RESUMEN
Objective: To explore the spatial relationship between A1 segment proximal anterior cerebral artery aneurysms and their main trunks, classify them anatomically and develop targeted treatment strategies. Methods: This single-center retrospective analysis involved 39 patients diagnosed with aneurysms originating from the proximal of A1 segment of the anterior cerebral artery (2014-2023). Classify the patient's aneurysm into 5 types based on the location of the neck involving the carrier artery and the spatial relationship and projection direction of the aneurysm body with the carrier artery, and outcomes from treatment methods were compared. Results: Among 39 aneurysms, 18 cases underwent endovascular intervention treatment, including 6 cases of stent assisted embolization, 1 case of flow-diverter embolization, 5 cases of balloon assisted embolization, and 6 cases of simple coiling. At discharged, the mRS score of all endovascularly treated patients was 0, and the GOS score was 5 at 6 months after discharge. At discharge, the mRS score of microsurgical clipping treated patients was 0 for 15 cases, 3 for 1 case, 4 for 1 case and 5 for 2 cases. Six months after discharge, the GOS score was 5 for 16 cases, 4 for 2 cases, 3 for 2 cases, and 1 for 1 case. GOS outcomes at 6 months were better for endovascularly treated patients (p = 0.047). Conclusion: Results showed better outcomes for the endovascular treatment group compared to microsurgical clipping at 6 months after surgery. The anatomical classification of aneurysms in this region may be of help to develop effective treatment strategies.
RESUMEN
Platinum(II) drugs as a first-line anticancer reagent are limited by side effects and drug resistance. Stimuli-responsive nanosystems hold promise for precise spatiotemporal manipulation of drug delivery, with the aim to promote bioavailability and minimize side effects. Herein, a multitargeting octahedral platinum(IV) prodrug with octadecyl aliphatic chain and histone deacetylase inhibitor (phenylbutyric acid, PHB) at axial positions to improve the therapeutic effect of cisplatin was loaded on the upconversion nanoparticles (UCNPs) through hydrophobic interaction. Followed attachment of DSPE-PEG2000 and arginine-glycine-aspartic (RGD) peptide endowed the nanovehicles with high biocompatibility and tumor specificity. The fabricated nanoparticles (UCNP/Pt(IV)-RGD) can be triggered by upconversion luminescence (UCL) irradiation and glutathione (GSH) reduction to controllably release Pt(II) species and PHB, inducing profound cytotoxicity. Both in vitro and in vivo experiments demonstrated that UCNP/Pt(IV)-RGD exhibited remarkable antitumor efficiency, high tumor-targeting specificity, and real-time UCL imaging capacity, presenting an intelligent platinum(IV) prodrug-loaded nanovehicle for UCL-guided dual-stimuli-responsive combination therapy.
Asunto(s)
Antineoplásicos , Glutatión , Nanopartículas , Oligopéptidos , Profármacos , Animales , Humanos , Ratones , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Cisplatino/química , Cisplatino/farmacología , Cisplatino/uso terapéutico , Glutatión/química , Glutatión/metabolismo , Rayos Infrarrojos , Ratones Endogámicos BALB C , Ratones Desnudos , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/diagnóstico por imagen , Oligopéptidos/química , Platino (Metal)/química , Platino (Metal)/farmacología , Platino (Metal)/uso terapéutico , Profármacos/química , Profármacos/farmacología , Profármacos/uso terapéutico , ProhibitinasRESUMEN
4-Coumarate-CoA ligase (4CL) gene plays vital roles in plant growth and development, especially the regulation of lignin metabolism and flavonoid synthesis. To investigate the potential function of 4CL in the lignin biosynthesis of Ginkgo biloba, this study identified two 4CL genes, Gb4CL1 and Gb4CL2, from G. biloba genome. Based on the phylogenetic tree analysis, Gb4CL1 and Gb4CL2 protein were classified into Class I, which has been confirmed to be involved in lignin biosynthesis. Therefore, it can be inferred that these two genes may also participate in lignin metabolism. The tissue-specific expression patterns of these two genes revealed that Gb4CL1 was highly expressed in microstrobilus, whereas Gb4CL2 was abundant in immature leaves. The onion transient expression assay indicated that Gb4CL1 was predominantly localized in the nucleus, indicating its potential involvement in nuclear functions, while Gb4CL2 was observed in the cell wall, suggesting its role in cell wall-related processes. Phytohormone response analysis revealed that the expression of both genes was upregulated in response to indole acetic acid, while methyl jasmonate suppressed it, gibberellin exhibited opposite effects on these genes. Furthermore, Gb4CL1 and Gb4CL2 expressed in all tissues containing lignin that showed a positive correlation with lignin content. Thus, these findings suggest that Gb4CL1 and Gb4CL2 are likely involved in lignin biosynthesis. Gb4CL1 and Gb4CL2 target proteins were successfully induced in Escherichia coli BL21 with molecular weights of 85.5 and 89.2 kDa, proving the integrity of target proteins. Our findings provided a basis for revealing that Gb4CL participated in lignin synthesis in G. biloba.
