ABSTRACT
Lymphoma, a blood tumor, has become the ninth most common cancer in the world in 2020. Targeted inhibition is one of the important treatments for lymphoma. At present, there are many kinds of targeted drugs for the treatment of lymphoma. Studies have shown that Histone deacetylase, Bruton's tyrosine kinase and phosphoinositide 3-kinase all play an important role in the occurrence and development of tumors and become important and promising inhibitory targets. This article mainly expounds the important role of these target protein in tumors, and introduces the mechanism of action, structure-activity relationship and clinical research of listed small molecule inhibitors of these targets, hoping to provide new ideas for the treatment of lymphoma.
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Waste cooking oil's (WCO's) potential as a rejuvenator of aged asphalt has received attention in recent years, with the acid value of WCO affecting its rejuvenation effect. This study explored the rejuvenation effect of WCO with a high acid value on aged asphalt by using molecular dynamics simulation. First, the representative molecules of WCO with a high acid value and asphalt were determined. The rejuvenation effect of WCO on aged asphalt was analyzed by adding different contents of WCO to an aged asphalt model. The effect of WCO on the thermodynamic properties of the aged asphalt was analyzed. The results show that WCO can restore the thermodynamic properties of aged asphalt binder to a certain extent. Regarding the microstructure of rejuvenated asphalt, WCO molecules dispersed around asphaltenes weakened the latter's aggregation and improved the colloidal structure of the aged asphalt. In terms of interface adhesion properties, WCO can improve the adhesion properties between asphalt binder and SiO2, but it has limited influence on water sensitivity. The results allowed us to comprehensively evaluate the rejuvenation effect of WCO with a high acid value on aged asphalt and to explore its rejuvenation mechanism.
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INTRODUCTION: This study is a retrospective study. This study aims to explore the association between lobectomy in lung cancer patients and subsequent compensatory lung growth (CLG), and to identify factors that may be associated with variations in CLG. METHODS: 207 lung cancer patients who underwent lobectomy at Yunnan Cancer Hospital between January 2020 and December 2020. All patients had stage IA primary lung cancer and were performed by the same surgical team. And computed tomography examinations were performed before and 1 y postoperatively. Based on computed tomography images, the volume of each lung lobe was measured using computer software and manual, the radiological lung weight was calculated. And multiple linear regressions were used to analyze the factors related to the increase in postoperative lung weight. RESULTS: One year after lobectomy, the radiological lung weight increased by an average of 112.4 ± 20.8%. Smoking history, number of resected lung segments, preoperative low attenuation volume, intraoperative arterial oxygen partial pressure/fraction of inspired oxygen ratio and postoperative visual analog scale scores at 48 h were significantly associated with postoperative radiological lung weight gain. CONCLUSIONS: Our results suggest that CLG have occurred after lobectomy in adults. In addition, anesthetists should maintain high arterial oxygen partial pressure/fraction of inspired oxygen ratio during one-lung ventilation and improve acute postoperative pain to benefit CLG.
