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1.
Am J Cancer Res ; 14(6): 2755-2769, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39005687

RESUMEN

As numerous countries around the world have entered an aging society currently, understanding the impact of aging on human health becomes critically important. Notably, aging is associated with increased prevalence of age-related diseases, with the lungs being particularly susceptible. Aging contributes to a decline in lung function, including respiratory disorders, inflammation, and oxidative stress. Therefore, it is a very important to identify and develop active substances that can mitigate lung cell aging. In current study, we evaluated the impact of Taraxasterol on lung cell senescence, showing that Taraxasterol can alleviate lung cell senescence, as evidenced by reductions in senescence-related marker molecules, including p16 and p21. Additionally, Taraxasterol was found to ameliorate inflammation and oxidative stress in lung cells. Further mechanistic studies indicated that Taraxasterol exerts anti-aging effects through the PGC1α/NRF1 signaling pathway in lung cell models. Since aging is also closely related to lung cancer, we also explored the potential anti-tumor effect of taraxasterol. Utilizing non-small cell lung cancer cells (NSCLC) as a model, we systematically study the anti-tumor effect of Taraxasterol both in vivo and in vitro. Our findings suggest that Taraxasterol exhibited anti-cancer effect through EGFR-mediated signaling. Taken together, Taraxasterol shows dual biological activities, offering promising anti-aging and anti-lung cancer benefits.

2.
PLoS One ; 19(7): e0306775, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38985836

RESUMEN

BACKGROUND: This study evaluated the effect of microvesicles(MVs) from quiescent and TGF-ß1 stimulated hepatic stellate cells (HSC-MVs, TGF-ß1HSC-MVs) on H2O2-induced human umbilical vein endothelial cells (HUVECs) injury and CCl4-induced rat hepatic vascular injury. METHODS: HUVECs were exposed to hydrogen peroxide (H2O2) to establish a model for vascular endothelial cell injury. HSC-MVs or TGF-ß1HSC-MVs were co-cultured with H2O2-treated HUVECs, respectively. Indicators including cell survival rate, apoptosis rate, oxidative stress, migration, invasion, and angiogenesis were measured. Simultaneously, the expression of proteins such as PI3K, AKT, MEK1+MEK2, ERK1+ERK2, VEGF, eNOS, and CXCR4 was assessed, along with activated caspase-3. SD rats were intraperitoneally injected with CCl4 twice a week for 10 weeks to induce liver injury models. HSC-MVs or TGF-ß1HSC-MVs were injected into the tail vein of rats. Liver and hepatic vascular damage were also detected. RESULTS: In H2O2-treated HUVECs, HSC-MVs increased cell viability, reduced cytotoxicity and apoptosis, improved oxidative stress, migration, and angiogenesis, and upregulated protein expression of PI3K, AKT, MEK1/2, ERK1/2, VEGF, eNOS, and CXCR4. Conversely, TGF-ß1HSC-MVs exhibited opposite effects. CCl4- induced rat hepatic injury model, HSC-MVs reduced the release of ALT and AST, hepatic inflammation, fatty deformation, and liver fibrosis. HSC-MVs also downregulated the protein expression of CD31 and CD34. Conversely, TGF-ß1HSC-MVs demonstrated opposite effects. CONCLUSION: HSC-MVs demonstrated a protective effect on H2O2-treated HUVECs and CCl4-induced rat hepatic injury, while TGF-ß1HSC-MVs had an aggravating effect. The effects of MVs involve PI3K/AKT/VEGF, CXCR4, and MEK/ERK/eNOS pathways.


Asunto(s)
Células Estrelladas Hepáticas , Células Endoteliales de la Vena Umbilical Humana , Peróxido de Hidrógeno , Factor de Crecimiento Transformador beta1 , Animales , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/efectos de los fármacos , Humanos , Factor de Crecimiento Transformador beta1/metabolismo , Peróxido de Hidrógeno/farmacología , Ratas , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Masculino , Hígado/patología , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/lesiones , Ratas Sprague-Dawley , Apoptosis/efectos de los fármacos , Micropartículas Derivadas de Células/metabolismo , Supervivencia Celular/efectos de los fármacos , Tetracloruro de Carbono/toxicidad , Movimiento Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo
3.
Nano Lett ; 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38975929

