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1.
Small ; 19(29): e2207786, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37052507

RESUMEN

Immunocheckpoint inhibitors combined with Lenvatinib is the first line treatment for hepatocellular carcinoma (HCC), but their potency is hampered by the low response rate and adverse events. Herein, a targeted therapeutic strategy through the coassembly of Lenvatinib, Adriamycin, Fe3+ ion, and a natural polyphenol (metallo-nanodrugs) is presented by coordination effect for potentiating tumor vascular normalization and systematic chemo-immunotherapy to effectively inhibit the progression of HCC in both orthotopic model and patients-derived organoids. In mice with orthotopic HCC, the obtained metallo-nanodrugs efficiently increase the drug accumulation in orthotopic tumors and can respond to acidic tumor environment. The promotion of tumor vascular normalization by metallo-nanodrugs is observed, which enhances the infiltrating T lymphocytes in tumor, and reinforces the calreticulin-mediated antitumor immunity through alleviating hypoxia, reducing regulatory T cells, and down-regulating PDL1 expression of tumors. The excellent therapeutic efficiency with complete remission of orthotopic tumors (3/6) and long-term survival of mice (4/6, 42 days) are also achieved. Furthermore, the excellent therapeutic effect of metallo-nanodrugs is also validated in 5 patient-derived organoids, and hence can provide a marvelous systemic chemo-immunotherapy strategy for enhancing HCC treatment.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas , Ratones , Animales , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Calreticulina/metabolismo , Calreticulina/uso terapéutico , Nanopartículas/uso terapéutico , Inmunidad , Línea Celular Tumoral
2.
Cytokine ; 162: 156106, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36512935

RESUMEN

BACKGROUND: Through microarray results, we found that the C-X-C motif chemokine ligand 11 (CXCL11) was negatively regulated by mediator complex subunit 19 (MED19), a protumour factor. However, the biological role and potential mechanism of CXCL11 need to be explored in breast cancer (BRCA). METHODS: The BRCA dataset was obtained from the Cancer Genome Atlas (TCGA) dataset. Our microarray data and the BRCA dataset of TCGA were analysed and visualized using the R software package. The mRNA and protein levels were measured by qRT-PCR and western blotting. RESULTS: Inhibition of MED19 in MDA-MB-231 cells caused CXCL11 upregulation. The relative positive regulation of cytokine pathways was enriched after MED19 knockdown. High CXCL11 was determined to be positively correlated with immune response activation, increased antitumour immune cell infiltration, immune checkpoint molecule expression, and enhanced sensitivity to immunotherapy and chemotherapy. Collectively, CXCL11 promoted antitumour immunity and was regulated by MED19 in BRCA. Clarifying the prognostic value and underlying mechanism of CXCL11 in BRCA could provide a theoretical basis to find new diagnostic and therapeutic targets.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Proliferación Celular/genética , Pronóstico , Quimiocina CXCL11/genética , Quimiocina CXCL11/metabolismo , Complejo Mediador/genética , Complejo Mediador/metabolismo
3.
BMC Med Inform Decis Mak ; 21(1): 182, 2021 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-34098959

RESUMEN

BACKGROUND: Early diagnosis for the diabetes complications is clinically demanding with great significancy. Regarding the complexity of diabetes complications, we applied a multi-label classification (MLC) model to predict four diabetic complications simultaneously using data in the modern electronic health records (EHRs), and leveraged the correlations between the complications to further improve the prediction accuracy. METHODS: We obtained the demographic characteristics and laboratory data from the EHRs for patients admitted to Changzhou No. 2 People's Hospital, the affiliated hospital of Nanjing Medical University in China from May 2013 to June 2020. The data included 93 biochemical indicators and 9,765 patients. We used the Pearson correlation coefficient (PCC) to analyze the correlations between different diabetic complications from a statistical perspective. We used an MLC model, based on the Random Forest (RF) technique, to leverage these correlations and predict four complications simultaneously. We explored four different MLC models; a Label Power Set (LP), Classifier Chains (CC), Ensemble Classifier Chains (ECC), and Calibrated Label Ranking (CLR). We used traditional Binary Relevance (BR) as a comparison. We used 11 different performance metrics and the area under the receiver operating characteristic curve (AUROC) to evaluate these models. We analyzed the weights of the learned model and illustrated (1) the top 10 key indicators of different complications and (2) the correlations between different diabetic complications. RESULTS: The MLC models including CC, ECC and CLR outperformed the traditional BR method in most performance metrics; the ECC models performed the best in Hamming loss (0.1760), Accuracy (0.7020), F1_Score (0.7855), Precision (0.8649), F1_micro (0.8078), F1_macro (0.7773), Recall_micro (0.8631), Recall_macro (0.8009), and AUROC (0.8231). The two diabetic complication correlation matrices drawn from the PCC analysis and the MLC models were consistent with each other and indicated that the complications correlated to different extents. The top 10 key indicators given by the model are valuable in medical application. CONCLUSIONS: Our MLC model can effectively utilize the potential correlation between different diabetic complications to further improve the prediction accuracy. This model should be explored further in other complex diseases with multiple complications.


