.
Environ Monit Assess ; 195(1): 151, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36434297

RESUMO

In order to understand the sources of pollutants and the temporal and spatial distribution characteristics of the water quality in Cihu Lake, China, the monitoring data of seven water quality indicators from 12 sampling sites from 2015 to 2019 were selected, and the temporal and spatial variation laws of the water quality and pollution sources were analyzed by the use of the multivariate statistical analysis method. The results show that nitrogen and phosphorus pollution in the lake is dominant. The average concentrations of total nitrogen (TN) and total phosphorus (TP) exceed the surface water quality Class III standards by 1.6 and 2.2 times, respectively. Spatially, the results of the cluster analysis showed that the water quality in Cihu Lake can be categorized into three regions: the northern half of the lake, the southern half of the lake, and the canal entering the lake. Temporally, the water quality in these three regions can be classified into three categories: March to May (the northern half of Cihu Lake), September to November (the southern half of Cihu Lake), and September (the canal entering Cihu Lake). The discriminant analysis results showed that NH3-N, TN, CODCr, and BOD5 are the main factors that affect the uneven spatial distribution of the water quality of Cihu Lake, while TN, DO, and CODMn are the main factors that affect the temporal difference in the northern half of Cihu Lake, and NH3-N, TP, CODCr, DO, CODMn, TN, and TP are the main factors affecting the temporal difference in the southern half of Cihu Lake and the canal entering Cihu Lake. It was found that the water pollution in the study area can be mainly attributed to the incoming water and urban domestic pollution. The main pollution sources for the canal entering Cihu Lake and the southern half of Cihu Lake are the water from the sewage treatment plant and the domestic sewage that has not been intercepted, while the northern half of Cihu Lake is mainly affected by surface runoff, mixed rainwater and sewage, and internal pollution.


Assuntos
Poluentes Químicos da Água , Poluentes da Água , Lagos/análise , Poluentes da Água/análise , Esgotos/análise , Monitoramento Ambiental/métodos , Poluentes Químicos da Água/análise , Qualidade da Água , Fósforo/análise , Nitrogênio/análise
10.
World J Clin Cases ; 10(27): 9743-9749, 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36186195

RESUMO

BACKGROUND: The prognosis of intrahepatic cholangiocarcinoma (ICC) with lymph node metastasis is poor. The feasibility of surgery is not certain, which is a contraindication according to the National Comprehensive Cancer Network guidelines. The role of immunotherapy as a neoadjuvant therapy for ICC is not clear. We herein describe a case of ICC with lymph node metastasis that was successfully treated with neoadjuvant therapy. CASE SUMMARY: A 60-year-old man with a liver tumor was admitted to our hospital. Enhanced computed tomography and magnetic resonance imaging revealed a space-occupying lesion in the right lobe of the liver. Multiple subfoci were found around the tumor, and the right posterior branch of the portal vein was invaded. Liver biopsy indicated poorly differentiated cholangiocytes. According to the American Joint Committee on Cancer disease stage classification, ICC with hilar lymph node metastasis (stage IIIB) and para-aortic lymph node metastasis was suspected. A report showed that two patients with stage IIIB ICC achieved a complete response (CR) 13 mo and 16 mo after chemotherapy with a PD-1 monoclonal antibody. After multidisciplinary consultation, the patient was given neoadjuvant therapy, surgical resection and lymph node dissection, and postoperative adjuvant therapy. After three rounds of PD-1 immunotherapy (camrelizumab) and two rounds of gemcitabine combined with cisplatin regimen chemotherapy, the tumor size was reduced. Therefore, a partial response was achieved. Exploratory laparotomy found that the lymph nodes of Group 16 were negative, and the tumor could be surgically removed. Therefore, the patient underwent right hemihepatectomy plus lymph node dissection. The patient received six rounds of chemotherapy and five rounds of PD-1 treatment postoperatively. After 8 mo of follow-up, no recurrence was found, and a CR was achieved. CONCLUSION: Neoadjuvant therapy combined with surgical resection is useful for advanced-stage ICC. This is the first report of successful treatment of stage IIIB ICC using neoadjuvant therapy with a PD-1 inhibitor.

11.
Dis Markers ; 2022: 3631532, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36193499

RESUMO

The development of low-cost and effective natural products for treating neuron degenerative diseases have proven to be safe and potentially effective. Echium amoenum L. (Boraginaceae) is an annual herb that grows wildly in Europe and western Asia. The aim of this study was to evaluate the neuroprotective properties of an ethanol extract of E. amoenum L. The effects of E. amoenum L. extract on oxidative stress were measured in the rat R28 retinal precursor cell line. Furthermore, the protective role of the extract on the glutamate-induced and optic nerve crush (ONC) injury-induced cell death were evaluated in vitro and in vivo, respectively. Our results showed that the ethanol extract of E. amoenum L. prevented the glutamate-induced decrease in cell viability and increase in cell death in R28 cells and suppressed the overproduction of ROS induced by glutamate. Moreover, the extract significantly inhibited microglial activation and optic nerve damage induced by ONC injury in mice. In addition, the mechanism was attributed to the ability of the extract to decrease NF-κB pathway activation and its downstream inflammatory cytokine production. In conclusion, E. amoenum L. ethanol extract had a potent neuroprotective effect against glutamate-induced and ONC-induced cell death. This is likely due to its antioxidant and anti-inflammatory properties.


