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The pleiotropic effect of cancer-associated fibroblasts (CAFs) on tumour progression depends on the environment. circFARP1 is critical for CAFs-induced gemcitabine (GEM) resistance in pancreatic cancer. Its specific role and mechanism in non-small cell lung cancer (NSCLC) have not been reported yet. We prepared a cancer-associated fibroblasts-conditioned medium (CAF-CM) to incubate the A549 cells. Quantitative real-time polymerase chain reaction was used to detect RNA levels. We detected protein expression by immunohistochemistry, immunocytochemistry, western blot and immunofluorescence. We also detected the targeting impact between circFARP1, miR-338-3p and SRY-box transcription factor 4 (SOX4) by using dual-luciferase reporter and RNA pull-down assays. We determined cell proliferation, migration and invasion capabilities through Cell Counting Kit-8 and transwell assays. In addition, we measured tumour volume and weight in vivo by establishing a xenograft tumour model. CircFARP1 levels were remarkably high in the CAFs. The transfection experiments found that circFARP1 downregulation in CAFs caused migration, proliferation and invasion inhibition of CAFs and A549 cells, whereas inhibiting miR-38-3p or overexpressing SOX4 in CAFs could significantly reverse the inhibition. In vivo study in nude mice confirmed that CAFs could promote NSCLC tumour growth and knockdown of circFARP1 could inhibit tumour growth of NSCLC, whereas miR-38-3p downregulation or SOX4 overexpression could significantly reverse the inhibition. circFARP1 promotes NSCLC development by stimulating miR-338-3p/SOX4 signalling axis to regulate CAFs.
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Fibroblastos Asociados al Cáncer , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , MicroARNs , Invasividad Neoplásica , ARN Circular , Factores de Transcripción SOXC , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Factores de Transcripción SOXC/genética , Factores de Transcripción SOXC/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Animales , ARN Circular/genética , ARN Circular/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Proliferación Celular/genética , Ratones , Células A549 , Metástasis de la Neoplasia , Movimiento Celular , Regulación Neoplásica de la Expresión Génica , Ratones Desnudos , MasculinoRESUMEN
BACKGROUND: High-grade endometrial stromal sarcoma (HG-ESS) is a rare malignant tumor with poor prognosis. To overcome the limitations of current treatment for advanced patients, the intervention of targeted drug therapy is urgently needed. CASE PRESENTATION: A 74-year-old married woman who presented with abdominal distension and lower abdominal pain was admitted to Hebei General Hospital. After surgery, immunohistochemical staining revealed a malignant tumor which was consistent with HG-ESS. Tumor recurrence occurred 2 months after surgery. Then the patient underwent chemotherapy with two courses but responded poorly. Subsequently we observed ATM, BLM, and CDH1 co-mutations by Next Generation Sequencing (NGS). Then the patient received pamiparib, which resulted in a 10-month progression-free survival (PFS) and is now stable with the administration of sintilimab in combination with pamiparib and anlotinib. CONCLUSIONS: Due to the successful use of poly ADP-ribose polymerase inhibitor (PARPi) on HG-ESS, we suggest that the selection of effective targeted drugs combined with anti- programmed death-1 (PD-1) drug therapy based on genetic testing may become a new option for the treatment of homologous repair deficient (HR-deficient) HG-ESS.
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Proteínas de la Ataxia Telangiectasia Mutada , Cadherinas , Neoplasias Endometriales , RecQ Helicasas , Sarcoma Estromático Endometrial , Humanos , Femenino , Anciano , Neoplasias Endometriales/genética , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/patología , Sarcoma Estromático Endometrial/genética , Sarcoma Estromático Endometrial/tratamiento farmacológico , Sarcoma Estromático Endometrial/diagnóstico , Proteínas de la Ataxia Telangiectasia Mutada/genética , RecQ Helicasas/genética , Cadherinas/genética , Antígenos CD/genética , MutaciónRESUMEN
The mobility and fate of Cd in soil are mainly controlled by active substances such as iron minerals and organic matter. Iron minerals and organic matter often coexist in the form of iron-organic associations (IOA), which have large specific surface areas and many functional groups, potentially affecting Cd adsorption. However, little is known about Cd adsorption by IOA. This study investigated Cd adsorption by the synthetic IOA under different conditions. The results indicate Cd adsorption increased with the increasing amount of IOA, while the adsorption efficiency decreased gradually. pH significantly affects Cd adsorption, because the Cd speciation and the surface charge of IOA changed under different pH conditions. Under alkaline condition, part of Cd would form hydroxide precipitate, facilitating Cd adsorption by IOA. The composition of organic matter in IOA didn't significantly affect Cd adsorption.