Asunto(s)
Complicaciones de la Diabetes , Diabetes Mellitus , China , Atención a la Salud , Complicaciones de la Diabetes/diagnóstico , Diabetes Mellitus/diagnóstico , Registros Electrónicos de Salud , Humanos , Curva ROC
4.
Biochem Biophys Res Commun ; 524(4): 861-868, 2020 04 16.
Artículo en Inglés | MEDLINE | ID: mdl-32057364

RESUMEN

Moesin has been proved to be implicated in invasiveness and metastasis in many other cancers, but unclear in HCC. Thus, this study was performed to investigate the clinical significance of moesin and its biological functions in HCC. The results showed that moesin was significantly up-regulated in HCC tissues and was an independent prognostic factor for predicting the recurrence of HCC patients, postoperatively. Furthermore, we also demonstrated that moesin promoted the migration and invasion of HCC cells in vitro and in vivo. And the mechanism studies indicated that moesin overexpression increased the formation of invadopodia and improved the activation of ß-catenin/MMP9 axis. Taken together, our findings revealed that moesin acted as an important onco-protein participating in the metastasis of HCC.


Asunto(s)
Carcinoma Hepatocelular/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/genética , Metaloproteinasa 9 de la Matriz/genética , Recurrencia Local de Neoplasia/genética , beta Catenina/genética , Adulto , Anciano , Animales , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Femenino , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Metástasis Linfática , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Endogámicos NOD , Persona de Mediana Edad , Invasividad Neoplásica , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Podosomas/metabolismo , Podosomas/patología , Podosomas/ultraestructura , Transducción de Señal , Análisis de Supervivencia , Carga Tumoral , beta Catenina/metabolismo
5.
J Cell Sci ; 129(5): 994-1002, 2016 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-26813789

RESUMEN

Mitochondrial morphology is regulated by fusion and fission machinery. Impaired mitochondria dynamics cause various diseases, including Alzheimer's disease. Appoptosin (encoded by SLC25A38) is a mitochondrial carrier protein that is located in the mitochondrial inner membrane. Appoptosin overexpression causes overproduction of reactive oxygen species (ROS) and caspase-dependent apoptosis, whereas appoptosin downregulation abolishes ß-amyloid-induced mitochondrial fragmentation and neuronal death during Alzheimer's disease. Herein, we found that overexpression of appoptosin resulted in mitochondrial fragmentation in a manner independent of its carrier function, ROS production or caspase activation. Although appoptosin did not affect levels of mitochondrial outer-membrane fusion (MFN1 and MFN2), inner-membrane fusion (OPA1) and fission [DRP1 (also known as DNM1L) and FIS1] proteins, appoptosin interacted with MFN1 and MFN2, as well as with the mitochondrial ubiquitin ligase MITOL (also known as MARCH5) but not OPA1, FIS1 or DRP1. Appoptosin overexpression impaired the interaction between MFN1 and MFN2, and mitochondrial fusion. By contrast, co-expression of MFN1, MITOL and a dominant-negative form of DRP1, DRP1(K38A), partially rescued appoptosin-induced mitochondrial fragmentation and apoptosis, whereas co-expression of FIS1 aggravated appoptosin-induced apoptosis. Together, our results demonstrate that appoptosin can interact with mitochondrial outer-membrane fusion proteins and regulates mitochondrial morphology.


