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1.
Immunol Rev ; 321(1): 246-262, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37823450

RESUMEN

Cell death can be executed through distinct subroutines. PANoptosis is a unique inflammatory cell death modality involving the interactions between pyroptosis, apoptosis, and necroptosis, which can be mediated by multifaceted PANoptosome complexes assembled via integrating components from other cell death modalities. There is growing interest in the process and function of PANoptosis. Accumulating evidence suggests that PANoptosis occurs under diverse stimuli, for example, viral or bacterial infection, cytokine storm, and cancer. Given the impact of PANoptosis across the disease spectrum, this review briefly describes the relationships between pyroptosis, apoptosis, and necroptosis, highlights the key molecules in PANoptosome formation and PANoptosis activation, and outlines the multifaceted roles of PANoptosis in diseases together with a potential for therapeutic targeting. We also discuss important concepts and pressing issues for future PANoptosis research. Improved understanding of PANoptosis and its mechanisms is crucial for identifying novel therapeutic targets and strategies.


Asunto(s)
Apoptosis , Piroptosis , Humanos , Muerte Celular , Síndrome de Liberación de Citoquinas , Biología
2.
Chem Soc Rev ; 53(10): 5014-5053, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38600823

RESUMEN

Alumina materials, as one of the cornerstones of the modern chemical industry, possess physical and chemical properties that include excellent mechanical strength and structure stability, which also make them highly suitable as catalyst supports. Alumina-supported Pd-based catalysts with the advantages of exceptional catalytic performance, flexible regulated surface metal/acid sites, and good regeneration ability have been widely used in many traditional chemical industry fields and have also shown great application prospects in emerging fields. This review aims to provide an overview of the recent advances in alumina and its supported Pd-based catalysts. Specifically, the synthesis strategies, morphology transformation mechanisms, and structural properties of alumina with various morphologies are comprehensively summarized and discussed in-depth. Then, the preparation approaches of Pd/Al2O3 catalysts (impregnation, precipitation, and other emerging methods), as well as the metal-support interactions (MSIs), are revisited. Moreover, Some promising applications have been chosen as representative reactions in fine chemicals, environmental purification, and sustainable development fields to highlight the universal functionality of the alumina-supported Pd-based catalysts. The role of the Pd species, alumina support, promoters, and metal-support interactions in the enhancement of catalytic performance are also discussed. Finally, some challenges and upcoming opportunities in the academic and industrial application of the alumina and its supported Pd-based are presented and put forward.

3.
Gerontology ; 69(5): 603-614, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36882028

RESUMEN

BACKGROUND: Hypertension is the most common cardiovascular disease, and its main harmful effect is chronic damage to target organs. In some patients with well-controlled blood pressure, target organ damage still occurs. GLP-1 agonists have significant cardiovascular benefits, but their antihypertensive effect is limited. The cardiovascular protective effect of GLP-1 is worth studying. METHODS: The ambulatory blood pressure of spontaneously hypertensive rats (SHRs) was detected by ambulatory blood pressure monitoring, and the characteristics of blood pressure and the effect of subcutaneous intervention with a GLP-1R agonist on blood pressure were observed. To explore the mechanism of the cardiovascular benefit of GLP-1R agonists in SHRs, we evaluated the effects of GLP-1R agonists on vasomotor function and calcium homeostasis in vascular smooth muscle cells (VSMCs) in vitro. RESULTS: Although the blood pressure of SHRs was significantly higher than that of WKY rats, the blood pressure variability of SHRs was also significantly higher than that of the control group. The GLP-1R agonist significantly reduced blood pressure variability in SHRs, but the antihypertensive effect was not obvious. GLP-1R agonists can significantly improve the cytoplasmic calcium overload of VSMCs in SHRs by upregulating the expression of NCX1, improving the systolic and diastolic functions of arterioles, and reducing blood pressure variability. CONCLUSIONS: Taken together, these results provide evidence that GLP-1R agonists improved VSMC cytoplasmic Ca2+ homeostasis through upregulated NCX1 expression in SHRs, which plays a key role in blood pressure stability and broad cardiovascular benefits.