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Hierro , Contaminantes del Suelo , Adsorción , Cadmio , Minerales , SueloRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba L. is a well-known and highly regarded resource in Chinese traditional medicine due to its effectiveness and safety. Ginkgo Folium, the leaf of Ginkgo biloba L., contains biologically active constituents with diverse pharmacological activities. Recent studies have shown promising antitumor effects of the bioactive constituents found in Ginkgo Folium against various types of cancer cells, highlighting its potential as a natural source of antitumor agents. Further research is needed to elucidate the underlying mechanisms and optimize its therapeutic potential. AIM OF THE REVIEW: To provide a detailed understanding of the pharmacological activities of Ginkgo Folium and its potential therapeutic benefits for cancer patients. MATERIALS AND METHODS: In this study, we conducted a thorough and systematic search of multiple online databases, including PubMed, Web of Science, Medline, using relevant keywords such as "Ginkgo Folium," "flavonoids," "terpenoids," "Ginkgo Folium extracts," and "antitumor" to cover a broad range of studies that could inform our review. Additionally, we followed a rigorous selection process to ensure that the studies included in our review met the predetermined inclusion criteria. RESULTS: The active constituents of Ginkgo Folium primarily consist of flavonoids and terpenoids, with quercetin, kaempferol, isorhamnetin, ginkgolides, and bilobalide being the major compounds. These active constituents exert their antitumor effects through crucial biological events such as apoptosis, cell cycle arrest, autophagy, and inhibition of invasion and metastasis via modulating diverse signaling pathways. During the process of apoptosis, active constituents primarily exert their effects by modulating the caspase-8 mediated death receptor pathway and caspase-9 mediated mitochondrial pathway via regulating specific signaling pathways. Furthermore, by modulating multiple signaling pathways, active constituents effectively induce G1, G0/G1, G2, and G2/M phase arrest. Among these, the pathways associated with G2/M phase arrest are particularly extensive, with the cyclin-dependent kinases (CDKs) being most involved. Moreover, active constituents primarily mediate autophagy by modulating certain inflammatory factors and stressors, facilitating the fusion stage between autophagosomes and lysosomes. Additionally, through the modulation of specific chemokines and matrix metalloproteinases, active constituents effectively inhibit the processes of epithelial-mesenchymal transition (EMT) and angiogenesis, exerting a significant impact on cellular invasion and migration. Synergistic effects are observed among the active constituents, particularly quercetin and kaempferol. CONCLUSION: Active components derived from Ginkgo Folium demonstrate a comprehensive antitumor effect across various levels and pathways, presenting compelling evidence for their potential in new drug development. However, in order to facilitate their broad and adaptable clinical application, further extensive experimental investigations are required to thoroughly explore their efficacy, safety, and underlying mechanisms of action.
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Ginkgo biloba , Quercetina , Humanos , Quercetina/farmacología , Quempferoles , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , FlavonoidesRESUMEN
As a by-product of soybean processing, soybean hulls contain soybean hull polysaccharides (SHPS). This study aims to develop a plant-based yogurt with SHPS addition and assess the consequences of SHPS on the physicochemical properties and growth of lactic acid bacteria (LAB) in yogurts. The study investigated the water holding capacity (WHC), microstructure, rheological properties, texture, pH, organoleptic attributes, volatile compounds, flavor profile, and LAB population. The findings reveal that the addition of SHPS significantly impacted these properties. SHPS improved the physicochemical properties, increased the level of flavor compounds, and improved the organoleptic properties of yogurt. Yogurt with 0.6% SHPS demonstrated superior WHC, texture, rheological properties, and the highest organoleptic evaluation scores. However, when SHPS additions exceeded 0.6%, WHC, texture, and rheological properties of the yogurts decreased. Furthermore, SHPS-added yogurts contained more LAB compared to yogurt without SHPS. LAB grew better in media with SHPS than in media without glucose. Streptococcus thermophilus grew best among the LAB strains. This study highlights the potential of SHPS in yogurt production and its promising applications in fermented food products.