Asunto(s)
GTP Fosfohidrolasas/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de Transporte de Membrana Mitocondrial/metabolismo , Proteínas Mitocondriales/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Apoptosis , Dinaminas , Células HeLa , Humanos , Fusión de Membrana , Proteínas Asociadas a Microtúbulos/metabolismo , Mitocondrias/metabolismo , Mitocondrias/ultraestructura , Dinámicas Mitocondriales , Membranas Mitocondriales/metabolismo , Tamaño Mitocondrial
6.
Bioconjug Chem ; 29(9): 2884-2891, 2018 09 19.
Artículo en Inglés | MEDLINE | ID: mdl-30074757

RESUMEN

With the development of materials science and pharmaceutics, the application of mesoporous silica nanoparticles with a gated switch in the field of drug delivery has attracted much attention in the past decades. Cyclodextrins (CD) as promising gated materials have become a new area of interest in recent years due to their properties of self-assembly and function of host-guest interaction. CD is one kind of extensively studied host molecules and the host-guest interactions with different guest molecules can respond to different signals, and thus can be applied as intelligent gated switches for smart drug carriers. Switchable gatekeepers based on CD hosts with different guest molecules (such as benzimidazole, azobenzene, and ferrocene) respond to different stimuli modes (such as pH, light, and redox) that change the host-guest interactions and trigger drug release. The different structural features, mechanisms of action, and potent applications of these switchable gatekeepers are discussed. In addition, some personal perspectives and challenge on this field are presented.


Asunto(s)
Ciclodextrinas/química , Sistemas de Liberación de Medicamentos , Nanopartículas/química , Dióxido de Silicio/química , Compuestos Azo/química , Porosidad
7.
ISA Trans ; 147: 101-108, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38413311

RESUMEN

The problem of the resilient filtering for a class of discrete-time complex networks over switching topology is investigated. Taking into account the limitation of channel bandwidth, a refined adaptive event-triggered scheme is derived, whose threshold is determined by the change rate of measurement. The large change rate of measurement results in a smaller threshold, which means that more data packets will be transmitted to guarantee the performance of filtering, and the smaller one leads to a bigger threshold to save the network energy. Under the adaptive event-triggered scheme, considering the switching topology and uncertain inner coupling, a resilient filtering with a variable filtering gain is proposed. Additionally, the minimal upper bound of the covariance of estimation error is developed and the sufficient conditions are also given to obtain the exponentially bounded in mean square of the estimation error system. Finally, a simulation is presented to certify the effectiveness of the derived resilient filtering.

8.
Medicine (Baltimore) ; 103(21): e38272, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38787998

RESUMEN

BACKGROUND: Advanced gastric cancer (AGC) that does not respond to first-line therapy poses a challenge to clinical management. The objective of this study was to compare the efficacy and safety of apatinib combined with S-1 in second-line and above treatment of AGC. METHODS: Cochrane Library, Science Direct, EMBASE, PubMed, and CNKI were searched for randomized controlled trial until August 2023. Only patients who met "Standardized Diagnosis and Treatment Guide for Gastric Cancer" were included in the study. The accurate data and distinguishing between follow-up time and drug dose were extracted to reduce heterogeneity and the risk of bias of the included trials was evaluated according to the Cochrane Handbook. Finally, the survival benefit of the treatment was evaluated based on clinical response rate, survival period, biochemical index, and adverse event occurrence in the trial. RESULTS: The meta-analysis included 29 randomized controlled trials involving 2149 participants. Statistically significant increases in clinical effective rate (odds ratios = 2.61, 95% confidence interval [2.13-3.20], P < .00001) and disease control rate (odds ratios = 3.16, 95% confidence interval [2.54-3.94], P < .00001) were found when apatinib combined with S-1, and also had obvious advantages in reducing tumor markers and regulating immune factors. In addition, apatinib combined with S-1 significantly increased the risk of hypertension but reduced damage to liver function, while the improvement of other adverse events was not pronounced. DISCUSSION: Apatinib combined with S-1 is more effective and safe for second-line and above treatment of AGC. This study minimized the conclusion bias caused by the basic data sources, but more high-quality studies are still needed to validate these conclusions.