Assuntos
Produtos Biológicos , Lesões por Esmagamento , Echium , Fármacos Neuroprotetores , Traumatismos do Nervo Óptico , Animais , Antioxidantes/farmacologia , Produtos Biológicos/metabolismo , Produtos Biológicos/farmacologia , Sobrevivência Celular , Lesões por Esmagamento/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Etanol/farmacologia , Ácido Glutâmico/metabolismo , Camundongos , NF-kappa B/metabolismo , Fármacos Neuroprotetores/farmacologia , Nervo Óptico/metabolismo , Traumatismos do Nervo Óptico/tratamento farmacológico , Traumatismos do Nervo Óptico/metabolismo , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia , Ratos , Espécies Reativas de Oxigênio/metabolismo , Células Ganglionares da Retina/metabolismo
12.
PeerJ Comput Sci ; 8: e1108, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36262153

RESUMO

Short-term power load forecasting is essential in ensuring the safe operation of power systems and a prerequisite in building automated power systems. Short-term power load demonstrates substantial volatility because of the effect of various factors, such as temperature and weather conditions. However, the traditional short-term power load forecasting method ignores the influence of various factors on the load and presents problems of limited nonlinear mapping ability and weak generalization ability to unknown data. Therefore, a short-term power load forecasting method based on GRA and ABC-SVM is proposed in this study. First, the Pearson correlation coefficient method is used to select critical influencing factors. Second, the gray relational analysis (GRA) method is utilized to screen similar days in the history, construct a rough set of similar days, perform K-means clustering on the rough sets of similar days, and further construct the set of similar days. The artificial bee colony (ABC) algorithm is then utilized to optimize penalty coefficient and kernel function parameters of the support vector machine (SVM). Finally, the above method is applied on the basis of actual load data in Nanjing for simulation verification, and the results show the effectiveness of the proposed method.

13.
J Vis Exp ; (187)2022 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-36282688

RESUMO

Epitope peptides have attracted widespread attention in the field of tumor vaccines because of their safety, high specificity, and convenient production; in particular, some MHC I-restricted epitopes can induce effective cytotoxic T lymphocyte activity to clear tumor cells. Additionally, nasal administration is an effective and safe delivery technique for tumor vaccines due to its convenience and improved patient compliance. However, epitope peptides are unsuitable for nasal delivery because of their poor immunogenicity and lack of delivery efficiency. Nanoemulsions (NEs) are thermodynamically stable systems that can be loaded with antigens and delivered directly to the nasal mucosal surface. Ile-Lys-Val-Ala-Val (IKVAV) is the core pentapeptide of laminin, an integrin-binding peptide expressed by human respiratory epithelial cells. In this study, an intranasal self-assembled epitope peptide NE tumor vaccine containing the synthetic peptide IKVAV-OVA257-264 (I-OVA) was prepared by a low-energy emulsification method. The combination of IKVAV and OVA257-264 can enhance antigen uptake by nasal mucosal epithelial cells. Here, we establish a protocol to study the physicochemical characteristics by transmission electron microscopy (TEM), atomic force microscopy (AFM), and dynamic light scattering (DLS); stability in the presence of mucin protein; toxicity by examining the cell viability of BEAS-2B cells and the nasal and lung tissues of C57BL/6 mice; cellular uptake by confocal laser scanning microscopy (CLSM); release profiles by imaging small animals in vivo; and the protective and therapeutic effect of the vaccine by using an E.G7 tumor-bearing model. We anticipate that the protocol will provide technical and theoretical clues for the future development of novel T cell epitope peptide mucosal vaccines.


Assuntos
Vacinas Anticâncer , Camundongos , Animais , Humanos , Epitopos de Linfócito T , Laminina , Camundongos Endogâmicos C57BL , Peptídeos , Mucinas , Integrinas
14.
J Phys Chem Lett ; 13(43): 10222-10229, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36300795

RESUMO

The two-dimensional boron monolayer (borophene) stands out from the two-dimensional atomic layered materials due to its structural flexibility and tunable electronic and mechanical properties from a large number of allotropic materials. The stability of pristine borophene polymorphs could possibly be improved via hydrogenation with atomic hydrogen (referred to as borophane). However, the precise adsorption structures and the underlying mechanism are still elusive. Employing first-principles calculations, we demonstrate the optimal configurations of freestanding borophanes and the ones grown on metallic substrates. For freestanding borophenes, the energetically favored hydrogen adsorption sites are sensitive to the polymorphs and corresponding coordination numbers of boron atoms. With various metal substrates, the hydrogenation configurations of borophenes are modulated significantly, attributed to the overlap between B pz and H s orbitals. These findings provide a deep insight into the hydrogenating borophenes and facilitate the stabilization of two-dimensional boron polymorphs by engineering hydrogen adsorption sites and concentrations.

