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1.
J Transl Med ; 22(1): 692, 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39075464

RESUMEN

BACKGROUND: Molecularly targeted therapies have recently become a hotspot in the treatment of LUAD, with ongoing efforts to identify new effective targets due to individual variability. Among these potential targets, the mitochondrial transcription elongation factor (TEFM) stands out as a crucial molecule involved in mitochondrial synthetic transcriptional processing. Dysregulation of TEFM has been implicated in the development of various diseases; however, its specific role in LUAD remains unclear. METHODS: We conducted a comprehensive analysis of TEFM expression in LUAD, leveraging data from the TCGA database. Subsequently, we validated these findings using clinical specimens obtained from the First Affiliated Hospital of Soochow University, employing western blotting and qRT-PCR techniques. Further experimental validation was performed through the transfection of cells with TEFM overexpression, knockdown, and knockout lentiviruses. The effects of TEFM on LUAD were evaluated both in vitro and in vivo using a range of assays, including CCK-8, colony formation, EdU incorporation, Transwell migration, Tunel assay, flow cytometry, JC-1 staining, and xenograft tumour models. RESULTS: Our investigation uncovered that TEFM exhibited elevated expression levels in LUAD and exhibited co-localization with mitochondria. Overexpression of TEFM facilitated malignant processes in LUAD cells, whereas its silencing notably curbed these behaviors and induced mitochondrial depolarization, along with ROS production, culminating in apoptosis. Moreover, the absence of TEFM substantially influenced the expression of mitochondrial transcripts and respiratory chain complexes. Results from nude mouse xenograft tumors further validated that inhibiting TEFM expression markedly hindered tumor growth. CONCLUSION: TEFM promotes LUAD malignant progression through the EMT pathway and determines apoptosis by affecting the expression of mitochondrial transcripts and respiratory chain complexes, providing a new therapeutic direction for LUAD-targeted therapy.


Asunto(s)
Apoptosis , Mitocondrias , Factores de Elongación Transcripcional , Humanos , Animales , Mitocondrias/metabolismo , Línea Celular Tumoral , Factores de Elongación Transcripcional/metabolismo , Factores de Elongación Transcripcional/genética , Apoptosis/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/terapia , Ratones Desnudos , Regulación Neoplásica de la Expresión Génica , Proliferación Celular , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/terapia , Movimiento Celular , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones , Especies Reactivas de Oxígeno/metabolismo , Terapia Molecular Dirigida , Femenino , Masculino
2.
Plant Physiol ; 192(1): 616-632, 2023 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-36732924

RESUMEN

Hydrogen sulfide (H2S) is a gaseous signaling molecule reported to play multiple roles in fruit ripening. However, the molecular mechanisms underlying H2S-mediated delay in fruit ripening remain to be established. Here, the gene encoding a WRKY transcription factor, WRKY71, was identified as substantially upregulated in H2S-treated tomato (Solanum lycopersicum) via transcriptome profiling. The expression of WRKY71 was negatively associated with that of CYANOALANINE SYNTHASE1 (CAS1). Transient and stable genetic modification experiments disclosed that WRKY71 acts as a repressor of the tomato ripening process. CAS1 appears to play an opposite role, based on the finding that the ripening process was delayed in the cas1 mutant and accelerated in CAS1-OE tomatoes. Dual-luciferase reporter assay, yeast one-hybrid, electrophoretic mobility shift assay, and transient transformation experiments showed that WRKY71 bound to the CAS1 promoter and suppressed its activation. Moreover, the persulfidation of WRKY71 enhanced its binding ability to the CAS1 promoter. Data from luciferase complementation and Y2H assays confirmed that WRKY71 interacts with a BOI-related E3 ubiquitin-protein ligase 3 (BRG3) and is ubiquitinated in vitro. Further experiments showed that modification of BRG3 via persulfidation at Cys206 and Cys212 led to reduced ubiquitination activity. Our findings support a model whereby BRG3 undergoes persulfidation at Cys206 and Cys212, leading to reduced ubiquitination activity and decreased interactions with the WRKY71 transcript, with a subsequent increase in binding activity of the persulfidated WRKY71 to the CAS1 promoter, resulting in its transcriptional inhibition and thereby delayed ripening of tomatoes. Our collective findings provide insights into a mechanism of H2S-mediated regulation of tomato fruit ripening.