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Transcription factor EB, a member of the microphthalmia-associated transcription factor (MiTF/TFE) family, is a master regulator of autophagy, lysosome biogenesis, and TAMs. Metastasis is one of the main reasons for the failure of tumor therapy. Studies on the relationship between TFEB and tumor metastasis are contradictory. On the positive side, TFEB mainly affects tumor cell metastasis via five aspects, including autophagy, epithelial-mesenchymal transition (EMT), lysosomal biogenesis, lipid metabolism, and oncogenic signaling pathways; on the negative side, TFEB mainly affects tumor cell metastasis in two aspects, including tumor-associated macrophages (TAMs) and EMT. In this review, we described the detailed mechanism of TFEB-mediated regulation of metastasis. In addition, we also described the activation and inactivation of TFEB in several aspects, including the mTORC1 and Rag GTPase systems, ERK2, and AKT. However, the exact process by which TFEB regulates tumor metastasis remains unclear in some pathways, which requires further studies.
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Autofagia , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Transducción de Señal , Lisosomas/metabolismo , FosforilaciónRESUMEN
Exotic plant invasion is an urgent issue occurring in the biosphere, which can be stimulated by environmental nitrogen (N) loading. However, the allocation and assimilation of soil N sources between leaves and roots remain unclear for plants in invaded ecosystems, which hampers the understanding of mechanisms behind the expansion of invasive plants and the co-existence of native plants. This work established a new framework to use N concentrations and isotopes of soils, roots, and leaves to quantitatively decipher intra-plant N allocation and assimilation among plant species under no invasion and under the invasion of Chromolaena odorata and Ageratina adenophora in a tropical ecosystem of SW China. We found that the assimilation of N derived from both soil ammonium (NH4+) and nitrate (NO3-) were higher in leaves than in roots for invasive plants, leading to higher leaf N levels than native plants. Compared with the same species under no invasion, most native plants under invasion showed higher N concentrations and NH4+ assimilations in both leaves and roots, and increases in leaf N were higher than in root N for native plants under invasion. These results inform that preferential N allocation, dominated by NH4+-derived N, to leaves over roots as an important N-use strategy for plant invasion and co-existence in the studied tropical ecosystem.
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Ecosistema , Nitrógeno , Isótopos , Nitrógeno/análisis , Hojas de la Planta/química , Raíces de Plantas/química , SueloRESUMEN
OBJECTIVE: To investigate if a Family-Clinician Shared Decision-Making (FCSDM) intervention benefits patients, families and intensive care units (ICUs) clinicians. METHODS: Six ICUs in China were allocated to intervention or usual care. 548 patients with critical illness, 548 family members and 387 ICU clinicians were included into the study. Structured FCSDM family meetings were held in the intervention group. Scales of SSDM, HADS, QoL2 and CSACD were used to assess families' satisfaction and distress, patients' quality of life, and clinicians' collaboration respectively. RESULTS: Comparing the intervention group with the control group at post-intervention, there were significant differences in the families' satisfaction (P = 0.0001), depression level (P = 0.005), and patients' quality of life (P = 0.0007). The clinicians' mean CSCAD score was more positive in the intervention group than controls (P < 0.05). There was no significant between-group differences on ICU daily medical cost, but the intervention group demonstrated shorter number of days' stay in ICU (P = 0.0004). CONCLUSION: The FCSDM intervention improved families' satisfaction and depression, shortened patients' duration of ICU stay, and enhanced ICU clinicians' collaboration. PRACTICE IMPLICATIONS: Further improvement and promotion of the FCSDM model are needed to provide more evidence to this field in China.
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Toma de Decisiones Conjunta , Calidad de Vida , Enfermedad Crítica/terapia , Toma de Decisiones , Familia , Humanos , Unidades de Cuidados Intensivos , Relaciones Profesional-FamiliaRESUMEN
OBJECTIVE: To investigate the reliability and validity of the Chinese version of VR-CoDES. METHODS: The VR-CoDES was translated into Chinese, and a focus group was held to discuss its cultural adaptation. Video consultations between 75 fourth-year medical students and 2 standardized patients (SPs) were coded by two raters with the Chinese VR-CoDES. Inter-rater reliability was tested by using ICC. To obtain validity, the SPs reviewed the video consultations to confirm the cues and concerns. RESULTS: ICC was 0.79. Specificity and sensitivity were 0.99 and 0.96 respectively. The SPs expressed considerably more cues (mean = 7.00) than concerns (mean = 0.32). Half of the responses of medical students were explicit reducing space. Focus group participants raised some cultural considerations, and some interactions were difficult to code due to cultural differences. CONCLUSION: The Chinese VR-CoDES obtained good reliability and validity. Due to differences in the expression of emotions and other differences such as different medical systems between China and Western countries, the Chinese VR-CoDES needs further cultural adaptation. PRACTICE IMPLICATION: More consultations in real clinical settings need to be gathered to further support the Chinese VR-CoDES both on validation and cultural adaptation.