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1.
Anal Chem ; 94(2): 1178-1186, 2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-34985881

RESUMO

As a class of electrochemiluminescence (ECL) enhancers, silver-based materials have broad application prospects. In this work, a novel silver metal-organic framework (AgMOF) was developed as a self-enhanced ECL emitter by one-step mixing and standing at room temperature. The AgMOF could produce strong and stable ECL emissions based on a double-amplification method, which originated from the aggregation-induced ECL emission of ligands and catalyzing S2O82- to produce more SO4•- by silver. Moreover, an ECL resonance energy transfer (ECL-RET) biosensor with AgMOF as a donor and BHQ2 as an acceptor was fabricated by duplex-specific nuclease (DSN)-assisted target recycling amplification to detect miRNA-107. The biosensor exhibited a strong ECL-RET effect due to the higher ECL emission of the AgMOF and perfect match of spectra between the AgMOF and BHQ2. Upon the introduction of DSN and target miRNAs, the specific DNA-RNA binding and nuclease cleaving could trigger the detachment of BHQ2, resulting in an increased ECL signal of AgMOF. Benefiting from the ECL-RET and DSN-assisted target recycling amplification methods, this biosensor achieved a wide linear relationship range from 20 to 120 fM with a low limit of detection (4.33 fM). This research presents an effective emitter for self-enhanced ECL systems, which broadens the potential ECL applications of silver-based nanomaterials.


Assuntos
Técnicas Biossensoriais , Estruturas Metalorgânicas , MicroRNAs , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Transferência de Energia , Limite de Detecção , Medições Luminescentes/métodos , Prata
2.
Int J Mol Sci ; 23(16)2022 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-36012548

RESUMO

Chitosan-based composite films with good biodegradability, biocompatibility, and sustainability are extensively employed in the field of food packaging. In this study, novel chitosan/tannic acid (CTA) and chitosan/oxidized tannic acid (COTA) composite films with excellent mechanical and antibacterial properties were prepared using a tape casting method. The results showed that, when 20% tannic acid (TA) was added, the tensile strength of the CTA composite film was 80.7 MPa, which was 89.4% higher than that of the pure chitosan (CS) film. TA was oxidized to oxidized tannic acid (OTA) with laccase, and the phenolic hydroxyl groups were oxidized to an o-quinone structure. With the addition of OTA, a Schiff base reaction between the OTA and CS occurred, and a dual network structure consisting of a chemical bond and hydrogen bond was constructed, which further improved the mechanical properties. The tensile strength of 3% COTA composite film was increased by 97.2% compared to that of pure CS film. Furthermore, these CTA films with significant antibacterial effects against Escherichia coli (E. coli) are likely to find uses in food packaging applications.


Assuntos
Quitosana , Antibacterianos/química , Antibacterianos/farmacologia , Quitosana/química , Escherichia coli , Embalagem de Alimentos/métodos , Ligação de Hidrogênio , Bases de Schiff/farmacologia , Taninos/química , Resistência à Tração
3.
Anal Chem ; 93(42): 14178-14186, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34637279

RESUMO

Developing a coreactant-free ratiometric electrochemiluminescence (ECL) strategy based on a single luminophore to achieve more accurate and sensitive microRNA (miRNA) detection is highly desired. Herein, utilizing zinc-metal organic frameworks (Zn-MOFs) as the single luminophore, a novel dual-potential ratiometric ECL biosensor was constructed for ultrasensitive detection of miRNA-133a. The as-prepared Zn-MOFs exhibited simultaneous cathode and anode ECL emission. Furthermore, the Zn-MOFs were confirmed to be a multichannel ECL sensing platform with excellent annihilation and coreactant ECL emission. The corresponding ECL behaviors were investigated in detail. Benefiting from the hybridization chain reaction (HCR) amplification technology, N,N-diethylethylenediamine (DEAEA) was modified on hairpin DNA, and the gained products loaded with quantities of DEAEA enhanced the anodic ECL intensity of Zn-MOFs. In the presence of miRNA-133a, the ECL intensity ratio of anode to cathode (Ia/Ic) was significantly increased, which realized the ultrasensitive ratiometric detection of miRNA-133a. In addition, without an exogenous coreactant, the biosensor revealed superb accuracy and stability. Under optimal conditions, the detection linearity of miRNA-133a was from 50 aM to 50 fM with a low detection limit of 35.8 aM (S/N = 3). This is the first work to use Zn-MOFs as a single emitter for reliable ratiometric ECL bioanalysis, which provides a new perspective for fabricating a ratiometric ECL biosensor platform.