Asunto(s)
Combinación de Medicamentos , Ácido Oxónico , Piridinas , Neoplasias Gástricas , Tegafur , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Ácido Oxónico/administración & dosificación , Ácido Oxónico/uso terapéutico , Ácido Oxónico/efectos adversos , Piridinas/uso terapéutico , Piridinas/administración & dosificación , Piridinas/efectos adversos , Tegafur/administración & dosificación , Tegafur/uso terapéutico , Tegafur/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Antineoplásicos/uso terapéutico , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Resultado del Tratamiento
9.
Clin Breast Cancer ; 24(7): e545-e553.e6, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38760263

RESUMEN

INTRODUCTION: Patients with metastatic triple-negative breast cancer (mTNBC) have poor prognosis and survival outcomes. Sacituzumab govitecan was newly approved into Chinese market for mTNBC. However, whether its price matches the survival benefit still needs exploring. Here, this study aimed to evaluate the cost-effectiveness of sacituzumab govitecan versus chemotherapy in patients with mTNBC from the perspective of Chinese healthcare system. METHODS: A partitioned survival model consisting of three discrete health states was constructed to assess the cost-effectiveness of sacituzumab govitecan versus single-agent chemotherapy. The key clinical data in the model were from the ASCENT trial. Costs and utility inputs were collected from published literatures. Life-years gained, quality adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), incremental net health benefits, and incremental net monetary benefits were calculated between 2 treatment strategies. One-way and probabilistic sensitivity analyses were conducted to account for uncertainty and verify model robustness. Subgroup and cost-threshold analysis were also performed. RESULTS: Sacituzumab govitecan provided an additional 0.25 QALYs and an incremental cost of $ 81,778.61 compared with chemotherapy, which was associated with an ICER of $ 323,603.84/QALY. One-way sensitivity analysis revealed that the model was most sensitive to the cost of sacituzumab govitecan, weight, and utility of progression-free survival. The probabilistic sensitivity analysis indicated that the probability of sacituzumab govitecan being cost-effective was 0%. Considering a willingness-to-pay (WTP) of 3 times GDP, the maximum cost of sacituzumab govitecan that would make it cost-effective was $155.65 per unit (180 mg). CONCLUSIONS: Sacituzumab govitecan was not cost-effective for patients with mTNBC compared with chemotherapy at the commonly adopted WTP threshold of 3 times GDP per capita per QALY in China.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Análisis Costo-Beneficio , Años de Vida Ajustados por Calidad de Vida , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/economía , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/mortalidad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/economía , China , Camptotecina/análogos & derivados , Camptotecina/uso terapéutico , Camptotecina/economía , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/economía , Inmunoconjugados
10.
Sci Total Environ ; 925: 171792, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38508251

RESUMEN

Aiming at the sustainable management of high-moisture Chinese medicine residues (CMR), an alternative way integrating hydrothermal carbonization (HTC), humic acids (HAs) extraction and combustion of remained hydrochar has been proposed in this study. Effect of HTC temperature, HTC duration, and feedwater pH on the mass yield and properties of HAs was examined. The associated formation mechanism of HAs during HTC was proposed. The combustion performance of remained hydrochar after HAs extraction was evaluated. Results show that the positive correlation between hydrochar yield and HAs yield is observed. According to three-dimensional excitation emission matrix (3D EEM) fluorescence intensity, the best quality of HAs is achieved with a yield of 8.17 % at feedwater pH of 13 and HTC temperature of 200 °C. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy analyses show abundant aromatic and aliphatic structure as well as oxygenated functional groups in HAs, which is like commercial HAs (HA-C). Besides, in terms of comprehensive combustion index (CCI), HTC can improve the combustion performance of CMR, while it becomes a bit worse after HAs extraction. Higher weighted mean apparent activation energy (Em) of hydrochar indicating its highly thermal stability. HAs extraction reduces Em and CCI of remained hydrochar. However, it can be regarded a potential renewable energy. This work confirms a more sustainable alternative way for CMR comprehensive utilization in near future.