Subject(s)
Lung Neoplasms , Lung , Pneumonectomy , Tomography, X-Ray Computed , Humans , Lung Neoplasms/surgery , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Male , Retrospective Studies , Middle Aged , Female , Lung/diagnostic imaging , Lung/surgery , Lung/growth & development , Aged , Adult , Organ Size , Postoperative PeriodABSTRACT
In recent years, polyurethane has drawn great attention because of its many advantages in physical and chemical performance. In this work, firstly, polyurethane was impregnated in a non-woven fabric (NWF). Then, polyurethane-impregnated NWF was coagulated utilizing a wet phase inversion. Finally, after alkali treatment, microfiber non-woven fabrics with a porous polyurethane matrix (PNWF) were fabricated and used as substrates. SnIn4S8 (SIS) prepared by a microwave-assisted method was used as a photocatalyst and a novel SIS/PNWF substrate with multiple uses and highly efficient catalytic degradation ability under visible light was successfully fabricated. The surface morphology, chemical and crystal structures, optical performance, and wettability of SIS/PNWF substrates were observed. Subsequently, the photocatalytic performance of SIS/PNWF substrates was investigated by the decomposition of rhodamine B (RhB) under visible light irradiation. Compared with SIS/PNWF-2% (2%, the weight ratio of SIS and PNWF, same below), SIS/PNWF-5% as well as SIS/PNWF-15%, SIS/PNWF-10% substrates exhibited superior photocatalytic efficiency of 97% in 2 h. This may be due to the superior photocatalytic performance of SIS and the inherent hierarchical porous structure of PNWF substrates. Additionally, the hydrophobicity of SIS/PNWF substrates can enable them to float on the solution and further be applied on an open-water surface. Furthermore, tensile strength and recycle experiments demonstrated that SIS/PNWF substrates possessed superior mechanical strength and excellent recycle stability. This work provides a facile and efficient pathway to prepare SIS/PNWF substrates for the degradation of organic pollutants with enhanced catalytic efficiency.
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BACKGROUND: Yeast is often used to build cell factories to produce various chemicals or nutrient substances, which means the yeast has to encounter stressful environments. Previous research reported that unsaturated fatty acids were closely related to yeast stress resistance. Engineering unsaturated fatty acids may be a viable strategy for enhancing the stress resistance of cells. RESULTS: In this study, two desaturase genes, OLE1 and FAD2 from Z. rouxii, were overexpressed in S. cerevisiae to determine how unsaturated fatty acids affect cellular stress tolerance of cells. After cloning and plasmid recombination, the recombinant S. cerevisiae cells were constructed. Analysis of membrane fatty acid contents revealed that the recombinant S. cerevisiae with overexpression of OLE1 and FAD2 genes contained higher levels of fatty acids C16:1 (2.77 times), C18:1 (1.51 times) and C18:2 (4.15 times) than the wild-type S. cerevisiae pY15TEF1. In addition, recombinant S. cerevisiae cells were more resistant to multiple stresses, and exhibited improved membrane functionality, including membrane fluidity and integrity. CONCLUSION: These findings demonstrated that strengthening the expression of desaturases was beneficial to stress tolerance. Overall, this study may provide a suitable means to build a cell factory of industrial yeast cells with high tolerance during biological manufacturing. © 2023 Society of Chemical Industry.
Subject(s)
Fatty Acid Desaturases , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Fatty Acid Desaturases/genetics , Fatty Acid Desaturases/metabolism , Stearoyl-CoA Desaturase/genetics , Stearoyl-CoA Desaturase/metabolism , Fatty Acids, Unsaturated/metabolism , Fatty Acids/metabolismABSTRACT
This study aimed to investigate the effects of mesenchymal stem cell exosomes loaded with Fe3O4 magnetic particles (Fe3O4@ MSC-exo) on the survival and neural differentiation of PC12 cells. Exosomes were separated from Fe3O4 magnetic nanoparticles-primed umbilical cord mesenchymal stem cells condition medium by ultracentrifugation and characterized by transmission electron microscopy, flow nano analysis, and western blotting. PC12 cells were treated with culture medium containing exosomes. The effects of Fe3O4@ MSC-exo on PC12 cell proliferation, migration, and neural differentiation were analyzed using CCK-8 assay, transwell migration assay, RT-qPCR, and immunofluorescence, respectively. Additionally, miRNA sequencing was performed on Fe3O4@ MSC-exo, followed by bioinformatic analysis of the results. We found that Fe3O4@ MSC-exo can promote PC12 cell proliferation, migration, and neural differentiation. According to the sequencing results, there were a total of 43 differentially expressed miRNAs. The present study indicated that Fe3O4@ MSC-exo might enhance nerve cell function, laying the foundation for targeted therapy of nerve injury.