Assuntos
Técnicas Biossensoriais , Estruturas Metalorgânicas , MicroRNAs , Técnicas Eletroquímicas , Limite de Detecção , Medições Luminescentes , Zinco
4.
Proc Natl Acad Sci U S A ; 114(4): 687-692, 2017 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-28069943

RESUMO

Tyrosyl-tRNA synthetase (TyrRS) is well known for its essential aminoacylation function in protein synthesis. Recently, TyrRS has been shown to translocate to the nucleus and protect against DNA damage due to oxidative stress. However, the mechanism of TyrRS nuclear localization has not yet been determined. Herein, we report that TyrRS becomes highly acetylated in response to oxidative stress, which promotes nuclear translocation. Moreover, p300/CBP-associated factor (PCAF), an acetyltransferase, and sirtuin 1 (SIRT1), a NAD+-dependent deacetylase, regulate the nuclear localization of TyrRS in an acetylation-dependent manner. Oxidative stress increases the level of PCAF and decreases the level of SIRT1 and deacetylase activity, all of which promote the nuclear translocation of hyperacetylated TyrRS. Furthermore, TyrRS is primarily acetylated on the K244 residue near the nuclear localization signal (NLS), and acetylation inhibits the aminoacylation activity of TyrRS. Molecular dynamics simulations have shown that the in silico acetylation of K244 induces conformational changes in TyrRS near the NLS, which may promote the nuclear translocation of acetylated TyrRS. Herein, we show that the acetylated K244 residue of TyrRS protects against DNA damage in mammalian cells and zebrafish by activating DNA repair genes downstream of transcription factor E2F1. Our study reveals a previously unknown mechanism by which acetylation regulates an aminoacyl-tRNA synthetase, thus affecting the repair pathways for damaged DNA.


Assuntos
Núcleo Celular/metabolismo , Dano ao DNA/fisiologia , Estresse Oxidativo/fisiologia , Tirosina-tRNA Ligase/metabolismo , Acetilação , Animais , Linhagem Celular , Linhagem Celular Tumoral , Fator de Transcrição E2F1/metabolismo , Células HEK293 , Células HeLa , Humanos , Transporte Proteico/fisiologia , Transdução de Sinais/fisiologia , Sirtuína 1/metabolismo , Peixe-Zebra , Fatores de Transcrição de p300-CBP/metabolismo
5.
J Neuroinflammation ; 16(1): 101, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31092253

RESUMO

BACKGROUND: Blood-brain barrier (BBB) disruption and neuroinflammation are considered key mechanisms of pathogenic Escherichia coli invasion of the brain. However, the specific molecules involved in meningitic E. coli-induced BBB breakdown and neuroinflammatory response remain unclear. Our previous RNA-sequencing data from human brain microvascular endothelial cells (hBMECs) revealed two important host factors: platelet-derived growth factor-B (PDGF-B) and intercellular adhesion molecule-1 (ICAM-1), which were significantly upregulated in hBMECs after meningitic E. coli infection. Whether and how PDGF-B and ICAM-1 contribute to the development of E. coli meningitis are still unclear. METHODS: The western blot, real-time PCR, enzyme-linked immunosorbent assay, immunohistochemistry, and immunofluorescence were applied to verify the significant induction of PDGF-B and ICAM-1 by meningitic E. coli in vivo and in vitro. Evan's blue assay and electric cell-substrate impedance sensing assay were combined to identify the effects of PDGF-B on BBB permeability. The CRISPR/Cas9 technology, cell-cell adhesion assay, and electrochemiluminescence assay were used to investigate the role of ICAM-1 in neuroinflammation subversion. RESULTS: We verified the significant induction of PDGF-B and ICAM-1 by meningitic E. coli in mouse as well as monolayer hBMECs models. Functionally, we showed that the increase of PDGF-B may directly enhance the BBB permeability by decreasing the expression of tight junction proteins, and the upregulation of ICAM-1 contributed to neutrophils or monocytes recruitment as well as neuroinflammation subversion in response to meningitic E. coli infection. CONCLUSIONS: Our findings demonstrated the roles of PDGF-B and ICAM-1 in mediating bacterial-induced BBB damage as well as neuroinflammation, providing new concepts and potential targets for future prevention and treatment of bacterial meningitis.


