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1.
Heliyon ; 10(9): e30379, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38765147

RESUMO

Introduction: Obesity, mainly caused by excessive accumulation of visceral fat, excessive fat metabolism will cause hormone secretion imbalance and inflammation and other diseases. is extremely detrimental to human health. Although many treatments are available for obesity, most treatments fail to exert a radical effect or are associated with several side effects. Traditional Chinese medicine (TCM) for regulating the intestinal flora, lipid content and inflammation is considered effective. Based on previous studies, Artemisia capillaris, Astragalus propinquus, Phellodendron amurense, Salvia miltiorrhiza, Poria cocos, and Anemarrhena asphodeloides were selected to prepare an innovative herbal formula. Methods: TCM was characterized by UHPLC-Q-Orbitrap-MS. The anti-inflammatory and lipid-lowering effects of the TCM formula prepared were evaluated in a high-fat diet-fed obese mouse model. The effects of the TCM formula on the intestinal flora were also investigated. Results: Weights and insulin resistance, as well as inflammation, decreased in the mice after treatment. At the same time, lipid metabolism increased after the mice were gavaged with the TCM formula for 2 weeks. The intestinal motility of the drug administration group was enhanced, with partial restoration of the intestinal flora. Conclusion: In summary, our innovative Chinese herbal formula significantly reduced weight, reduced intestinal inflammation, improved intestinal motility, and improved lipid metabolism in obese mice. Furthermore, the innovative formula effectively prevented relevant obesity-induced metastatic diseases in the mice.

2.
Front Oncol ; 14: 1333020, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38347846

RESUMO

Objective: To develop and validate a multiparametric MRI-based radiomics model for prediction of microsatellite instability (MSI) status in patients with endometrial cancer (EC). Methods: A total of 225 patients from Center I including 158 in the training cohort and 67 in the internal testing cohort, and 132 patients from Center II were included as an external validation cohort. All the patients were pathologically confirmed EC who underwent pelvic MRI before treatment. The MSI status was confirmed by immunohistochemistry (IHC) staining. A total of 4245 features were extracted from T2-weighted imaging (T2WI), contrast enhanced T1-weighted imaging (CE-T1WI) and apparent diffusion coefficient (ADC) maps for each patient. Four feature selection steps were used, and then five machine learning models, including Logistic Regression (LR), k-Nearest Neighbors (KNN), Naive Bayes (NB), Support Vector Machine (SVM), and Random Forest (RF), were built for MSI status prediction in the training cohort. Receiver operating characteristics (ROC) curve and decision curve analysis (DCA) were used to evaluate the performance of these models. Results: The SVM model showed the best performance with an AUC of 0.905 (95%CI, 0.848-0.961) in the training cohort, and was subsequently validated in the internal testing cohort and external validation cohort, with the corresponding AUCs of 0.875 (95%CI, 0.762-0.988) and 0.862 (95%CI, 0.781-0.942), respectively. The DCA curve demonstrated favorable clinical utility. Conclusion: We developed and validated a multiparametric MRI-based radiomics model with gratifying performance in predicting MSI status, and could potentially be used to facilitate the decision-making on clinical treatment options in patients with EC.

3.
ACS Nano ; 18(4): 3783-3790, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38236194

RESUMO

Significant advancements in electronic devices and integrated circuits have been facilitated by semiconducting single-walled carbon nanotubes (SWCNTs) sorted by conjugated polymers (CPs). However, the variety of CPs with single-chirality selectivity is limited, and the sorting results are strongly dependent on the chiral distribution of the starting materials. To address this, we develop an iterative strategy to achieve single-chirality SWCNT separation from aqueous to organic systems, based on a multistep tandem extraction technique that allows a gentle and nondestructive separation of surfactants from SWCNTs, ensuring an efficient system transfer. In parallel, we refined the iterative sorting process between CPs. Employing two starting materials with narrow diameter distributions, using three CPs, we successfully sorted out five single-chirality SWCNTs of the (9,5), (8,6), (10,5), (8,7), and (11,3) species in organic systems. This strategy bridges the gap between aqueous and organic separation systems, achieving efficient complementarity between them.