Asunto(s)
Clonación Molecular , Ginkgo biloba , Lignina , Proteínas de Plantas , Ginkgo biloba/genética , Ginkgo biloba/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Lignina/biosíntesis , Lignina/metabolismo , Regulación de la Expresión Génica de las Plantas , Filogenia , Coenzima A Ligasas/genética , Coenzima A Ligasas/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismoRESUMEN
Digital transformation and green innovation are powerful initiatives to achieve carbon peaking, carbon neutrality targets and high-quality economic development. Using a sample of high energy-consuming listed enterprises from 2012 to 2021, a double fixed-effect model is constructed to verify the effect of green innovation on the carbon emission reduction performance of high energy-consuming enterprises, and digital transformation is used as a moderating variable to analyze the inner mechanism of green innovation affecting the carbon emission reduction performance of high energy-consuming enterprises under the effect of digital transformation. The empirical results show that green innovation can significantly improve the carbon emission reduction performance of energy-consuming enterprises, while digital transformation positively moderates the effect of green innovation on the carbon emission reduction performance of energy-consuming enterprises. When considering the industry heterogeneity, the moderation effect of digital transformation is significant in the chemical raw materials and chemical products manufacturing industry and the electricity and heat production and supply industry, but the petroleum processing and coking and nuclear fuel processing industry, the non-metallic mineral products industry, the ferrous metal smelting and rolling processing industry and the non-ferrous metal smelting and rolling processing industry are not yet significantly affected by green innovation and digital transformation. The findings of the study provide empirical evidence to promote the improvement of carbon emission reduction performance of energy-intensive enterprises in China and to achieve the "double carbon" target.
RESUMEN
A novel multi-functional fluorescence probe HMIC based on hydrazide Schiff base has been successfully synthesized and characterized. It can distinguish Al3+/Zn2+/Cd2+ in ethanol, in which fluorescence emission with different colors (blue for Al3+, orange for Zn2+, and green for Cd2+) were presented. The limits of detection of HMIC towards three ions were calculated from the titration curve as 7.70 × 10- 9 M, 4.64 × 10- 9 M, and 1.35 × 10- 8 M, respectively. The structures of HMIC and its complexes were investigated using UV-Vis spectra, Job's plot, infrared spectra, mass spectrometry, 1H-NMR and DFT calculations. Practical application studies have also demonstrated that HMIC can be applied to real samples with a low impact of potential interferents. Cytotoxicity and cellular imaging assays have shown that HMIC has good cellular permeability and potential antitumor effects. Interestingly, HMIC can image Al3+, Zn2+ and Cd2+ in the cells with different fluorescence signals.
RESUMEN
The adsorption behaviors of biochar are largely impacted by biomassfeedstock. In this study, two biochars were prepared from torrefaction of ammonium persulfate- and potassium persulfate-pretreated bamboo and then activated by cold alkali, which are named as ASBC and KSBC, respectively. The two biochars were characterized by different instruments, and their adsorption properties over cationic methylene blue (MB) were compared. The type of persulfates little affected the specific surface areas, but significantly impacted O (29.54 % vs. 35.113 %) and N (12.13 % vs. 3.74 %) contents, functional groups, and zeta potentials of biochars. MB adsorption onto ASBC/KSBC is a single-layer chemical endothermic process and ASBC/KSBC exhibit high adsorption capacity over MB (475/881 mg·g-1) at 303 K. Obviously, the sorption capacity of MB onto KSBC much surpasses that of MB onto ASBC. These results indicate biomass pre-treatment is a cheap and convenient method to prepare biochars with unique physicochemical and adsorptive properties.
