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1.
J Asian Nat Prod Res ; : 1-28, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38958647

RESUMEN

The SwissTargetPrediction was employed to predict the potential drug targets of the active component of Si-Miao-Yong-An decoction (SMYAD). The therapeutic targets for HF were searched in the Genecard database, and Cytoscape3.9.1 software was used to construct the "drug-component-target-disease network" diagram. In addition, the String platform was used to construct Protein-Protein Interaction (PPI) network, and the DAVID database was used for GO and KEGG analysis. AutoDockTools-1.5.6 software was used for molecular docking verification. Network pharmacology studies have shown that AKT 1, ALB, and CASP 3 are the key targets of action of SMYAD against heart failure. The active compounds are quercetin and kaempferol.

2.
Nat Prod Res ; : 1-8, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38962949

RESUMEN

The phytochemical investigation on the rhizomes of Paris yunnanensis Franch. resulted in the discovery and characterisation of six compounds, including two new saponins named parisyunnanosides M-N (1-2), and four known ones (3-6). The structures of isolated compounds were determined by spectroscopic data analysis and chemical methods. Compound 2 is a pregnane-type saponin with a special α,ß-unsaturated carboxylic acid moiety at C-17, which is first discovered in genus Paris. The anti-inflammatory activity of the isolated compounds was assessed in vitro. The results demonstrated that compounds 3 and 4 could significantly inhibit the production of NO which was induced by LPS in RAW 264.7 cells with IC50 values of 0.67 ± 0.17 µM and 0.85 ± 0.12 µM, respectively.

3.
Nanoscale ; 16(25): 12149-12162, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38833269

RESUMEN

Together, tumor and virus-specific tissue-resident CD8+ memory T cells (TRMs) of hepatocellular carcinoma (HCC) patients with Hepatitis B virus (HBV) infection can provide rapid frontline immune surveillance. The quantity and activity of CD8+ TRMs were correlated with the relapse-free survival of patients with improved health. However, HBV-specific CD8+ TRMs have a more exhausted phenotype and respond more actively under anti-PDL1 or PD1 treatment of HBV+HCC patients. Vaccination strategies that induce a strong and sustained CD8+ TRMs response are quite promising. Herein, a biodegradable poly(D,L-lactide-co-glycolide) microsphere and nanosphere particle (PLGA N.M.P) delivery system co-assembled by anti-PD1 antibodies (aPD1) and loaded with ovalbumin (OVA-aPD1 N.M.P) was fabricated and characterized for size (200 nm and 1 µm diameter), charge (-15 mV), and loading efficiencies of OVA (238 µg mg-1 particles) and aPD1 (40 µg mg-1 particles). OVA-aPD1 N.M.P could stimulate the maturation of BMDCs and enhance the antigen uptake and presentation by 2-fold compared to free OVA. The nanoparticles also induced the activation of macrophages (RAW 264.7) to produce a high level of cytokines, including TNF-α, IL-6 and IL-10. In vivo stimulation of mice using OVA-aPD1 N.M.P robustly enhanced IFN-γ-producing-CD8+ T cell infiltration in tumor tissues and the secretion of IgG and IgG2a/IgG1 antibodies. OVA-aPD1 N.M.P delivered OVA to increase the activation and proliferation of OVA-specific CD8+ TRMs, and its combination with anti-PD1 antibodies promoted complete tumor rejection by the reversal of tumor-infiltrating CD8+ T cell exhaustion. Thus, PLGA N.M.P could induce a strong CD8+ TRMs response, further highlighting its therapeutic potential in enhancing an antitumor immune response.


