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BACKGROUND: The tumour mutation burden (TMB) is a valuable indicator of the accumulation of somatic mutations, and is thought to be associated with the biological behaviour and prognosis of tumours. However, the related genetic mechanism for these association is still unclear. The aim of the present study was to identify the key gene(s) associated with TMB in hepatocellular carcinoma (HCC) and to investigate its biological functions, downstream transcription factors, and mechanism of action. METHODS: Patients in The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) database were classified according to TMB signature-related genes. Key genes related to the TMB signature and tumour prognosis were identified. Immunohistochemistry and Quantitative Real-Time Polymerase Chain Reaction (qPCR) were then used to assess gene expression in clinical HCC tissues and HCC cells. Cells with altered gene expression were evaluated for the effect on cell proliferation and apoptosis, both in vitro and in vivo. Three independent databases and cell sequencing data were used to identify the mechanisms involved and the downstream transcription factors. The mechanism was also studied by altering the expression of downstream transcription factors in vitro. RESULT: The integrated cluster (IC) 2 group, characterized by 99 TMB signature-related genes, showed a significant different TMB score compared to the IC1 group (p < 0.001), as well as more favourable tumour prognosis (p = 0.031). We identified five key prognostic genes that were differentially expressed between IC2 and IC1 and were associated with overall survival. The expression of one of these key prognostic genes, RCAN2, was negatively correlated with TMB in 18 out of 33 tumour types examined. A high level of RCAN2 was correlated with better overall survival in HCC (p = 0.0009). Overexpression of RCAN2 enhanced apoptosis in vitro and in vivo, whereas knockdown of RCAN2 attenuated apoptosis. The mechanism by which RCAN2 promotes apoptosis may involve upregulation of the expression of ETS homologous factor (EHF) and of death receptor 5 (DR5). CONCLUSIONS: Downregulation of RCAN2 expression was found to correlate with elevated TMB in multiple cancer types. RCAN2 was also found to be a biomarker of HCC prognosis, and to promote the apoptosis of HCC cells through the EHF/DR5 pathway. These findings provide a new perspective on systemic treatment for advanced HCC with a high TMB.
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Apoptosis , Carcinoma Hepatocelular , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas , Proteínas Musculares , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF , Factores de Transcripción , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Apoptosis/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Ratones Desnudos , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Mutación , Pronóstico , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/genética , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Transducción de Señal/genética , Regulación hacia Arriba/genética , Factores de Transcripción/metabolismoRESUMEN
Nanosized ultrafine particles (UFPs) from natural and anthropogenic sources are widespread and pose serious health risks when inhaled by humans. However, tracing the inhaled UFPs in vivo is extremely difficult, and the distribution, translocation, and metabolism of UFPs remain unclear. Here, we report a label-free, machine learning-aided single-particle inductively coupled plasma mass spectrometry (spICP-MS) approach for tracing the exposure pathways of airborne magnetite nanoparticles (MNPs), including external emission sources, and distribution and translocation in vivo using a mouse model. Our results provide quantitative analysis of different metabolic pathways in mice exposed to MNPs, revealing that the spleen serves as the primary site for MNP metabolism (84.4%), followed by the liver (11.4%). The translocation of inhaled UFPs across different organs alters their particle size. This work provides novel insights into the in vivo fate of UFPs as well as a versatile and powerful platform for nanotoxicology and risk assessment.