RESUMEN

Manipulation of physical properties in multidimensional tunable moiré superlattice systems is a key focus in nanophotonics, especially for interlayer excitons (IXs) in two-dimensional materials. However, the impact of defects on IXs remains unclear. Here, we thoroughly study the optical properties of WS2/WSe2 heterobilayers with varying defect densities. Low-temperature photoluminescence (PL) characterizations reveal that the low-energy IXs are more susceptible to defects compared to the high-energy IXs. The low-energy IXs also show much faster PL quenching rate with temperature, faster peak width broadening rate with laser power, shorter lifetime, and lower circular polarization compared to the low-energy IXs in the region with fewer defects. These effects are attributed to the combined effects of increased electron scattering, exciton-phonon interactions, and nonradiative channels introduced by the defects. Our findings aid in optimizing moiré superlattice structures.

4.
J Environ Manage ; 366: 121725, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38971070

RESUMEN

Co-digestion of kitchen waste (KW) and black water (BW) can be considered as an attractive method to efficiently achieve the clean energy from waste. To find the optimal operation parameters for the co-digestion, the effects of different temperatures (35 and 55 °C) and BW:KW ratios on the reactor performances, microbial communities and metabolic pathways were studied. The results showed that the optimum BW:KW ratio was 1:3.6 and 1:4.5 for mesophilic and thermophilic optimal reactors, with methane production of 449.04 mL/g VS and 411.90 mL/g VS, respectively. Microbial communities showed significant differences between the reactors under different temperatures. For bacteria, increasing BW:KW ratio significantly promoted Defluviitoga enrichment (1.1%-9.5%) under thermophilic condition. For Archaea, the increase in BW:KW ratio promoted the enrichment of Methanosaeta (8.6%-56.4%) in the mesophilic reactor and Methanothermobacter (62.0%-89.2%) in the thermophilic reactor. The analysis of the key enzymes showed that, acetoclastic methanogenic pathway performed as the dominant under mesophilic condition, with high abundance of Acetate-CoA ligase (EC:6.2.1.1) and Pyruvate synthase (EC:1.2.7.1). Hydrogenotrophic methanogenic pathway was the main pathway in the thermophilic reactors, with high abundance of Formylmethanofuran dehydrogenase (EC:1.2.99.5).

5.
Front Oncol ; 14: 1382154, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38894864

RESUMEN

The incidence of multiple primary tumors(MPTs) is on the rise in recent years, but patients having four or more primary tumors is still rare. Lynch syndrome (LS) patients have a high risk of developing MPTs. NGS sequencing could identify the genetic alterations in different tumors to make a definite diagnosis of uncommon cases in clinical practice. Here, we report the case of a 66-year-old female patient who develops four MPTS between the ages of 41 and 66, that is sigmoid colon cancer, acute non-lymphocytic leukemia, urothelial carcinoma and ascending colon cancer. She has survived for more than 26 years since the first discovery of tumor. Targeted sequencing indicates that she has a pathogenic germline mutation in the exon 13 of MSH2, and her 2020 ureteral cancer sample and 2023 colon cancer sample have completely different mutation profiles. To the best of our knowledge, this is the first case of multiple primary tumors with an acute non-lymphocytic leukemia in LS patients.

6.
BMC Cancer ; 24(1): 737, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38879516

RESUMEN

BACKGROUND: Bladder cancer (BC) is among the most prevalent malignant urothelial tumors globally, yet the prognosis for patients with muscle-invasive bladder cancer (MIBC) remains dismal, with a very poor 5-year survival rate. Consequently, identifying more effective and less toxic chemotherapeutic alternatives is critical for enhancing clinical outcomes for BC patients. Isorhapontigenin (ISO), a novel stilbene isolated from a Gnetum found in certain provinces of China, has shown potential as an anticancer agent due to its diverse anticancer activities. Despite its promising profile, the specific anticancer effects of ISO on BC and the underlying mechanisms are still largely unexplored. METHODS: The anchorage-independent growth, migration and invasion of BC cells were assessed by soft agar and transwell invasion assays, respectively. The RNA levels of SOX2, miR-129 and SNHG1 were quantified by qRT-PCR, while the protein expression levels were validated through Western blotting. Furthermore, methylation-specific PCR was employed to assess the methylation status of the miR-129 promoter. Functional assays utilized siRNA knockdown, plasmid-mediated overexpression, and chemical inhibition approaches. RESULTS: Our study demonstrated that ISO treatment significantly reduced SNHG1 expression in a dose- and time-dependent manner in BC cells, leading to the inhibition of anchorage-independent growth and invasion in human basal MIBC cells. This effect was accompanied by the downregulation of MMP-2 and MMP-9 and the upregulation of the tumor suppressor PTEN. Further mechanistic investigations revealed that SOX2, a key upstream regulator of SNHG1, played a crucial role in mediating the ISO-induced transcriptional suppression of SNHG1. Additionally, we found that ISO treatment led to a decrease in DNMT3b protein levels, which in turn mediated the hypomethylation of the miR-129 promoter and the subsequent suppression of SOX2 mRNA 3'-UTR activity, highlighting a novel pathway through which ISO exerts its anticancer effects. CONCLUSIONS: Collectively, our study highlights the critical role of SNHG1 downregulation as well as its upstream DNMT3b/miR-129/SOX2 axis in mediating ISO anticancer activity. These findings not only elucidate the mechanism of action of ISO but also suggest novel targets for BC therapy.