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Light-degradable hydrogels have a wide range of application prospects in the field of biomedicine. However, the provision of a facile synthetic approach to light-degradable hydrogels under mild conditions remains a challenge for researchers. To surmount this challenge, a facile synthetic approach to UV-degradable hydrogels is demonstrated in this manuscript. Initially, an UV-degradable crosslinker (UVDC) having o-nitrobenzyl ester groups was synthesized in a single step through the employment of the Passerini three-component reaction (P-3CR). Both 1H NMR and MS spectra indicated the successful synthesis of high-purity UVDC, and it was experimentally demonstrated that the synthesized UVDC was capable of degradation under 368 nm light. Furthermore, this UVDC was mixed with 8-arm PEG-thiol (sPEG20k-(SH)8) to promptly yield an UV-degradable hydrogel through a click reaction. The SEM image of the fabricated hydrogel exhibits the favorable crosslinking network of the hydrogel, proving the successful synthesis of the hydrogel. After continuous 368 nm irradiation, the hydrogel showed an obvious gel-sol transition, which demonstrates that the hydrogel possesses a desirable UV-degradable property. In summary, by utilizing solely a two-step reaction devoid of catalysts and hazardous raw materials, UV-degradable hydrogels can be obtained under ambient conditions, which greatly reduces the difficulty of synthesizing light-degradable hydrogels. This work extends the synthetic toolbox for light-degradable hydrogels, enabling their accelerated development.
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The objective was to explore the relationships between computed tomography (CT) lung volume parameters and pulmonary function test (PFT) indexes and develop predictive scores to predict PFT indexes in Chinese preoperative patients suspected with lung cancer. Preoperative patients suspected with lung cancer aged 18 years or more and examined by chest CT scan and PET were consecutively recruited from April to August 2020, at Yunnan Cancer Hospital. CT and PET data were selected from medical record. Pearson correlation was used to explore the relationships between CT parameters and PFT indexes. Predictive scores of PFT indexes were developed from unstandardized coefficients of linear regression models of using CT parameters as predictors. The assessments of predictive ability of scores were conducted by receiver operating characteristics curves. A total of 124 preoperative patients suspected with lung cancer participated in this study. Total lung volume significantly correlated with total lung capacity (r = 0.708), residual volume (r = 0.411), forced expiratory volume in one second (FEV1, r = 0.535), forced vital capacity (FVC, r = 0.687), and FEV1/FVC (r = -0.319). Percent of low attenuation volume significantly correlated with total lung capacity (r = 0.200), residual volume (r = 0.215), FEV1 percentage of predictive value (FEV1%, r = -0.204) and FEV1/FVC (r = -0.345). Four predictive scores for FEV1, FEV1%, FEV1/FVC and FVC% were developed. The area under the curve of receiver operating characteristics for FEV1 <2L, FEV1% <80%, FEV1/FVC <80% and FVC% <80% were 0.856, 0.667, 0.749 and 0.715, respectively. A prediction of poor lung function in preoperative patients suspected with lung cancer, using total lung volume and percent of low attenuation volume was possible. The predictive scores should be further evaluated for external validity.
Subject(s)
Lung Neoplasms , Lung , Humans , China , Lung/diagnostic imaging , Lung Volume Measurements , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/surgery , Respiratory Function Tests , Forced Expiratory Volume , Vital CapacityABSTRACT
The prickly nightshade Solanum rostratum, an annual malignant weed, is native to North America and has globally invaded 34 countries, causing serious threats to ecosystems, agriculture, animal husbandry, and human health. In this study, we constructed a chromosome-level genome assembly and annotation of S. rostratum. The contig-level genome was initially assembled in 898.42 Mb with a contig N50 of 62.00 Mb from PacBio high-fidelity reads. With Hi-C sequencing data scaffolding, 96.80% of the initially assembled sequences were anchored and orientated onto 12 pseudo-chromosomes, generating a genome of 869.69 Mb with a contig N50 of 72.15 Mb. We identified 649.92 Mb (72.26%) of repetitive sequences and 3,588 non-coding RNAs in the genome. A total of 29,694 protein-coding genes were predicted, with 28,154 (94.81%) functionally annotated genes. We found 99.5% and 91.3% complete embryophyta_odb10 genes in the pseudo-chromosomes genome and predicted gene datasets by BUSCO assessment. The present genomic resource provides essential information for subsequent research on the mechanisms of environmental adaptation of S. rostratum and host shift in Colorado potato beetles.