4.
Nano Lett ; 24(2): 741-747, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38166145

RESUMO

The emergence of one-dimensional van der Waals heterostructures (1D vdWHs) opens up potential fields with unique properties, but precise synthesis remains a challenge. The utilization of mixed conductive types of carbon nanotubes as templates has imposed restrictions on the investigation of the electrical behavior and interlayer interaction of 1D vdWHs. In this study, we efficiently encapsulated silver iodide in high-purity semiconducting single-walled carbon nanotubes (sSWCNTs), forming 1D AgI@sSWCNT vdWHs. We characterized the semiconductor-metal transition and increased the carrier concentration of individual AgI@sSWCNTs via sensitive dielectric force microscopy and confirmed the results through electrical device tests. The electrical behavior transition was attributed to an interlayer charge transfer, as demonstrated by Kelvin probe force microscopy. Furthermore, we showed that this method of synthesizing 1D heterostructures can be extended to other metal halides. This work opens the door for the further exploration of the electrical properties of 1D vdWHs.

5.
Med Res Rev ; 44(3): 1013-1054, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38140851

RESUMO

The burgeoning prodrug strategy offers a promising avenue toward improving the efficacy and specificity of cytotoxic drugs. Elevated intracellular levels of glutathione (GSH) have been regarded as a hallmark of tumor cells and characteristic feature of the tumor microenvironment. Considering the pivotal involvement of elevated GSH in the tumorigenic process, a diverse repertoire of GSH-triggered prodrugs has been developed for cancer therapy, facilitating the attenuation of deleterious side effects associated with conventional chemotherapeutic agents and/or the attainment of more efficacious therapeutic outcomes. These prodrug formulations encompass a spectrum of architectures, spanning from small molecules to polymer-based and organic-inorganic nanomaterial constructs. Although the GSH-triggered prodrugs have been gaining increasing interests, a comprehensive review of the advancements made in the field is still lacking. To fill the existing lacuna, this review undertakes a retrospective analysis of noteworthy research endeavors, based on a categorization of these molecules by their diverse recognition units (i.e., disulfides, diselenides, Michael acceptors, and sulfonamides/sulfonates). This review also focuses on explaining the distinct benefits of employing various chemical architecture strategies in the design of these prodrug agents. Furthermore, we highlight the potential for synergistic functionality by incorporating multiple-targeting conjugates, theranostic entities, and combinational treatment modalities, all of which rely on the GSH-triggering. Overall, an extensive overview of the emerging field is presented in this review, highlighting the obstacles and opportunities that lie ahead. Our overarching goal is to furnish methodological guidance for the development of more efficacious GSH-triggered prodrugs in the future. By assessing the pros and cons of current GSH-triggered prodrugs, we expect that this review will be a handful reference for prodrug design, and would provide a guidance for improving the properties of prodrugs and discovering novel trigger scaffolds for constructing GSH-triggered prodrugs.


Assuntos
Antineoplásicos , Pró-Fármacos , Humanos , Pró-Fármacos/farmacologia , Pró-Fármacos/química , Estudos Retrospectivos , Antineoplásicos/farmacologia , Antineoplásicos/química , Glutationa/química , Linhagem Celular Tumoral
6.
Sensors (Basel) ; 23(19)2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37836939

RESUMO

The real-time monitoring of food freshness in refrigerators is of significant importance in detecting potential food spoiling and preventing serious health issues. One method that is commonly reported and has received substantial attention is the discrimination of food freshness via the tracking of volatile molecules. Nevertheless, the ambient environment of low temperature (normally below 4 °C) and high humidity (90% R.H.), as well as poor selectivity in sensing gas species remain the challenge. In this research, an integrated smart gas-tracking device is designed and fabricated. By applying pump voltage on the yttria-stabilized zirconia (YSZ) membrane, the oxygen concentration in the testing chamber can be manually tailored. Due to the working principle of the sensor following the mixed potential behavior, distinct differences in sensitivity and selectivity are observed for the sensor that operated at different oxygen concentrations. Typically, the sensor gives satisfactory selectivity to H2S, NH3, and C2H5OH at the oxygen concentrations of 10%, 30%, and 40%, respectively. In addition, an acceptable response/recovery rate (within 24 s) is also confirmed. Finally, a refrigerator prototype that includes the smart gas sensor is built, and satisfactory performance in discriminating food freshness status of fresh or semi-fresh is verified for the proposed refrigerator prototype. In conclusion, these aforementioned promising results suggest that the proposed integrated smart gas sensor could be a potential candidate for alarming food spoilage.