Assuntos
Barreira Hematoencefálica/metabolismo , Infecções por Escherichia coli/metabolismo , Mediadores da Inflamação/metabolismo , Molécula 1 de Adesão Intercelular/biossíntese , Linfocinas/biossíntese , Meningites Bacterianas/metabolismo , Fator de Crescimento Derivado de Plaquetas/biossíntese , Animais , Barreira Hematoencefálica/microbiologia , Barreira Hematoencefálica/patologia , Células Cultivadas , Escherichia coli , Infecções por Escherichia coli/patologia , Feminino , Meningites Bacterianas/patologia , Camundongos , Junções Íntimas/metabolismo , Junções Íntimas/microbiologia , Regulação para Cima/fisiologia
6.
Parasitol Res ; 115(2): 663-72, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26486943

RESUMO

Malaria has been one of the most devastating tropical parasite infectious diseases popular around the world. Severe malaria is characterized by multiple organ dysfunctions, especially liver damage. However, the mechanisms of malarial liver injury remain to be better clarified. In this study, Kunming mice inoculated intraperitoneally (i.p.) with 10(6) Plasmodium berghei ANKA (PbANKA)-infected red blood cells (iRBCs) were investigated at days 5, 10, 15, and 20 post-infection (p.i.) to elucidate the profiles of T-cell immunoglobulin and mucin domain-3 (Tim-3) and its ligand galecin-9 (Gal-9) in the development of liver injury. The histopathology of livers and spleens from PbANKA-infected mice were observed, the parasite burdens of the livers and spleens using quantitative real-time PCR (qRT-PCR), Tim-3- and Gal-9-positive cells in the livers and spleens using immunohistochemical staining, and the mRNA levels of Tim-3, Gal-9, and cytokines in both the livers and spleens using qRT-PCR were examined. Our results showed that parasite burdens in the livers and spleens were significantly increased with time after PbANKA infection. Histological scores of both the liver and spleen tissues were significantly increased with time; the numbers of Tim-3- and Gal-9-positive cells were significantly increased in both the livers and spleens using immunohistochemical staining, and the mRNA levels of Tim-3 and Gal-9 in the livers and spleens were also significantly increased after infection. Our data suggests that the increase of Tim-3/Gal-9 expressions may play an important role in the liver damage during P. berghei infection.


Assuntos
Galectinas/metabolismo , Hepatopatias Parasitárias/patologia , Fígado/patologia , Malária/patologia , Plasmodium berghei/fisiologia , Receptores Virais/metabolismo , Animais , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Galectinas/genética , Regulação da Expressão Gênica , Receptor Celular 2 do Vírus da Hepatite A , Imuno-Histoquímica , Fígado/metabolismo , Hepatopatias Parasitárias/parasitologia , Malária/imunologia , Malária/parasitologia , Camundongos , Parasitemia , Plasmodium berghei/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Receptores Virais/genética , Transdução de Sinais , Baço/metabolismo , Baço/patologia , Regulação para Cima
7.
Parasitol Res ; 115(2): 587-95, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26494364

RESUMO

Malaria is the most relevant parasitic disease worldwide, and severe malaria is characterized by cerebral edema, acute lung injury (ALI), and multiple organ dysfunctions; however, the mechanisms of lung damage need to be better clarified. In this study, we used Kunming outbred mice infected with Plasmodium berghei ANKA (PbANKA) to elucidate the profiles of T cell immunoglobulin and mucin domain-3 (Tim-3) and its ligand galecin-9 (Gal-9) in the development of ALI. Mice were injected intraperitoneally with 10(6) PbANKA-infected red blood cells. The lungs and mediastinal lymph nodes (MLNs) were harvested at days 5, 10, 15, and 20 post infections (p.i.). The grade of lung injury was histopathologically evaluated. Tim-3- and Gal-9-positive cells in the lungs and MLNs were stained by immunohistochemistry, and the messenger RNA (mRNA) expressions of Tim-3, Gal-9, and related cytokines were assessed using quantitative real-time polymerase chain reaction (qRT-PCR). Bronchoalveolar lavage fluid (BALF) analyses were performed from days 18 to 20 p.i. The results showed that the pathological severities in the lungs were increased with times and the total protein level in the BALFs was significantly elevated in PbANKA-infected mice. The numbers of Gal-9(+) and Tim-3(+) cells in the lungs were significantly increased, and the mRNA levels of both Gal-9 and Tim-3 in the lungs and MLNs were over-expressed in PbANKA-infected mice. In conclusion, our data suggested that Tim-3/Gal-9 may play a role in PbANKA-induced ALI.