11.
Mol Ther Nucleic Acids ; 35(1): 102125, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38356866

RESUMEN

Hepatocellular carcinoma (HCC) is a common malignancy with poor prognosis. In recent years, immune checkpoint inhibitors (ICIs) have enabled breakthroughs in the clinical treatment of patients with HCC, but the overall response rate to ICIs in HCC patients is still low, and no validated biomarker is available to guide clinical decision making. Here, we demonstrated that the long non-coding RNA Lnc-CCNH-8 is highly expressed in HCC and correlates with poor prognosis. Functionally, elevated Lnc-CCNH-8 inactivated co-cultured T cells in vitro and compromised antitumor immunity in an immunocompetent mouse model. Mechanistically, up-regulated Lnc-CCNH-8 can sponge microRNA (miR)-217 to regulate the expression of PD-L1. In addition, Lnc-CCNH-8 can also stabilize PD-L1 through miR-3173/PKP3 axis. Furthermore, mice bearing tumors with high Lnc-CCNH-8 expression had significant therapeutic sensitivity to anti-PD-L1 monoclonal antibody treatment. More important, HCC patients with high levels of plasma exosomal Lnc-CCNH-8 had a better therapeutic response to ICIs. Taken together, our results reveal the function of Lnc-CCNH-8 in inducing immune escape from CD8+ T-cell-mediated killing by up-regulating PD-L1 in a miR-217/miR-3173-dependent manner, which also reveals a novel mechanism of PD-L1 regulation in HCC, and exosomal Lnc-CCNH-8 can serve as a predictive marker for immunotherapy response in HCC.

13.
Biomass Convers Biorefin ; : 1-18, 2023 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-36627933

RESUMEN

High moisture in Chinese medicine residues (CMR) can decrease the energy efficiency of thermochemical conversion, which necessitates the pre-drying. Owing to the complex constituents and decoction, CMR may possess distinct drying characteristics. It is necessary to understand its drying behaviors, effective moisture diffusivity, and pollutant emissions for future design and optimization of an industrial-level dryer. In this study, the drying of four types of typical CMR in hot nitrogen was performed. Their condensate and exhaust gas were collected and characterized. The results indicated that their drying process was dominated by internal moisture transport mechanism with a long falling rate stage. Drying temperature influenced their drying process more greatly than N2 velocity did. Residual sum of squares, root mean square error, and coefficient of determination indicated that Weibull model demonstrated their drying process best. Their effective moisture diffusivity was in the range of 1.224 × 10-8 to 4.868 × 10-8 m2/s, while their drying activation energy ranged from 16.93 to 30.39 kJ/mol. The acidic condensate had high chemical oxygen demand and total nitrogen concentration and yet low total phosphorus concentration. The concentration of total volatile organic compounds, non-methane hydrocarbons, H2S, and NH3 in the exhaust gas met the national emission limitation, while the deodorization of exhaust gas was required to remove odor smell. Supplementary information: The online version contains supplementary material available at 10.1007/s13399-022-03722-4.

14.
Materials (Basel) ; 16(13)2023 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-37445203

RESUMEN

Electromagnetic spring active isolators have attracted extensive attention in recent years. The standard Bouc-Wen model is widely used to describe hysteretic behavior but cannot accurately describe asymmetric behavior. The standard Bouc-Wen model is improved to better describe the dynamic characteristic of a toothed electromagnetic spring. The hysteresis model of toothed electromagnetic spring is established by adding mass, damping, and asymmetric correction terms with direction. Subsequently, the particle swarm optimization algorithm is used to identify the parameters of the established model, and the results are compared with those obtained from the experiment. The results show that the current has a significant impact on the dynamic curve. When the current increases from 0.5 A to 2.0 A, the electromagnetic force sharply increases from 49 N to 534 N. Under different excitations and currents, the residual points predicted by the model proposed in this work fall basically in the horizontal band region of -20-20 N (for an applied current of 1.0 A) and -40-80 N (for an application of 4.5 mm/s). Furthermore, the maximum relative error of the model is 12.75%. The R2 of the model is higher than 0.98 and the highest value is 0.9993, proving the accuracy of the established model.