Asunto(s)
Linfocitos T CD8-positivos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Animales , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Ratones , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Ratones Endogámicos C57BL , Ovalbúmina/inmunología , Ovalbúmina/química , Receptor de Muerte Celular Programada 1/inmunología , Receptor de Muerte Celular Programada 1/metabolismo , Nanopartículas/química , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/química , Células T de Memoria/inmunología , Vacunación , Humanos , Células RAW 264.7 , Memoria Inmunológica
4.
ACS Appl Mater Interfaces ; 16(26): 33021-33037, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38888460

RESUMEN

Hypoxia can lead to liver fibrosis and severely limits the efficacy of photodynamic therapy (PDT). Herein, carbon nitride (CN)-based hybrid nanoparticles (NPs) VPSGCNs@TSI for light-driven water splitting were utilized to solve this problem. CNs were doped with selenide glucose (Se-glu) to enhance their red/NIR region absorption. Then, vitamin A-poly(ethylene glycol) (VA-PEG) fragments and aggregation-induced emission (AIE) photosensitizers TSI were introduced into Se-glu-doped CN NPs (VPSGCNs) to construct VPSGCNs@TSI NPs. The introduction of VA-PEG fragments enhanced the targeting of the NPs to activated hepatic stellate cells (HSCs) and reduced their toxicity to ordinary liver cells. VPSGCN units could trigger water splitting to generate O2 under 660 nm laser irradiation, improve the hypoxic environment of the fibrosis site, downregulate HIF-1α expression, and activate HSC ferroptosis via the HIF-1α/SLC7A11 pathway. In addition, generated O2 could also increase the reactive oxygen species (ROS) production of TSI units in a hypoxic environment, thereby completely reversing hypoxia-triggered PDT resistance to enhance the PDT effect. The combination of water-splitting materials and photodynamic materials showed a 1 + 1 > 2 effect in increasing oxygen levels in liver fibrosis, promoting ferroptosis of activated HSCs and reversing PDT resistance caused by hypoxia.


Asunto(s)
Ferroptosis , Células Estrelladas Hepáticas , Cirrosis Hepática , Nanopartículas , Fotoquimioterapia , Nanopartículas/química , Animales , Ferroptosis/efectos de los fármacos , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/patología , Cirrosis Hepática/metabolismo , Ratones , Células Estrelladas Hepáticas/efectos de los fármacos , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/patología , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Nitrilos/química , Nitrilos/farmacología , Humanos , Hipoxia/tratamiento farmacológico , Hipoxia/metabolismo , Especies Reactivas de Oxígeno/metabolismo
5.
Nucleic Acids Res ; 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38884260

RESUMEN

Horizontal gene transfer (HGT) phenomena pervade the gut microbiome and significantly impact human health. Yet, no current method can accurately identify complete HGT events, including the transferred sequence and the associated deletion and insertion breakpoints from shotgun metagenomic data. Here, we develop LocalHGT, which facilitates the reliable and swift detection of complete HGT events from shotgun metagenomic data, delivering an accuracy of 99.4%-verified by Nanopore data-across 200 gut microbiome samples, and achieving an average F1 score of 0.99 on 100 simulated data. LocalHGT enables a systematic characterization of HGT events within the human gut microbiome across 2098 samples, revealing that multiple recipient genome sites can become targets of a transferred sequence, microhomology is enriched in HGT breakpoint junctions (P-value = 3.3e-58), and HGTs can function as host-specific fingerprints indicated by the significantly higher HGT similarity of intra-personal temporal samples than inter-personal samples (P-value = 4.3e-303). Crucially, HGTs showed potential contributions to colorectal cancer (CRC) and acute diarrhoea, as evidenced by the enrichment of the butyrate metabolism pathway (P-value = 3.8e-17) and the shigellosis pathway (P-value = 5.9e-13) in the respective associated HGTs. Furthermore, differential HGTs demonstrated promise as biomarkers for predicting various diseases. Integrating HGTs into a CRC prediction model achieved an AUC of 0.87.