Assuntos
Lesão Pulmonar Aguda/patologia , Galectinas/metabolismo , Pulmão/patologia , Linfonodos/patologia , Malária/patologia , Receptores Virais/metabolismo , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/parasitologia , Animais , Líquido da Lavagem Broncoalveolar/química , Citocinas/genética , Citocinas/metabolismo , Feminino , Galectinas/genética , Regulação da Expressão Gênica , Receptor Celular 2 do Vírus da Hepatite A , Imuno-Histoquímica , Ligantes , Pulmão/metabolismo , Linfonodos/metabolismo , Malária/complicações , Malária/metabolismo , Mediastino , Camundongos , Parasitemia , Plasmodium berghei/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Receptores Virais/genética , Organismos Livres de Patógenos Específicos , Regulação para Cima
8.
Chem Pharm Bull (Tokyo) ; 62(9): 915-20, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25007750

RESUMO

A series of novel potentially platelet aggregation-inhibiting 1,4-benzoxazine-3(4H)-one derivatives was designed and synthesized through Smiles rearrangement, reduction and acetylation reactions. The antiaggregatory activities of the target molecules on arterial blood samples from rabbits, expressed by IC50 values (µM), were then evaluated in vitro against ADP induced platelet aggregation. The favorable IC50 values of compound 8c (IC50=8.99 µM) and 8d (IC50=8.94 µM) indicated that these two compounds were the most potent molecules among all the synthesized compounds. A detailed molecular docking study to explore the interaction of compounds 8c and 8d with GP IIb/IIIa receptor showed that they these two compounds were docked into the active site of GPIIb/IIIa receptor. These results suggest that the 1,4-benzoxazine-3(4H)-one derivatives are promising lead compounds to develop new platelet aggregation inhibitors.


Assuntos
Benzoxazinas/química , Benzoxazinas/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Animais , Benzoxazinas/síntese química , Estrutura Molecular , Espectroscopia de Prótons por Ressonância Magnética , Coelhos , Espectrometria de Massas por Ionização por Electrospray , Relação Estrutura-Atividade
9.
Jpn J Radiol ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38664363

RESUMO

OBJECTIVE: To identify important MRI features to differentiate hepatic mucinous cystic neoplasms (MCN) from septated hepatic cysts (HC) using random forest and compared with logistic regression algorithm. METHODS: Pathologically diagnosed hepatic cysts and hepatic MCNs with pre-operative contrast-enhanced MRI in our hospital from 2010 to 2023 were collected and only septated lesions on enhanced MRI were enrolled. A total of 21 septated HC and 18 MCNs were included in this study. Eighteen MRI features were analyzed and top important features were identified based on random forest (RF) algorithm. The results were evaluated by the prediction performance of a RF model combining the important features and compared with the performance of the logistic regression (LR) algorithm. Finally, for each identified feature, diagnostic probability, sensitivity, and specificity were calculated and compared. RESULTS: Four variables, i.e., the septation arising from wall without indentation, multiseptate, intracapsular cyst sign, and solitary lesion were extracted as top important features with significance for MCNs by the random forest algorithm. The RF model using these variables had an AUC of 0.982 (0.95CI, 0.950-1.000), compared with the LR model based on two identified features with AUC of 0.931 (0.95CI, 0.846-1.000), p = 0.202. Among the four important features, multiseptate had the highest specificity (95.2%) and good sensitivity (72.2%, lower than the septation from wall without indentation, 94.4%) to diagnose MCNs. CONCLUSION: Four out of 18 MRI features were extracted as reliably important factors to differ hepatic MCNs from septated HC. The combination of these four features in a RF model could achieve satisfactory diagnostic efficacy.