Asunto(s)
Hipertensión , Hipotensión , Ratas , Animales , Presión Sanguínea , Músculo Liso Vascular/metabolismo , Calcio/metabolismo , Calcio/farmacología , Antihipertensivos/metabolismo , Antihipertensivos/farmacología , Péptido 1 Similar al Glucagón/metabolismo , Péptido 1 Similar al Glucagón/farmacología , Ratas Endogámicas WKY , Monitoreo Ambulatorio de la Presión Arterial , Hipertensión/tratamiento farmacológico , Ratas Endogámicas SHR , Homeostasis
4.
Foodborne Pathog Dis ; 20(10): 442-452, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37669036

RESUMEN

In this study, we investigated the inhibitory effects of coenzyme Q0 (CoQ0) on biofilm formation and the expression of virulence genes by Cronobacter sakazakii. We found that the minimum inhibitory concentration of CoQ0 against C. sakazakii strains ATCC29544 and ATCC29004 was 100 µg/mL, while growth curve assays showed that subinhibitory concentrations (SICs) of CoQ0 for both strains were 6.4, 3.2, 1.6 and 0.8 µg/mL. Assays exploring the inhibition of specific biofilm formation showed that SICs of CoQ0 inhibited biofilm formation by C. sakazakii in a dose-dependent manner, which was confirmed by scanning electron microscopy and confocal laser scanning microscopy analyses. CoQ0 inhibited the swimming and swarming motility of C. sakazakii and reduced its ability to adhere to and invade HT-29 cells. In addition, CoQ0 impeded the ability of C. sakazakii to survive and replicate within RAW 264.7 cells. Finally, real-time polymerase chain reaction analysis confirmed that nine C. sakazakii genes associated with biofilm formation and virulence were downregulated in response to CoQ0 treatment. Overall, our findings suggest that CoQ0 is a promising antibiofilm agent and provide new insights for the prevention and control of infections caused by C. sakazakii.


Asunto(s)
Cronobacter sakazakii , Ubiquinona/farmacología , Factores de Virulencia/genética , Pruebas de Sensibilidad Microbiana , Biopelículas
5.
Gastric Cancer ; 25(3): 503-514, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34826008

RESUMEN

BACKGROUND: Fibroblasts are the predominant cell type in the stroma of tumor, and cancer-associated fibroblasts (CAFs) promote cancer chemoresistance by secreting various bioactive molecules. However, the differential expression between CAFs and normal fibroblasts (NFs) and how can CAFs uniquely impact cancer cells are still unexplored. METHODS: Primary CAFs and NFs were cultured from gastric cancer specimens, and their variant expression was analyzed by RNA-sequencing. Chemoresistance was evaluated by measuring cell viability, apoptosis, and 3D-coculture techniques. RESULTS: CAFs were isolated from gastric cancers and defined by specific cell-surface markers. CAFs decreased the sensitivity of gastric cancer cells to 5-FU. RNA-sequencing showed that CAFs expressed a higher level of NRP2 than NFs. And the high expression of NRP2 was correlated with worse oncological outcomes in gastric cancer patients. Further study showed that the knockdown of NRP2 eradicated the resistance to 5-FU. And the secretion of stromal cell-derived factor-1 (SDF-1) was reduced following NRP2 knockdown. Furthermore, we found that the increased sensitivity to 5-FU was induced by DNA damage. And this process was mediated by predominant effectors of the Hippo pathway, YAP/TAZ. CONCLUSIONS: The present study indicated that CAFs within gastric cancers promote chemoresistance through the expression of NRP2. The secretion of SDF-1 that mediated by VEGF/NRP2 signaling in CAFs and the activation of Hippo pathway in cancer cells in large part participated in this project.