Asunto(s)
Carbón Orgánico , Contaminantes Químicos del Agua , Adsorción , Carbón Orgánico/química , Álcalis , Azul de Metileno/química , Contaminantes Químicos del Agua/químicaRESUMEN
Functionalization can change the physicochemical properties of hydrochar and improve its ability to adsorb pollutants. Herein, a trithiocyanurate-functionalized hydrochar (TTHC) was obtained from acylation of chloroacetyl chloride and hydrochar and modification with trithiocyanuric acid in alkaline conditions. TTHC can efficiently remove cationic methylene blue (MB) and Pb(II) from wastewater. The removal can be expressed with pseudo-second-order kinetic and Langmuir models. The MB and Pb(II) removed uptakes by TTHC at 298 K exceeded 909.9 and 182.8 mg g-1 respectively, and the removal rates reached 90% and 98% within 120 min respectively. Characterizations show TTHC is functionalized with trithiocyanurate, and rich in thiolate and aromaticity, and tends to adsorb MB/Pb(II) via multiple adsorption mechanisms. After five sorption-desorption regeneration cycles, TTHC maintained 80% and 99% adsorption capacities for MB and Pb(II) respectively. Therefore, TTHC is a promising efficient sorbent for removing MB and Pb(II) from effluents.
Asunto(s)
Contaminantes Ambientales , Contaminantes Químicos del Agua , Contaminantes Químicos del Agua/análisis , Azul de Metileno/química , Plomo , Aguas Residuales , Adsorción , CinéticaRESUMEN
Developing non-fullerene acceptors (NFAs) by modifying the backbone, side chains and end groups is the most important strategy to improve the power conversion efficiency of organic solar cells (OSCs). Among numerous developed NFAs, Y6 and its derivatives are famous NFAs in the OSC field due to their good performance. Herein, in order to understand the mechanism of tuning the photovoltaic performance by modifying the Y6's center backbone, π-spacer and side-chains, we selected the PM6:Y6 OSC as a reference and systematically studied PM6:AQx-2, PM6:Y6-T, PM6:Y6-2T, PM6:Y6-O, PM6:Y6-1O and PM6:Y6-2O OSC systems based on extensive quantum chemistry calculations. The results indicate that introducing quinoxaline to substitute thiadiazole in the backbone induces a blue-shift of absorption spectra, reduces the charge transfer (CT) distance (Δd) and average electrostatic potential (ESP), and increases the singlet-triplet energy gap (ΔEST), CT excitation energy and the number of CT states in low-lying excitations. Inserting thienyl and dithiophenyl as π spacers generates a red-shift of absorption spectra, enlarges Δd and average ESP, and reduces ΔEST and the number of CT states. Introducing furo[3,2-b]furan for substituting one thieno[3,2-b]thiophene unit in the Y6's backbone causes a red-shift of absorption spectra and increases ΔEST, Δd and average ESP as well as CT excitation energy. Introducing alkoxyl as a side chain results in a blue-shift of absorption spectra, and increases ΔEST, Δd, average ESP, CT excitation energy and the number of CT states. The rate constants calculated using Marcus theory suggest that all the molecular modifications of Y6 reduce the exciton dissociation and charge recombination rates at the heterojunction interface, while introducing furo[3,2-b]furan and alkoxyl enlarges CT rates.