Assuntos
Temperatura Baixa , Alimentos , Umidade , Oxigênio
7.
Biosensors (Basel) ; 13(8)2023 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-37622897

RESUMO

The modulation of numerous signaling pathways is orchestrated by redox regulation of cellular environments. Maintaining dynamic redox homeostasis is of utmost importance for human health, given the common occurrence of altered redox status in various pathological conditions. The cardinal component of the thioredoxin system, mammalian thioredoxin reductase (TrxR) plays a vital role in supporting various physiological functions; however, its malfunction, disrupting redox balance, is intimately associated with the pathogenesis of multiple diseases. Accordingly, the dynamic monitoring of TrxR of live organisms represents a powerful direction to facilitate the comprehensive understanding and exploration of the profound significance of redox biology in cellular processes. A number of classic assays have been developed for the determination of TrxR activity in biological samples, yet their application is constrained when exploring the real-time dynamics of TrxR activity in live organisms. Fluorescent probes offer several advantages for in situ imaging and the quantification of biological targets, such as non-destructiveness, real-time analysis, and high spatiotemporal resolution. These benefits facilitate the transition from a poise to a flux understanding of cellular targets, further advancing scientific studies in related fields. This review aims to introduce the progress in the development and application of TrxR fluorescent probes in the past years, and it mainly focuses on analyzing their reaction mechanisms, construction strategies, and potential drawbacks. Finally, this study discusses the critical challenges and issues encountered during the development of selective TrxR probes and proposes future directions for their advancement. We anticipate the comprehensive analysis of the present TrxR probes will offer some glitters of enlightenment, and we also expect that this review may shed light on the design and development of novel TrxR probes.


Assuntos
Corantes Fluorescentes , Tiorredoxina Dissulfeto Redutase , Humanos , Animais , Bioensaio , Mamíferos
8.
Bioorg Chem ; 138: 106589, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37320912

RESUMO

Inhibiting thioredoxin reductase (TrxR) to disrupt the redox equilibrium and induce tumor cell apoptosis is a significant tumor therapeutic strategy. Piperine, a natural product from black pepper, has been demonstrated to suppress tumor cell proliferation by enhancing reactive oxygen species (ROS), subsequently leading to cell death. However, the development of Piperine as an active molecule is hampered by its weak cytotoxicity. To develop a compound with higher activity, we synthesized 22 Piperine analogs and evaluated their pharmacological properties. Ultimately, B5 was screened by the results of cytotoxicity and inhibition of TrxR activity. In contrast to Piperine, B5 had significant cytotoxicity with a 4-fold increase. The structure-activity relationship demonstrated that the introduction of an electron-withdrawing group into the benzene ring adjacent to the amino group, particularly in the meta-position, was positive and that shortening the olefin double bond had no appreciable impact on cytotoxicity. Further investigating the physiological activity of B5 in HeLa cells, we found that B5 selectively inhibits the activity of TrxR by binding to Sec residues on TrxR. B5 then induces cellular oxidative stress and finally leads to apoptosis. As a result, the study of B5 paved the way for further investigation into the modification and function of Piperine analogs as TrxR inhibitors.


Assuntos
Neoplasias , Tiorredoxina Dissulfeto Redutase , Humanos , Células HeLa , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Apoptose
9.
J Med Chem ; 66(5): 3250-3261, 2023 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-36855911

RESUMO

Overexpression of the selenoprotein thioredoxin reductase (TrxR) has been documented in malignant tissues and is of pathological significance for many types of tumors. The antibiotic puromycin (Puro) is a protein synthesis inhibitor causing premature polypeptide chain termination during translation. The well-defined action mechanism of Puro makes it a useful tool in biomedical studies. However, the nonselective cytotoxicity of Puro limits its therapeutic applications. We report herein the construction and evaluation of two Puro prodrugs, that is, S1-Puro with a five-membered cyclic disulfide trigger and S2-Puro with a linear disulfide trigger. S1-Puro is selectively activated by TrxR and shows the TrxR-dependent cytotoxicity to cancer cells, while S2-Puro is readily activated by thiols. Furthermore, S1-Puro displays higher stability in plasma than S2-Puro. We expect that this prodrug strategy may promote the further development of Puro as a therapeutic agent.