Asunto(s)
ADN (Citosina-5-)-Metiltransferasas , ADN Metiltransferasa 3B , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , ARN Largo no Codificante , Estilbenos , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/metabolismo , ARN Largo no Codificante/genética , Línea Celular Tumoral , Estilbenos/farmacología , Estilbenos/uso terapéutico , Regulación hacia Abajo/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , ADN (Citosina-5-)-Metiltransferasas/genética , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Invasividad Neoplásica , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Metilación de ADN/efectos de los fármacos , MicroARNs/genética
7.
J Agric Food Chem ; 72(25): 14433-14447, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38866717

RESUMEN

JHBp2 is a peptide purified from Jinhua ham broth with antibacterial activity against Salmonella typhimurium. Untargeted metabolomics and label-free quantitative proteomics were used to analyze metabolic and protein expression changes in S. typhimurium after JHBp2 treatment. Cell wall and membrane damage results indicate that JHBp2 has membrane-disruptive properties, causing leakage of intracellular nucleic acids and proteins. Metabolomics revealed 516 differentially expressed metabolites, involving cofactor biosynthesis, purine metabolism, ABC transporters, glutathione metabolism, pyrimidine metabolism, etc. Proteomics detected 735 differentially expressed proteins, involving pyruvate metabolism, amino acid biosynthesis, purine metabolism, carbon metabolism, glycolysis/gluconeogenesis, etc. RT-qPCR and proteomics results showed a positive correlation, and molecular docking demonstrated stable binding of JHBp2 to some differentially expressed proteins. In summary, JHBp2 could disrupt the S. typhimurium cell wall and membrane structure, interfere with synthesis of membrane-related proteins, trigger intracellular substance leak, and reduce levels of enzymes and metabolites involved in energy metabolism, amino acid anabolism, and nucleotide anabolism.


Asunto(s)
Antibacterianos , Proteínas Bacterianas , Metabolómica , Simulación del Acoplamiento Molecular , Proteómica , Salmonella typhimurium , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genética , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/química , Porcinos , Animales , Antibacterianos/farmacología , Antibacterianos/química , Péptidos/química , Péptidos/farmacología , Péptidos/metabolismo , Productos de la Carne/microbiología , Productos de la Carne/análisis
8.
Int Immunopharmacol ; 137: 112468, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-38906004

RESUMEN

Prolonged or excessive oxidative stress can lead to premature cellular and body aging. Mannan-binding lectin (MBL) is synthesized by the liver and plays an important role in innate immunity, anti-inflammation, and anti-oxidation, and has a positive impact on health and longevity. To date, few studies investigated the role of MBL in attenuating oxidative stress-induced senescence. In this study, we evaluated the role of MBL in oxidative stress-induced premature aging and explored its underlying mechanism in C57BL/6 mice and mouse embryonic fibroblasts (NIH/3T3). First, we established an oxidative premature senescence model induced by D-galactose in C57BL/6 mice. We found that MBL-deficient mice had a marked aging-like appearance, reduced learning and spatial exploration abilities, severe liver pathological damage, and significantly upregulated expression of Senescence-associated proteins (p53 and p21), inflammatory kinesins (IL-1ß and IL-6), and the senescence ß-galactosidase (SA-ß-Gal) positive rate as compared with WT mice. In the H2O2-induced oxidative senescence model of NIH/3T3 cells, consistent results were obtained after MBL intervention. In addition, MBL effectively inhibited G1 phase arrest, ROS levels, DNA damage, and mitochondrial dysfunction in premature senescent cells. Mechanistically, we found that oxidative stress inhibited the nicotinamide adenine dinucleotide (NAD+)/ silent information regulator 1 (Sirt1) signaling pathway, while MBL activated the NAD+/Sirt1 signaling pathway inhibited by oxidative stress. In addition, MBL could activate the NAD+/Sirt1 pathway by upregulating NAMPT, which in turn inhibited p38 phosphorylation by activating the NAD+/Sirt1 pathway. In conclusion, MBL inhibits oxidative aging, which may facilitate the development of therapeutics to delay oxidative aging.