Subject(s)
Genome, Plant , Solanum , Chromosomes , Ecosystem , Molecular Sequence Annotation , Phylogeny , Solanum/geneticsABSTRACT
Objective: To explore the molecular mechanism of sevoflurane-induced neurotoxicity and to determine whether lncRNA HOXA11-AS affects sevoflurane-induced neuronal apoptosis and inflammation by regulating miR-98-5p/EphA4. Methods: Morris water maze (MWM) test was used to detect the learning and memory ability of rats, HE staining was used to observe hippocampal pathology, TUNEL staining was used to detect the level of neuronal apoptosis, and RT-qPCR was used to detect the expression of HOXA11-AS, miR-98-5p, IL-6, IL-1ß, and TNF-α. At the same time, the contents of IL-6, IL-1ß, and TNF-α in serum were detected by ELISA. The expressions of apoptosis-related proteins EphA4, Bax, Cleaved caspase 3, and Bcl-2 were detected by Western blot. The dual-luciferase gene reporter verified the targeting relationship between HOXA11-AS and miR-98-5p and the targeting relationship between miR-98-5p and EphA4. Results: The expression of HOXA11-AS was observed in sevoflurane-treated rats or cells and promoted neuronal apoptosis and inflammation. HOXA11-AS was knocked out alone, or miR-98-5p was overexpressed which attenuates neuronal apoptosis and inflammatory inflammation after sevoflurane treatment. Furthermore, knockdown of HOXA11-AS alone was partially restored by knockdown of miR-98-5p or overexpression of EphA4. Conclusion: Inhibition of lncRNA HOXA11-AS attenuates sevoflurane-induced neuronal apoptosis and inflammatory responses via miR-98-5p/EphA4.
Subject(s)
MicroRNAs , RNA, Long Noncoding , Receptor, EphA4 , Sevoflurane , Animals , Rats , Apoptosis , Inflammation , Interleukin-6/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Sevoflurane/toxicity , Transcription Factors/metabolism , Tumor Necrosis Factor-alpha/metabolism , Receptor, EphA4/genetics , Receptor, EphA4/metabolismABSTRACT
BACKGROUND: Iris lactea var. chinensis, a perennial herbaceous species, is widely distributed and has good drought tolerance traits. However, there is little information in public databases concerning this herb, so it is difficult to understand the mechanism underlying its drought tolerance. RESULTS: In this study, we used Illumina sequencing technology to conduct an RNA sequencing (RNA-seq) analysis of I. lactea var. chinensis plants under water-stressed conditions and rehydration to explore the potential mechanisms involved in plant drought tolerance. The resulting de novo assembled transcriptome revealed 126,979 unigenes, of which 44,247 were successfully annotated. Among these, 1187 differentially expressed genes (DEGs) were identified from a comparison of the water-stressed treatment and the control (CK) treatment (T/CK); there were 481 upregulated genes and 706 downregulated genes. Additionally, 275 DEGs were identified in the comparison of the rehydration treatment and the water-stressed treatment (R/T). Based on Quantitative Real-time Polymerase Chain Reaction (qRT-PCR) analysis, the expression levels of eight randomly selected unigenes were consistent with the transcriptomic data under water-stressed and rehydration treatment, as well as in the CK. According to Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, proline metabolism-related DEGs, including those involved in the 'proline catabolic process', the 'proline metabolic process', and 'arginine and proline metabolism', may play important roles in plant drought tolerance. Additionally, these DEGs encoded 43 transcription factors (TFs), 46 transporters, and 22 reactive oxygen species (ROS)-scavenging system-related proteins. Biochemical analysis and histochemical detection showed that proline and ROS were accumulated under water-stressed conditions, which is consistent with the result of the transcriptomic analysis. CONCLUSIONS: In summary, our transcriptomic data revealed that the drought tolerance of I. lactea var. chinensis depends on proline metabolism, the action of TFs and transporters, and a strong ROS-scavenging system. The related genes found in this study could help us understand the mechanisms underlying the drought tolerance of I. lactea var. chinensis.