6.
Ying Yong Sheng Tai Xue Bao ; 35(5): 1312-1320, 2024 May.
Artículo en Chino | MEDLINE | ID: mdl-38886430

RESUMEN

Understanding the influences of climate change and human activities on vegetation change is the foundation for effective ecosystem management. Based on the 250 m MODIS-NDVI data from 2002 to 2020, we employed Theil-Sen Median trend analysis and the Mann-Kendall test to quantify vegetation change in Hunan Province. By combining with meteorological, nighttime light index, land cover and other data, residual analysis and correlation analysis, we examined the impacts of human activities and climate change on vegetation dynamics at both the pixel level and the county level. The results showed that the normalized difference vegetation index (NDVI) in Hunan Province exhibited a spatial pattern of "overall improvement with localized degradation" during 2002-2020. Approximately 64.9% of the study area experienced significant vegetation improvement, mainly occurring in the western and central-southern parts of Hunan Province. 1.4% of the study area experienced significant vegetation degradation, mostly in the newly developed urban areas and the farmland in the Dongting Lake Plain. Human activities and climate change jointly promoted vegetation improvement in 67.9% of the study area. Human activities and climate contributed to 96% and 4% of the NDVI change, respectively. At the county level, human activities contributed to over 80% of the NDVI change in each district or county. The impacts of human activities on vegetation change exhibited significant spatial heterogeneity. Urban expansion led to vegetation degradation in the newly developed areas, while vegetation growth appeared in the old developed urban areas. The ecological restoration projects promoted vegetation restoration in the western part of Hunan Province. This study could help us better understand the spatiotemporal variations of vegetation and their responses to climate change and human activities, which would offer scientific basis for effective ecological restoration policy.


Asunto(s)
Cambio Climático , Ecosistema , Monitoreo del Ambiente , China , Monitoreo del Ambiente/métodos , Conservación de los Recursos Naturales , Imágenes Satelitales , Actividades Humanas , Desarrollo de la Planta , Árboles/crecimiento & desarrollo
7.
Anal Chem ; 96(24): 10074-10083, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38848224

RESUMEN

Numerous high-performance nanotechnologies have been developed, but their practical applications are largely restricted by the nanomaterials' low stabilities and high operation complexity in aqueous substrates. Herein, we develop a simple and high-reliability hydrogel-based nanotechnology based on the in situ formation of Au nanoparticles in molybdenum disulfide (MoS2)-doped agarose (MoS2/AG) hydrogels for electrophoresis-integrated microplate protein recognition. After the incubation of MoS2/AG hydrogels in HAuCl4 solutions, MoS2 nanosheets spontaneously reduce Au ions, and the hydrogels are remarkably stained with the color of as-synthetic plasmonic Au hybrid nanomaterials (Au staining). Proteins can precisely mediate the morphologies and optical properties of Au/MoS2 heterostructures in the hydrogels. Consequently, Au staining-based protein recognition is exhibited, and hydrogels ensure the comparable stabilities and sensitivities of protein analysis. In comparison to the fluorescence imaging and dye staining, enhanced sensitivity and recognition performances of proteins are implemented by Au staining. In Au staining, exfoliated MoS2 semiconductors directly guide the oriented growth of plasmonic Au nanostructures in the presence of formaldehyde, showing environment-friendly features. The Au-stained hydrogels merge the synthesis and recognition applications of plasmonic Au nanomaterials. Significantly, the one-step incubation of the electrophoretic hydrogels leads to high simplicity of operation, largely challenging those multiple-step Ag staining routes which were performed with high complexity and formaldehyde toxicity. Due to its toxic-free, simple, and sensitive merits, the Au staining integrated with electrophoresis-based separation and microplate-based high-throughput measurements exhibits highly promising and improved practicality of those developing nanotechnologies and largely facilitates in-depth understanding of biological information.