10.
Microbiol Spectr ; : e0421423, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38912810

RESUMO

Previous work identified a pair of specific effectors AsCEP19 and AsCEP20 in Alternaria solani as contributors to the virulence of A. solani. Here, we constructed AsCEP19 and AsCEP20 deletion mutants in A. solani strain HWC168 to further reveal the effects of these genes on the biology and pathogenicity of A. solani. Deletion of AsCEP19 and AsCEP20 did not affect vegetative growth but did affect conidial maturation, with an increase in the percentage of abnormal conidia produced. Furthermore, we determined the expression patterns of genes involved in the conidiogenesis pathway and found that the regulatory gene abaA was significantly upregulated and chsA, a positive regulator for conidiation, was significantly downregulated in the mutant strains compared to the wild-type strain. These results suggest that AsCEP19 and AsCEP20 indirectly affect the conidial development and maturation of A. solani. Pathogenicity assays revealed significantly impaired virulence of ΔAsCEP19, ΔAsCEP20, and ΔAsCEP19 + AsCEP20 mutants on potato and tomato plants. Moreover, we performed localization assays with green fluorescent protein-tagged proteins in chili pepper leaves. We found that AsCEP19 can specifically localize to the chloroplasts of chili pepper epidermal cells, while AsCEP20 can localize to both chloroplasts and the plasma membrane. Weighted gene co-expression network analysis revealed enrichment of genes of this module in the photosynthesis pathway, with many hub genes associated with chloroplast structure and photosynthesis. These results suggest that chloroplasts are the targets for AsCEP19 and AsCEP20. IMPORTANCE: Alternaria solani is an important necrotrophic pathogen causing potato early blight. Previous studies have provide preliminary evidence that specific effectors AsCEP19 and AsCEP20 contribute to virulence, but their respective functions, localization, and pathogenic mechanisms during the infection process of A. solani remain unclear. Here, we have systematically studied the specific effectors AsCEP19 and AsCEP20 for the first time, which are essential for conidial maturation. The deletion of AsCEP19 and AsCEP20 can significantly impair fungal pathogenicity. Additionally, we preliminarily revealed that AsCEP19 and AsCEP20 target the chloroplasts of host cells. Our findings further enhance our understanding of the molecular mechanisms underlying the virulence of necrotrophic pathogens.

11.
Comput Biol Med ; 174: 108457, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38599071

RESUMO

Glioma is a common malignant brain tumor with great heterogeneity and huge difference in clinical outcomes. Although lymphotoxin (LT) beta receptor (LTBR) has been linked to immune system and response development for decades, the expression and function in glioma have not been investigated. To confirm the expression profile of LTBR, integrated RNA-seq data from glioma and normal brain tissues were analyzed. Functional enrichment analysis, TMEscore analysis, immune infiltration, the correlation of LTBR with immune checkpoints and ferroptosis, and scRNAseq data analysis in gliomas were in turn performed, which pointed out that LTBR was pertinent to immune functions of macrophages in gliomas. In addition, after being trained and validated in the tissue samples of the integrated dataset, an LTBR DNA methylation-based prediction model succeeded to distinguish gliomas from non-gliomas, as well as the grades of glioma. Moreover, by virtue of the candidate LTBR CpG sites, a prognostic risk-score model was finally constructed to guide the chemotherapy, radiotherapy, and immunotherapy for glioma patients. Taken together, LTBR is closely correlated with immune functions in gliomas, and LTBR DNA methylation could serve as a biomarker for diagnosis and prognosis of gliomas.


Assuntos
Biomarcadores Tumorais , Neoplasias Encefálicas , Glioma , Humanos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Metilação de DNA/genética , Glioma/imunologia , Glioma/genética , Glioma/metabolismo
12.
Bioresour Technol ; 370: 128576, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36603751

RESUMO

Rational design of adsorbed materials with three-dimensional (3D) hierarchical porous structure, sustainable, high adsorption capacity, and excellent selective is of great significance in practical applications. Herein, a novel aerogel adsorbed material with 3D hierarchical porous architecture was fabricated by employing naturally abundant sodium alginate (SA)/gellan gum (GG) as basic construction blocks to achieve sustainability as well as applying polyethyleneimine (PEI) as functional material for highly efficient and selective capture of Congo red (CR). The aerogel sorbent exhibited strong microstructure, numerous active adsorption sites and being ultralight. The resulting aerogel adsorbent showed high adsorption capacity (3017.23 mg/g) toward CR, exceedingly most previously reported sorbents. Furthermore, the aerogel adsorbent was accompanied by outstanding selectivity for CR in four binary dye systems. Meanwhile, after 3 cycles, the adsorption capacity decreased by 14.8 %, but still maintained the adsorption capacity of 559.79 mg/g. Therefore, excellent adsorption performance, and superb selectivity prefigures its great prospects for wastewater purification.


Assuntos
Vermelho Congo , Poluentes Químicos da Água , Vermelho Congo/química , Água , Porosidade , Alginatos/química , Poluentes Químicos da Água/química , Adsorção
13.
Front Oncol ; 13: 1166796, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37621691