15.
Front Mol Biosci ; 9: 986556, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36304929

RESUMO

Phenylketonuria (PKU) is a genetic disorder with amino acid metabolic defect, which does great harms to the development of newborns and children. Early diagnosis and treatment can effectively prevent the disease progression. Here we developed a PKU screening model using random forest classifier (RFC) to improve PKU screening performance with excellent sensitivity, false positive rate (FPR) and positive predictive value (PPV) in all the validation dataset and two testing Chinese populations. RFC represented outstanding advantages comparing several different classification models based on machine learning and the traditional logistic regression model. RFC is promising to be applied to neonatal PKU screening.

16.
J Neuroinflammation ; 19(1): 262, 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36289519

RESUMO

BACKGROUND: Glaucoma, the major cause of irreversible blindness worldwide, is characterized by progressive degeneration of retinal ganglion cells (RGCs). Current treatments for glaucoma only slow or partially prevent the disease progression, failing to prevent RGCs death and visual field defects completely. Glutamate excitotoxicity via N-methyl-D-aspartic acid (NMDA) receptors plays a vital role in RGCs death in glaucoma, which is often accompanied by oxidative stress and NLRP3 inflammasome activation. However, the exact mechanisms remain unclear. METHODS: The glutamate-induced R28 cell excitotoxicity model and NMDA-induced mouse glaucoma model were established in this study. Cell counting kit-8, Hoechst 33342/PI dual staining and lactate dehydrogenase release assay were performed to evaluate cell viability. Annexin V-FITC/PI double staining was used to detect apoptosis and necrosis rate. Reactive oxygen species (ROS) and glutathione (GSH) were used to detect oxidative stress in R28 cells. Levels of proinflammatory cytokines were measured by qRT-PCR. Transmission electron microscopy (TEM) was used to detect necroptotic morphological changes in RGCs. Retinal RGCs numbers were detected by immunofluorescence. Hematoxylin and eosin staining was used to detect retinal morphological changes. The expression levels of RIP1, RIP3, MLKL and NLRP3 inflammasome-related proteins were measured by immunofluorescence and western blotting. RESULTS: We found that glutamate excitotoxicity induced necroptosis in RGCs through activation of the RIP1/RIP3/MLKL pathway in vivo and in vitro. Administration of the RIP3 inhibitor GSK872 and RIP1 inhibitor necrostatin-1 (Nec-1) prevented glutamate-induced RGCs loss, retinal damage, neuroinflammation, overproduction of ROS and a decrease in GSH. Furthermore, after suppression of the RIP1/RIP3/MLKL pathway by GSK872 and Nec-1, glutamate-induced upregulation of key proteins involved in NLRP3 inflammasome activation, including NLRP3, pro-caspase-1, cleaved-caspase-1, and interleukin-1ß (IL-1ß), was markedly inhibited. CONCLUSIONS: Our findings suggest that the RIP1/RIP3/MLKL pathway mediates necroptosis of RGCs and regulates NLRP3 inflammasome activation induced by glutamate excitotoxicity. Moreover, GSK872 and Nec-1 can protect RGCs from necroptosis and suppress NLRP3 inflammasome activation through inhibition of RIP1/RIP3/MLKL pathway, conferring a novel neuroprotective treatment for glaucoma.


Assuntos
Glaucoma , Necroptose , Camundongos , Animais , Espécies Reativas de Oxigênio/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-1beta/metabolismo , N-Metilaspartato , Inflamassomos/metabolismo , Caspase 1/metabolismo , Células Ganglionares da Retina/metabolismo , Ácido Glutâmico/toxicidade , Hematoxilina , Amarelo de Eosina-(YS) , Apoptose , Glaucoma/induzido quimicamente , Glaucoma/tratamento farmacológico , Glutationa/metabolismo , Lactato Desidrogenases/metabolismo
17.
Diagnostics (Basel) ; 12(10)2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36292227