Asunto(s)
Senescencia Celular , Galactosa , Lectina de Unión a Manosa , Ratones Endogámicos C57BL , NAD , Estrés Oxidativo , Transducción de Señal , Sirtuina 1 , Animales , Sirtuina 1/metabolismo , Sirtuina 1/genética , Estrés Oxidativo/efectos de los fármacos , Ratones , Senescencia Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Células 3T3 NIH , NAD/metabolismo , Lectina de Unión a Manosa/metabolismo , Lectina de Unión a Manosa/genética , Ratones Noqueados , Peróxido de Hidrógeno/metabolismo , Masculino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo
9.
Gene ; 927: 148719, 2024 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-38917875

RESUMEN

Renal cell carcinoma (RCC) represents a significant portion of genitourinary cancers, marked by challenging prognosis and high metastasis rates. Immunotherapy has been applied in managing advanced renal cell carcinoma, but the therapeutic outcomes are unsatisfactory. In this study, we order to construct a Janus kinase/signal transduction and activator transcriptional (JAK/STAT)-related signature linked to kidney patient outcomes for better predicting the efficacy to immune checkpoint inhibitors (ICIs) and to provide guidance for effective combination therapy. We screened 25 differentially expressed genes (DEGs) that exhibited high expression in RCC samples and were enriched in the JAK-STAT signaling pathway. Among these genes, 11 key genes were identified and correlated with the expectation of Kidney Clear Cell Carcinoma (KIRC) patients and all these genes was significantly elevated in RCC tumor tissues and cancer cells compared to para-cancer tissues and normal renal cells. Utilizing these 11 genes, we divided RCC patients into high-risk and low-risk groups. We found a clear correlation between the clinicopathologic factors of KIRC patients and the JAK-STAT-related risk score. And the IHC results shown that the JAK3 and STAT4 expression of tumor was significantly higher than normal tissue in RCC patients, the level of JAK3 and STAT4 was positively related to the T stage of RCC patients. In addition, high-risk patients had a poorer prognosis and greater protumor immune cell infiltration, and benefitted less from immunotherapy than did low-risk patients. Furthermore, the JAK-STAT-related risk score can predict disease-free survival (DFS) in RCC patients according to the nomogram, which constructed in combination with other clinical features such as age, TNM-staging and stage. Our study demonstrated the JAK-STAT signaling pathway's important regulatory function in RCC tumor immunity. This insight not only enhances our ability to accurately predict the survival rate of RCC patients, but also underscores a potential therapeutic alternative for RCC, involving the combined targeting of the JAK-STAT pathway and immune checkpoints.

10.
PLoS One ; 19(5): e0296930, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38709729

RESUMEN

BACKGROUND: During the COVID pandemic, residency program's social media presence increased to aid in residency recruitment by attempting to increase engagement and readily available information for applicants across specialties. However, little information exists on what characteristics and content on obstetrics and gynecology (OBGYN) residency program accounts attract more followers or engagement. OBJECTIVES: To identify social media trends in OBGYN residencies and determine which aspects of programs influence the number of followers and interaction with content posted. METHODS: We performed a retrospective review of ACGME accredited OBGYN programs and determined their presence on Instagram and X in the fall of 2021. Content from the thirty programs with the most followers was analyzed independently by two authors. Multivariate analysis and a linear mixed model were used to characterize and evaluate content on Instagram and X. RESULTS: Most programs utilized Instagram (88.5%, N = 262/296) and were managed solely by residents (84.4%, N = 108/128). Number of followers on Instagram positively correlated with features such as program size, Instagram profile duration, and Doximity rankings (p < 0.0x01). Programs on X had more followers if their profile had a longer duration, followed more individuals, or were ranked higher on Doximity. The most posted Instagram content was biographical and social in nature. Instagram posts with the highest engagement were awards and/or the Match. CONCLUSIONS: Understanding what social media content attracts more followers and increases engagement is crucial as it likely impacts OBGYN resident recruitment. Professional groups should establish guidelines for social media use in recruitment for the protection of both residents and applicants.