Asunto(s)
Fibroblastos Asociados al Cáncer , Neoplasias Gástricas , Fibroblastos Asociados al Cáncer/patología , Línea Celular Tumoral , Proliferación Celular/fisiología , Resistencia a Antineoplásicos , Fibroblastos/patología , Fluorouracilo/farmacología , Humanos , ARN/metabolismo , Neoplasias Gástricas/patología
6.
Foodborne Pathog Dis ; 18(6): 398-404, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33709804

RESUMEN

Coenzyme Q0 (CoQ0) is a natural compound found in Antrodia cinnamomea, which has a variety of biological activities. Here, the antibacterial activity and possible antibacterial mechanism of CoQ0 against Escherichia coli were investigated. The antibacterial effect was evaluated by determining minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values, and by assessing bacterial survival and the effect on the growth of E. coli after CoQ0 treatment in Luria-Bertani (LB) broth. To reveal the antibacterial mechanism of CoQ0, changes in intracellular adenosine triphosphate (ATP) concentration, membrane potential, and bacterial protein content, as well as effects on cell morphology and membrane integrity, were investigated. Both the MICs and MBCs of CoQ0 against E. coli were 0.1 mg/mL. After treatment of E. coli (6.5 log colony-forming units/mL) with 0.1 mg/mL of CoQ0 in LB broth for 3 h, the number of viable cells dropped below the detection limit. In addition, CoQ0 treatment resulted in the reduction in intracellular ATP concentration, cell membrane hyperpolarization, decreased bacterial protein concentrations, and damage to cell membrane integrity and cellular morphology. These results indicated that CoQ0 has effective antibacterial activity against E. coli, suggesting potential applications in food industry safety.


Asunto(s)
Antibacterianos/farmacología , Benzoquinonas/farmacología , Escherichia coli/efectos de los fármacos , Adenosina Trifosfato/metabolismo , Membrana Celular/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Polyporales/química
7.
Appl Environ Microbiol ; 86(10)2020 05 05.
Artículo en Inglés | MEDLINE | ID: mdl-32169938

RESUMEN

Biofilm formation by Pseudomonas aeruginosa contributes to its survival on surfaces and represents a major clinical threat because of the increased tolerance of biofilms to disinfecting agents. This study aimed to investigate the efficacy of 405-nm light-emitting diode (LED) illumination in eliminating P. aeruginosa biofilms formed on stainless steel coupons under different temperatures. Time-dependent killing assays using planktonic and biofilm cells were used to determine the antimicrobial and antibiofilm activities of LED illumination. We also evaluated the effects of LED illumination on the disinfectant susceptibility, biofilm structure, extracellular polymeric substance (EPS) structure and composition, and biofilm-related gene expression of P. aeruginosa biofilm cells. Results showed that the abundance of planktonic P. aeruginosa cells was reduced by 0.88, 0.53, and 0.85 log CFU/ml following LED treatment for 2 h compared with untreated controls at 4, 10, and 25°C, respectively. For cells in biofilms, significant reductions (1.73, 1.59, and 1.68 log CFU/cm2) were observed following LED illumination for 2 h at 4, 10, and 25°C, respectively. Moreover, illuminated P. aeruginosa biofilm cells were more sensitive to benzalkonium chloride or chlorhexidine than untreated cells. Scanning electron microscopy and confocal laser scanning microscopic observation indicated that both the biofilm structure and EPS structure were disrupted by LED illumination. Further, reverse transcription-quantitative PCR revealed that LED illumination downregulated the transcription of several genes associated with biofilm formation. These findings suggest that LED illumination has the potential to be developed as an alternative method for prevention and control of P. aeruginosa biofilm contamination.IMPORTANCEPseudomonas aeruginosa can form biofilms on medical implants, industrial equipment, and domestic surfaces, contributing to high morbidity and mortality rates. This study examined the antibiofilm activity of 405-nm light-emitting diode (LED) illumination against mature biofilms formed on stainless steel coupons. We found that the disinfectant susceptibility, biofilm structure, and extracellular polymeric substance structure and composition were disrupted by LED illumination. We then investigated the transcription of several critical P. aeruginosa biofilm-related genes and analyzed the effect of illumination temperature on the above characteristics. Our results confirmed that LED illumination could be developed into an effective and safe method to counter P. aeruginosa biofilm contamination. Further research will be focused on the efficacy and application of LED illumination for elimination of complicated biofilms in the environment.