Assuntos
Pró-Fármacos , Tiorredoxina Dissulfeto Redutase , Tiorredoxina Dissulfeto Redutase/metabolismo , Pró-Fármacos/farmacologia , Puromicina/farmacologia
10.
J Xray Sci Technol ; 31(2): 373-391, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36641733

RESUMO

BACKGROUND: Dual-energy computed tomography (DECT) can reconstruct electron density ρe and effective atomic number Zeff distribution for material discrimination. Image-domain basis material decomposition (IBMD) method is a widely used DECT method. However, IBMD method cannot be used for mineral identification directly due to limitations of complex basis material determination, beam hardening artifacts, and inherent errors caused by approximate empirical formulas. OBJECTIVE: This study proposes an improved IBMD (IIBMD) method to overcome the above limitations. METHODS: In IIBMD method, the composition of basis material is optimized to obtain accurate decomposition coefficients, which enables accurate ρe and Zeff distribution. Moreover, the thickness of basis material is optimized to reduce the effect of beam hardening. Furthermore, two formulas in place of empirical formulas are proposed to calculate ρe and Zeff. Finally, a threshold technique is applied to separate different mineral phases. RESULTS: Numerical simulations and practical experiments using a photon-counting detector CT system are implemented to verify IIBMD method. Results show that the relative errors of ρe and Zeff for seven common minerals are down to 5%, lower than most of the existing DECT methods for rocks. Reasonable volume fraction results of mineral phases are thus obtained through threshold segmentation. CONCLUSIONS: This study demonstrates that the proposed IIBMD method has high practical value in mineralogical identification.


Assuntos
Tomografia Computadorizada por Raios X , Imagens de Fantasmas , Tomografia Computadorizada por Raios X/métodos
11.
Molecules ; 27(18)2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36144654

RESUMO

The majority of diseases' biomarkers are enzymes, and the regulation of enzymes is fundamental but crucial. Biological system disorders and diseases can result from abnormal enzymatic activity. Given the biological significance of enzymes, researchers have devised a plethora of tools to map the activity of particular enzymes in order to gain insight regarding their function and distribution. Near-infrared (NIR) fluorescence imaging studies on enzymes may help to better understand their roles in living systems due to their natural imaging advantages. We review the NIR fluorescent probe design strategies that have been attempted by researchers to develop NIR fluorescent sensors of enzymes, and these works have provided deep and intuitive insights into the study of enzymes in biological systems. The recent enzyme-activated NIR fluorescent probes and their applications in imaging are summarized, and the prospects and challenges of developing enzyme-activated NIR fluorescent probes are discussed.


Assuntos
Corantes Fluorescentes , Imagem Óptica , Biomarcadores , Imagem Óptica/métodos
12.
Crit Rev Eukaryot Gene Expr ; 32(8): 69-80, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36017917

RESUMO

The problem facing gastric cancer treatment is the uncontrollable prognosis. Long noncoding RNAs (lncRNAs) are the current hotspot for gastric cancer prognostic markers. This study was targeted at determining THUMPD3-AS1 expression in gastric cancer, and then exploring whether THUMPD3-AS1 is associated with prognosis and its role in cancerous cell function. THUMPD3-AS1 expression levels were quantified in human tissues and cell lines. The prognostic biomarker potential of THUMPD3-AS1 was evaluated by Kaplan-Meier and multivariate Cox regression analyses. The biological impact of THUMPD3-AS1 in gastric cancer cells was investigated by WST-1, Tran-swell, and reactive oxygen species (ROS) accumulation assay. The binding between THUMPD3-AS1, miR-1252-3p and CXCL17 was verified by luciferase reporter assay and RNA pulled down assay. THUMPD3-AS1 was significantly decreased in gastric cancer tissues and cells by comparing them with normal ones. THUMPD3-AS1 was related to the advanced TNM stage, lymphatic infiltration, and vascular infiltration. Downregulated THUMPD3-AS1 was associated with reduced 5-year overall survival. Overexpression of THUMPD3-AS1 inhibits proliferation, migration, invasion and ROS accumulation of gastric cancer cells by regulation of miR-1252-3p and CXCL17. THUMPD3-AS1 could be a potent prognostic symbol for patients with gastric cancer. THUMPD3-AS1 provides a therapeutic potential for gastric cancer.