Asunto(s)
Disulfuros , Oro , Hidrogeles , Molibdeno , Molibdeno/química , Disulfuros/química , Oro/química , Hidrogeles/química , Nanopartículas del Metal/química , Electroforesis , Proteínas/análisis , Proteínas/química
8.
Opt Lett ; 49(11): 3066-3069, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38824329

RESUMEN

We present a space-angle dual multiplexing holographic recording system for realizing single-exposure multi-wavelength optical diffraction tomographic (ODT) imaging. This system is achieved by combining the principle of single-exposure multi-wavelength holographic imaging technique based on angle-division multiplexing with the principle of single-exposure ODT imaging technique based on microlens array multi-angle illuminations and space-division multiplexing. Compared with the existing multi-wavelength ODT imaging methods, it enables the holographic recording of all the diffraction tomography information of a measured specimen at multiple illumination wavelengths in a single camera exposure without any scan mechanism. Using our proposed data processing method, the multi-wavelength three-dimensional (3D) refractive index tomograms of a specimen can be eventually reconstructed from single recorded multiplexing hologram. Experimental results of a static polystyrene bead and a living C. elegans worm demonstrate the feasibility of this system.

9.
Redox Rep ; 29(1): 2345455, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38723197

RESUMEN

OBJECTIVES: Cancer cells undergo metabolic reprogramming to adapt to high oxidative stress, but little is known about how metabolic remodeling enables gastric cancer cells to survive stress associated with aberrant reactive oxygen species (ROS) production. Here, we aimed to identify the key metabolic enzymes that protect gastric cancer (GC) cells from oxidative stress. METHODS: ROS level was detected by DCFH-DA probes. Multiple cell biological studies were performed to identify the underlying mechanisms. Furthermore, cell-based xenograft and patient-derived xenograft (PDX) model were performed to evaluate the role of MTHFD2 in vivo. RESULTS: We found that overexpression of MTHFD2, but not MTHFD1, is associated with reduced overall and disease-free survival in gastric cancer. In addition, MTHFD2 knockdown reduces the cellular NADPH/NADP+ ratio, colony formation and mitochondrial function, increases cellular ROS and cleaved PARP levels and induces in cell death under hypoxia, a hallmark of solid cancers and a common inducer of oxidative stress. Moreover, genetic or pharmacological inhibition of MTHFD2 reduces tumor burden in both tumor cell lines and patient-derived xenograft-based models. DISCUSSION: our study highlights the crucial role of MTHFD2 in redox regulation and tumor progression, demonstrating the therapeutic potential of targeting MTHFD2.


Asunto(s)
Progresión de la Enfermedad , Homeostasis , Metilenotetrahidrofolato Deshidrogenasa (NADP) , Estrés Oxidativo , Neoplasias Gástricas , Animales , Humanos , Ratones , Aminohidrolasas/metabolismo , Aminohidrolasas/genética , Línea Celular Tumoral , Metilenotetrahidrofolato Deshidrogenasa (NADP)/metabolismo , Metilenotetrahidrofolato Deshidrogenasa (NADP)/genética , Enzimas Multifuncionales/metabolismo , Enzimas Multifuncionales/genética , Oxidación-Reducción , Especies Reactivas de Oxígeno/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Neoplasias Gástricas/genética , Ensayos Antitumor por Modelo de Xenoinjerto
10.
Front Pharmacol ; 15: 1379338, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38738180

RESUMEN

Background: Chinese patent medicine is commonly used in China as an important treatment mechanism to thwart the progression of chronic kidney disease (CKD) stages 3-5, among which Niaoduqing granules are a representative Chinese patent medicine; however, its long-term efficacy on CKD prognosis remains unclear. Methods: Patients were grouped according to Niaoduqing granule prescription duration (non-Niaoduqing granule (non-NDQ) group vs Niaoduqing granule (NDQ) group). Serum creatinine (SCr) variation was compared using a generalized linear mixed model (GLMM). Multivariate Cox regression models were constructed, adjusting for confounding factors, to explore the risk of composite outcomes (receiving renal replacement therapy (RRT) or having an estimated glomerular filtration rate (eGFR)<5 mL/min/1.73 m2, ≥50% decline in the eGFR from the baseline, and doubling of SCr) in individuals consuming Niaoduqing granules. Results: A total of 1,271 patients were included, with a median follow-up duration of 29.71 (12.10, 56.07) months. The mean SCr Z-scores for the non-NDQ group and NDQ group were -0.175 and 0.153, respectively, at baseline (p = 0.015). The coefficients of the NDQ group from visit 1 to visit 5 were -0.207 (95% CI: -0.346, -0.068, p = 0.004), -0.214 (95% CI: 0.389, -0.039, p = 0.017), -0.324 (95% CI: 0.538, -0.109, p = 0.003), -0.502 (95% CI: 0.761, -0.243, p = 0.000), and -0.252 (95% CI: 0.569, 0.065, p = 0.119), respectively. The survival probability was significantly higher in the NDQ group (p = 0.0039). Taking Niaoduqing granules was a significant protective factor for thwarting disease progression (model 1: HR 0.654 (95% CI 0.489-0.875, p = 0.004); model 2: HR 0.646 (95% CI 0.476, 0.877, p = 0.005); and model 3: HR 0.602 (95% CI 0.442, 0.820, p = 0.001)). Conclusion: The long-term use of Niaoduqing granules improved SCr variation and lowered the risk of CKD progression by 39.8%.