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Hígado , Aprendizaje Automático , Nanopartículas de Magnetita , Espectrometría de Masas , Tamaño de la Partícula , Animales , Ratones , Nanopartículas de Magnetita/química , Espectrometría de Masas/métodos , Hígado/metabolismo , Bazo/metabolismo , Material Particulado/análisis , Material Particulado/química , Distribución TisularRESUMEN
Chronic myeloid leukemia (CML) is a type of hematologic malignancies caused by BCR-ABL chimeric oncogene. Resistance to tyrosine kinase inhibitors (TKIs) leads to the progression of CML into advanced stages. Selinexor is a small molecule inhibitor that targets a nuclear transporter called Exportin 1. Combined with imatinib, selinexor has been shown to disrupt nuclear-cytoplasmic transport signal of leukemia stem cells, resulting in cell death. The objective of this study was to investigate the mechanism of drug resistance to selinexor in CML. We established K562 cell line resistant to selinexor and conducted single cell dynamic transcriptome sequencing to analyze the heterogeneity within the parental and selinexor resistant cell populations. We identified specific gene expression changes associated with resistance to selinexor. Our results revealed differential expression patterns in genes such as MT2A, TFPI, MTND3, and HMGCS1 in the total RNA, as well as MT-TW, DNAJB1, and HSPB1 in the newly synthesized RNA, between the parental and drug-resistant groups. By applying pseudo-time analysis, we discovered that a specific cluster of cells exhibited characteristics of tumor stem cells. Furthermore, we observed a gradual decrease in the expression of ferroptosis-related molecules as drug resistance developed. In vitro experiments confirmed that the combination of a ferroptosis inducer called RSL3 effectively overcame drug resistance. In conclusion, this study revealed the resistance mechanism of selinexor in CML. In conclusion, we identified a subgroup of CML cells with tumor stem cell properties and demonstrated that ferroptosis inducer improved the efficacy of selinexor in overcoming drug resistance.
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Resistencia a Antineoplásicos , Hidrazinas , Leucemia Mielógena Crónica BCR-ABL Positiva , Triazoles , Humanos , Hidrazinas/farmacología , Hidrazinas/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Resistencia a Antineoplásicos/genética , Triazoles/farmacología , Células K562 , Análisis de la Célula Individual , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , RNA-Seq , Análisis de Expresión Génica de una Sola CélulaRESUMEN
With the increasing use of metal-organic frameworks (MOFs), they will inevitably enter the environment intentionally or unintentionally. However, the effects of MOFs on plant growth are poorly understood. Here, we investigated the effects of exposure of the rhizosphere to MOFs on plant growth. MIL-101(Cr) was selected as a research model due to its commercial availability and wide use. Soybean plants at the two-leaf stage were subjected to various durations (1-7 days) and concentrations (0-1000 mg/L) of exposure in hydroculture with a control group treated with ultrapure water. We found that MIL-101(Cr) had a positive effect on soybean growth at a lower dose (i.e., 200 mg/L); however, at higher doses (i.e., 500 and 1000 mg/L), it exhibited significant toxicity to plant growth, which is evidenced by leaf damage. To investigate the mechanism of this effect, we used Cr as an indicator to quantify, track, and image MIL-101(Cr) in the plant with laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Results indicated that MIL-101(Cr) primarily accumulated in the cortex of roots (up to 40 times higher than that in stems), with limited translocation to stems and negligible presence in leaves and cotyledons. In addition, metabolomic analysis of soybeans indicated that low-dose MIL-101(Cr) could increase the sucrose content of soybean roots to promote plant growth, while a high dose could induce lipid oxidation in roots. This study provides valuable insights into the ecological toxicology of MOFs and underscores the importance of assessing their environmental impact for sustainable agricultural practices.
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Glycine max , Estructuras Metalorgánicas , Glycine max/efectos de los fármacos , Glycine max/crecimiento & desarrollo , Desarrollo de la Planta/efectos de los fármacosRESUMEN
The widespread application of metal-organic frameworks (MOFs) is seriously hindered by their structural instability and it is still very challenging to probe the stability of MOFs during application by current techniques. Here, we report a novel structure-responsive mass spectrometry (SRMS) imaging technique to probe the stability of MOFs. We discovered that intact CuBTC (as a model of MOFs) could generate the characteristic peaks of organic ligands and carbon cluster anions in laser desorption/ionization mass spectrometry, but these peaks were significantly changed when the structure of CuBTC was dissociated, thus enabling a label-free probing of the stability. Furthermore, SRMS can be performed in imaging mode to visualize the degradation kinetics and reveal the spatial heterogeneity of the stability of CuBTC. This technique was successfully applied in different application scenarios (in water, moist air, and CO2) and also validated with different MOFs. It thus provides a versatile new tool for better design and application of environment-sensitive materials.