Asunto(s)
Solanum lycopersicum , Solanum lycopersicum/genética , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación , Regiones Promotoras Genéticas/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Frutas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Etilenos/metabolismo
3.
Nucleic Acids Res ; 50(D1): D236-D245, 2022 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-34850956

RESUMEN

Repeats are prevalent in the genomes of all bacteria, plants and animals, and they cover nearly half of the Human genome, which play indispensable roles in the evolution, inheritance, variation and genomic instability, and serve as substrates for chromosomal rearrangements that include disease-causing deletions, inversions, and translocations. Comprehensive identification, classification and annotation of repeats in genomes can provide accurate and targeted solutions towards understanding and diagnosis of complex diseases, optimization of plant properties and development of new drugs. RepBase and Dfam are two most frequently used repeat databases, but they are not sufficiently complete. Due to the lack of a comprehensive repeat database of multiple species, the current research in this field is far from being satisfactory. LongRepMarker is a new framework developed recently by our group for comprehensive identification of genomic repeats. We here propose msRepDB based on LongRepMarker, which is currently the most comprehensive multi-species repeat database, covering >80 000 species. Comprehensive evaluations show that msRepDB contains more species, and more complete repeats and families than RepBase and Dfam databases. (https://msrepdb.cbrc.kaust.edu.sa/pages/msRepDB/index.html).


Asunto(s)
Elementos Transponibles de ADN , Bases de Datos de Ácidos Nucleicos , Genoma , Secuencias Repetitivas de Ácidos Nucleicos , Retroelementos , Interfaz Usuario-Computador , Animales , Secuencia de Bases , Humanos , Internet , Plantas/genética , Análisis de Secuencia de ADN
4.
Sensors (Basel) ; 24(7)2024 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-38610557

RESUMEN

Relative localization (RL) and circumnavigation is a highly challenging problem that is crucial for the safe flight of multi-UAVs (multiple unmanned aerial vehicles). Most methods depend on some external infrastructure for positioning. However, in some complex environments such as forests, it is difficult to set up such infrastructures. In this paper, an approach to infrastructure-free RL estimations of multi-UAVs is investigated for circumnavigating a slowly drifting UGV0 (unmanned ground vehicle 0), where UGV0 serves as the RL and circumnavigation target. Firstly, a discrete-time direct RL estimator is proposed to ascertain the coordinates of each UAV relative to the UGV0 based on intelligent sensing. Secondly, an RL fusion estimation method is proposed to obtain the final estimate of UGV0. Thirdly, an integrated estimation control scheme is also proposed for the application of the RL fusion estimation method to circumnavigation. The convergence and the performance are analyzed. The simulation results validate the effectiveness of the proposed algorithm for RL fusion estimations and of the integrated scheme.

5.
Molecules ; 29(12)2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38930942

RESUMEN

Naturally occurring substances and their derivatives function as vital resources for pesticides that can be used in fields, such as insecticide production and fungicide development. As a botanical entity displaying multifaceted biological functions, wormwood has received thorough scrutiny across multiple sectors. The insect repellency potency combined with antibacterial and antifungal activities of wormwood position it as a potential candidate for prospective development into eco-friendly chemical pesticides. In this research, Wormwood essential oil was procured via ethanol water under ultrasonic scenarios and subsequently diluted with PEG 400 to formulate green chemical pesticides. The defensive efficacy of this green pesticide on plants was validated through 2 weeks of clustered plant growth experiments. Active constituents that exerted their effects were scrutinized by GC-MS. Furthermore, this green pesticide also displays efficacious effects on the prevention and management of aphids, exhibiting a dose-dependent relationship. 4-terpenol, eucalyptol, carvacrol, and L-borneol were identified by GC-MS as the predominant active constituents in this green chemical pesticide. Wormwood can be leveraged to develop green chemical pesticides, which can protect plants without contaminating the environment.


Asunto(s)
Insecticidas , Aceites Volátiles , Insecticidas/química , Insecticidas/farmacología , Animales , Aceites Volátiles/química , Aceites Volátiles/farmacología , Cromatografía de Gases y Espectrometría de Masas , Cimenos/química , Cimenos/farmacología , Tecnología Química Verde/métodos , Áfidos/efectos de los fármacos , Eucaliptol/química , Eucaliptol/farmacología , Canfanos
6.
Mol Plant Microbe Interact ; 36(2): 95-108, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36366828