RESUMO

Objective: To explore the value of testing methylated SDC2 (SDC2) in stool DNA combined with fecal immunochemical test (FIT) and serum tumor markers (TM) for the early detection of colorectal neoplasms. Methods: A total of 533 patients, including 150 with CRC (67 with early-stage CRC), 23 with APL, 85 with non-advanced adenomas and general polyps, and 275 with benign lesions and healthy controls. SDC2 was detected by methylation-specific PCR, FIT (hemoglobin, Hb and transferrin, TF) was detected by immunoassay, and the relationships between SDC2, FIT, and clinicopathological features were analyzed. Pathological biopsy or colonoscopy were used as gold standards for diagnosis, and the diagnostic efficacy of SDC2 combined with FIT and TM in CRC and APL evaluated using receiver operating characteristic (ROC) curves. Results: SDC2 positive rates in early-stage CRC and APL were 77.6% (38/49) and 41.2% (7/17), respectively, and combination of SDC2 with FIT increased the positive rates to 98.0% (48/49) and 82.4% (14/17). The positive rates of SDC2 combined with FIT assay in the APL and CRC groups at stages 0-IV were 82.4% (14/17), 85.7% (6/7), 100% (16/16), 100% (26/26), 97.4% (38/39), and 100% (22/22), respectively. Compared to the controls, both the CRC and APL groups showed significantly higher positive detection rates of fecal SDC2 and FIT (χ2 = 114.116, P < 0.0001 and χ2 = 85.409, P < 0.0001, respectively). Our results demonstrate a significant difference in the qualitative methods of SDC2 and FIT for the detection of colorectal neoplasms (McNemar test, P < 0.0001). ROC curve analysis revealed that the sensitivities of SDC2 and FIT, alone or in combination, for the detection of early CRC and APL were 69.9%, 86.3%, and 93.9%, respectively (all P<0.0001). When combined with CEA, the sensitivity increased to 97.3% (P<0.0001). Conclusions: SDC2 facilitates colorectal neoplasms screening, and when combined with FIT, it enhances detection. Furthermore, the combination of SDC2 with FIT and CEA maximizes overall colorectal neoplasm detection.

14.
Spectrochim Acta A Mol Biomol Spectrosc ; 300: 122906, 2023 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-37257321

RESUMO

A novel silver(I)-based metal-organic gel (AgMOG) consisting of luminol as the ligand was synthesized by a facile strategy, which was found to exhibit self-enhancing chemiluminescence (CL) property. Based on this, a new AgMOG-K2S2O8 CL system without additional catalyst was established. According to the results of CL spectra, electron spin resonance (ESR) spectra as well as the influence of radical scavengers to AgMOG-K2S2O8 system, the possible CL mechanism of this system was discussed. In this CL system, AgMOG exhibited the dual properties of catalysis and luminescence. On the one hand, AgMOG can catalyze K2S2O8 to produce SO4•-. The generated SO4•- can be converted to hydroxyl radical (OH•) under alkaline condition, and further converted to other radical oxygen species (ROS, such as 1O2 and O2•-). Furthermore, the reaction between the K2S2O8 and H2O can form H2O2, which also can be catalyzed by AgMOG to produce ROS. On the other hand, the AgMOG can be oxidized by ROS to emit strong CL signal. Then, based on the quenching effect of uric acid (UA) to this CL system, a method for UA detection was established with a good linearity over the range from 0.08 to 10 µmol·L-1. In this work, a new CL luminant with catalytic property was synthesized by a simple method, and a self-enhancing AgMOG-K2S2O8 CL system was developed for the first time, providing a novel direction for the application of MOG in the CL field.


Assuntos
Luminescência , Luminol , Prata , Ácido Úrico , Espécies Reativas de Oxigênio , Peróxido de Hidrogênio , Medições Luminescentes/métodos
15.
J Biomater Appl ; 37(9): 1529-1541, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36693765

RESUMO

Glaucoma is the leading cause of irreversible blindness, and its treatment is attracting widespread attention. Drug-loaded lacrimal suppositories can effectively treat xerophthalmia, but there is little research on the treatment of glaucoma with drug-loaded lacrimal suppositories. This article explored and expanded the non-pharmacological model of lacrimal suppository therapy for glaucoma by using a combination of lacrimal suppository and medication. The drug-loaded lacrimal suppository was rationally designed through the conjugation of gelatin with polyamide (PAM) via the formation of amide linkages, followed by Schiff base reaction grafting with latanoprost. In vitro drug release studies showed that latanoprost released from drug-loaded lacrimal embolus had sustained-release properties with a release time of 33 days and a drug release volume of 82.6%. The biological evaluation of drug-loaded lacrimal thrombus was carried out by IOP test, retinal potential test, and retinal H&E staining. The results showed that the IOP decreased to 27.125 ± 1.1254 mmHg, and the a and b waves of retinal potential increased to 4.39 ± 0.16 µV and 67.9 ± 2.17 µV, respectively. It indicated that latanoprost lacrimal suppository has a good therapeutic effect on glaucoma.