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Altered DNA methylation is a crucial epigenetic event in hepatocellular carcinoma (HCC) development and progression. Through methylation-transcriptomic analysis, we identified a set of sixty potential DNA methylation-based epidriver genes. In this set of genes, we focused on the hypermethylation of EMX1, which is frequently observed in hepatobiliary tumors. Despite of its frequent occurrence, the function of EMX1 remains largely unknown. By utilizing bisulfite-next-generation sequencing, we have detected EMX1 DNA hypermethylation on the gene body, which is positively correlated with EMX1 mRNA expression. Further analysis revealed that EMX1 mRNA terminal exon splicing in HCC generated two protein isoforms: EMX1 full length (EMX1-FL) and alternative terminal exon splicing isoform (EMX1-X1). Cellular functional assays demonstrated that gain-of-function EMX1-FL, but not EMX1-X1, induced HCC cells migration and invasion while silencing EMX1-FL inhibited HCC cells motility. This result was further validated by in vivo tumor metastasis models. Mechanistically, EMX1-FL bound to EGFR promoter, promoting EGFR transcription and activating EGFR-ERK signaling to trigger tumor metastasis. Therefore, EGFR may be a potential therapeutic target for EMX1-high expression HCC. Our work illuminated the crucial role of gene body hypermethylation-activated EMX1-FL in promoting tumorigenesis and metastasis in HCC. These findings pave the way for targeting the EMX1-EGFR axis in HCC tumorigenicity and metastasis.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Metilación de ADN/genética , Neoplasias Hepáticas/patología , Línea Celular Tumoral , Receptores ErbB/genética , Receptores ErbB/metabolismo , ARN Mensajero/metabolismo , Regulación Neoplásica de la Expresión Génica , Metástasis de la NeoplasiaRESUMEN
Elemental carbon (EC) and organic carbon (OC) exist ubiquitously and interact mutually in the environment. Simultaneous analysis of EC and OC will greatly advance our understanding of the behavior and fate of EC and OC, but is however still a great challenge due to the lack of suitable analytical tools. Here, we report a matrix-free laser desorption/ionization mass spectrometry (LDI-MS) method capable of simultaneous analysis of EC and OC by monitoring two independent groups of specific MS fingerprint peaks. We found that EC itself can generate carbon cluster peaks in the low mass range under laser excitation, and meanwhile it can also serve as a matrix to assist the ionization of OC in LDI-MS. By using per- and polyfluoroalkyl substances (PFASs) as a typical set of OC and carbon black (CB) as a model EC, we successfully monitored the adsorption process of PFASs on CB enabled by LDI-MS. We show that hydrophobic interaction dominates the sorption of PFASs to CB, which was affected by the functional groups and carbon chain length of PFASs. Furthermore, environmental substances in water such as humic acid (HA) and surfactants can significantly affect the adsorption of PFASs on CB probably by changing the adsorption sites of CB. Overall, we demonstrate that LDI-MS offers a versatile and high-throughput tool for simultaneous analysis of EC and OC species in real environmental samples, which makes it promising for investigating the environmental behaviors and ecological risks of pollutants.