Subject(s)
Iris Plant , Transcription Factors , Transcription Factors/genetics , Transcription Factors/metabolism , Iris Plant/genetics , Iris Plant/metabolism , Reactive Oxygen Species/metabolism , Drought Resistance , Stress, Physiological/genetics , Transcriptome , Gene Expression Profiling , Dehydration/genetics , High-Throughput Nucleotide Sequencing , Water/metabolism , Gene Expression Regulation, Plant , DroughtsABSTRACT
Resveratrol has been garnering considerable attention as a promising chemopreventive and chemotherapeutic drug against metastatic tumors such as triple-negative breast cancer (TNBC). However, the potential in vivo application of resveratrol has been highly limited due to its poor solubility, rapid conjugation, low bioavailability, and bioactivity. In this study, a silica mesoporous nanoparticle (MSN)-based drug delivery system (DDS), named Au-Se@MSN, is developed to deliver the loaded resveratrol, endowing it with properties of targeted delivery, excellent bioavailability, and antioxidation of resveratrol. In Au-Se@MSN(RES), gold nanoparticles functionalized with selenol-modified uPA-specific peptides act as gatekeepers to avoid the interference of glutathione in the bloodstream and realize negligible premature release of resveratrol during delivery. Au-Se@MSN(RES) shows prolonged resveratrol release at the tumor site and endows resveratrol with a remarkable in vitro therapeutic effect. The pharmacological dose of resveratrol treatment on MDA-MB-231 cells was found to result in the generation of a high level of NAD(P)H other than H2O2, indicating reductive stress instead of oxidative stress involved in the resveratrol therapeutic process. In vivo experiments showed that Au-Se@MSN greatly improves the chemotherapeutic effect of resveratrol on mice bearing TNBC tumors, and damage to normal tissues and cells is negligible. Overall, Au-Se@MSN is a potential tool for further studies on the anticancer mechanism and clinical applications of resveratrol.
Subject(s)
Metal Nanoparticles , Nanoparticle Drug Delivery System , Resveratrol , Triple Negative Breast Neoplasms , Animals , Mice , Drug Carriers/chemistry , Drug Delivery Systems/methods , Gold/chemistry , Hydrogen Peroxide , Metal Nanoparticles/chemistry , Nanoparticles/chemistry , Peptides/chemistry , Porosity , Resveratrol/pharmacology , Resveratrol/therapeutic use , Silicon Dioxide/chemistry , Triple Negative Breast Neoplasms/drug therapy , Selenium/chemistry , Nanoparticle Drug Delivery System/pharmacology , Nanoparticle Drug Delivery System/therapeutic useABSTRACT
Using a photochemically isomerizable cucurbit[6]uril derivative as a building block, we succeeded in generating a large number of oversized 2D materials within the cytosol of a living cell via controlled self-assembly. Fluorescence recovery after a photobleaching assay indicated that the resulting 2D material pieces posed discernible hindrance to not only diffusive spreading but also motor-driven motion of intracellular components in the cytosol, which eventually induced apoptotic cell death. Such behavior was seldom observed in previous 2D material-bearing cells prepared by endocytosis, as the total lateral size constituted by the endocytosed 2D materials per cell failed to exceed a threshold level, leading to a tortuosity of transport path inadequate to impede cytosolic transport in an appreciable manner. By varying the initial concentration of the building block, the existence of such a threshold was experimentally demonstrated from the relationship between the flow cytometry side scatter of the treated cells and corresponding cell viability. With the otherwise well-regulated cytosolic transport dynamics of living cells being physically altered, therapeutics with a new mechanism of action that counteracts drug resistance or intracellular platforms that advance our understanding of subcellular pathology of certain intractable diseases are in sight.