RESUMEN

The accumulation of cadmium (Cd) in plants is strongly impacted by soil microbes, but its mechanism remains poorly understood. Here, we report the mechanism of reduced Cd accumulation in rice by coculture of Enterobacter and Comamonas species. In pot experiments, inoculation with the coculture decreased Cd content in rice grain and increased the amount of nonbioavailable Cd in Cd-spiked soils. Fluorescence in situ hybridization and scanning electron microscopy detection showed that the coculture colonized in the rhizosphere and rice root vascular tissue and intercellular space. Soil metagenomics data showed that the coculture increased the abundance of sulfate reduction and biofilm formation genes and related bacterial species. Moreover, the coculture increased the content of organic matter, available nitrogen, and potassium and increased the activities of arylsulfatase, ß-galactosidase, phenoloxidase, arylamidase, urease, dehydrogenase, and peroxidase in soils. In subsequent rice transcriptomics assays, we found that the inoculation with coculture activated a hypersensitive response, defense-related induction, and mitogen-activated protein kinase signaling pathway in rice. Heterologous protein expression in yeast confirmed the function of four Cd-binding proteins (HIP28-1, HIP28-4, BCP2, and CID8), a Cd efflux protein (BCP1), and three Cd uptake proteins (COPT4, NRAM5, and HKT6) in rice. Succinic acid and phenylalanine were subsequently proved to inhibit rice divalent Cd [Cd(II)] uptake and activate Cd(II) efflux in rice roots. Thus, we propose a model that the coculture protects rice against Cd stress via Cd immobilization in soils and reducing Cd uptake in rice. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Asunto(s)
Comamonas , Oryza , Contaminantes del Suelo , Cadmio/análisis , Cadmio/metabolismo , Oryza/metabolismo , Enterobacter/genética , Comamonas/metabolismo , Técnicas de Cocultivo , Hibridación Fluorescente in Situ , Suelo/química , Contaminantes del Suelo/análisis , Contaminantes del Suelo/metabolismo
7.
Antimicrob Agents Chemother ; 67(3): e0096922, 2023 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-36853030

RESUMEN

Bacterial persisters refer to a small fraction of dormant variants that survive treatment with high concentrations of antibiotics. Increasing research indicates that multidrug efflux pumps play a major role in persister formation in many Gram-negative organisms. In the present study, the roles of the repressor of the AcrAB efflux pump, AcrR, in the regulation of the activity and function of the efflux, as well as in the production of persisters, were investigated in the pathogen Aeromonas veronii, which causes huge economic losses in the aquatic industry and threatens human health. We observed that exclusively in exponential-phase cells, not in stationary-phase cells, the deletion of the acrR gene significantly (P < 0.05) promoted the expression of the acrA and acrB genes and reduced the intracellular accumulation of the efflux substrate Hoechst 33342. Moreover, overexpression of acrR triggered decreased transcription of the promoter of the acrAB operon. The persister assay indicated that the loss of the AcrAB pump decreased the formation of persisters under challenge with all tested antibiotic types of chloramphenicol, fluoroquinolone, tetracycline, and ß-lactam, while deletion of acrR caused an exponential-phase-specific increase in persister formation against chloramphenicol, tetracycline, and ß-lactam. Our results provide molecular insights into the mechanism of bacterial persistence by demonstrating for the first time that the local regulator AcrR is involved in the modulation of persister formation in A. veronii through its repressive activity on the function of the AcrAB efflux pump during the exponential growth period.


Asunto(s)
Aeromonas veronii , Proteínas de Escherichia coli , Humanos , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Antibacterianos/farmacología , Cloranfenicol/farmacología , beta-Lactamas , Tetraciclinas , Proteínas de Escherichia coli/genética
8.
Nucleic Acids Res ; 49(17): e100, 2021 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-34214175

RESUMEN

Numerous studies have shown that repetitive regions in genomes play indispensable roles in the evolution, inheritance and variation of living organisms. However, most existing methods cannot achieve satisfactory performance on identifying repeats in terms of both accuracy and size, since NGS reads are too short to identify long repeats whereas SMS (Single Molecule Sequencing) long reads are with high error rates. In this study, we present a novel identification framework, LongRepMarker, based on the global de novo assembly and k-mer based multiple sequence alignment for precisely marking long repeats in genomes. The major characteristics of LongRepMarker are as follows: (i) by introducing barcode linked reads and SMS long reads to assist the assembly of all short paired-end reads, it can identify the repeats to a greater extent; (ii) by finding the overlap sequences between assemblies or chomosomes, it locates the repeats faster and more accurately; (iii) by using the multi-alignment unique k-mers rather than the high frequency k-mers to identify repeats in overlap sequences, it can obtain the repeats more comprehensively and stably; (iv) by applying the parallel alignment model based on the multi-alignment unique k-mers, the efficiency of data processing can be greatly optimized and (v) by taking the corresponding identification strategies, structural variations that occur between repeats can be identified. Comprehensive experimental results show that LongRepMarker can achieve more satisfactory results than the existing de novo detection methods (https://github.com/BioinformaticsCSU/LongRepMarker).