11.
Am J Transl Res ; 16(4): 1353-1365, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38715836

RESUMEN

BACKGROUND: There is no reliable means to evaluate the immune status of liver transplant recipients. We proposed a novel score model, namely Mingdao immune cell analysis and Mingdao immune score system, to quantify the immunity. METHODS: Data from those who underwent a single liver transplant between January 2017 and June 2020 at Beijing Chaoyang Hospital, were collected. In addition, healthy volunteers were also enrolled. The score model was based on the immune cell populations determined by flow cytometry. RESULTS: There were a total of 376 healthy controls with 376 tests and 148 liver transplant recipients with 284 tests in this study. Evaluated by Mingdao immune cell analysis and Mingdao immune score system, the mean scores of healthy controls were near zero suggesting a balanced immune system. In contrast, the mean scores of liver transplant recipients were negative both before and after surgery indicating a compromised immune system. When liver transplant recipients were given a reduced or routine first dose according to their preoperative score, they had similar recovery of liver function. Moreover, liver transplant recipients with increased scores ≥ 5 were associated with elevated aspartate transaminase and alanine amiotransferase. Finally, on multivariate analysis the score model was the only significant independent risk factor for clinical acute rejection (P = 0.021; Odds ratio, 0.913; 95% confidence interval, 0.845-0.987). CONCLUSION: The novel score model could be used as an indicator to reflect immunity and to regulate immunosuppressants in liver transplant recipients after surgery.

12.
Int J Mol Sci ; 25(9)2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38731840

RESUMEN

Breast cancer (BC) is a global health risk for women and has a high prevalence rate. The drug resistance, recurrence, and metastasis of BC affect patient prognosis, thus posing a challenge to scientists. Exosomes are extracellular vesicles (EVs) that originate from various cells; they have a double-layered lipid membrane structure and contain rich biological information. They mediate intercellular communication and have pivotal roles in tumor development, progression, and metastasis and drug resistance. Exosomes are important cell communication mediators in the tumor microenvironment (TME). Exosomes are utilized as diagnostic and prognostic biomarkers for estimating the treatment efficacy of BC and have the potential to function as tools to enable the targeted delivery of antitumor drugs. This review introduces recent progress in research on how exosomes influence tumor development and the TME. We also present the research progress on the application of exosomes as prognostic and diagnostic biomarkers and drug delivery tools.


Asunto(s)
Biomarcadores de Tumor , Neoplasias de la Mama , Exosomas , Microambiente Tumoral , Humanos , Exosomas/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Neoplasias de la Mama/diagnóstico , Femenino , Biomarcadores de Tumor/metabolismo , Pronóstico , Comunicación Celular , Resistencia a Antineoplásicos , Sistemas de Liberación de Medicamentos/métodos , Animales
13.
J Cancer ; 15(11): 3580-3595, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38817875