15.
Protein Pept Lett ; 30(11): 930-940, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37870056

RESUMEN

BACKGROUND: Increasingly convincing evidence has revealed that circular RNAs (circRNAs) are critical regulatory components of hepatocellular carcinoma (HCC) genesis. However, the expression of circRNAs in HCC and the relevance of circRNAs to HCC progression remain largely unexplained. METHODS: qRT-PCR or western blotting was utilized to confirm circ_0001687, miR-140-3p, and Forkhead Box q1 (FOXQ1) levels in HCC tissues or cells. Cell proliferation ability was evaluated via CCK-8 and colony formation assay. The correlation of circ_0001687 or FOXQ1 and miR-140- 3p was determined using dual luciferase reporter assay. Nude mice xenograft tumor model was constructed to verify the effect of circ_0001687 on tumor growth. RESULTS: Circ_0001687 was elevated in HCC. Function assays and the nude mice xenograft tumor model indicated that circ_0001687 acts as a promoting gene in HCC to regulate the proliferation of the tumor cell and foster tumor growth. Further mechanistic exploration revealed that the tumor growth-promoting mechanism of circ_0001687 relied on blocking the inhibitory effect of miR-140- 3p on FOXQ1 and activating FOXQ1 expression. CONCLUSION: This research indicated the role of circ_0001687/miR-140-3p/FOXQ1 network in regulating HCC development. These may provide new insights into the treatment of HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , Animales , Ratones , Humanos , Carcinoma Hepatocelular/genética , ARN Endógeno Competitivo , Ratones Desnudos , ARN Circular/genética , Neoplasias Hepáticas/genética , Proliferación Celular , Modelos Animales de Enfermedad , MicroARNs/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Factores de Transcripción Forkhead/genética
16.
Front Plant Sci ; 14: 1300067, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38250446

RESUMEN

Sprouting is an irreversible deterioration of potato quality, which leads to the production of harmful toxins and loss of the commercial value of potatoes. However, there is no report on the changes in different stages of potato sprouting through transcriptome and metabonomics. In this study, 1471 differentially expressed genes (DEGs) were found between DP and BP. In comparison with SP, a total of 6309 DEGs were detected in BP. Additionally, 6624 DEGs were identified between DP and SP. Moreover, 96 and 117 differentially accumulated metabolites (DAMs) were detected between DP and BP and between BP and SP, respectively. Furthermore, 130 DAMs were identified in total between DP and SP. In each group, a correlation analysis of DAMs and DEGs was performed to examine the regulatory network. The results indicated that the sprouting of tubers is mainly regulated by plant hormone signals, and during the sprouting of tubers, significant changes in metabolic products occur in the body. According to the combined analysis of transcriptomics and metabolomics, multiple metabolites were both positive and negative regulated by genes.

17.
iScience ; 26(12): 108495, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-38089592

RESUMEN

Hypoxic microenvironment is clinically associated with metastasis and poor prognosis of numerous cancers. The mechanisms by which intratumoral hypoxia regulates metastasis are not fully understood. Our study identifies a downregulation of Lnc-CSMD1-7 in hepatocellular carcinoma (HCC) and correlated with poor prognosis of HCC patients. Lnc-CSMD1-7 negatively regulated HCC cell migration and invasion in vitro and suppressed lung metastasis in vivo. Mechanistically, Lnc-CSMD1-7 directly binds to RBFOX2, thereby affecting RBFOX2-regulated alternative splicing in epithelial and mesenchymal-specific events. More importantly, hypoxic microenvironment and m6A methylation mediate the downregulation of Lnc-CSMD1-7 expression. Specifically, hypoxia transcriptionally upregulates the expression of the m6A methyltransferase METTL16 via HIF-1α, and METTL16 directly binds to Lnc-CSMD1-7 and downregulates the RNA stability of Lnc-CSMD1-7 via m6A methylation, ultimately promoting HCC metastasis. Our findings highlight the regulatory function of the METTL16/Lnc-CSMD1-7/RBFOX2 axis in modulating hypoxia-induced HCC progression, which may provide potential prognostic and therapeutic targets for HCC treatment.