RESUMEN
Cancer treatment requires the participation of multiple targets/pathways, and single approach is hard to effectively curb the proliferation and metastasis of carcinoma cells. In this work, we conjugated FDA-approved riluzole and platinum(II) drugs into a series of unreported riluzole-Pt(IV) compounds, which were designed to simultaneously target DNA, the solute carrier family 7 member 11 (SLC7A11, xCT), and the human ether a go-go related gene 1 (hERG1), to exert synergistic anticancer effect. Among them, c,c,t-[PtCl2(NH3)2(OH)(glutarylriluzole)] (compound 2) displayed excellent antiproliferative activity with IC50 value of 300-times lower than that of cisplatin in HCT-116, and optimal selectivity index between carcinoma and human normal liver cells (LO2). Mechanism studies indicated that compound 2 released riluzole and active Pt(II) species after entering cells to exhibit a prodrug behavior against cancer, which obviously increased DNA-damage and cell apoptosis, as well as suppressed metastasis in HCT-116. Compound 2 persisted in the xCT-target of riluzole and blocked the biosynthesis of glutathione (GSH) to trigger oxidative stress, which could boost the killing to cancer cells and reduce Pt-drug resistance. Meanwhile, compound 2 significantly inhibited invasion and metastasis of HCT-116 cells by targeting hERG1 to interrupt the phosphorylation of phosphatidylinositide 3-kinases/proteinserine-threonine kinase (PI3K/Akt), and reverse epithelial-mesenchymal transformation (EMT). Based on our results, the riluzole-Pt(IV) prodrugs studied in this work could be regarded as a new class of very promising candidates for cancer treatment compared to traditional platinum drugs.
Asunto(s)
Antineoplásicos , Carcinoma , Profármacos , Humanos , Antineoplásicos/farmacología , Profármacos/farmacología , Riluzol/farmacología , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Platino (Metal)/farmacología , Línea Celular Tumoral , Cisplatino/farmacología , Daño del ADNRESUMEN
The intelligent city pilot policy is a major measure in China to promote urban development from factor driven and investment driven to innovation driven. Intelligent city construction can effectively coordinate specialized production factors and information sharing mechanism, promote digital information technology innovation, promote smart industry cluster, and expand ecological scenarios of clean industry application, so as to reduce carbon emissions. This paper reveals the internal mechanism of intelligent city construction to promote carbon emission reduction. Based on the quasi-natural experiments carried out in three batches of pilot construction of intelligent cities since 2012, the difference-in-difference model (DID) is used to identify its impact on urban carbon emissions. The research results show that the pilot construction of intelligent cities is conducive to reducing carbon emissions, which is still robust under multiple scenarios such as placebo test and endogenous test. Heterogeneity analysis shows that the pilot policies have a more significant carbon emission reduction effect on the Beijing-Tianjin-Hebei urban agglomeration, non-resource-based cities, and non-old industrial bases. After further quantitative analysis of 917 pilot policy texts based on Simhash algorithm, Jieba word segmentation, and word frequency statistics, it is found that intelligent industry policies reduce carbon emissions by driving data elements agglomeration and optimizing industrial structure, while intelligent government and intelligent people's livelihood policies improve energy efficiency and reduce carbon emissions through green technological innovation. Counterfactual tests using machine learning algorithms show that the later the pilot batch, the better the sustainable carbon emission reduction effect of intelligent city pilot policies.
Asunto(s)
Algoritmos , Carbono , Humanos , Ciudades , Beijing , China , Desarrollo EconómicoRESUMEN
Exploring multi-targeting chemotherapeutants with advantages over single-targeting agents and drug combinations is of great significance in drug discovery. Herein, we employed phytogenic evodiamine (EVO) and conventional Pt(II) drugs to design and synthesize multi-target EVO-Pt(IV) anticancer prodrugs (4-14). Among them, compound 10 exhibited a 118-fold enhancement in the IC50 value compared to cisplatin and low toxicity to normal cells. Further studies proved that 10 significantly enhanced intracellular Pt accumulation and DNA damage, perturbed mitochondrial membrane potential, inhibited cell migration and invasion, upregulated reactive oxygen species levels, and induced apoptosis and autophagic cell death. Molecular docking assay revealed that 10 fits perfectly into the extracellular signal-regulated protein kinase (ERK)-1 pocket, which was verified to produce profound ERK suppression. Most strikingly, compound 10 exhibited superior in vivo antitumor efficiency and effectively attenuated systemic toxicity. Our results emphasize that functionalizing platinum drugs with the multi-target EVO could generate synergistically excellent anticancer activity with low toxicity and decreased resistance, which may represent a brand-new cancer therapy modality.