RESUMO

OBJECTIVE: Among various assessment paradigms, the cardiopulmonary exercise test (CPET) provides rich evidence as part of the cardiopulmonary endurance (CPE) assessment. However, methods and strategies for interpreting CPET results are not in agreement. The purpose of this study is to validate the possibility of using machine learning to evaluate CPET data for automatically classifying the CPE level of workers in high-latitude areas. METHODS: A total of 120 eligible workers were selected for this cardiopulmonary exercise experiment, and the physiological data and completion of the experiment were recorded in the simulated high-latitude workplace, within which 84 sets of data were used for XGBOOST model training and36 were used for the model validation. The model performance was compared with Support Vector Machine and Random Forest. Furthermore, hyperparameter optimization was applied to the XGBOOST model by using a genetic algorithm. RESULTS: The model was verified by the method of tenfold cross validation; the correct rate was 0.861, with a Micro-F1 Score of 0.864. Compared with RF and SVM, all data achieved a better performance. CONCLUSION: With a relatively small number of training samples, the GA-XGBOOST model fits well with the training set data, which can effectively evaluate the CPE level of subjects, and is expected to provide automatic CPE evaluation for selecting, training, and protecting the working population in plateau areas.

18.
Front Endocrinol (Lausanne) ; 13: 986131, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36313740

RESUMO

Glaucoma is the leading cause of irreversible blindness. The progressive degeneration of retinal ganglion cells (RGCs) is the major characteristic of glaucoma. Even though the control of intraocular pressure could delay the loss of RGCs, current clinical treatments cannot protect them directly. The overactivation of N-methyl-D-aspartic acid (NMDA) receptors by excess glutamate (Glu) is among the important mechanisms of RGC death in glaucoma progression. Melatonin (MT) is an indole neuroendocrine hormone mainly secreted by the pineal gland. This study aimed to investigate the therapeutic effect of MT on glutamate excitotoxicity of mouse RGCs and R28 cells. The Glu-induced R28 cell excitotoxicity model and NMDA-induced retinal injury model were established. MT was applied to R28 cells and the vitreous cavity of mice by intravitreal injection. Cell counting kit-8 assay and propidium iodide/Hoechst were performed to evaluate cell viability. Reactive oxygen species and glutathione synthesis assays were used to detect the oxidative stress state of R28 cells. Retina immunofluorescence and hematoxylin and eosin staining were applied to assess RGC counts and retinal structure. Flash visual-evoked potential was performed to evaluate visual function in mice. RNA sequencing of the retina was performed to explore the underlying mechanisms of MT protection. Our results found that MT treatment could successfully protect R28 cells from Glu excitotoxicity and decrease reactive oxygen species. Also, MT rescued RGCs from NMDA-induced injury and protected visual function in mice. This study enriches the indications of MT in the treatment of glaucoma, providing practical research ideas for its comprehensive prevention and treatment.


Assuntos
Glaucoma , Melatonina , Fármacos Neuroprotetores , Animais , Camundongos , Células Ganglionares da Retina , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , N-Metilaspartato/toxicidade , N-Metilaspartato/uso terapêutico , Ácido Glutâmico/toxicidade , Ácido Glutâmico/uso terapêutico , Melatonina/farmacologia , Melatonina/uso terapêutico , Espécies Reativas de Oxigênio , Glaucoma/tratamento farmacológico , Receptores de N-Metil-D-Aspartato/uso terapêutico
19.
Inorg Chem ; 61(43): 16971-16975, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36265083

RESUMO

A photoluminescent organic-inorganic hybrid coating is synthesized by the incorporation of an emissive Cu4I4 core into a cross-linked coating network through Cu-P coordination bonds. The hybrid coating not only emits strong yellow emission under UV-light irradiation but also exhibits corrosion protection of the metallic surface. Moreover, bactericidal properties are studied that were first reported for Cu4I4-based hybrid light-emitting materials.


Assuntos
Cobre , Iodetos , Corrosão , Cobre/farmacologia , Cobre/química , Luminescência , Antibacterianos/farmacologia , Antibacterianos/química
20.
Exp Eye Res ; 225: 109271, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36195208

RESUMO

There are many theories surrounding the pathogenesis of glaucoma, and glutamate excitatory toxicity has been suggested to play an important role. Some studies have shown that glutamate excitatory toxicity is associated with mitochondrial dynamics; however, the relationship between glutamate excitatory toxicity and mitochondrial dynamics in the pathogenesis of glaucoma remains unclear. In this study, the glutamate transporter inhibitor, threohydroxyaspartate, was used to simulate the glutamate excitatory toxicity cell model of rat retinal neurons in vitro, and the changes in the level of proteins related to mitochondrial dynamics, mitochondrial morphology, and length of neuronal axons were measured. We found that in the glutamate excitotoxicity model, retinal neurons can promote mitochondrial fusion by reducing the phosphorylation of ERK1/2 and its downstream protein DRP1 S585, and enhance its ability to resist the excitotoxicity of glutamate. At the same time, the DRP1-specific inhibitor, Mdivi-1, could promote the mitochondrial fusion of retinal neurons.

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