Asunto(s)
Biopelículas/efectos de la radiación , Desinfección/métodos , Luz , Pseudomonas aeruginosa/efectos de la radiación , Acero Inoxidable , Iluminación , Pseudomonas aeruginosa/fisiología , Temperatura
8.
Fish Shellfish Immunol ; 106: 431-440, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32810530

RESUMEN

The extensive use of antibiotics in aquaculture has resulted in the prevalence of antibiotic-resistant bacteria and, consequently, new antibacterial strategies or drugs with clear modes of action are urgently needed. Antimicrobial peptides (AMPs) are currently widely considered as alternatives to antibiotics in the treatment of infections in aquatic animals. In this study, we aimed to evaluate the effects of NKL-24, a truncated peptide derived from zebrafish NK-lysin, against Yesso scallop (Patinopecten yessoensis) pathogen, Vibrio parahaemolyticus. The results showed that NKL-24 had a potent antibacterial effect against V. parahaemolyticus via a membrane active cell-killing mechanism. The in vitro study showed that sub-lethal levels of NKL-24 obviously reduced bacterial swimming ability and downregulated the transcription of the selected genes associated with V. parahaemolyticus virulence. Studies on NKL-24 biosafety in hemocytes and in Yesso scallop have shown no adverse effects from this peptide. Bacteria challenge test results demonstrated that NKL-24 significantly decreased the mortality and inhibited bacterial growth in the scallop infected with V. parahaemolyticus, while further in vivo examination revealed that NKL-24 could enhance non-specific immune parameters. Moreover, NKL-24 was capable of modulating a series of V. parahaemolyticus-responsive genes in the scallop. These results suggest the protective action of NKL-24 against V. parahaemolyticus and the potential of this peptide as a promising candidate for aquaculture applications.


Asunto(s)
Antibacterianos/farmacología , Pectinidae/inmunología , Proteínas Citotóxicas Formadoras de Poros/farmacología , Proteolípidos/farmacología , Vibrio parahaemolyticus/efectos de los fármacos , Animales , Vibrio parahaemolyticus/fisiología , Pez Cebra
9.
Food Microbiol ; 86: 103337, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31703870

RESUMEN

Coenzyme Q0 (CoQ0) has demonstrated antitumor, anti-inflammatory, and anti-angiogenic activities. Cronobacter sakazakii is an opportunistic foodborne pathogen associated with high mortality in neonates. In this study, the antimicrobial activity and possible antimicrobial mechanism of CoQ0 against C. sakazakii were investigated. Moreover, the inactivation effect of CoQ0 on C. sakazakii in biofilms was also evaluated. The minimum inhibitory concentration (MIC) of CoQ0 against C. sakazakii strains ranged from 0.1 to 0.2 mg/mL. Treatment caused cell membrane dysfunction, as evidenced by cell membrane hyperpolarization, decreased intracellular ATP concentration and cell membrane integrity, and changes in cellular morphology. CoQ0 combined with mild heat treatment (45, 50, or 55 °C) decreased the number of viable non-desiccated and desiccated C. sakazakii cells in a time- and dose-dependent manner in reconstituted infant milk. Furthermore, CoQ0 showed effective inactivation activity against C. sakazakii in biofilms on stainless steel, reducing the number of viable cells and damaging the structure of the biofilm. These findings suggest that CoQ0 has a strong inactivate effect on C. sakazakii and could be used in food production environments to effectively control C. sakazakii and reduce the number of illnesses associated with it.


Asunto(s)
Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Cronobacter sakazakii/efectos de los fármacos , Ubiquinona/análogos & derivados , Membrana Celular/efectos de los fármacos , Cronobacter sakazakii/crecimiento & desarrollo , Cronobacter sakazakii/fisiología , Fórmulas Infantiles/análisis , Fórmulas Infantiles/microbiología , Pruebas de Sensibilidad Microbiana , Plancton/efectos de los fármacos , Plancton/crecimiento & desarrollo , Plancton/fisiología , Ubiquinona/farmacología
10.
IEEE Trans Robot ; 36(1): 28-41, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33746643