Subject(s)
Apoptosis , Endocytosis , Biological Transport , Cytosol/metabolism , Flow CytometryABSTRACT
In C4 plants, the pyruvate (Pyr), phosphate dikinase regulatory protein (PDRP) regulates the activity of the C4 pathway enzyme Pyr, phosphate dikinase (PPDK) in a light-/dark-dependent manner. The importance of this regulatory action to C4 pathway function and overall C4 photosynthesis is unknown. To resolve this question, we assessed in vivo PPDK phospho-regulation and whole leaf photophysiology in a CRISPR-Cas9 PDRP knockout (KO) mutant of the NADP-ME C4 grass green millet (Setaria viridis). PDRP enzyme activity was undetectable in leaf extracts from PDRP KO lines. Likewise, PPDK phosphorylated at the PDRP-regulatory Thr residue was immunologically undetectable in leaf extracts. PPDK enzyme activity in rapid leaf extracts was constitutively high in the PDRP KO lines, irrespective of light or dark pretreatment of leaves. Gas exchange analysis of net CO2 assimilation revealed PDRP KO leaves had markedly slower light induction kinetics when leaves transition from dark to high-light or low-light to high-light. In the initial 30 min of the light induction phase, KO leaves had an â¼15% lower net CO2 assimilation rate versus the wild-type (WT). Despite the impaired slower induction kinetics, we found growth and vigor of the KO lines to be visibly indistinguishable from the WT when grown in normal air and under standard growth chamber conditions. However, the PDRP KO plants grown under a fluctuating light regime exhibited a gradual multi-day decline in Fv/Fm, indicative of progressive photosystem II damage due to the absence of PDRP. Collectively, our results demonstrate that one of PDRP's functions in C4 photosynthesis is to ensure optimal photosynthetic light induction kinetics during dynamic changes in incident light.
Subject(s)
Pyruvate, Orthophosphate Dikinase , Setaria Plant , Carbon Dioxide/metabolism , NADP/metabolism , Phosphates/metabolism , Photosynthesis , Photosystem II Protein Complex/metabolism , Plant Extracts/metabolism , Plants/metabolism , Pyruvate, Orthophosphate Dikinase/chemistry , Pyruvic Acid/metabolism , Setaria Plant/genetics , Setaria Plant/metabolism , Transcription Factors/metabolism , Zea mays/metabolismABSTRACT
We report a phosphine-directed ruthenium-catalyzed C8-selective alkylation of naphthalenes with alkenes. This protocol provides straightforward access to a large library of electron-rich C8-alkyl substituent 1-naphthphosphines, which outperformed common commercial phosphines and their precursors in the Pd-catalyzed Suzuki-Miyaura coupling of aryl bromides with alkylboronic acid.
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OBJECTIVES: To estimate the incidence of chronic postthoracotomy pain (CPTP) in lung tumor patients and to explore the influencing factors of the intensity of CPTP. METHODS: Lung tumor patients who underwent video-assisted thoracoscopic surgery (VATS) or thoracotomy were consecutively recruited from October 2016 to December 2017 at Yunnan Cancer Hospital. All the eligible patients were interviewed via telephone at the end of the third month after surgeries to identify the presence of CPTP. The potential influencing factors of CPTP, including pre-, intra-, and postoperative variables, were collected from medical records. A cumulative logit regression model was used to identify the independent influencing factors of the intensity of CPTP. RESULTS: Three hundred and forty-three patients completed a telephone interview. The estimated overall incidence of CPTP was 67.6% (95% of confidence interval, 95% CI: 62.4%, 72.6%) in lung tumor patients; 70.8% (95% CI: 63.8%, 77.1%) in benign patients and 63.5% (95% CI: 55.2%, 71.3%) in malignant patients; and 78.1% (95% CI: 66.0%, 87.5%) in open chest and 65.2% (95% CI: 59.3%, 70.8%) in VATS. Cumulative logit regression models (intensity order, NRS, 0 ⶠ1-3 ⶠ4-) revealed independent influencing factors of CPTP to be patients with diabetes (OR = 0.32; 95% CI: 0.14, 0.76), usage of VATS (OR = 0.47; 95% CI: 027, 0.82), and the amount of intraoperative blood loss (OR = 1.09; 95% CI: 1.00, 1.19). CONCLUSIONS: A high incidence of CPTP is detected in lung tumor patients following the thoracic operation. Patients with diabetes and using VATS are the independent protective factors of the intensity of CPTP, and the increasing amount of intraoperative blood loss is an independent risk factor of the intensity of CPTP.