Asunto(s)
Antineoplásicos , Profármacos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Profármacos/farmacología , Profármacos/uso terapéutico , Simulación del Acoplamiento Molecular , Línea Celular Tumoral , Cisplatino/farmacología , Quinasas MAP Reguladas por Señal Extracelular , Apoptosis , Daño del ADN , AutofagiaRESUMEN
OBJECTIVES: Periodontitis is closely associated with kidney disease and reactive oxygen species (ROS) involvement. Mitochondria are the primary source of both endogenous ROS and renal energy. We investigated whether resveratrol (RSV) prevents renal injury and mitochondrial dysfunction in periodontitis rats. METHODS: Thirty male Wistar rats were divided into control, experimental periodontitis (Ep) and Ep-RSV groups. To induce periodontitis, a steel ligature was placed on the cervix of the bilateral first maxillary molars. RSV (50 mg/kg/day) to the Ep-RSV group and vehicle to the Ep and control groups were gavaged. After 8 weeks, alveolar bone loss, pocket depth, gingival blood index and tooth mobility were assessed. Oxidative stress parameters, mitochondrial structure, mitochondrial membrane potential (MMP), mitochondrial ROS, adenosine triphosphate (ATP), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) were analysed in renal. Renal function and histology were also evaluated. RESULTS: Compared with the control group, the Ep group showed renal structural destruction, elevated oxidative stress levels, mitochondrial structure destruction, MMP loss, mitochondrial ROS accumulation, ATP reduction, and decreased SIRT1 and PGC-1α levels. RSV prevented these destruction (p < 0.05). However, there was no significant impairment in renal function (p > 0.05). CONCLUSIONS: Periodontitis induces mitochondrial dysfunction in renal tissues. Resveratrol exerts a preventive effect on periodontitis-induced kidney injury by preventing mitochondrial dysfunction.
Asunto(s)
Periodontitis , Sirtuina 1 , Femenino , Ratas , Masculino , Animales , Resveratrol/farmacología , Resveratrol/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Sirtuina 1/metabolismo , Sirtuina 1/farmacología , Ratas Wistar , Estrés Oxidativo , Periodontitis/complicaciones , Periodontitis/prevención & control , Periodontitis/metabolismo , Riñón/metabolismo , Mitocondrias , Adenosina Trifosfato/metabolismo , Adenosina Trifosfato/farmacologíaRESUMEN
Combination of immune- and chemo-therapy has become a new trend in cancer treatment. Food and Drug Administration (FDA)-approved immune-modulatory agent, thalidomide, can modulate the related proteins of upstream signaling pathway of programmed cell death-ligand 1 (PD-L1), including nuclear transcription factor κB (NF-κB), hypoxia inducible factor-1α (HIF-1α), epidermal growth factor receptor (EGFR), and signal transducer and activator of transcription 3 (STAT3), all acting as key antitumor target proteins. In this work, we conjugated thalidomide with oxidized cisplatin to construct multi-functional Pt(IV) prodrugs, named thaliplatins 4-6, to investigate the anti-tumor effect of immuno- and chemo-therapy. Among them, thaliplatin 6 exerted remarkable cytotoxicity against the tested cancer cell lines, showing 15-26 and 9-20 times higher IC50 values than those of single cisplatin or the combination of cisplatin + thalidomide, respectively. Moreover, thaliplatin 6 could rapidly accumulated into cells, markedly triggered DNA damage, and induced cell S phase arrest and apoptosis, as well as inhibited cell migration and invasion in breast carcinoma cell line (MCF-7). Fluorescent confocal and western blotting experiments proved that 6 significantly regulated NF-κB, EGFR, HIF-1α and phosphor-signal transducer and activator of transcription 3 (p-STAT3), and simultaneously inhibited PD-L1 expression to interrupt programmed cell death 1 (PD-1)/PD-L1 signaling pathway, suggesting a synergistic action of cisplatin and thalidomide. Most strikingly, in vivo tests indicated that 6 effectively decreased tumor growth with no observable systemic toxicity, being superior to the anticancer efficacy of cisplatin.