RESUMEN

The possibility of regulating the behavior of live animals using biologically-inspired robots has attracted the interest of biologists and engineers for over twenty-five years. From early work on insects to recent endeavors on mammals, we have witnessed fascinating applications that have pushed forward our understanding of animal behavior along new directions. Despite significant progress, most of the research has focused on open-loop control systems, in which robots execute predetermined actions, independent of the animal behavior. We integrate mathematical modeling of social behavior toward the design of realistic feedback laws for robots to interact with a live animal. In particular, we leverage recent advancements in data-driven modeling of zebrafish behavior. Ultimately, we establish a novel robotic platform that allows real-time actuation of a biologically-inspired 3D-printed zebrafish replica to implement model-based control of animal behavior. We demonstrate our approach through a series of experiments, designed to elucidate the appraisal of the replica by live subjects with respect to conspecifics and to quantify the biological value of closed-loop control.

11.
Appl Microbiol Biotechnol ; 103(20): 8545-8557, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31468089

RESUMEN

Salmonella Typhimurium, a common Gram-negative foodborne pathogen, threatens public health and hinders the development of the food industry. In this study, we evaluated the antibiofilm activity of coenzyme Q0 (CoQ0) against S. Typhimurium. Besides, the inhibition of the S. Typhimurium's adhesion to and invasion of Caco-2 cells and its survival and replication in RAW 264.7 cells by CoQ0 were also explored. The minimum inhibitory concentrations and minimal bactericidal concentrations of CoQ0 against Salmonella were both 100-400 µg/mL. Salmonella Typhimurium biofilm formation was effectively inhibited by subinhibitory concentrations (SICs) of CoQ0. The CoQ0-affected biofilm morphology was observed with light microscopy and field-emission scanning electron microscopy. CoQ0 at SICs reduced the swimming motility and quorum sensing of S. Typhimurium and repressed the transcription of critical virulence-related genes. CoQ0 at SICs also clearly reduced the adhesion of S. Typhimurium to and its invasion of Caco-2 cells and reduced its survival and replication within RAW 264.7 macrophage cells. These findings suggest that CoQ0 has strong antibiofilm activity and can be used as an anti-infectious agent against Salmonella.


Asunto(s)
Antibacterianos/metabolismo , Adhesión Bacteriana/efectos de los fármacos , Benzoquinonas/metabolismo , Biopelículas/efectos de los fármacos , Endocitosis/efectos de los fármacos , Viabilidad Microbiana/efectos de los fármacos , Salmonella typhimurium/efectos de los fármacos , Animales , Células CACO-2 , Humanos , Ratones , Pruebas de Sensibilidad Microbiana , Células RAW 264.7
12.
Imeta ; 3(3): e196, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38898984

RESUMEN

Akkermansia muciniphila pretreatment mitigated Listeria monocytogenes infection in mice. A. muciniphila improved gut microbiota disturbed by L. monocytogenes infection and significantly increased the level of intestinal linoleic acid in mice. Linoleic acid strengthened the intestinal epithelial barrier and reduced pathogen translocation partly by regulating NF-κB/MLCK pathway in a GPR40-dependent manner.

13.
Cell Biochem Biophys ; 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38319584

RESUMEN

The ubiquitin proteasome system is a highly specific and selective protein regulatory system that plays an essential role in the regulation of the cell cycle. Despite its significance, the role of ubiquitination in cardiomyocyte proliferation remains largely unclear. This study aimed to investigate the potential impact of E3 ubiquitin ligase ASB14 (Ankyrin Repeat And SOCS Box Containing 14) on cardiac regeneration. We conducted a microarray analysis of apical resection ventricle tissues, and our findings revealed that ASB14 was down-regulated during the cardiac regenerative response. Subsequently, we examined the effect of ASB14 silencing on cardiomyocyte nuclear proliferation both in vitro and in vivo. Our results indicated that ASB14 silencing promoted cardiomyocyte nuclear proliferation, suggesting that ASB14 may play a role in regulating cardiac regeneration. To further investigate the potential therapeutic implications of ASB14 deficiency, we examined the cardiac function of mice with ASB14 deficiency in response to ischemic injury. Our findings showed that mice with ASB14 deficiency exhibited preserved cardiac function and a therapeutic effect in response to ischemic injury, which was attributed to the enhancement of cardiomyocyte nuclear proliferation. To elucidate the underlying mechanisms, we investigated the effect of ASB14 on microtubule-associated protein RP/EB family member 2 (MAPRE2) protein degradation. Our results indicated that the loss of ASB14 decreased the degradation of MAPRE2 protein, subsequently promoting cardiomyocyte nuclear proliferation and enhancing cardiac repair after myocardial infarction (MI). In conclusion, our study provides evidence that inhibition of ASB14-mediated MAPRE2 ubiquitination promotes cardiomyocyte nuclear proliferation, which may serve as a potential target for treating heart failure induced by MI injury.