Assuntos
MicroRNAs , RNA Longo não Codificante , Neoplasias Gástricas , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Quimiocinas CXC/genética , Quimiocinas CXC/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo
13.
Neuropsychiatr Dis Treat ; 18: 1545-1551, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35923298

RESUMO

Purpose: To explore the different outcomes between male and female patients with schizophrenia after long-term follow-up. Patients and Methods: Schizophrenia patients were participants in our study. First, two senior psychiatrists collected data on the demographic characteristics and clinical symptoms of patients from the Hospital Information System between February 2009 and January 2010. Second, two other senior psychiatrists called the patients and their guardians between February 2019 and January 2020 to get general information on the patients and assess their psychiatric symptoms and social functioning using the Positive and Negative Syndrome Scale (PANSS) and the Personal and Social Performance (PSP) scale. Results: Of the 610 participants, the 306 female participants were younger (48.32 ± 12.99 vs 49.84 ± 12.60) and had received more education (8.08 ± 3.76 vs 7.94 ±3 0.73). After 10 years, women were found to have more outpatient visits than men (20.86 ± 22.21 vs 16.11 ± 16.87, P < 0.05). However, there was no significant gender difference in number of hospitalizations (3.12 ± 5.34 vs 2.77 ± 5.84, P > 0.05). The PANSS scores were lower for both groups at the 10-year follow-up. Women had significantly lower scores than men after the 10-year period (P < 0.05). With regard to social functioning, there was a significant difference in social functioning between baseline scores and 10-year follow-up scores indicating an improvement in social functioning. PSP scores had significantly increased in women (P < 0.01) but not in men (P > 0.05). Conclusion: Female patients had significantly lower levels of psychiatric symptoms and higher levels of social functioning at 10-year follow-up than male patients. They also reported more outpatient visits, which may have contributed to the gender differences in outcomes. Family members and doctors of patients should urge patients to make regular outpatient visits for better outcomes after hospitalization.

14.
Dis Markers ; 2022: 5709259, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35783012

RESUMO

Background: Bladder cancer is a common urinary system tumor. In the treatment of clinical patients, it is particularly important to find an effective treatment method to inhibit tumor growth. The world's first PARP inhibitor olaparib is mainly used for the treatment of BRCA1/BRCA2 mutated tumors. Metformin, an antidiabetic drug, has been reported to reduce cancer incidence in humans and improve survival in cancer patients. Methods: Cell viability and proliferation were detected by CCK-8 assay and colony formation assay; cell apoptosis was detected by flow cytometry; cell migration and invasion abilities were detected by scratch assay and Transwell assay; STAT3/C-MYC signaling pathway protein were detected by western blotting. Results: Olaparib combined with metformin has better effects on the proliferation, clone formation, migration, invasion, and apoptosis of bladder cancer cells than single drug, indicating that metformin can enhance the inhibitory effect of olaparib on tumor growth and regulate the expression of STAT3/C-MYC signaling pathway proteins. Conclusion: The results of this study showed that metformin could significantly enhance the antitumor effect of olaparib on bladder cancer cells, and these effects were mediated by downregulating STAT3/C-MYC signaling pathway proteins. This finding may have potential clinical application in the treatment of bladder cancer.


Assuntos
Metformina , Neoplasias da Bexiga Urinária , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Metformina/farmacologia , Metformina/uso terapêutico , Ftalazinas , Piperazinas , Proteínas Proto-Oncogênicas c-myc , Transdução de Sinais , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia
15.
J Immunol Res ; 2022: 3079823, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35664354

RESUMO

Objective: Deoxyschizandrin has a significant inhibitory effect on a variety of tumor cells. However, the effect of Deoxyschizandrin on bladder cancer cells and its mechanism are still unclear. Methods: Bladder cancer cells were treated with different concentrations of Deoxyschizandrin for 24 h, 48 h, and 72 h. The inhibition rate of cell proliferation was detected by CCK-8 assay. The changes of cell migration and invasion were detected by wound healing and Transwell assay. Based on the structure of Deoxyschizandrin, the protein targets of Deoxyschizandrin were predicted by bioinformatics database and verified by RNA and protein. Then, the expressions of ALOX5 and PI3K-AKT signaling pathway proteins were detected by Western blot in bladder cancer cells treated with Deoxyschizandrin. Result: Deoxyschizandrin inhibited the proliferation, migration, and invasion of bladder cancer cells in a time- and concentration-dependent manner. Bioinformatics analysis showed that Deoxyschizandrin had 100 protein targets; among them, the score of ALOX5 was the highest, and the mRNA and protein levels of ALOX5 decreased after treatment with different concentrations of Deoxyschizandrin. Western blot results showed that compared with the control group, Deoxyschizandrin could significantly reduce the expression of p-PI3K and p-AKT, and overexpression of ALOX5 could significantly enhance the expression of p-PI3K and p-AKT. Compared with Deoxyschizandrin or overexpression of ALOX5, the expression of p-PI3K and p-AKT of Deoxyschizandrin combined with overexpression of ALOX5 recovered. Conclusion: Deoxyschizandrin inhibits the proliferation, migration, and invasion of bladder cancer cells through ALOX5 regulating PI3K-AKT signaling pathway.