Asunto(s)
Algoritmos , Biología Computacional/métodos , Genoma/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Secuencias Repetitivas de Ácidos Nucleicos/genética , Análisis de Secuencia de ADN/métodos , Animales , Secuencia de Bases , Mapeo Cromosómico/métodos , Simulación por Computador , Bases de Datos Genéticas , Humanos , Internet , Reproducibilidad de los Resultados , Alineación de Secuencia/métodos
9.
BMC Surg ; 23(1): 38, 2023 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-36803511

RESUMEN

BACKGROUND: Patients with normal preoperative serum albumin still suffer from a significant reduction in serum albumin after major abdominal surgery. The current study aims to explore the predictive value of ∆ALB for AL in patients with normal serum albumin and examine whether there is a gender difference in the prediction of AL. METHODS: Medical reports of consecutive patients undergoing elective sphincter-preserving rectal surgery between July 2010 and June 2016 were reviewed. Receiver operating characteristic (ROC) analysis was adopted to examine the predictive ability of ∆ALB and determine the cut-off value according to the Youden index. The logistic regression model was performed identify independent risk factors for AL. RESULTS: Out of the 499 eligible patients, 40 experienced AL. Results of the ROC analyses showed that ΔALB displayed a significant predictive value for females, and the AUC value was 0.675 (P = 0.024), with a sensitivity of 93%. In male patients, the AUC was 0.575 (P = 0.22), but did not reach a significant level. In the multivariate analysis, ∆ALB ≥ 27.2% and low tumor location prove to be independent risk factors for AL in female patients. CONCLUSIONS: The current study suggested that there may be a gender difference in the prediction of AL and ∆ ALB can serve as a potential predictive biomarker for AL in females. A cut-off value of the relative decline in serum albumin can help predict AL in female patients as early as postoperative day 2. Although our study needs further external validation, our findings may provide an earlier, easier and cheaper biomarker for the detection of AL.


Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo , Neoplasias del Recto , Humanos , Masculino , Femenino , Fuga Anastomótica/diagnóstico , Fuga Anastomótica/etiología , Albúmina Sérica/análisis , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Biomarcadores , Curva ROC , Neoplasias del Recto/cirugía , Neoplasias del Recto/complicaciones , Estudios Retrospectivos , Factores de Riesgo
10.
Molecules ; 28(3)2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36771049

RESUMEN

High dietary intake of ß-cryptoxanthin (BCX, an oxygenated provitamin A carotenoid) is associated with a lower risk of lung disease in smokers. BCX can be cleaved by ß-carotene-15,15'-oxygenase (BCO1) and ß-carotene-9',10'-oxygenase (BCO2) to produce retinol and apo-10'-carotenoids. We investigated whether BCX has protective effects against cigarette smoke (CS)-induced lung injury, dependent or independent of BCO1/BCO2 and their metabolites. Both BCO1-/-/BCO2-/- double knockout mice (DKO) and wild type (WT) littermates were supplemented with BCX 14 days and then exposed to CS for an additional 14 days. CS exposure significantly induced macrophage and neutrophil infiltration in the lung tissues of mice, regardless of genotypes, compared to the non-exposed littermates. BCX treatment significantly inhibited CS-induced inflammatory cell infiltration, hyperplasia in the bronchial epithelium, and enlarged alveolar airspaces in both WT and DKO mice, regardless of sex. The protective effects of BCX were associated with lower expression of IL-6, TNF-α, and matrix metalloproteinases-2 and -9. BCX treatment led to a significant increase in hepatic BCX levels in DKO mice, but not in WT mice, which had significant increase in hepatic retinol concentration. No apo-10'-carotenoids were detected in any of the groups. In vitro BCX, at comparable doses of 3-OH-ß-apo-10'-carotenal, was effective at inhibiting the lipopolysaccharide-induced inflammatory response in a human bronchial epithelial cell line. These data indicate that BCX can serve as an effective protective agent against CS-induced lung lesions in the absence of carotenoid cleavage enzymes.