14.
Sci Total Environ ; 927: 172039, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38552977

RESUMEN

Alpine grassland is the main vegetation on the Qinghai-Tibetan Plateau (QTP) and exhibits high sensitivity to extreme weather events. With global warming, extreme weather events are projected to become more frequent on the QTP. However, the impact of these extreme weather events on the carbon cycle of alpine grassland remains unclear. The long-term in-situ carbon fluxes data was collected from 2013 to 2022 at an alpine grassland site to examine the impact of extreme low air temperature (ELT) and reduced moisture (including air and soil) on carbon fluxes during the growing season. Our findings indicated that a significant increase in net ecosystem production (NEP) after 2019, with the average NEP increasing from 278.91 ± 43.27 g C m-2 year-1 during 2013-2018 to 415.45 ± 45.29 g C m-2 year-1 during 2019-2022. The ecosystem carbon use efficiency (CUE) increased from 0.38 ± 0.06 during 2013-2018 to 0.62 ± 0.11 during 2019-2022. By combining concurrently measured environmental factors and remote sensing data, we identified the factors responsible for the abrupt change in the NEP after 2019. This phenomenon was caused by an abrupt decrease in ecosystem respiration (Reco) after 2019, which resulted from the inhibition imposed by ELT and reduced moisture. In contrast, gross primary production (GPP) remained stable from 2013 to 2022, which was confirmed by the remotely sensed vegetation index. This study highlights that combined extreme weather events associated with climate change can significantly impact the NEP of alpine grassland, potentially affecting different carbon fluxes at different rates. These findings provide new insights into the mechanisms governing the carbon cycle of alpine grassland.


Asunto(s)
Ciclo del Carbono , Monitoreo del Ambiente , Pradera , Tibet , Cambio Climático , Frío , Ecosistema
15.
World J Gastroenterol ; 30(6): 565-578, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38463028

RESUMEN

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a deadly malignancy with limited treatment options. Deubiquitinases (DUBs) have been confirmed to play a crucial role in the development of malignant tumors. JOSD2 is a DUB involved in controlling protein deubiquitination and influencing critical cellular processes in cancer. AIM: To investigate the impact of JOSD2 on the progression of ESCC. METHODS: Bioinformatic analyses were employed to explore the expression, prognosis, and enriched pathways associated with JOSD2 in ESCC. Lentiviral transduction was utilized to manipulate JOSD2 expression in ESCC cell lines (KYSE30 and KYSE150). Functional assays, including cell proliferation, colony formation, drug sensitivity, migration, and invasion, were performed, revealing the impact of JOSD2 on ESCC cell lines. JOSD2's role in xenograft tumor growth and drug sensitivity in vivo was also assessed. The proteins that interacted with JOSD2 were identified using mass spectrometry. RESULTS: Preliminary research indicated that JOSD2 was highly expressed in ESCC tissues, which was associated with poor prognosis. Further analysis demonstrated that JOSD2 was upregulated in ESCC cell lines compared to normal esophageal cells. JOSD2 knockdown inhibited ESCC cell activity, including proliferation and colony-forming ability. Moreover, JOSD2 knockdown decreased the drug resistance and migration of ESCC cells, while JOSD2 overexpression enhanced these phenotypes. In vivo xenograft assays further confirmed that JOSD2 promoted tumor proliferation and drug resistance in ESCC. Mechanistically, JOSD2 appears to activate the MAPK/ERK and PI3K/AKT signaling pathways. Mass spectrometry was used to identify crucial substrate proteins that interact with JOSD2, which identified the four primary proteins that bind to JOSD2, namely USP47, IGKV2D-29, HSP90AB1, and PRMT5. CONCLUSION: JOSD2 plays a crucial role in enhancing the proliferation, migration, and drug resistance of ESCC, suggesting that JOSD2 is a potential therapeutic target in ESCC.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/patología , Neoplasias Esofágicas/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Enzimas Desubicuitinizantes/genética , Regulación Neoplásica de la Expresión Génica , Proteína-Arginina N-Metiltransferasas
16.
Comput Struct Biotechnol J ; 21: 5039-5048, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37867973