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Carbono , Fluorocarburos , Espectrometría de Masas , Espectrometría de Masas/métodos , Carbono/análisis , Hollín/análisis , Monitoreo del Ambiente , Aguas Residuales/química , Absorción , Fluorocarburos/química , Contaminantes Ambientales/análisisRESUMEN
To understand the nanotoxicity effects on plants, it is necessary to systematically study the distribution of NPs in vivo. Herein, elemental and particle-imaging techniques were used to unravel the size effects of ZnO NPs on phytotoxicity. Small-sized ZnO NPs (5, 20, and 50 nm) showed an inhibitory effect on the length and biomass of rice (Oryza sativa L.) used as a model plant. ZnO NP nanotoxicity caused rice root cell membrane damage, increased the malondialdehyde content, and activated antioxidant enzymes. As a control, the same dose of Zn2+ salt did not affect the physiological and biochemical indices of rice, suggesting that the toxicity is caused by the entry of the ZnO NPs and not the dissolved Zn2+. Laser ablation inductively coupled plasma optical emission spectroscopy analysis revealed that ZnO NPs accumulated in the rice root vascular tissues of the rhizodermis and procambium. Furthermore, transmission electron microscopy confirmed that the NPs were internalized to the root tissues. These results suggest that ZnO NPs may exist in the rice root system and that their particle size could be a crucial factor in determining toxicity. This study provides evidence of the size-dependent phytotoxicity of ZnO NPs.
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Oryza , Óxido de Zinc , Tamaño de la Partícula , Óxido de Zinc/toxicidad , Antioxidantes , BiomasaRESUMEN
Atmospheric particulate matter (PM) perturbs hematological homeostasis by targeting the plasma kallikrein-kinin system (KKS), causing a cascade of zymogen activation events. However, the causative components involved in PM-induced hematological effects are largely unknown. Herein, the standard reference materials (SRMs) of atmospheric PM, including emissions from the diesel (2975), urban (1648a), and bituminous coal (2693), were screened for their effects on plasma KKS activation, and the effective constituent contributing to PM-induced KKS activation was further explored by fraction isolation and chemical analysis. The effects of three SRMs on KKS activation followed the order of 2975 > 1648a > 2693, wherein the fractions of 2975 isolated by acetone and water, together with the insoluble particulate residues, exerted significant perturbations in the hematological homeostasis. The soot contents in the SRMs and corresponding isolated fractions matched well with their hematological effects, and the KKS activation could be dependent on the soot surface oxidation degree. This study, for the first time, uncovered the soot content in atmospheric PM with different origins contributed to the distinct effects on plasma KKS activation. The finding would be of utmost importance for the health risk assessment on inhaled airborne fine PM, given its inevitable contact with human circulatory system.
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Contaminantes Atmosféricos , Sistema Calicreína-Quinina , Material Particulado , Humanos , Sistema Calicreína-Quinina/fisiología , Hollín , Contaminantes Atmosféricos/análisisRESUMEN
The overall survival (OS) rate of patients with colorectal cancer (CRC) remains low due to the lack of clear prognostic markers. Therefore, the identification of valuable prognostic markers is urgently required. Snail and E-Cadherin (E-Cad) are important protein molecules in the EMT process and play a crucial role in tumor invasion and metastasis. The present study investigated the clinical significance of Snail and E-cad expression in CRC. Compared with those in adjacent tissue, the expression levels of Snail and E-cad were significantly increased and decreased, respectively, in CRC. Moreover, low Snail and high E-cad expression were associated with clinicopathological features and longer OS time. Furthermore, Snail and E-cad could predict the prognosis of patients with CRC. Reverse transcription-qPCR, Western blotting, Wound scratch assay, High content cell migration experiment, which showed that low Snail or high E-cad expression inhibited invasion and metastasis of CRC. In conclusion, Snail can promote CRC invasion and metastasis by regulating E-cad. Snail and E-cad expression constitute a novel prognostic marker for CRC, and the present study revealed a greater combined effect of Snail and E-cad as effective prognostic markers in CRC for the first time.
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Background: Perivascular epithelioid cell neoplasm (PEComa) is a rare mesenchymal tumour. Due to its low incidence, a standard treatment regimen for PEComa has not yet been established. Radiotherapy has a synergistic effect with PD-1 inhibitors and GM-CSF. We treated advanced malignant PEComa with a triple regimen of PD-1 inhibitor, SBRT and GM-CSF to provide better therapeutic effect. Case presentation: A 63-year-old woman was diagnosed with malignant PEComa after presenting with postmenopausal vaginal bleeding. Despite two surgeries, the neoplasm eventually metastasized throughout the body. We formulated triple therapy with SBRT, a PD-1 inhibitor, and GM-CSF for the patient. The patient's local symptoms were controlled at the radiotherapy site, and the lesions at the unirradiated sites were also relieved. Conclusions: For the first time, a triple regimen of PD-1 inhibitor, SBRT and GM-CSF was used in the treatment of malignant PEComa and achieved good efficacy. Considering the lack of prospective clinical studies in PEComa, we believe that this triple therapy is a good-quality regimen for advanced malignant PEComa.