Assuntos
Fosfatidilinositol 3-Quinases , Neoplasias da Bexiga Urinária , Araquidonato 5-Lipoxigenase/metabolismo , Araquidonato 5-Lipoxigenase/farmacologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Ciclo-Octanos , Humanos , Lignanas , Fosfatidilinositol 3-Quinases/metabolismo , Compostos Policíclicos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética
16.
Plant Cell Rep ; 41(9): 1827-1841, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35732839

RESUMO

KEY MESSAGE: Our results confirmed that StATL2-like could interact with StCBFs and regulate plant growth. Meanwhile, StATL2-like acted as a negative regulator on low-temperature tolerance in plants. As important transcription factors for resisting many kinds of stresses, C-repeat-binding factors (CBF) play a key role in plant low-temperature tolerance by increasing COR genes expressions. Here, we report that StATL2-like, a RING-H2 E3 ubiquitin in Solanum tuberosum L., interacted with StCBF1 and StCBF4, respectively. AtATL2 is a highly homologous gene of StATL2-like in Arabidopsis thaliana. Under normal conditions, atl2 Arabidopsis mutant showed a growth inhibition phenotype while overexpressed StATL2-like in wild type Arabidopsis and atl2 mutant promoted plant growth. Besides, atl2 mutant had better low-temperature tolerance compared with wild type and StATL2-like transgenic lines which demonstrated that StATL2-like acted as a negatively regulator on low-temperature tolerance in plant. Moreover, atl2 mutant improved the scavenging capacity of reactive oxygen species (ROS) and alleviate the damage of photosynthetic system II (PSII) compared with StATL2-like transgenic lines under cold conditions. These results suggested a new component in CBF-dependent pathway to regulate plant growth and response to low-temperature stress in potato plants.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Solanum tuberosum , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Temperatura Baixa , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Solanum tuberosum/metabolismo , Estresse Fisiológico
17.
Front Genet ; 13: 877870, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35495148

RESUMO

Currently, most of the personal health data (PHD) are managed and stored separately by individual medical institutions. When these data need to be shared, they must be transferred to a trusted management center and approved by data owners through the third-party endorsement technology. Therefore, it is difficult for personal health data to be shared and circulated over multiple medical institutions. On the other hand, the use of directly exchanging and sharing the original data has become inconsistent with the data rapid growth of medical institutions because of the need of massive data transferring across agencies. In order to secure sharing and managing the mass personal health data generated by various medical institutions, a federal personal health data management framework (PHDMF, https://hvic.biosino.org/PHDMF) has been developed, which had the following advantages: 1) the blockchain technology was used to establish a data consortium over multiple medical institutions, which could provide a flexible and scalable technical solution for member extension and solve the problem of third-party endorsement during data sharing; 2) using data distributed storage technology, personal health data could be majorly stored in their original medical institutions, and the massive data transferring process was of no further use, which could match up with the data rapid growth of these institutions; 3) the distributed ledger technology was utilized to record the hash value of data, given the anti-tampering feature of the technology, malicious modification of data could be identified by comparing the hash value; 4) the smart contract technology was introduced to manage users' access and operation of data, which made the data transaction process traceable and solved the problem of data provenance; and 5) a trusted computing environment was provided for meta-analysis with statistic information instead of original data, the trusted computing environment could be further applied to more health data, such as genome sequencing data, protein expression data, and metabolic profile data through combining the federated learning and blockchain technology. In summary, the framework provides a convenient, secure, and trusted environment for health data supervision and circulation, which facilitate the consortium establish over medical institutions and help achieve the value of data sharing and mining.