Asunto(s)
Ginecología , Internado y Residencia , Obstetricia , Medios de Comunicación Sociales , Obstetricia/educación , Ginecología/educación , Humanos , Estudios Retrospectivos , COVID-19/epidemiología , Femenino
11.
Technol Health Care ; 32(S1): 79-93, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38759039

RESUMEN

BACKGROUND: In recent years, exoskeleton robot technology has developed rapidly. Exoskeleton robots that can be worn on a human body and provide additional strength, speed or other abilities. Exoskeleton robots have a wide range of applications, such as medical rehabilitation, logistics and disaster relief and other fields. OBJECTIVE: The study goal is to propose a lower limb assistive exoskeleton robot to provide extra power for wearers. METHODS: The mechanical structure of the exoskeleton robot was designed by using bionics principle to imitate human body shape, so as to satisfy the coordination of man-machine movement and the comfort of wearing. Then a gait prediction method based on neural network was designed. In addition, a control strategy according to iterative learning control was designed. RESULTS: The experiment results showed that the proposed exoskeleton robot can produce effective assistance and reduce the wearer's muscle force output. CONCLUSION: A lower limb assistive exoskeleton robot was introduced in this paper. The kinematics model and dynamic model of the exoskeleton robot were established. Tracking effects of joint angle displacement and velocity were analyzed to verify feasibility of the control strategy. The learning error of joint angle can be improved with increase of the number of iterations. The error of trajectory tracking is acceptable.


Asunto(s)
Diseño de Equipo , Dispositivo Exoesqueleto , Extremidad Inferior , Humanos , Extremidad Inferior/fisiología , Fenómenos Biomecánicos , Robótica/instrumentación , Marcha/fisiología , Redes Neurales de la Computación
12.
Nucleic Acids Res ; 52(W1): W439-W449, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38783035

RESUMEN

High-throughput screening rapidly tests an extensive array of chemical compounds to identify hit compounds for specific biological targets in drug discovery. However, false-positive results disrupt hit compound screening, leading to wastage of time and resources. To address this, we propose ChemFH, an integrated online platform facilitating rapid virtual evaluation of potential false positives, including colloidal aggregators, spectroscopic interference compounds, firefly luciferase inhibitors, chemical reactive compounds, promiscuous compounds, and other assay interferences. By leveraging a dataset containing 823 391 compounds, we constructed high-quality prediction models using multi-task directed message-passing network (DMPNN) architectures combining uncertainty estimation, yielding an average AUC value of 0.91. Furthermore, ChemFH incorporated 1441 representative alert substructures derived from the collected data and ten commonly used frequent hitter screening rules. ChemFH was validated with an external set of 75 compounds. Subsequently, the virtual screening capability of ChemFH was successfully confirmed through its application to five virtual screening libraries. Furthermore, ChemFH underwent additional validation on two natural products and FDA-approved drugs, yielding reliable and accurate results. ChemFH is a comprehensive, reliable, and computationally efficient screening pipeline that facilitates the identification of true positive results in assays, contributing to enhanced efficiency and success rates in drug discovery. ChemFH is freely available via https://chemfh.scbdd.com/.


Asunto(s)
Descubrimiento de Drogas , Ensayos Analíticos de Alto Rendimiento , Programas Informáticos , Descubrimiento de Drogas/métodos , Ensayos Analíticos de Alto Rendimiento/métodos , Evaluación Preclínica de Medicamentos/métodos , Reacciones Falso Positivas , Bibliotecas de Moléculas Pequeñas/farmacología , Bibliotecas de Moléculas Pequeñas/química , Humanos
13.
Cancer Lett ; 592: 216923, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38697462