Asunto(s)
Profármacos , Factor de Transcripción STAT3 , Antígeno B7-H1/metabolismo , Línea Celular Tumoral , Cisplatino , Receptores ErbB/metabolismo , Inmunomodulación , FN-kappa B/metabolismo , Profármacos/farmacología , Factor de Transcripción STAT3/metabolismo , Talidomida/farmacologíaRESUMEN
Pt(IV) anticancer compounds have been developed for several decades to overcome the drawbacks of their Pt(II) congeners, and the reduction of Pt(IV) to Pt(II) has been commonly regarded as a necessary step in the activation of Pt(IV) compounds prior to targeting DNA. However, blockage of glutathione (GSH) biosynthesis resulted in a slight effect on the cytotoxicity of oxoplatin in yeast Saccharomyces cerevisiae strains, urging us to reconsider the mechanism of actions for the "inert" Pt(IV) complexes. Using X-ray absorption near-edge spectroscopy (XANES), our data demonstrated that Pt(IV) complex oxoplatin could bind to DNA in a tetravalent state. Both alkaline denaturing agarose electrophoresis and thermal denaturation-renaturation assay revealed that oxoplatin could rapidly produce stable interstrand crosslinks (ICLs), which can further translate into a fast cell-killing process in cancer cells. Using quantitative real-time PCR and immunofluorescence analysis, we also proved that Pt(IV) complex oxoplatin could induce a quick intracellular response of the FA/BRCA pathway in cancer cells that involves the DNA interstrand crosslinking repair system, and this quick response to ICLs was independent with the intracellular GSH levels. Cell cycle analysis showed that short incubation with oxoplatin can induce a strong S phase arrest in HeLa cells, indicating that the rapid interstrand crosslinks produced by oxoplatin might stall the replication fork, result in the double-strand breaks, and eventually induce cell death. Our results implied that, besides the reduction mechanism to release the Pt(II) congeners, direct and rapid interstrand cross-linking with DNA by Pt(IV) compounds might be a unique mechanism for Pt(IV) compounds, which may provide new insight for the development of next-generation platinum-based drugs.
Asunto(s)
Antineoplásicos , ADN , Antineoplásicos/química , Antineoplásicos/farmacología , Reactivos de Enlaces Cruzados/química , Reactivos de Enlaces Cruzados/farmacología , ADN/metabolismo , Daño del ADN , Reparación del ADN , Glutatión , Células HeLa , HumanosRESUMEN
Pancreatic cancer is one of the most lethal gastrointestinal tumours, the most common pathological type is pancreatic adenocarcinoma (PAAD). In recent year, immune imbalanced in tumour microenvironment has been shown to play an important role in the evolution of tumours progression, and the efficacy of immunotherapy has been gradually demonstrated in clinical practice. In this study, we propose to construct an immune-related prognostic risk model based on immune-related genes MMP14 and INHBA expression that can assess the prognosis of pancreatic cancer patients and identify potential therapeutic targets for pancreatic cancer, to provide new ideas for the treatment of pancreatic cancer. We also investigate the correlation between macrophage infiltration and MMP14 and INHBA expression. First, the gene expression data of pancreatic cancer and normal pancreatic tissue were obtained from The Cancer Genome Atlas Program (TCGA) and The Genotype-Tissue Expression public database (GTEx). The differentially expressed immune-related genes between pancreatic cancer samples and normal sample were screened by R software. Secondly, univariate Cox regression analysis were used to evaluate the relationship between immune-related genes and the prognosis of pancreatic cancer patients. A polygenic risk score model was constructed by Cox regression analysis. The prognostic nomogram was constructed, and its performance was evaluated comprehensively by internal calibration curve and C-index. Using the risk model, each patient gets a risk score, and was divided into high- or low- risk groups. The proportion of 22 types of immune cells infiltration in pancreatic cancer samples was inferred by CIBERSOFT algorithm, correlation analysis (Pearson method) was used to analyse the correlation between the immune-related genes and immunes cells. Then, we applied macrophage conditioned medium to culture pancreatic cancer cell line PANC1, detected the expression of MMP14 and INHBA by qRT-PCR and Western blot methods. Knock-down MMP14 and INHBA in PANC1 cells by transfected with shRNA lentiviruses. Detection of migration ability of pancreatic cells was done by trans-well cell migration assay. A subcutaneous xenograft tumour model of human pancreatic cancer in nude mice was constructed. In conclusion, an immune-related gene prognostic model was constructed, patients with high-risk scores have poorer survival status, M2-phenotype tumour-associated macrophages (TAMs) up-regulate two immune-related genes, MMP14 and INHBA, which were used to establish the prognostic model. Knock-down of MMP14 and INHBA inhibited invasion of pancreatic cancer.