Asunto(s)
Dioxigenasas , Productos de Tabaco , Ratones , Animales , Humanos , beta Caroteno/metabolismo , beta-Criptoxantina/farmacología , Vitamina A , Dioxigenasas/metabolismo , beta-Caroteno 15,15'-Monooxigenasa/genética , beta-Caroteno 15,15'-Monooxigenasa/metabolismo , Carotenoides/farmacología , Carotenoides/metabolismo , Oxigenasas , Pulmón/metabolismo , Ratones Noqueados
11.
Biochem Biophys Res Commun ; 598: 1-8, 2022 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-35149432

RESUMEN

BACKGROUND: ADAMTS8 expression has been identified to be low in many cancers including lung cancer. However, the specific functions and regulatory system of ADAMTS8 remain to be unveiled. PURPOSE: To study the potential modulatory mechanism of ADAMTS8 in lung cancer in cell and xenograft mice models. METHODS: Differential expression of ADAMTS8 in lung cancer was analyzed on online tools. So was the overall survival curve in association with ADAMTS8/VEGFA expression in lung cancer patients. RT-qPCR was applied to validate the ADAMTS8 expression in lung cancer cell lines H460 and A549, with the normal lung epithelial cell Beas-2b as a control. Thereafter, overexpressed and knockdown plasmids were constructed for transfection. Colony and flow cytometry methods were used for cell proliferation and apoptosis. RT-qPCR and Western blot methods validated the changes in VEGFA after ADAMTS8 regulation in cells. Tube formation and Transwell methods were applied to observe the changes in tube formation and migration in HUVECs induced by tumor conditioned medium (TCM). Stable-transfected cells were injected subcutaneously into nude mice. H&E and Immunohistochemistry were applied to analyze the pathological differences and protein changes of ADAMTS8, VEGFA and CD31. RESULTS: High ADAMTS8 was correlated with high overall survival rate in lung cancer patients. ADAMTS8 was also abnormally downregulated in NSCLC cells. Upregulation of ADAMTS8 suppressed cell proliferation and enhanced apoptosis while downregulation of ADAMTS8 promoted cell proliferation and decreased apoptosis. VEGFA was negatively correlated with ADAMTS8 in lung cancer tissues. Upregulation of ADAMTS8 inhibited VEGFA in mRNA and protein levels. Further, knockdown of ADAMTS8 induced tube formation and migration of HUVECs and upregulation of ADAMTS8 inhibited this. In addition, upregulation of ADAMTS8 in nude mice inhibited tumor growth and also suppressed VEGFA and CD31 in tumors. CONCLUSION: ADAMTS8 inhibited lung cancer progression through suppressing VEGFA in lung cancer.


Asunto(s)
Proteínas ADAMTS/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Factor A de Crecimiento Endotelial Vascular/genética , Proteínas ADAMTS/metabolismo , Animales , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Células Endoteliales de la Vena Umbilical Humana , Humanos , Neoplasias Pulmonares/genética , Ratones Endogámicos BALB C , Neovascularización Patológica/genética , Tasa de Supervivencia , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
12.
Bioinformatics ; 37(17): 2757-2760, 2021 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-33532819

RESUMEN

MOTIVATION: Compared with the second-generation sequencing technologies, the third-generation sequencing technologies allows us to obtain longer reads (average ∼10 kbps, maximum 900 kbps), but brings a higher error rate (∼15% error rate). Nanopolish is a variant and methylation detection tool based on hidden Markov model, which uses Oxford Nanopore sequencing data for signal-level analysis. Nanopolish can greatly improve the accuracy of assembly, whereas it is limited by long running time since most executive parts of Nanopolish is a serial and computationally expensive process. RESULTS: In this paper, we present an effective polishing tool, Multithreading Nanopolish (MultiNanopolish), which decomposes the whole process of iterative calculation in Nanopolish into small independent calculation tasks, making it possible to run this process in the parallel mode. Experimental results show that MultiNanopolish reduces running time by 50% with read-uncorrected assembler (Miniasm) and 20% with read-corrected assembler (Canu and Flye) based on 40 threads mode compared to the original Nanopolish. AVAILABILITY AND IMPLEMENTATION: MultiNanopolish is available at GitHub: https://github.com/BioinformaticsCSU/MultiNanopolish. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