18.
Analyst ; 147(5): 834-840, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35107099

RESUMO

Thioredoxins (Trxs) and glutaredoxins (Grxs) are the two major thiol-dependent reductases, participating in many important cellular events such as defense against oxidative stress, DNA synthesis and repair. Both Trxs and Grxs have diverse disulfide-containing substrates in the cells to exert their activities, with overlapping functions. Specific methods for measuring the intracellular overall activities of Trxs and Grxs are still lacking. Here we find that TRFS-green, a disulfide containing fluorescent probe which was used to detect thioredoxin reductase (TrxR) in mammalian cells, is a substrate of bacterial Trxs and Grxs, but not a substrate of bacterial TrxR and GSH. This property made TRFS-green work as a probe to measure the overall activities of Trxs and Grxs in bacterial cells. Using various E. coli Trx or Grx null mutant strains, the contribution of different Trxs and Grxs to cellular redox regulation has been clarified, judged by the reducibility towards TRFS-green. E. coli Grx2 and Grx3 unexpectedly exhibited higher activity in reducing the disulfide probe than the other redoxins. In addition, the bacterial disulfide reductase activity was detected to be affected in the ofloxacin bactericidal process. These results show that TRFS-green may be a useful tool for investigating bacterial redox regulation and demonstrating the critical role of E. coli Grxs in maintaining the bacterial intracellular redox balance.


Assuntos
Corantes Fluorescentes , Glutarredoxinas , Animais , Escherichia coli/genética , Glutarredoxinas/química , Glutarredoxinas/genética , Glutarredoxinas/metabolismo , Oxirredução , Tiorredoxina Dissulfeto Redutase , Tiorredoxinas/química , Tiorredoxinas/genética , Tiorredoxinas/metabolismo
19.
J Biomed Inform ; 127: 103999, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35104642

RESUMO

The coronavirus disease (COVID-19) has claimed the lives of over 350,000 people and infected more than 173 million people worldwide, it triggers researchers from diverse fields are accelerating their research to help diagnostics, therapies, and vaccines. Researchers also publish their recent research progress through scientific papers. However, manually writing the abstract of a paper is time-consuming, and it increases the writing burden of the researchers. Abstractive summarization technique which automatically provides researchers reliable draft abstracts, can alleviate this problem. In this work, we propose a linguistically enriched SciBERT-based summarization model for COVID-19 scientific papers, named COVIDSum. Specifically, we first extract salient sentences from source papers and construct word co-occurrence graphs. Then, we adopt a SciBERT-based sequence encoder and a Graph Attention Networks-based graph encoder to encode sentences and word co-occurrence graphs, respectively. Finally, we fuse the above two encodings and generate an abstractive summary of each scientific paper. When evaluated on the publicly available COVID-19 open research dataset, the performance of our proposed model achieves significant improvement compared with other document summarization models.


Assuntos
COVID-19 , Humanos , Idioma , Editoração , SARS-CoV-2
20.
J Med Chem ; 64(24): 17979-17991, 2021 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-34852457

RESUMO

A diselenide/disulfide unit was introduced into camptothecin (CPT), and two selenoprodrugs (e.g., CPT-Se3 and CPT-Se4) were identified to show improved potency in killing cancer cells and inhibiting tumor growth in vivo. Interestingly, the intrinsic fluorescence of CPT was severely quenched by the diselenide bond. Both the selenoprodrugs were activated by glutathione with a nearly complete recovery of CPT's fluorescence. The activation of prodrugs was accompanied by the production of selenol intermediates, which catalyzed the constant conversion of glutathione and oxygen to oxidized glutathione and superoxides. The diselenide unit is widely employed in constructing thiol-responsive materials. However, the selenol intermediates were largely ignored in the activation process prior to this study. Our work verified that integration of the diselenide unit may further enhance the parent drug's efficacy. Also, the discovery of the fluorescence quenching property of the diselenide/disulfide bond further shed light on constructing novel theranostic agents.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Camptotecina/química , Camptotecina/farmacologia , Proliferação de Células/efeitos dos fármacos , Corantes Fluorescentes/química , Pró-Fármacos/síntese química , Compostos de Selênio/química , Inibidores da Topoisomerase I/farmacologia , Animais , Apoptose/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Glutationa/metabolismo , Células Hep G2 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Imagem Óptica , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
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