RESUMEN

Liver metastasis is common in patients with gallbladder cancer (GBC), imposing a significant challenge in clinical management and serving as a poor prognostic indicator. However, the mechanisms underlying liver metastasis remain largely unknown. Here, we report a crucial role of tyrosine aminotransferase (TAT) in liver metastasis of GBC. TAT is frequently up-regulated in GBC tissues. Increased TAT expression is associated with frequent liver metastasis and poor prognosis of GBC patients. Overexpression of TAT promotes GBC cell migration and invasion in vitro, as well as liver metastasis in vivo. TAT knockdown has the opposite effects. Intriguingly, TAT promotes liver metastasis of GBC by potentiating cardiolipin-dependent mitophagy. Mechanistically, TAT directly binds to cardiolipin and leads to cardiolipin externalization and subsequent mitophagy. Moreover, TRIM21 (Tripartite Motif Containing 21), an E3 ubiquitin ligase, interacts with TAT. The histine residues 336 and 338 at TRIM21 are essential for this binding. TRIM21 preferentially adds the lysine 63 (K63)-linked ubiquitin chains on TAT principally at K136. TRIM21-mediated TAT ubiquitination impairs its dimerization and mitochondrial location, subsequently inhibiting tumor invasion and migration of GBC cells. Therefore, our study identifies TAT as a novel driver of GBC liver metastasis, emphasizing its potential as a therapeutic target.


Asunto(s)
Movimiento Celular , Neoplasias de la Vesícula Biliar , Neoplasias Hepáticas , Ribonucleoproteínas , Ubiquitinación , Animales , Humanos , Ratones , Línea Celular Tumoral , Neoplasias de la Vesícula Biliar/patología , Neoplasias de la Vesícula Biliar/genética , Neoplasias de la Vesícula Biliar/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Ratones Endogámicos BALB C , Ratones Desnudos , Mitofagia , Invasividad Neoplásica , Ribonucleoproteínas/metabolismo , Ribonucleoproteínas/genética , Tirosina Transaminasa
14.
Sci Rep ; 14(1): 11704, 2024 05 22.
Artículo en Inglés | MEDLINE | ID: mdl-38778121

RESUMEN

Chemotherapeutic agents can inhibit the proliferation of malignant cells due to their cytotoxicity, which is limited by collateral damage. Dihydroartemisinin (DHA), has a selective anti-cancer effect, whose target and mechanism remain uncovered. The present work aims to examine the selective inhibitory effect of DHA as well as the mechanisms involved. The findings revealed that the Lewis cell line (LLC) and A549 cell line (A549) had an extremely rapid proliferation rate compared with the 16HBE cell line (16HBE). LLC and A549 showed an increased expression of NRAS compared with 16HBE. Interestingly, DHA was found to inhibit the proliferation and facilitate the apoptosis of LLC and A549 with significant anti-cancer efficacy and down-regulation of NRAS. Results from molecular docking and cellular thermal shift assay revealed that DHA could bind to epidermal growth factor receptor (EGFR) molecules, attenuating the EGF binding and thus driving the suppressive effect. LLC and A549 also exhibited obvious DNA damage in response to DHA. Further results demonstrated that over-expression of NRAS abated DHA-induced blockage of NRAS. Moreover, not only the DNA damage was impaired, but the proliferation of lung cancer cells was also revitalized while NRAS was over-expression. Taken together, DHA could induce selective anti-lung cancer efficacy through binding to EGFR and thereby abolishing the NRAS signaling pathway, thus leading to DNA damage, which provides a novel theoretical basis for phytomedicine molecular therapy of malignant tumors.


Asunto(s)
Artemisininas , Proliferación Celular , Daño del ADN , Receptores ErbB , GTP Fosfohidrolasas , Neoplasias Pulmonares , Proteínas de la Membrana , Transducción de Señal , Receptores ErbB/metabolismo , Humanos , Proliferación Celular/efectos de los fármacos , Artemisininas/farmacología , Daño del ADN/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , GTP Fosfohidrolasas/metabolismo , Animales , Apoptosis/efectos de los fármacos , Simulación del Acoplamiento Molecular , Células A549 , Ratones , Antineoplásicos/farmacología , Línea Celular Tumoral , Unión Proteica
15.
Toxicol Appl Pharmacol ; 487: 116960, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38735592