Asunto(s)
Adenocarcinoma , Subunidades beta de Inhibinas/metabolismo , Neoplasias Pancreáticas , Adenocarcinoma/genética , Animales , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Metaloproteinasa 14 de la Matriz/metabolismo , Ratones , Ratones Desnudos , Neoplasias Pancreáticas/patología , Fenotipo , Pronóstico , Microambiente Tumoral/genética , Macrófagos Asociados a Tumores , Neoplasias PancreáticasRESUMEN
Professor SHAO Ming-xi 's experience in treatment of arthralgia in breast cancer is summarized. Professor SHAO believes that the dysfunction of liver, spleen and kidney is the primary and the invasion of the exogenous wind, cold and damp is the secondary in arthralgia in breast cancer. Emphasized on syndrome/pattern differentiation, this disorder is identified as 4 patterns, i.e. liver qi stagnation, blockage by phlegm and stasis, qi and blood deficiency and obstruction by wind, cold and damp. Acupuncture-moxibustion is applied to Hegu (LI 4), Taichong (LR 3) and Waiguan (TE 5). The supplementary acupoints are selected on the base of syndrome/pattern differentiation. Tuina is combined with acupuncture-moxibustion and the reinforcing and reducing techniques are used appropriately. Shaoyang meridian is specially considered, due to which, Waiguan (TE 5) and Zhongzhu (TE 3) of triple energizer meridian of hand-shaoyang and Yanglingquan (GB 34) and Zulinqi (GB 41) of gallbladder meridian of foot-shaoyang are combined. Additionally, it stresses the combination of the local and distal acupoints and the coordination of various therapies of TCM to achieve the better effect.
Asunto(s)
Terapia por Acupuntura , Acupuntura , Neoplasias de la Mama , Moxibustión , Puntos de Acupuntura , Artralgia , Neoplasias de la Mama/terapia , HumanosRESUMEN
Non-small-cell lung cancer (NSCLC), with its aggressive biological behavior, is one of the most diagnosed cancers. Tumor-associated inflammatory cells play important roles in the interaction between chronic inflammation and lung cancer, however the mechanisms involved are far from defined. In the present study, by developing an orthotopic NSCLC mouse model based on chronic inflammation, we proved that an inflammatory microenvironment accelerated the growth of orthotopic xenografts in vivo. Tumor-associated macrophages, the most abundant population of inflammatory cells, were identified. Treatment with macrophage-conditioned medium (MCM) promoted the growth and migration of NSCLC cells. Using bioinformatics analysis, we identified downregulated PP2Ac expression in NSCLC cells upon treatment with MCM. We further confirmed that this downregulation was executed in an NF-κB pathway-dependent manner. As IκB kinase (IKK) has been proved to be a substrate of PP2Ac, inhibition on PP2Ac could result in amplification of NF-κB pathway signaling. Overexpression of PP2Ac, or the dominant-negative forms of IKK or IκB, attenuated the acceleration of growth and metastasis by MCM. Using bioinformatics analysis, we further identified that CXCL1 and COL6A1 could be downstream of NF-κB/PP2Ac pathway. Luciferase assay and ChIP assay further confirmed the location of response elements on the promoter regions of CXCL1 and COL6A1. Elevated CXCL1 facilitated angiogenesis, whereas upregulated COL6A1 promoted proliferation and migration.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , FN-kappa B/metabolismo , Proteína Fosfatasa 2/metabolismo , Macrófagos Asociados a Tumores/metabolismo , Animales , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Línea Celular Tumoral , Proliferación Celular , Quimiocina CXCL1/genética , Quimiocina CXCL1/metabolismo , Colágeno Tipo VI/genética , Colágeno Tipo VI/metabolismo , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Retroalimentación Fisiológica , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/metabolismo , Ratones , Persona de Mediana Edad , Neovascularización Patológica , Proteína Fosfatasa 2/genética , Transducción de SeñalRESUMEN