RESUMEN

Copper, an indispensable trace element for the human body, serves not only as a crucial auxiliary factor in redox reactions within the organism but also as a significant constituent of numerous key metabolic enzymes. The COMMD family plays a vital role in regulating copper at both the cellular and systemic levels, particularly in the realm of tumor research, an area notably deficient in gastric cancer investigations. With the advancement of precision medical techniques, individualized and precise screening and treatment have become paramount considerations in the contemporary medical landscape for gastric cancer therapy. In light of this, we meticulously scrutinized existing transcriptomic datasets for gastric cancer, validating the expression levels and prognostic value of COMMD family genes. Simultaneously, employing the ssGSEA algorithm, we devised the COMMDs score. Enrichment analysis, gene mutations, and clinical features were incorporated into the assessment of this score. Furthermore, we contextualized the COMMDs score within the framework of the immune microenvironment, evaluating the relationship between the COMMDs family and immune factors as well as immune cells. The results suggest a correlation between the COMMDs score and various immune-related features. Based on this foundation, multiple machine learning approaches indicated Logistic Regression, with a remarkable ROC of 0.972, as the optimal diagnostic model. To accentuate the translational medical value of the COMMDs family, we selected COMMD10 as a differential gene in gastric cancer for further validation. Functional experiments revealed a decline in the proliferative and migratory capabilities of gastric cancer cells upon silencing COMMD10. Additionally, through pathway intervention, we unveiled the PI3K-AKT pathway as a potential mechanism through which COMMD10 influences gastric cancer activity. In summary, our study affirms the prospective role of the COMMDs family as potential markers for the diagnosis and treatment of gastric cancer in the future.

14.
Zhongguo Zhong Yao Za Zhi ; 49(4): 1073-1081, 2024 Feb.
Artículo en Chino | MEDLINE | ID: mdl-38621914

RESUMEN

The present study aimed to investigate the effect and mechanism of Bupleuri Radix-Paeoniae Radix Alba medicated plasma on HepG2 hepatoma cells by regulating the microRNA-1297(miR-1297)/phosphatase and tensin homologue deleted on chromosome 10(PTEN) signaling axis. Real-time quantitative PCR(RT-qPCR) was carried out to determine the mRNA levels of miR-1297 and PTEN in different hepatoma cell lines. The dual luciferase reporter assay was employed to verify the targeted interaction between miR-1297 and PTEN. The cell counting kit-8(CCK-8) was used to detect cell proliferation, and the optimal concentration and intervention time of the medicated plasma were determined. The cell invasion and migration were examined by Transwell assay and wound healing assay. Cell cycle distribution was detected by PI staining, and the apoptosis of cells was detected by Annexin V-FITC/PI double staining. The mRNA levels of miR-1297, PTEN, protein kinase B(Akt), and phosphatidylinositol 3-kinase(PI3K) were determined by RT-qPCR. Western blot was employed to determine the protein levels of PTEN, Akt, p-Akt, caspase-3, caspase-9, B-cell lymphoma-2(Bcl-2), and Bcl-2-associated X protein(Bax). The results showed that HepG2 cells were the best cell line for subsequent experiments. The dual luciferase reporter assay confirmed that miR-1297 could bind to the 3'-untranslated region(3'UTR) in the mRNA of PTEN. The medicated plasma inhibited the proliferation of HepG2 cells, and the optimal intervention concentration and time were 20% and 72 h. Compared with the blank plasma, the Bupleuri Radix-Paeoniae Radix Alba medicated plasma, miR-1297 inhibitor, miR-1297 inhibitor + medicated plasma all inhibited the proliferation, invasion, and migration of HepG2 cells, increased the proportion of cells in the G_0/G_1 phase, decreased the proportion of cells in the S phase, and increased the apoptosis rate. The medicated plasma down-regulated the mRNA levels of miR-1297, PI3K, and Akt and up-regulated the mRNA level of PTEN. In addition, it up-regulated the protein levels of PTEN, Bax, caspase-3, and caspsae-9 and down-regulated the protein levels of p-Akt, p-PI3K, and Bcl-2. In conclusion, Bupleuri Radix-Paeoniae Radix Alba medicated plasma can inhibit the expression of miR-1297 in HepG2 hepatoma cells, promote the expression of PTEN, and negatively regulate PI3K/Akt signaling pathway, thereby inhibiting the proliferation and inducing the apoptosis of HepG2 cells.