RESUMEN

BACKGROUND: The intestinal metabolites are involved in the initiation, progression and metastasis of colorectal cancer (CRC). They are a potential source of agents for cancer therapy. Our previous study identified altered faecal metabolites between CRC patients and healthy volunteers. However, no specific metabolite was clearly illustrated for CRC therapy. RESULTS: We found that the level of xylulose was lower in the stools of CRC patients than in those of healthy volunteers. Xylulose inhibited cell growth without affecting the cell cycle by inducing apoptosis in CRC cells, which was evidenced by increased expression of the proapoptotic proteins C-PARP and C-Caspase3 and decreased expression of the antiapoptotic protein BCL-2 in CRC cells. Mechanistically, xylulose reduced the activity of the MAPK signalling pathway, represented by reduced phosphorylation of JNK, ERK, and P38. Furthermore, an ALI model was used to show the tumour killing ability of xylulose on human CRC spheres, as well as human colorectal adenoma (AD) spheres. CONCLUSION: Xylulose inhibits CRC growth by inducing apoptosis through attenuation of the MAPK signalling pathway. These results suggest that xylulose may serve as an effective agent for CRC therapy.


Asunto(s)
Apoptosis , Neoplasias Colorrectales , Sistema de Señalización de MAP Quinasas , Xilulosa , Humanos , Apoptosis/efectos de los fármacos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Xilulosa/farmacología , Xilulosa/metabolismo , Masculino , Animales , Femenino , Proliferación Celular/efectos de los fármacos , Heces/química , Persona de Mediana Edad , Línea Celular Tumoral , Antineoplásicos/farmacología , Células HT29 , Anciano
16.
Int J Biol Macromol ; 271(Pt 2): 132575, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38788863

RESUMEN

Rice husks are rich in xylan, which can be hydrolyzed by xylanase to form xylooligosaccharides (XOS). XOS are a functional oligosaccharide such as improving gut microbiota and antioxidant properties. In this study, the structure and functional characteristics of XOS were studied. The optimal xylanase hydrolysis conditions through response surface methodology (RSM) were: xylanase dosage of 3000 U/g, hydrolysis time of 3 h, hydrolysis temperature of 50 °C. Under this condition, the yield of XOS was 150.9 mg/g. The TG-DTG curve showed that XOS began to decompose at around 200 °C. When the concentration of XOS reached 1.0 g/L, the clearance rate of DPPH reached 65.76 %, and the scavenging rate of OH reached 62.10 %, while the clearance rate of ABTS free radicals reached 97.70 %, which was equivalent to the clearance rate of VC. XOS had a proliferative effect on four probiotics: Lactobacillus plantarum, Lactobacillus brucelli, Lactobacillus acidophilus, and Lactobacillus rhamnosus. However, the further experiments are needed to explore the improvement effect of XOS on human gut microbiota, laying a foundation for the effective utilization of XOS. XOS have a wide range of sources, low price, and broad development prospects. The reasonable utilization of XOS can bring greater economic benefits.


Asunto(s)
Antioxidantes , Glucuronatos , Oligosacáridos , Oryza , Probióticos , Oligosacáridos/farmacología , Oligosacáridos/química , Oryza/química , Glucuronatos/farmacología , Glucuronatos/química , Antioxidantes/farmacología , Antioxidantes/química , Hidrólisis , Endo-1,4-beta Xilanasas/metabolismo , Lactobacillus
17.
Plants (Basel) ; 13(10)2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38794447

RESUMEN

In response to the challenge of low recognition rates for similar phenotypic symptoms of tea diseases in low-light environments and the difficulty in detecting small lesions, a novel adaptive method for tea disease severity detection is proposed. This method integrates an image enhancement algorithm based on an improved EnlightenGAN network and an enhanced version of YOLO v8. The approach involves first enhancing the EnlightenGAN network through non-paired training on low-light-intensity images of various tea diseases, guiding the generation of high-quality disease images. This step aims to expand the dataset and improve lesion characteristics and texture details in low-light conditions. Subsequently, the YOLO v8 network incorporates ResNet50 as its backbone, integrating channel and spatial attention modules to extract key features from disease feature maps effectively. The introduction of adaptive spatial feature fusion in the Neck part of the YOLOv8 module further enhances detection accuracy, particularly for small disease targets in complex backgrounds. Additionally, the model architecture is optimized by replacing traditional Conv blocks with ODConv blocks and introducing a new ODC2f block to reduce parameters, improve performance, and switch the loss function from CIOU to EIOU for a faster and more accurate recognition of small targets. Experimental results demonstrate that YOLOv8-ASFF achieves a tea disease detection accuracy of 87.47% and a mean average precision (mAP) of 95.26%. These results show a 2.47 percentage point improvement over YOLOv8, and a significant lead of 9.11, 9.55, and 7.08 percentage points over CornerNet, SSD, YOLOv5, and other models, respectively. The ability to swiftly and accurately detect tea diseases can offer robust theoretical support for assessing tea disease severity and managing tea growth. Moreover, its compatibility with edge computing devices and practical application in agriculture further enhance its value.