RESUMEN

The CRISPR/Cas9 system has significantly advanced the field of gene editing, yet its clinical application is constrained by the considerable challenge of off-target effects. Although numerous deep learning models for off-target prediction have been proposed, most struggle to effectively extract the nuanced features of guide RNA (gRNA) and DNA sequence pairs and to mitigate information loss during data transmission within the model. To address these limitations, we introduce a novel Hybrid Neural Network (HNN) model that employs a parallelized network structure to fully extract pertinent features from different positions and types of bases in the sequence to minimize information loss. Notably, this study marks the first application of word embedding techniques to extract information from sequence pairs that contain insertions and deletions (Indels). Comprehensive evaluation across diverse datasets indicates that our proposed model outperforms existing state-of-the-art prediction methods in off-target prediction. The datasets and source codes supporting this study can be found at https://github.com/Yang-k955/CRISPR-HW.

17.
Sci Total Environ ; 880: 163255, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-37031934

RESUMEN

Glacial sediments as an important end member of the global dust system, could indicate changes in global climate, aerosols sources, ocean elements, and productivity. With global warming, ice caps shrinking and glaciers retreat at high latitudes have attracted concern. To understand the response of glacier to environment and climate in modern high latitude ice-marginal environments, this paper investigated glacial sediments in the Ny-Ålesund region of the Arctic and clarified the response of polar environmental to global changes through geochemical characteristics of glacial sediments. The results showed that: 1) main factors affecting the elements distribution of the Ny-Ålesund glacial sediments were thought as soil formation, bedrock and weathering, and biological activity; 2) variations of SiO2/Al2O3 and SiO2/Al2O3 + Fe2O3, indicating low weathering of the soil. The ratio of Na2O/K2O indicating a weak chemical weathering, was negatively correlated to the CIA. With the average CIA of Ny-Ålesund glacial sediments for main minerals of quartz, feldspar, and muscovite as well as dolomite and calcite 50.13, which implied glacial sediments at the early stage of chemical weathering and depletion of Ca and Na; 3) the separating effect of stones and soils by stone circle formation due to thermal conductivity and frost heave makes sediments in stone circle have lower chemical weathering with only two main minerals, albite and quartz; 4) changes of carbonate content in sediments with glacier front retreating in different period implied that weathering rate of calcite averagely reached an estimate of 0.0792%wt/year in glacier A. The succession of vegetation made biological weathering become an important driving force for carbonate leaching from glacial sediments. These results and data provide scientifically significant archive for future global change studies.

18.
Am J Cancer Res ; 12(11): 5095-5104, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36504890

RESUMEN

Despite advances in rectal cancer treatments, its local recurrence rate is still 4-10 percent. And an evidence-based definition of early recurrence is lacking. Our study hopes to establish a clear threshold to distinguish early and late recurrence, and analyze risk and prognostic factors for them. Rectal cancer patients who underwent proctectomy from 2009 to 2019 were included. Patients who received neoadjuvant treatment and with incomplete records were excluded. The optimal interval was obtained using the minimum P value approach. Risk factors for early recurrence were analyzed by logistic regression models, and prognostic factors associated with additional surgery were assessed by Cox proportional hazards models. The optimal interval for the definition of early recurrence was 26 months based on the subsequent prognosis (P < 0.001). The 5-year survival rate of early and late recurrence cohort was 32.5% and 57.1%, respectively (P < 0.001). Adjuvant radiotherapy was the independent protective factor for early recurrence. And the presence of lymphovascular invasion, positive surgical margin, and no re-neoadjuvant radiotherapy were independent prognostic factors for the survival of LRRC patients under additional surgery.