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Background: The effect of post-operation sub-Tenon's bupivacaine injection for pediatric strabismus surgery is controversial. The objective of this meta-analysis is to compare the outcome of sub-Tenon injection of bupivacaine and placebo duringstrabismus surgery. Methods: We searched the databases (Pubmed, Cochrane library and EMBASE) and reference lists systematically. Randomized controlled trials (RCTs) comparing sub-Tenon's bupivacaine and placebo injection for pediatric strabismus surgery were included. The methodological quality was evaluated by the Cochrane risk of bias (ROB) tool. Outcome measurements were pain score, oculocardiac reflex (OCR), additional drug consumption and related complications. RevMan 5.4 was used for the statistical analysis and graph preparation. For the outcomes that are not suitable for statistical analysis, descriptive analysis was performed. Results: A total of 5 RCTs with 217 patients were finally identified and analyzed. Sub-Tenon's bupivacaine injection showed pain relief within 30â min after operation. But with the extension of time, the analgesic effect gradually disappeared at 1â h. It can reduce the incidence of OCR, vomiting and supplementary drug requirements. However, in terms of nausea, there is no difference between the two groups. Conclusion: Sub-Tenon's bupivacaine injection can relieve short-term postoperative pain, reduce the incidence of OCR and vomiting, and reduce the use of supplementary drugs in strabismus surgery.
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Increasing concerns have been raised on the health risks of parabens in the regard of their widespread applications and potential endocrine disrupting activities. In this study, four typical parabens, including methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP), and butyl paraben (BuP) were systematically investigated for their estrogen receptor- and steroid hormone-related endocrine disruptions using multi-level approaches. Paraben exposure promoted the proliferation of MCF-7 cells, increased the luciferase activity in MVLN cells, and induced the vitellogenin (vtg) expression in zebrafish larvae, showing the typical estrogenic effects. The in vitro protein assays further revealed that PrP and BuP could bind with two isoforms of estrogen receptors (ERs). The estrogenic activities of parabens were predicted to be positively correlated with their chemical structure complexity by using molecular docking analysis. Furthermore, the synthesis and secretion of estradiol (E2) and testosterone (T) were significantly disturbed in H295R cells and zebrafish larvae, which could be regulated by paraben-induced transcriptional disturbance in both in vitro steroidogenesis and in vivo hypothalamic-pituitary-gonadal (HPG) axis. Parabens could disturb the endocrine system by activating the ERs and disrupting the steroid hormone synthesis and secretion, suggesting their potential deleterious risks to the environment and human health.
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Disruptores Endocrinos , Parabenos , Receptores de Estrógenos , Animales , Humanos , Estradiol , Simulación del Acoplamiento Molecular , Parabenos/toxicidad , Parabenos/metabolismo , Receptores de Estrógenos/metabolismo , Pez Cebra/metabolismo , Disruptores Endocrinos/metabolismo , Disruptores Endocrinos/farmacologíaRESUMEN
Gastrodiae rhizoma (GR) formula granules and preparations have been used as a popular traditional Chinese medicine for clinical treatment since they have good pharmacological activity to treat nervous system diseases. Gastrodin and parishins have been the main active components in aqueous extracts for GR formula granules, but their pharmacological activities and metabolism are different. For quality control of the extracts, the extraction conditions should be investigated to accurately control the contents of two kinds of components. In this paper, the transfer rate of six index components (including gastrodin, p-hydroxybenzyl alcohol, parishin A, parishin B, parishin C, and parishin E) obtained by HPLC were used as indicators to investigate the effect of pH on the GR extraction process. The results demonstrated that pH is a key factor for preventing transforming parishins into gastrodin and maintaining high content of parishins in the extracts. It can be concluded that the weak acid environment could improve the transfer rate of parishins, thus ensuring the gastrodin and parishins consistency between GR raw materials and its aqueous extracts. Therefore, pH is an essential condition for accurate quality control of the extracts.