18.
Pestic Biochem Physiol ; 201: 105891, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38685253

RESUMEN

The fall armyworm (Spodoptera frugiperda) was found to have invaded China in December 2018, and in just one year, crops in 26 provinces were heavily affected. Currently, the most effective method for emergency control of fulminant pests is to use of chemical pesticides. Recently, most fall armyworm populations in China were begining to exhibite low level resistance to chlorantraniliprole. At present, it is not possible to sensitively reflect the low level resistance of S. frugiperda by detecting target mutation and detoxification enzyme activity. In this study we found that 12 successive generations of screening with chlorantraniliprole caused S. frugiperda to develop low level resistance to this insecticide, and this phenotype was not attribute to genetic mutations in S. frugiperda, but rather to a marked increase in the relative amount of the symbiotic bacteria Sphingomonas. Using FISH and qPCR assays, we determined the amount of Sphingomonas in the gut of S. frugiperda and found Sphingomonas accumulation to be highest in the 3rd-instar larvae. Additionally, Sphingomonas was observed to provide a protective effect to against chlorantraniliprole stress to S. frugiperda. With the increase of the resistance to chlorantraniliprole, the abundance of bacteria also increased, we propose Sphingomonas monitoring could be adapted into an early warning index for the development of chlorantraniliprole resistance in S. frugiperda populations, such that timely measures can be taken to delay or prevent the widespread propagation of resistance to this highly useful agricultural chemical in S. frugiperda field populations.


Asunto(s)
Insecticidas , Larva , Sphingomonas , Spodoptera , ortoaminobenzoatos , Animales , Spodoptera/efectos de los fármacos , Spodoptera/microbiología , ortoaminobenzoatos/farmacología , Insecticidas/farmacología , Insecticidas/toxicidad , Larva/efectos de los fármacos , Sphingomonas/efectos de los fármacos , Sphingomonas/genética , Resistencia a los Insecticidas/genética
19.
Plant J ; 119(1): 478-489, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38659310

RESUMEN

The Q transcription factor plays important roles in improving multiple wheat domestication traits such as spike architecture, threshability and rachis fragility. However, whether and how it regulates abiotic stress adaptation remain unclear. We found that the transcriptional expression of Q can be induced by NaCl and abscisic acid treatments. Using the q mutants generated by CRISPR/Cas9 and Q overexpression transgenic lines, we showed that the domesticated Q gene causes a penalty in wheat salt tolerance. Then, we demonstrated that Q directly represses the transcription of TaSOS1-3B and reactive oxygen species (ROS) scavenging genes to regulate Na+ and ROS homeostasis in wheat. Furthermore, we showed that wheat salt tolerance protein TaWD40 interacts with Q to competitively interfere with the interaction between Q and the transcriptional co-repressor TaTPL. Taken together, our findings reveal that Q directly represses the expression of TaSOS1 and some ROS scavenging genes, thus causing a harmful effect on wheat salt tolerance.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Plantas Modificadas Genéticamente , Especies Reactivas de Oxígeno , Tolerancia a la Sal , Triticum , Triticum/genética , Triticum/fisiología , Triticum/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Tolerancia a la Sal/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacología
20.
Sci Rep ; 14(1): 8203, 2024 04 08.
Artículo en Inglés | MEDLINE | ID: mdl-38589529

RESUMEN

The neural network method is a type of machine learning that has made significant advances over the past few years in a variety of fields, particularly text, speech, images, videos, etc. In areas where data is unstructured, traditional machine learning has not been able to surpass the 'glass ceiling'; therefore, researchers have turned to neural networks as auxiliary tools to achieve significant breakthroughs or develop new research methods. An array of computational chemistry challenges can be addressed using neural networks, including virtual screening, quantitative structure-activity relationships, protein structure prediction, materials design, quantum chemistry, and property prediction, among others. This paper proposes a strategy for predicting the chemical properties of fruits by using graph neural networks, and it aims to provide some guidance to researchers and streamline the identification process.


Asunto(s)
Frutas , Redes Neurales de la Computación , Aprendizaje Automático , Relación Estructura-Actividad Cuantitativa
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