18.
Drug Deliv Transl Res ; 13(3): 782-794, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36114310

RESUMEN

Circular RNAs (circRNAs) are a class of highly stable and closed-loop noncoding RNA that are involved in the occurrence and development of hepatocellular carcinoma (HCC). However, little is known about the therapeutic role of circRNAs in HCC. We found that high circ_0058051 expression was negatively correlated with the prognosis of HCC patients. Circ_0058051 knockdown attenuated the proliferation and colony formation, meanwhile inhibited migration of HCC cells. Circ_0058051 may be used as a target for HCC gene therapy. We synthesized a novel small interfering RNA (siRNA) delivery system, PEG-PCL-PEI-C14-SPIONs (PPPCSs), based on superparamagnetic iron oxide nanoparticles (SPIONs). PPPCSs protected the siRNA of circ_0058051 from degradation in serum and effectively delivered siRNA into SMMC-7721 cells. Meanwhile, intravenous injection of the PPPCSs/siRNA complex could inhibit tumor growth in the subcutaneous tumor model. In addition, the nanocomposite is not toxic to the organs of nude mice. The above results show that PPPCSs/si-circ_0058051 complex may provide a novel and promising method of HCC treatment.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , Animales , Ratones , Carcinoma Hepatocelular/genética , ARN Circular/genética , ARN Circular/metabolismo , Neoplasias Hepáticas/genética , MicroARNs/genética , Ratones Desnudos , ARN Interferente Pequeño/genética , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral
19.
Heliyon ; 9(4): e15357, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37151623

RESUMEN

Mixing different kind inhalation medications for simultaneous inhalation is widely used in the treatment of chronic respiratory diseases, and it can minimize the administration time and improve patient adherence. To our knowledge, it is unclear whether beclomethasone (BDP, Clenil®) can bemixed with acetylcysteine (NAC, Fluimucil®), because the in vitro physico-chemical compatibility and aerosol characteristics of the mixture are unknown. In this study, we investigated physical compatibility, including the appearance, pH, osmotic pressure and chemical stability, as well as aerosol characteristics, including particle size corresponding to 10%/50%/90% of the cumulative percentage of total particle volume (X10/X50/X90), volume median droplet diameter (VMD), mass median aerodynamic diameter (MMAD), fine particle fraction (FPF), fine particle dose (FPD) and geometric standard deviation (GSD), delivery rate, and total delivery of the above solutions. After mixing, there were no significant changes in visual appearance, pH, osmolality and drug content of the mixtures at room temperature for 12 h. The FDP of BDP in the mixture decreased by 16.49%, whereas the NAC increased by 10.85%. The delivery rates of BDP and NAC in the mixture decreased by 66.05% and 45.54%, and total delivery increased by 13.20% and 25.29%, respectively. However, the MMAD, FPF, particle size and GSD of the mixture were almost unchanged. We demonstrated that these admixtures are physico-chemically compatible but that coadministration of beclomethasone with acetylcysteine can markedly affect output and aerosol characteristics.

20.
Food Chem ; 416: 135688, 2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-36905709

RESUMEN

Lignin is a crucial component in the wound tissue of tubers. The biocontrol yeast Meyerozyma guilliermondii increased the activities of phenylalanine ammonia lyase, cinnamate-4-hydroxylase, 4-coenzyme coenzyme A ligase, and cinnamyl alcohol dehydrogenase, and elevated the levels of coniferyl, sinapyl, and p-coumaryl alcohol. The yeast also enhanced the activities of peroxidase and laccase, as well as the content of hydrogen peroxide. The lignin promoted by the yeast was identified as guaiacyl-syringyl-p-hydroxyphenyl type using Fourier transform infrared spectroscopy and two-dimensional heteronuclear single quantum coherence nuclear magnetic resonance. Furthermore, a larger signal area for G2, G5, G'6, S2, 6, and S'2, 6 units was observed in the treated tubers, and the G'2 and G6 units were only detected in the treated tuber. Taken together, M. guilliermondii could promote deposition of guaiacyl-syringyl-p-hydroxyphenyl type lignin by activating the biosynthesis and polymerization of monolignols at the wounds of potato tubers.


Asunto(s)
Lignina , Solanum tuberosum , Lignina/química , Polimerizacion
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