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Gastrodia , Gastrodia/química , Rizoma/química , Cromatografía Líquida de Alta Presión , Concentración de Iones de HidrógenoRESUMEN
Soot, mainly derived from incomplete combustion of fossil fuel and biomass, exists ubiquitously in different environmental matrixes. To study the detrimental effects of soot on climate, air quality, and human health, accurate quantification of soot is an important prerequisite. However, until now, quantification of soot in environmental media, especially in carbonaceous media, is still very challenging. Here, we report a matrix-free laser desorption/ionization mass spectrometry (LDI-MS) method for in situ imaging of soot particles in size-segregated aerosol samples collected on filter membranes. A series of round-shaped sample spots in filter membranes were selected and subjected to MS imaging analysis, enabling direct in situ quantification of soot without solvent extraction or separation. Especially, the MS imaging with serial sample spots can overcome the problems of sweet-spot in LDI-MS and inhomogeneous distribution of soot in the filter membrane, thus greatly improving the precision of quantification. The limit of detection of soot was 4 ng/m2 and the recovery was 84.4-126%. By using this method, we found that a higher soot content was present in larger-sized particulate matter than smaller-sized particles, suggesting that aerosol soot was mainly derived from primary emission sources. Furthermore, this method also shows the potential to analyze nitrate and sulfate species in PM2.5. To the best of our knowledge, it is the first method capable of simultaneous analysis of inorganic salts and soot in air samples. It represents a novel strategy for in situ quantification of aerosol soot with the advantages of high specificity, high sensitivity, separation-, solvent- and matrix-free.
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Contaminantes Atmosféricos , Hollín , Humanos , Hollín/química , Contaminantes Atmosféricos/análisis , Material Particulado/análisis , Aerosoles/análisis , Espectrometría de Masas/métodos , Solventes/análisis , Carbono/química , Monitoreo del AmbienteRESUMEN
With the ever-evolving cannabis industry, low-cost and high-throughput analytical methods for cannabinoids are urgently needed. Normally, (potentially) psychoactive cannabinoids, typically represented by Δ9-tetrahydrocannabinol (Δ9-THC), and nonpsychoactive cannabinoids with therapeutic benefits, typically represented by cannabidiol (CBD), are the target analytes. Structurally, the former (tetrahydrocannabinolic acid (THCA), cannabinol (CBN), and THC) have one olefinic double bond and the latter (cannabidiolic acid (CBDA), cannabigerol (CBG), and CBD) have two, which results in different affinities toward Ag(I) ions. Thus, a silica gel thin-layer chromatography (TLC) plate with the lower third impregnated with Ag(I) ions enabled within minutes a digital chromatographic separation of strongly retained CBD analogues and poorly retained THC analogues. The resolution (Rs) between the closest two spots from the two groups was 4.7, which is almost 8 times higher than the resolution on unmodified TLC. After applying Fast Blue BB as a chromogenic reagent, smartphone-based color analysis enabled semiquantification of the total percentage of THC analogues (with a limit of detection (LOD) of 11 ng for THC, 54 ng for CBN, and 50 ng for THCA when the loaded volume is 1.0 µL). The method was validated by analyzing mixed cannabis extracts and cannabis extracts. The results correlated with those of high-performance liquid chromatography with ultraviolet detection (HPLC-UV) (R2 = 0.97), but the TLC approach had the advantages of multi-minute analysis time, high throughput, low solvent consumption, portability, and ease of interpretation. In a desiccator, Ag(I)-TLC plates can be stored for at least 3 months. Therefore, this method would allow rapid distinction between high and low THC varieties of cannabis, with the potential for on-site applicability.