Asunto(s)
Carcinoma Hepatocelular , Medicamentos Herbarios Chinos , Neoplasias Hepáticas , MicroARNs , Paeonia , Extractos Vegetales , Humanos , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Células Hep G2 , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Caspasa 3/metabolismo , Proteína X Asociada a bcl-2 , MicroARNs/genética , MicroARNs/metabolismo , Transducción de Señal , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Apoptosis , Proliferación Celular , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , ARN Mensajero , Luciferasas/metabolismo , Luciferasas/farmacología , Línea Celular Tumoral
15.
Bioinformatics ; 40(4)2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38603603

RESUMEN

MOTIVATION: Genome sequencing technologies reveal a huge amount of genomic sequences. Neural network-based methods can be prime candidates for retrieving insights from these sequences because of their applicability to large and diverse datasets. However, the highly variable lengths of genome sequences severely impair the presentation of sequences as input to the neural network. Genetic variations further complicate tasks that involve sequence comparison or alignment. RESULTS: Inspired by the theory and applications of "spaced seeds," we propose a graph representation of genome sequences called "gapped pattern graph." These graphs can be transformed through a Graph Convolutional Network to form lower-dimensional embeddings for downstream tasks. On the basis of the gapped pattern graphs, we implemented a neural network model and demonstrated its performance on diverse tasks involving microbe and mammalian genome data. Our method consistently outperformed all the other state-of-the-art methods across various metrics on all tasks, especially for the sequences with limited homology to the training data. In addition, our model was able to identify distinct gapped pattern signatures from the sequences. AVAILABILITY AND IMPLEMENTATION: The framework is available at https://github.com/deepomicslab/GCNFrame.

16.
Sci Rep ; 14(1): 7638, 2024 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-38561452

RESUMEN

Hypomyelinating leukodystrophy (HLD) is a rare genetic heterogeneous disease that can affect myelin development in the central nervous system. This study aims to analyze the clinical phenotype and genetic function of a family with HLD-7 caused by POLR3A mutation. The proband (IV6) in this family mainly showed progressive cognitive decline, dentin dysplasia, and hypogonadotropic hypogonadism. Her three old brothers (IV1, IV2, and IV4) also had different degrees of ataxia, dystonia, or dysarthria besides the aforementioned manifestations. Their brain magnetic resonance imaging showed bilateral periventricular white matter atrophy, brain atrophy, and corpus callosum atrophy and thinning. The proband and her two living brothers (IV2 and IV4) were detected to carry a homozygous mutation of the POLR3A (NM_007055.4) gene c. 2300G > T (p.Cys767Phe), and her consanguineous married parents (III1 and III2) were p.Cys767Phe heterozygous carriers. In the constructed POLR3A wild-type and p.Cys767Phe mutant cells, it was seen that overexpression of wild-type POLR3A protein significantly enhanced Pol III transcription of 5S rRNA and tRNA Leu-CAA. However, although the mutant POLR3A protein overexpression was increased compared to the wild-type protein overexpression, it did not show the expected further enhancement of Pol III function. On the contrary, Pol III transcription function was frustrated (POLR3A, BC200, and tRNA Leu-CAA expression decreased), and MBP and 18S rRNA expressions were decreased. This study indicates that the POLR3A p.Cys767Phe variant caused increased expression of mutated POLR3A protein and abnormal expression of Pol III transcripts, and the mutant POLR3A protein function was abnormal.