13.
Cancer Cell Int ; 22(1): 13, 2022 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-34996459

RESUMEN

BACKGROUND: N6-methyladenosine (m6A) is a dynamic and reversible internal RNA structure of eukaryotic mRNA. YTH domain family 2 (YTHDF2), an m6A-specific reader YTH domain family, plays fundamental roles in several types of cancer. However, the function of YTHDF2 in lung squamous cell carcinoma (LUSC) remains elusive. METHODS: The knockdown and overexpression of YTHDF2 in LUSC cells were conducted to detect the biological characteristics of YTHDF2. In vivo assays, the role of YTHDF2 in tumor growth was further uncovered. In vitro assays, YTHDF2 was confirmed to be involved in activating the mTOR/AKT signaling and YTHDF2 overexpression induced the EMT process in LUSC. Clinically, immunohistochemical staining revealed the relationship between YTHDF2 expression levels and the clinicopathological characteristics of lung squamous cell carcinoma patients. Moreover, quantitative PCR (qPCR), western blot, CCK8 assay, transwell assay, and wound-healing assay were used to detect the expression level and function of YTHDF2 under hypoxia exposure in LUSC cells. RESULTS: The results showed that hypoxia-mediated YTHDF2 overexpression promotes cell proliferation and invasion by activating the mTOR/AKT axis, and YTHDF2 overexpression induces the EMT process in LUSC. Moreover, YTHDF2 is closely associated with pN (pN- 37.0%, pN + 73.9%; P = 0.002) and pTNM stage (pI 50.0%, PII 43.3%, pIIIa 80.6%; P = 0.007), ultimately resulting in poor survival for LUSC patients. CONCLUSION: In brief, the results highlight high-YTHDF2 expression predicted a worse prognosis of LUSC, while hypoxia-mediated YTHDF2 overexpression promotes lung squamous cell carcinoma progression by activation of the mTOR/AKT signaling pathway.

14.
Cancer Cell Int ; 22(1): 133, 2022 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-35331234

RESUMEN

Lung cancer remains one of the major causes of cancer-related death globally. Recent studies have shown that aberrant m6A levels caused by METTL3 are involved in the malignant progression of various tumors, including lung cancer. The m6A modification, the most abundant RNA chemical modification, regulates RNA stabilization, splicing, translation, decay, and nuclear export. The methyltransferase complex plays a key role in the occurrence and development of many tumors by installing m6A modification. In this complex, METTL3 is the first identified methyltransferase, which is also the major catalytic enzyme. Recent findings have revealed that METTL3 is remarkably associated with different aspects of lung cancer progression, influencing the prognosis of patients. In this review, we will focus on the underlying mechanism of METT3 in lung cancer and predict the future work and potential clinical application of targeting METTL3 for lung cancer therapy.

15.
Environ Sci Technol ; 56(18): 12873-12885, 2022 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-36083258

RESUMEN

The light-absorbing organic aerosol (OA) constitutes an important fraction of absorbing components, counteracting major cooling effect of aerosols to climate. The mechanisms in linking the complex and changeable chemistry of OA with its absorbing properties remain to be elucidated. Here, by using solvent extraction, ambient OA from an urban environment was fractionated according to polarity, which was further nebulized and online characterized with compositions and absorbing properties. Water extracted high-polar compounds with a significantly higher oxygen to carbon ratio (O/C) than methanol extracts. A transition O/C of about 0.6 was found, below and above which the enhancement and reduction of OA absorptivity were observed with increasing O/C, occurring on the less polar and high polar compounds, respectively. In particular, the co-increase of nitrogen and oxygen elements suggests the important role of nitrogen-containing functional groups in enhancing the absorptivity of the less polar compounds (e.g., forming nitrogen-containing aromatics), while further oxidation (O/C > 0.6) on high-polar compounds likely led to fragmentation and bleaching chromophores. The results here may reconcile the previous observations about darkening or whitening chromophores of brown carbon, and the parametrization of O/C has the potential to link the changing chemistry of OA with its polarity and absorbing properties.


Asunto(s)
Contaminantes Atmosféricos , Metanol , Aerosoles/análisis , Contaminantes Atmosféricos/análisis , Carbono/análisis , Nitrógeno , Oxígeno , Material Particulado/análisis , Solventes , Agua/química
16.
Acta Pharmacol Sin ; 43(3): 541-551, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34035485

RESUMEN

We previously showed that oral administration of exogenous glutathione (GSH) exerted a direct and/or indirect therapeutic effect on ischemic stroke rats, but the underlying mechanisms remain elusive. In the current study, we conducted a quantitative proteomic analysis to explore the pathways mediating the therapeutic effect of GSH in cerebral ischemia/reperfusion (I/R) model rats. Rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion. The rats were treated with GSH (250 mg/kg, ig) or levodopa (L-dopa, 100 mg/kg, ig) plus carbidopa (10 mg/kg, ig). Neurologic deficits were assessed, and the rats were sacrificed at 24 h after cerebral I/R surgery to measure brain infarct sizes. We conducted a proteomic analysis of the lesion side striatum samples and found that tyrosine metabolism and dopaminergic synapse were involved in the occurrence of cerebral stroke and the therapeutic effect of GSH. Western blot assay revealed that tyrosine hydroxylase (TH) mediated the occurrence of I/R-induced ischemic stroke and the therapeutic effect of GSH. We analyzed the regulation of GSH on endogenous small molecule metabolites and showed that exogenous GSH had the most significant effect on intrastriatal dopamine (DA) in I/R model rats by promoting its synthesis and inhibiting its degradation. To further explore whether DA-related alterations were potential targets of GSH, we investigated the therapeutic effect of DA accumulation on ischemic brain injury. The combined administration of the precursor drugs of DA (L-dopa and carbidopa) significantly ameliorated neurological deficits, reduced infarct size, and oxidative stress, and decreased pro-inflammatory cytokines levels in the striatum of I/R injury rats. More interestingly, exogenous L-dopa/carbidopa could also greatly enhance the exposure of intracerebral GSH by upregulating GSH synthetases and enhancing homocysteine (HCY) levels in the striatum. Thus, administration of exogenous GSH exerts a therapeutic effect on ischemic stroke by increasing intrastriatal DA, and the accumulated DA can, in turn, enhance the exposure of GSH and its related substances, thus promoting the therapeutic effect of GSH.