Assuntos
Glaucoma , Prostaglandinas F Sintéticas , Humanos , Latanoprosta/uso terapêutico , Supositórios , Prostaglandinas F Sintéticas/farmacologia , Prostaglandinas F Sintéticas/uso terapêutico , Hidrogéis/uso terapêutico , Glaucoma/tratamento farmacológico
16.
Cancer Med ; 12(24): 22170-22184, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38093622

RESUMO

OBJECTIVE: As a single-transmembrane protein of the FXYD family, FXYD6 plays different roles under physiological and pathological status, especially in the nervous system. This study aims to identify FXYD6 as a biomarker for glioma, by analyzing its expression and methylation patterns. METHODS: Using TCGA and GTEx datasets, we analyzed FXYD6 expression in various tissues, confirming its levels in normal brain and different glioma grades via immunoblotting and immunostaining. FXYD6 biological functions were explored through enrichment analysis, and tumor immune infiltration was assessed using ESTIMATE and TIMER algorithms. Pearson correlation analysis probed FXYD6 associations with biological function-related genes. A glioma detection model was developed using FXYD6 methylation data from TCGA and GEO. Consistently, a FXYD6 methylation-based prognostic model was constructed for glioma via LASSO Cox regression. RESULTS: FXYD6 was observed to be downregulated in GBM and implicated in a range of cellular functions, including synapse formation, cell junctions, immune checkpoint, ferroptosis, EMT, and pyroptosis. Hypermethylation of specific FXYD6 CpG sites in gliomas was identified, which could be used to build a diagnostic model. Additionally, FXYD6 methylation-based prognostic model could serve as an independent factor as well. CONCLUSIONS: FXYD6 is a promising biomarker for the diagnosis and prognosis of glioma, with its methylation-based prognostic model serving as an independent factor. This highlights its potential in clinical application for glioma management.


Assuntos
Metilação de DNA , Glioma , Humanos , Biomarcadores , Glioma/diagnóstico , Glioma/genética , Algoritmos , Encéfalo , Prognóstico , Canais Iônicos
17.
Int J Biol Macromol ; 211: 1-14, 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35551949

RESUMO

Herein, functionalization cellulose-based composite aerogels with the addition of carboxyl cellulose nanofibers (CNF), montmorillonite (MMT) and polyethyleneimine (PEI) were fabricated by solution blending and freeze-drying technology. MMT was blended into the cellulose framework as a reinforcing agent. PEI combined with cellulose through amidation reaction, and the synergism of hydrogen bond and chemical bond helped the CNF/MMT/PEI composite aerogels (CMP) with good mechanical properties. The morphology, chemical structure and thermal stability of the CMP were characterized. The adsorption properties and mechanism of the CMP were discussed, using Congo red (CR) dye as an adsorbate. The results showed that the CMP formed a three-dimensional network structure with abundant pores. The addition of PEI regulated the surface charge distribution of cellulose and improved the adsorption performance of CMP for CR with the adsorption capacity of 3114 mg/g calculated by the Langmuir model. The adsorption process of CMP-30 for CR was more in line with the pseudo-second-order kinetic model and Langmuir isotherm model, indicating chemical adsorption of a single molecular layer. After functionalized by octadecyl trichlorosilane (OTS), the contact angle of the aerogel surface was 151.80°. Meanwhile, the CMP-30 was transformed from hydrophilic and lipophilic properties to hydrophobic and lipophilic properties.


Assuntos
Celulose , Nanofibras , Adsorção , Celulose/química , Vermelho Congo/química , Nanofibras/química , Polietilenoimina
18.
J Cardiovasc Aging ; 2(3)2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35891703

RESUMO

Introduction: The adult heart lacks the regenerative capacity to self-repair. Serum response factor (SRF) is essential for heart organogenesis, sarcomerogenesis, and contractility. SRF interacts with co-factors, such as NKX2.5 and GATA4, required for cardiac specified gene activity. ETS factors such as ELK1 interact with SRF and drive cell replication. To weaken SRF interactions with NKX2.5 and GATA4, one mutant, SRF153(A3) named STEMIN, did not bind CArG boxes, yet induced stem cell factors such as NANOG and OCT4, cardiomyocyte dedifferentiation, and cell cycle reentry. The mutant YAP5SA of the Hippo pathway also promotes cardiomyocyte proliferation and growth. Aim: Infarcted adult mouse hearts were injected with translatable STEMIN and YAP5SA mmRNA to evaluate their clinical potential. Methods and Results: Mice were pulsed one day later with alpha-EDU and then heart sections were DAPI stained. Replicating cells were identified by immuno-staining against members of the DNA replisome pathway that mark entry to S phase of the cell cycle. Echocardiography was used to determine cardiac function following infarcts and mRNA treatment. To monitor cardiac wall repair, microscopic analysis was performed, and the extent of myocardial fibrosis was analyzed for immune cell infiltration. Injections of STEMIN and YAP5SA mmRNA into the left ventricles of infarcted adult mice promoted a greater than 17-fold increase in the DAPI stained and alpha-EDU marked cardiomyocyte nuclei, within a day. We observed de novo expression of phospho-histone H3, ORC2, MCM2, and CLASPIN. Cardiac function was significantly improved by four weeks post-infarct, and fibrosis and immune cell infiltration were diminished in hearts treated with STEMIN and YAP5SA mmRNA than each alone. Conclusion: STEMIN and YAP5SA mmRNA improved cardiac function and myocardial fibrosis in left ventricles of infarcted adult mice. The combinatorial use of mmRNA encoding STEMIN and YAP5SA has the potential to become a powerful clinical strategy to treat human heart disease.