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Cannabidiol , Cannabinoides , Cannabis , Alucinógenos , Cannabidiol/análisis , Cannabinoides/análisis , Cannabinol/análisis , Cannabis/química , Cromatografía en Capa Delgada , Dronabinol/análisis , Extractos Vegetales/química , Gel de Sílice , Teléfono Inteligente , SolventesRESUMEN
Objectives: Colorectal cancer(CRC) is a common malignant tumor. Recent studies have found that lncRNAs play an important role in the occurrence and development of colorectal cancer. Methods: Based on high-throughput sequencing results of fresh CRC tissues and adjacent tissues, we identified lncRNA-ENST00000543604 (lncRNA 604) as the research object by qRT-PCR in CRC tissues and cells. We explored the mechanism of lncRNA 604 action by using luciferin reporter, qRT-PCR and Western blot assays. Kaplan-Meier survival analysis and a Cox regression model were used to analyze the correlation of lncRNA 604 and its regulatory molecules with the prognosis of and chemotherapy efficacy in CRC patients. Results: In this study, we found that the expression levels of lncRNA 604 were increased in CRC. LncRNA 604 could promote CRC cell proliferation and metastasis through the miRNA 564/AEG-1 or ZNF326/EMT signaling axis in vivo and in vitro. LncRNA 604 could predict the prognosis of CRC and was an independent negative factor. LncRNA 604 exerted a synergistic effect with miRNA 564 or ZNF326 on the prognosis of CRC. LncRNA 604 could improve chemoresistance by increasing the expression of AEG-1, NF-κB, and ERCC1. Conclusions: Our study demonstrated that lncRNA 604 could promote the progression of CRC via the lncRNA 604/miRNA 564/AEG-1/EMT or lncRNA 604/ZNF326/EMT signaling axis. LncRNA 604 could improve chemoresistance by increasing drug resistance protein expression.
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OBJECTIVE: To compare the clinical therapeutic effect on acute ischemic stroke between Naochang Tongtiao acupuncture (acupuncture for brain-gut homology) and conventional acupuncture, and to explore the possible mechanism. METHODS: A total of 64 patients with acute ischemic stroke were randomized into an observation group and a control group, 32 cases in each one. Basic western medical therapy was adopted in both groups. In the observation group, Naochang Tongtiao acupuncture was applied at anterior oblique line of vertex-temporal, Zhongwan (CV 12), Guanyuan (CV 4), Tianshu (ST 25), Zusanli (ST 36), Shangjuxu (ST 37) and Xiajuxu (ST 39). In the control group, conventional acupuncture was applied. The treatment was given once a day, 6 days a week for 3 weeks in both groups. Before and after treatment, National Institution of Health stroke scale (NIHSS) score, serum levels of interleukin-17 (IL-17) and hypersensitive C reactive protein (hs-CRP), and plasma level of trimethylamine oxide (TMAO) were compared in the two groups. RESULTS: After treatment, NIHSS scores, serum levels of IL-17 and hs-CRP, and plasma levels of TMAO were decreased compared before treatment in both groups (P<0.01), and those in the observation group were lower than the control group (P<0.05). CONCLUSION: Naochang Tongtiao acupuncture can improve the nerve function in patients with acute ischemic stroke, its therapeutic effect is superior to conventional acupuncture, the mechanism may relate to the regulation on inflammatory reaction and the level of intestinal flora metabolite.