Asunto(s)
Dopamina/metabolismo , Glutatión/farmacología , Accidente Cerebrovascular Isquémico/patología , Animales , Carbidopa/farmacología , Citocinas/efectos de los fármacos , Modelos Animales de Enfermedad , Homocistina/efectos de los fármacos , Infarto de la Arteria Cerebral Media/patología , Levodopa/farmacología , Masculino , Estrés Oxidativo/genética , Proteómica , Ratas , Ratas Wistar , Daño por Reperfusión/patología , Tirosina 3-Monooxigenasa/efectos de los fármacos , Regulación hacia Arriba
17.
Environ Res ; 211: 113107, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35305979

RESUMEN

The oxidation of polycyclic aromatic hydrocarbons (PAHs) determines their lifetime, toxicity and consequent environmental and climate impacts. The residential solid fuel burning composes of a substantial fraction of PAH emissions; however, their oxidation rate is yet to be explicitly understood, which is complicated by the contrasting emission factors under different combustion conditions and their subsequent evolution in the atmosphere. Here we used a plume evolution chamber using ambient oxidants to simulate the evolution of residential solid fuel burning emissions under real-world solar radiation, and then to investigate the oxidation process of the emitted PAHs. Contrasting oxidation rate of PAHs was found to be influenced by particles with or without presence of substantial amount of black carbon (BC). In the flaming burning phase, which contained 46% of BC mass fraction and 8% of organic aerosol (OA) internally mixed with BC, the larger PAHs (with 4-7 rings) was rapidly oxidized 12% for every hour of evolution under solar radiation; however, the larger PAHs from smoldering phase tended to maintain unmodified during the evolution, when 95% of OA was externally mixed with only minor fraction of BC (<5%). This may be ascribed to the complex morphology of BC, allowing more exposure for the internally-mixed OA to the oxidants; in contrast with those externally-mixed OA which was prone to be coated by condensed secondary substances. This raises an important consideration about the particle mixing state in influencing the oxidation of PAHs, particularly the coating on PAHs which may extend their lifetime and environmental impacts.


Asunto(s)
Contaminantes Atmosféricos , Hidrocarburos Policíclicos Aromáticos , Aerosoles/análisis , Contaminantes Atmosféricos/análisis , Biomasa , Monitoreo del Ambiente , Oxidantes , Hidrocarburos Policíclicos Aromáticos/análisis , Hollín
18.
Langenbecks Arch Surg ; 407(7): 2959-2967, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35802267

RESUMEN

BACKGROUND: Currently, the relationship between temporary stoma reversal and the severity of postoperative complications (POCs) after the index surgery based on the Clavien-Dindo classification has not yet been explored. METHODS: From July 2010 to June 2016, 380 patients undergoing sphincter-preserving surgery for rectal cancer with a temporary stoma in our hospital were included. Temporary stoma nonclosure rates, disease-free survival rates, and overall survival rates were estimated utilizing the Kaplan-Meier method. RESULTS: Of all the 380 patients, primary stomas were created in 335 patients and secondary stomas in 45 patients. After the index surgery, 36.6% (139/380) of patients developed at least one postoperative complication. In the first analysis, which included all the patients, 24.7% of temporary stomas remained unclosed. In the second analysis for 335 patients with a primary stoma, 23.3% were left with unclosed stomas. After the COX regression analysis, both major POCs and minor POCs were found to be independent risk factors for the permanent stoma, and there was an increasing tendency toward the risk of permanent stoma with the increase in POC severity. CONCLUSION: POCs are independent predictors of permanent stoma after rectal cancer surgery. Even minor POCs may affect the outcome, while there is a clear direct relationship between POC severity and permanent stoma rates.