Subject(s)
Chronic Pain , Lung Neoplasms , Blood Loss, Surgical , China/epidemiology , Chronic Pain/complications , Chronic Pain/epidemiology , Humans , Incidence , Lung Neoplasms/surgery , Pain, Postoperative/epidemiology , Pain, Postoperative/etiologyABSTRACT
BACKGROUND: Recent studies have shown that propofol and sevoflurane, two common anesthetics, can prevent tumor development. The prevalence of lung adenocarcinoma in China is highest in Yunnan Xuanwei, and many patients with lung cancer in this area are often resistant to platinum-based treatments. OBJECTIVE: The objective of the study was to investigate the effects of propofol and sevoflurane on malignant biological behavior and cisplatin resistance of Xuanwei lung adenocarcinoma. METHODS: Herein, XWLC-05/R, a cisplatin-resistant cell line of XWLC-05 cells from Xuanwei lung adenocarcinoma, was constructed. The XWLC-05 cells and XWLC-05/R cells were treated with propofol and sevoflurane singly or as a combination and subjected to CCK-8 assay, clone formation tests, and flow cytometry analysis to assess the proliferation level of cells. The morphology and number of apoptotic bodies in XWLC-05 cells and XWLC-05/R were examined with a transmission electron microscope. The ANNEXIN V-FITC/PI and transwell assays were performed to evaluate apoptosis, invasion, and migration of the cells. Subsequently, we constructed a Xuanwei lung adenocarcinoma xenograft model to investigate the effects of propofol and sevoflurane on the tumorigenicity of XWLC-05 cells in vivo. RESULTS: Treatment with propofol and sevoflurane significantly inhibited proliferation, invasion, migration, and induced apoptosis of XWLC-05 and XWLC-05/R cells. These effects were more pronounced when propofol and sevoflurane were co-incubated with the cells. Moreover, both propofol and sevoflurane significantly inhibited Wnt/ß- catenin and PI3K/AKT pathways. Moreover, the two drugs effects suppressed the malignant biological behavior of XWLC-05 cells and XWLC-05/R cells, and this effect was counteracted by 740Y-P (PI3K/AKT pathway activator) and Wnt pathway activator 1 (Wnt/ß-catenin pathway activator). In vivo experiments confirmed that propofol and sevoflurane alleviated the tumorigenicity of XWLC-05 cells. CONCLUSIONS: In summary, this study shows, for the first time, that propofol and sevoflurane decrease the proliferation, invasion, migration and induce apoptosis of XWLC-05 cells and XWLC-05/R cells by impeding the Wnt/ß-catenin and PI3K/AKT signaling pathways, thereby alleviating the development of Xuanwei lung adenocarcinoma in vivo. Moreover, these effects are more pronounced when the two drugs are combined.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Propofol , Adenocarcinoma of Lung/drug therapy , Apoptosis , Cell Line, Tumor , Cell Proliferation , China , Cisplatin/pharmacology , Cisplatin/therapeutic use , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/pathology , Phosphatidylinositol 3-Kinases/metabolism , Propofol/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Sevoflurane/pharmacology , Sevoflurane/therapeutic use , Wnt Signaling Pathway , beta Catenin/metabolismABSTRACT