19.
Patient Educ Couns ; 105(6): 1532-1538, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34657779

RESUMO

OBJECTIVE: To investigate if a Family-Clinician Shared Decision-Making (FCSDM) intervention benefits patients, families and intensive care units (ICUs) clinicians. METHODS: Six ICUs in China were allocated to intervention or usual care. 548 patients with critical illness, 548 family members and 387 ICU clinicians were included into the study. Structured FCSDM family meetings were held in the intervention group. Scales of SSDM, HADS, QoL2 and CSACD were used to assess families' satisfaction and distress, patients' quality of life, and clinicians' collaboration respectively. RESULTS: Comparing the intervention group with the control group at post-intervention, there were significant differences in the families' satisfaction (P = 0.0001), depression level (P = 0.005), and patients' quality of life (P = 0.0007). The clinicians' mean CSCAD score was more positive in the intervention group than controls (P < 0.05). There was no significant between-group differences on ICU daily medical cost, but the intervention group demonstrated shorter number of days' stay in ICU (P = 0.0004). CONCLUSION: The FCSDM intervention improved families' satisfaction and depression, shortened patients' duration of ICU stay, and enhanced ICU clinicians' collaboration. PRACTICE IMPLICATIONS: Further improvement and promotion of the FCSDM model are needed to provide more evidence to this field in China.


Assuntos
Tomada de Decisão Compartilhada , Qualidade de Vida , Estado Terminal/terapia , Tomada de Decisões , Família , Humanos , Unidades de Terapia Intensiva , Relações Profissional-Família
20.
Neoplasia ; 33: 100835, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36113195

RESUMO

Peptidylarginine deiminase 4 (PAD4), a Ca2+-dependent enzyme, catalyzes the conversion of arginine to citrulline and has been strongly associated with many malignant tumors. However, the molecular mechanisms of PAD4 in the development and progression of colorectal cancer (CRC) remain unclearly defined. In our study, PAD4 expression was increased in CRC tissues and cells, and was closely related to tumor size, lymph node metastasis. Moreover, the transcription factor KLF9 directly bound to PADI4 gene promoter, leading to overexpression of PAD4 in CRC cells, which augmented cell growth and migration. We revealed that PAD4 interacted with and citrullinated glycogen synthase kinase-3ß (GSK3ß) in CRC cells, and GSK3ß Arg-344 was the dominating PAD4-citrullination site. Furthermore, IgL2 and catalytic domains of PAD4 directly bound to the kinase domain of GSK3ß in CRC cells. Mechanistically, PAD4 promoted the transport of GSK3ß from the cytoplasm to the nucleus, thereby increasing the ubiquitin-dependent proteasome degradation of nuclear cyclin-dependent kinase inhibitor 1 (CDKN1A). Our study is the first to reveal the details of a critical PAD4/GSK3ß/CDKN1A signaling axis for CRC progression, and provides evidence that PAD4 is a potential diagnosis biomarker and therapeutic target in CRC.


Assuntos
Citrulinação , Neoplasias Colorretais , Arginina/genética , Biomarcadores/metabolismo , Citrulina/genética , Citrulina/metabolismo , Neoplasias Colorretais/genética , Inibidor de Quinase Dependente de Ciclina p21 , Quinases Ciclina-Dependentes/genética , Quinases Ciclina-Dependentes/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Hidrolases/genética , Hidrolases/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteína-Arginina Desiminase do Tipo 4 , Desiminases de Arginina em Proteínas/genética , Desiminases de Arginina em Proteínas/metabolismo , Fatores de Transcrição/genética , Ubiquitinas/genética
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