Asunto(s)
Complicaciones Posoperatorias , Neoplasias del Recto , Estomas Quirúrgicos , Humanos , Complicaciones Posoperatorias/epidemiología , Neoplasias del Recto/cirugía , Factores de Riesgo , Estomas Quirúrgicos/efectos adversos
19.
BMC Med Educ ; 22(1): 447, 2022 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-35681190

RESUMEN

BACKGROUND: BOPPPS (bridge-in, learning objective, pretest, participatory learning, posttest, and summary) is a student-centered modular teaching model that improves classroom teaching effectiveness. This study's primary aim was to explore whether the BOPPPS model has advantages over traditional instructional approaches in teaching lung cancer courses to clinical medical interns. METHODS: A total of 88 students majoring in clinical medicine of Shandong First Medical University and Shandong University, who had clinical practice in thoracic surgery from January 2018 to December 2019, were divided into two groups, receiving the same lung cancer teaching content. The experimental group (n = 44) utilized the BOPPPS model, while the control group (n = 44) used the traditional instructional approach. A questionnaire was used to attain the students' satisfaction and self-evaluation of the course, and a post-study examination was used to assess end-of-course performance. RESULTS: The experimental group's theoretical examination scores with the BOPPPS teaching model were significantly higher than those in the control group. Students preferred the BOPPPS model more than the traditional instructional approach in course satisfaction, student-teacher interaction, learning initiative, analytical ability, clinical thinking ability, and self-study ability (p < 0.05). CONCLUSIONS: Compared with the traditional instructional approach. The BOPPPS model can better inspire clinical medical students' enthusiasm for thoracic surgery and enhance the students' comprehensive ability. In a word, the BOPPPS model has better teaching effectiveness in the clinical teaching practice of thoracic surgery, which is worthy of reference and popularization.


Asunto(s)
Neoplasias Pulmonares , Estudiantes de Medicina , Cirugía Torácica , Evaluación Educacional , Humanos , Aprendizaje , Enseñanza
20.
Int J Mol Sci ; 23(20)2022 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-36293095

RESUMEN

Ethylene is a key phytohormone that regulates the ripening of climacteric fruits, and methionine is an indirect precursor of ethylene. However, whether methionine synthase plays a role in fruit ripening in Solanum lycopersicum (tomato) is still unknown. In this study, we find that a tomato methionine synthase (named SlMS1), which could be repressed at the transcriptional level by hydrogen sulfide (H2S), acts as a positive regulator for tomato fruit ripening. By a bioinformatics analysis, it is found that SlMS1 and SlMS2 in tomato are highly homologous to methionine synthases in Arabidopsis thaliana. The expression pattern of SlMS1 and SlMS2 is analyzed in tomato, and SlMS1 expression is up-regulated during fruit ripening, suggesting its potential role in regulating fruit ripening. A potential bipartite nuclear localization signal is found in the amino acid sequence of SlMS1; thus, SlMS1 is tagged with GFP and observed in the leaves of Nicotiana benthamiana. Consistently, SlMS1-GFP shows strong nuclear localization and also cytoplasmic localization. The role of SlMS1 in regulating fruit ripening is investigated in tomato fruit by transient silencing (virus-induced gene silencing, VIGS) and transient overexpression. The results show that SlMS1 silencing causes delayed fruit ripening, evidenced by more chlorophyll and less carotenoid accumulation, while SlMS1 overexpression accelerates fruit ripening significantly compared with control. Further investigation shows that SlMS1 overexpression could up-regulate the expression of carotenoid-synthesis-related genes (PSY1, PDS, ZDS), chlorophyll-degradation-related genes (NYC1, PAO, PPH, SGR1), cell-wall-metabolism-related genes (CEL2, EXP, PG, TBG4, XTH5) and ethylene-synthesis-pathway-related genes (ACO1, ACO3, ACS2), while SlMS1 silencing causes the opposite results. The correlation analysis indicates that SlMS1 expression is negatively correlated with chlorophyll content and positively correlated with carotenoid and ripening-related gene expressions. Taken together, our data suggest that SlMS1 is a positive regulator of tomato fruit ripening and a possible target gene for the ripening-delaying effect of H2S.


Asunto(s)
Sulfuro de Hidrógeno , Solanum lycopersicum , Solanum lycopersicum/metabolismo , Frutas/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Sulfuro de Hidrógeno/metabolismo , 5-Metiltetrahidrofolato-Homocisteína S-Metiltransferasa/genética , Señales de Localización Nuclear/genética , Proteínas de Plantas/metabolismo , Etilenos/metabolismo , Carotenoides/metabolismo , Clorofila/metabolismo , Metionina/metabolismo , Hidrógeno/metabolismo , Sulfuros/metabolismo
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