The unique structural advantage and physicochemical properties render some 2D materials emerging platforms for intracellular bioimaging, biosensing, or disease theranostics. Despite recent advances in this field, one major challenge lies in bypassing the endocytic uptake barrier to allow internalization of very large 2D materials that have longer retention time in cells, and hence greater potency as intracellular functional platforms than small, endocytosable counterparts. Here, an engineered cucurbit[6]uril carrying at its periphery multiple spiropyran pendants that readily translocates into cytosol, and then polymerizes laterally and non-covalently in a controlled manner, enabling direct generation of 2D materials inside living cells, is reported. The resultant 2D materials are single-monomer-thick and can in situ grow up to 0.8-1.2 µm in lateral size, experimentally proved too large to be endocytosed from outside the cells even after surface engineered with biorecognition entities. A Förster resonance energy transfer assay is further devised for real-time visualization of the polymerization dynamics in vivo, clearly demonstrating the rationale in this study. With the otherwise non-endocytosable large 2D materials gaining access to cytosol, potent intracellular signaling or theranostic platform that surpasses the intrinsic performance limit of conventional small counterparts are in sight.
Subject(s)
Bridged-Ring Compounds , Imidazoles , Benzopyrans , Indoles , Nitro CompoundsABSTRACT
Patients receiving lipid emulsions are at increased risk of contracting catheter-related bloodstream infections (CRBSIs) in the clinic. More than 15% of CRBSIs are polymicrobial. The objective of this study was to explore the effects of lipid emulsions on the formation of Escherichia coli (E. coli)-Candida albicans (C. albicans) mixed-species biofilms (BFs) on polyvinyl chloride (PVC) surfaces and the underlying mechanism. Mixed-species BFs were produced by coculturing E. coli and C. albicans with PVC in various concentrations of lipid emulsions. Crystal violet staining and XTT assays were performed to test the mixed-species BF biomass and the viability of microbes in the BFs. The microstructures of the BFs were observed by an approach that combined confocal laser scanning microscopy, fluorescence in situ hybridization, and scanning electron microscopy. The study found that lipid emulsions could promote the formation of E. coli-C. albicans mixed-species BFs, especially with 10% lipid emulsions. The mechanism by which lipid emulsions promote mixed-species BF formation may involve significant upregulation of the expression of the flhDC, iha, HTA1, and HWP1 genes, which are associated with bacterial motility, adhesion, and BF formation. The results derived from this study necessitate strict aseptic precautions when handling lipid emulsions and avoiding the use of high concentrations of lipid emulsions for as long as possible.
Subject(s)
Biofilms , Candida albicans , Emulsions/pharmacology , Escherichia coli , Biofilms/drug effects , Biofilms/growth & development , Candida albicans/drug effects , Candida albicans/pathogenicity , Escherichia coli/drug effects , Escherichia coli/pathogenicity , Polyvinyl Chloride/chemistryABSTRACT
Owing to deep activation in biotissues and enhanced targeting efficiency, developing photoresponsive polymer-upconversion nanoparticles (PP-UCNPs) nanovectors has witnessed rapid growth in the past decade. However, up to date, all developed nanovectors require high-order photon processes to initiate the release of cargos. The photodamage caused by high-power near-infrared laser light may be a critical obstacle to their clinical application. Here, for the first time, by leveraging absorption-emission spectral matching between donor-acceptor Stenhouse adducts (DASA) PP and UCNPs (λex , 808 nm) in the green region (≈530 nm), the designed nanovector is capable of releasing cargos at a low-power 808 nm excitation (0.2 W). Considering the high molar absorptivity, biobenign, and synthetic tunability of DASA, DASA PP can be utilized as an up-and-coming candidate to design and synthesize the next generation of upconversion nanovectors without photodamage.