19.
Syst Rev ; 11(1): 136, 2022 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-35788246

RESUMEN

BACKGROUND: Surgery is the main treatment option for patients with local gastric cancer. However, surgery alone is usually not sufficient for stomach cancer patients, and combined therapies are recommended for these patients. In recent studies, some preoperative treatments have shown benefits. However, the treatment selection is still uncertain because previous studies failed to obtain a statistically significant difference between preoperative chemotherapy and preoperative chemoradiotherapy. Therefore, we plan to perform a systematic review and meta-analysis to compare the benefits among these preoperative treatments. METHODS/DESIGN: This review includes randomized controlled trials with or without blinding as well as published studies, high-quality unpublished studies, full articles and meeting abstracts with an English context if sufficient results were provided for analysis. Data sources include the Cochrane Central Register of Controlled Trials, Embase, MEDLINE, major relevant international conferences and manual screening of references. Patients with a diagnosis of resectable primary gastric or EGJ adenocarcinoma (stage II or higher) who underwent surgery alone or preoperative treatment followed by surgery and who were pathologically confirmed as proposed by the AJCC 2017 guidelines without age, sex, race, subtypes of adenocarcinoma and molecular pathology limitations will be included. The following three interventions will be included: surgery alone, neoadjuvant chemistry followed by surgery and neoadjuvant chemoradiotherapy followed by surgery. All-cause mortality, overall survival (OS, the time interval from diagnosis to death) and/or progression-free survival (PFS, the time interval from diagnosis to disease progression or death from any cause) will be defined as major results of concern. The clinical and pathological response rate (according to RECIST and tumour regression score), R0 resection rate, quality of life and grade 3 or above adverse events (according to the National Cancer Institute Common Terminology Criteria for Adverse Events, NCI-CTCAE) will be defined as the secondary outcomes. DISCUSSION: The aim of this systematic review is to compare the benefits of different preoperative treatments for patients with locoregional stomach cancer. This systematic review will improve the understanding of the relative efficacy of these treatment options by providing the latest evidence on the efficacy of various treatment options in the management of gastric cancer patients and may guide clinical practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD4202123718.


Asunto(s)
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Adenocarcinoma/etiología , Humanos , Terapia Neoadyuvante/métodos , Calidad de Vida , Neoplasias Gástricas/terapia
20.
J Colloid Interface Sci ; 617: 372-382, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35279572

RESUMEN

With continuous development of artificial intelligence technology, strain sensors have attracted widespread attention. In this work, a novel high-performance wearable strain sensor is prepared by using a kind of ultra-stretchable, super-hydrophobic and high-conductive composite. The preparation process is as follows, i.e., using common elastic band (EB) as the polymer matrix, nano carbon black (CB) and carbon nanotubes (CNTs) as mixed conductive filler, and then modified by polydimethylsiloxane (PDMS) to obtain the PDMS/(CB + CNTs)/EB composite for assembling assemble flexible wearable strain sensors. Experimental results reveal the following excellent properties: 1) The composite exhibits excellent mechanical properties and super-hydrophobicity, i.e., the tensile strength is up to 996.5%, and the elastic modulus and tensile strength increase 49.2% and 59.2%, compared with pristine EB; 2) The composite strain sensor exhibits high sensitivity (the gauge factor reaches up to 648.83 under strain range of 979.9-996.5%), and it still shows stable performance after 3000 cycles tests (100% strain); 3) It is a well candidate to be used for monitoring human body motions including large and subtle body movements; 4) The composite sensor also has advantages of easy access of raw materials, simple preparation, easy mass production and relatively low production cost, showing a broad application prospect in wearable electronic products.


Asunto(s)
Nanotubos de Carbono , Dispositivos Electrónicos Vestibles , Inteligencia Artificial , Conductividad Eléctrica , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Nanotubos de Carbono/química
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