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Terapia por Acupuntura , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Puntos de Acupuntura , Eje Cerebro-Intestino , Proteína C-Reactiva , Humanos , Interleucina-17 , Accidente Cerebrovascular Isquémico/terapia , Metilaminas , Accidente Cerebrovascular/terapia , Resultado del TratamientoRESUMEN
Objective: In recent years, with the attention of the general people to health, the surgical treatment of small nodules has become necessary. However, some nodules are too small, too deep, or difficult to reach, and it is difficult to accurately locate small nodules in the process of routine resection. In order to solve this problem and increase the success rate of puncture surgery, this study analyzed the application value of zoning localization method guided by CT in patients with pulmonary nodules. Methods: The clinical history of patients with pulmonary nodules treated in Anhui Third Affiliated Hospital was retrospectively studied and analyzed. 97 patients with solitary pulmonary nodules treated in Anhui Third Affiliated Hospital from June 2021 to August 2021 were divided into observation group and reference group according to whether CT-guided localization method was used during operation. The operation rate, 1-year survival rate, recurrence rate, and pulmonary nodule metastasis rate of the two groups were compared; the results showed that the CT-guided zonal localization method was long and short, accurate, safe, and reliable. Comprehensive comparison through market survey on postoperative recovery compares the variability of patient data by using the statistical bivariatet-calibration method and using sensitivity specificity to analyze whether the CT-guided positioning method has advantages. Results: The data underlying the results presented in the study are available within the manuscript. The results showed that there were 37 cases of pulmonary nodules, accounting for 38.14%; there were 8 patients with lung cancer, accounting for 8.24%; the proportion of diagnosis and analysis results of pulmonary nodules in hospitalized patients was significant; the medical history and clinical diagnosis information of 37 patients with pulmonary nodules were tracked and analyzed in detail. The diagnostic results were as follows: 8 patients (21.62%) with stage I, 11 patients (29.72%) with stage II, and 18 patients (48.64%) with stage III. The proportion of severe patients in the third stage was significantly higher than that in the first two stages; the results of CT-guided localization and conventional surgical resection were T < 10.000 and P < 0.05; the observation of prognosis and quality of life in the later stage of resection treatment showed that the observation group had obvious advantages over the reference group in terms of postoperative survival rate, recurrence rate, and nodule deterioration rate. The results show that the CT-guided zoning positioning operation is accurate, safe, and reliable. Conclusion: The application of the CT-guided localization in the surgical treatment of pulmonary nodules is more safe and reliable. It can not only reduce the trauma but also improve the success rate of operation and reduce postoperative complications. It has the value of clinical promotion.
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Objective: Four and a half Lin-11, Isl-1, Mac-3 (LIM) protein 1 (FHL1) is one of the FHL protein family, which is regarded as a tumor suppressor in the multiple malignant tumors. In this study, we aimed to explore the regulatory effects and mechanisms of FHL1 on lung cancer cell invasion. Materials and Methods: In this experimental study, bioinformatics analysis of FHL1 transcripts in human lung adenocarcinomas of TCGA database was performed. Quantitative real-time polymerase chain reaction (PCR) was performed to detect FHL1 mRNA expression in 15 paired human lung cancer tissues and their adjacent normal lung tissues, or lung cancer cell lines (A549 and H1299) in comparison with human bronchial epithelial cell line (Beas- 2B). Moreover, western blot was used to analyze FHL1 and rho GDP-dissociation inhibitor beta (RhoGDIß) protein expression in the indicated cell lines. Also, transwell assays were employed to measure the migrated, and invaded of indicated cell lines. Results: FHL1 transcripts were downregulated in the human lung adenocarcinoma. The impaired FHL1 transcripts were positively correlated with advanced tumor node metastasis (TNM) stage. Moreover, as compared to the adjacent normal lung tissues, FHL1 mRNA was low expressed in 15 paired human lung cancer tissues than their adjacent normal lung tissues. Besides, FHL1 mRNA and protein expression were also reduced in H1299 and A549 cell lines in comparison with Beas-2B cell line. Overexpressed FHL1 protein inhibited the invasive ability of H1299 and A549 cell lines. Mechanically, FHL1 protein overexpression increased the RhoGDIß protein and mRNA abundance, while knockdown of RhoGDIß protein, completely restored the invasion ability of A549 (Flag-FHL1) cell line. Conclusion: Our findings indicated that as a key FHL1 downstream regulator, RhoGDIß is in charge of FHL1 inhibiting lung cancer cell invasion abilities, providing a critical insight into understanding the role of FHL1 for lung cancer development.