Asunto(s)
Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias , Masculino , Femenino , Humanos , Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias/genética , Mutación , Fenotipo , Atrofia , ARN de Transferencia , ARN Polimerasa III/genética , ARN Polimerasa III/metabolismo
17.
Adv Mater ; 36(23): e2314063, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38444248

RESUMEN

Polymer/ceramic-based composite solid electrolytes (CSE) are promising candidates for all-solid-state lithium metal batteries (SLBs), benefiting from the combined mechanical robustness of polymeric electrolytes and the high ionic conductivity of ceramic electrolytes. However, the interfacial instability and poorly understood interphases of CSE hinder their application in high-voltage SLBs. Herein, a simple but effective CSE that stabilizes high-voltage SLBs by forming multiple intermolecular coordination interactions between polyester and ceramic electrolytes is discovered. The multiple coordination between the carbonyl groups in poly(ε-caprolactone) and the fluorosulfonyl groups in anions with Li6.5La3Zr1.5Ta0.5O12 nanoparticles is directly visualized by cryogenic transmission electron microscopy and further confirmed by theoretical calculation. Importantly, the multiple coordination in CSE not only prevents the continuous decomposition of polymer skeleton by shielding the vulnerable carbonyl sites but also establishes stable inorganic-rich interphases through preferential decomposition of anions. The stable CSE and its inorganic-rich interphases enable Li||Li symmetric cells with an exceptional lifespan of over 4800 h without dendritic shorting at 0.1 mA cm-2. Moreover, the high-voltage SLB with LiNi0.5Co0.2Mn0.3O2 cathode displays excellent cycling stability over 1100 cycles at a 1C charge/discharge rate. This work reveals the underlying mechanism behind the excellent stability of coordinating composite electrolytes and interfaces in high-voltage SLBs.

19.
Inorg Chem ; 63(13): 5961-5971, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38494631

RESUMEN

Titanium-oxo cluster (TOC)-based metal-organic frameworks (MOFs) have received considerable attention in recent years due to their ability to expand the application of TOCs to fields that require highly stable frameworks. Herein, a new cyclic TOC formulated as [Ti6O6(OiPr)8(TTFTC)(phen)2]2 (1, where TTFTC = tetrathiafulvalene tetracarboxylate and phen = phenanthroline) was crystallographically characterized. TOC 1 takes a rectangular ring structure with two phen-modified Ti6 clusters as the width and two TTFTC ligands as the length. An intracluster ligand-to-ligand (TTF-to-phen) charge transfer in 1 was found for TOCs for the first time. Compound 1 undergoes topotactic conversion to generate stable TOC-MOF P1, in which the rectangular framework in 1 formed by a TOC core and ligands is retained, as verified by comprehensive characterization. P1 shows an efficient and rapid selective adsorption capacity for cationic dyes. The experimental adsorption capacity (qex) of P1 reaches a value of up to 789.2 mg/g at 298 K for the crystal violet dye, which is the highest among those of various adsorbents. The calculated models are first used to reveal the structure-property relationship of the cyclic host to different guest dyes. The results further confirmed the host MOF structure of P1.

20.
Water Res ; 253: 121336, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38382291

RESUMEN

Aerobic granular sludge is one of the most promising biological wastewater treatment technologies, yet maintaining its stability is still a challenge for its application, and predicting the state of the granules is essential in addressing this issue. This study explored the potential of dynamic texture entropy, derived from settling images, as a predictive tool for the state of granular sludge. Three processes, traditional thickening, often overlooked clarification, and innovative particle sorting, were used to capture the complexity and diversity of granules. It was found that rapid sorting during settling indicates stable granules, which helps to identify the state of granules. Furthermore, a relationship between sorting time and granule heterogeneity was identified, helping to adjust selection pressure. Features of the dynamic texture entropy well correlated with the respirogram, i.e., R2 were 0.86 and 0.91 for the specific endogenous respiration rate (SOURe) and the specific quasi-endogenous respiration rate (SOURq), respectively, providing a biologically based approach for monitoring the state of granules. The classification accuracy of models using features of dynamic texture entropy as an input was greater than 0.90, significantly higher than the input of conventional features, demonstrating the significant advantage of this approach. These findings contributed to developing robust monitoring tools that facilitate the maintenance of stable granular sludge operations.

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