BACKGROUND: Ginkgo biloba, a typical dioecious plant, is a traditional medicinal plant widely planted. However, it has a long juvenile period, which severely affected the breeding and cultivation of superior ginkgo varieties. RESULTS: In order to clarify the complex mechanism of sexual differentiation in G. biloba strobili. Here, a total of 3293 miRNAs were identified in buds and strobili of G. biloba, including 1085 known miRNAs and 2208 novel miRNAs using the three sequencing approaches of transcriptome, small RNA, and degradome. Comparative transcriptome analysis screened 4346 and 7087 differentially expressed genes (DEGs) in male buds (MB) _vs_ female buds (FB) and microstrobilus (MS) _vs_ ovulate strobilus (OS), respectively. A total of 6032 target genes were predicted for differentially expressed miRNA. The combined analysis of both small RNA and transcriptome datasets identified 51 miRNA-mRNA interaction pairs that may be involved in the process of G. biloba strobili sexual differentiation, of which 15 pairs were verified in the analysis of degradome sequencing. CONCLUSIONS: The comprehensive analysis of the small RNA, RNA and degradome sequencing data in this study provided candidate genes and clarified the regulatory mechanism of sexual differentiation of G. biloba strobili from multiple perspectives.
Asunto(s)
Flores/crecimiento & desarrollo , Flores/genética , Flores/ultraestructura , Ginkgo biloba/genética , MicroARNs/genética , ARN de Planta/genética , Diferenciación Sexual/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Ginkgo biloba/crecimiento & desarrollo , Secuenciación de Nucleótidos de Alto Rendimiento , Plantas Medicinales/genética , Plantas Medicinales/crecimiento & desarrollo , Análisis de Secuencia de ARN , TranscriptomaRESUMEN
OBJECTIVE: As an epidermal growth factor, receptor-tyrosine kinase inhibitor (EGFR-TKI), gefitinib demonstrates a good therapeutic effect in patients with EGFR-mutant non-small-cell lung cancer (NSCLC). However, an overwhelming majority of these patients inevitably develop resistance against gefitinib. Unfortunately, the mechanism underlying this phenomenon is still not fully understood. Here we aim to reveal the mechanism of gefitinib resistance in NSCLC induced by FGFR1. MATERIALS AND METHODS: We used high-throughput sequencing to compare the mRNA expression profiles of PC9 and PC9-GR (gefitinib-resistant) cells. The clinical significance of fibroblast growth factor receptor 1 (FGFR1) in NSCLC was also investigated using immunohistochemistry and Kaplan-Meier survival analysis. Finally, the in vitro molecular mechanisms were analyzed using confocal laser microscopy, Western blotting, transwell assay, colony formation assay, CCK-8 assay, and apoptosis assay. RESULTS: We observed that FGFR1 was highly expressed in NSCLC tissues and was closely associated with poor prognosis. Cytological experiments showed that FGFR1 promoted the proliferation and migration of PC9-GR cells and mediated their resistance to gefitinib. Furthermore, studies aimed at unraveling this mechanism revealed that FGFR1 activated the AKT/mTOR signaling pathway. These findings show that the FGFR1/AKT/mTOR signaling pathway plays a vital role in acquired resistance against gefitinib in NSCLC. CONCLUSION: This work provides new evidence that FGFR1 functions as a key regulator of gefitinib resistance, thereby demonstrating its potential as a novel biomarker and therapeutic target for NSCLC.