Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 263
Filtrar
1.
J Chem Phys ; 160(15)2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38629601

RESUMO

Many solid crystals exhibit a structural phase transition where a subset of its ions or entire molecules become orientationally ordered. As to why such ordering occurs remains mostly unresolved. We consider the extremely weak magnetic elements arising from the reorientations of the molecules experiencing mutual resonance to play the chief role. Two new features are identified in d-camphor: (1) the magnetic susceptibility abruptly changes when crossing the order-disorder phase transition at TII-III = 239.8 K during cooling and at TIII-II = 245.2 K during warming and (2) the complex dielectric constant exhibits two successive discontinuities only 0.2 K apart near the critical temperatures when the sweeping rate is only 0.1 K/min. We discuss how the change in entropy associated with order-disorder transitions in plastic crystals represents temporal changes rather than spatial changes in the system. Our findings may be extended to study why many other crystalline solids exhibit orientational ordering and irreversibility.

2.
Ital J Pediatr ; 50(1): 62, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38581027

RESUMO

BACKGROUND: Atrial septal defect (ASD) is a common form of congenital heart disease. Although several genes related to ASD have been found, the genetic factors of ASD remain unclear. This study aimed to evaluate the correlation between 10 candidate single nucleotide polymorphisms (SNPs) and sporadic atrial septal defects. METHODS: Based on the results of 34 individual whole exome sequences, 10 candidate SNPs were selected. In total, 489 ASD samples and 420 normal samples were collected. The 10 SNPs in the case group and the control group were identified through Snapshot genotyping technology. The χ2-test and unconditional regression model were used to evaluate the relationship between ASD and each candidate SNP. Haploview software was used to perform linkage disequilibrium and haplotype analysis. RESULTS: The χ2 results showed that the FLT4 rs383985 (P = 0.003, OR = 1.115-1.773), HYDIN rs7198975 (P = 0.04621, OR = 1.003-1.461), and HYDIN rs1774266 (P = 0.04621, OR = 1.003-1.461) alleles were significantly different between the control group and the case group (P < 0.05). Only the association with the FLT4 polymorphism was statistically significant after adjustment for multiple comparisons. CONCLUSION: These findings suggest that a possible molecular pathogenesis associated with sporadic ASD is worth exploring in future studies.


Assuntos
Comunicação Interatrial , Polimorfismo de Nucleotídeo Único , Humanos , Alelos , Estudos de Casos e Controles , China/epidemiologia , Predisposição Genética para Doença , Genótipo , Comunicação Interatrial/genética , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/genética
3.
Ecotoxicol Environ Saf ; 276: 116302, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38608381

RESUMO

Benzene is a known contributor to human leukaemia through its toxic effects on bone marrow cells, and epigenetic modification is believed to be a potential mechanism underlying benzene pathogenesis. However, the specific roles of N6-methyladenosine (m6A), a newly discovered RNA post-transcriptional modification, in benzene-induced hematotoxicity remain unclear. In this study, we identified self-renewing malignant proliferating cells in the bone marrow of benzene-exposed mice through in vivo bone marrow transplantation experiments and Competitive Repopulation Assay. Subsequent analysis using whole transcriptome sequencing and RNA m6A methylation sequencing revealed a significant upregulation of RNA m6A modification levels in the benzene-exposed group. Moreover, RNA methyltransferase METTL14, known as a pivotal player in m6A modification, was found to be aberrantly overexpressed in Lin-Sca-1+c-Kit+ (LSK) cells of benzene-exposed mice. Further analysis based on the GEO database showed a positive correlation between the expression of METTL14, mTOR, and GFI and benzene exposure dose. In vitro cellular experiments, employing experiments such as western blot, q-PCR, m6A RIP, and CLIP, validated the regulatory role of METTL14 on mTOR and GFI1. Mechanistically, continuous damage inflicted by benzene exposure on bone marrow cells led to the overexpression of METTL14 in LSK cells, which, in turn, increased m6A modification on the target genes' (mTOR and GFI1) RNA. This upregulation of target gene expression activated signalling pathways such as mTOR-AKT, ultimately resulting in malignant proliferation of bone marrow cells. In conclusion, this study offers insights into potential early targets for benzene-induced haematologic malignant diseases and provides novel perspectives for more targeted preventive and therapeutic strategies.

4.
J Cell Mol Med ; 28(8): e18247, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38520212

RESUMO

Malignant melanoma (MM) is a highly aggressive and deadly form of skin cancer, primarily caused by recurrence and metastasis. Therefore, it is crucial to investigate the regulatory mechanisms underlying melanoma recurrence and metastasis. Our study has identified a potential targeted regulatory relationship between LINC02202, miR-526b-3p and XBP1 in malignant melanoma. Through the regulation of the miR-526b-3p/XBP1 signalling pathway, LINC02202 may play a role in tumour progression and immune infiltration and inhibiting the expression of LINC02202 can increase the efficacy of immunotherapy for melanoma. Our findings shed light on the impact of LINC02202/XBP1 on the phenotype and function of malignant melanoma cells. Furthermore, this study provides a theoretical foundation for the development of novel immunotherapy strategies for malignant melanoma.


Assuntos
Melanoma , MicroRNAs , Neoplasias Cutâneas , Humanos , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/patologia , MicroRNAs/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Linhagem Celular Tumoral , Neoplasias Cutâneas/genética , Sistemas de Liberação de Medicamentos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Proteína 1 de Ligação a X-Box/genética , Proteína 1 de Ligação a X-Box/metabolismo
5.
J Ethnopharmacol ; 326: 117996, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38431110

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis, the dried and ripe fruit of the magnolia family plant Schisandra chinensis (Turcz.) Baill, was commonly used in traditional analgesic prescription. Studies have shown that the extract of Schisandra chinensis (SC) displayed analgesic activity. However, the analgesic active component and the exact mechanisms have yet to be revealed. AIM OF THE STUDY: The present study was to investigate the anti-nociceptive constituent of Schisandra chinensis, assess its analgesic effect, and explore the potential molecular mechanisms. MATERIALS AND METHODS: The effects of a series of well-recognized compounds from SC on glycine receptors were investigated. The analgesic effect of the identified compound was evaluated in three pain models. Mechanistic studies were performed using patch clamp technique on various targets expressed in recombinant cells. These targets included glycine receptors, Nav1.7 sodium channels, Cav2.2 calcium channels et al. Meanwhile, primary cultured spinal dorsal horn (SDH) neurons and dorsal root ganglion (DRG) neurons were also utilized. RESULTS: Schisandrin B (SchB) was a positive allosteric modulator of glycine receptors in spinal dorsal horn neurons. The EC50 of SchB on glycine receptors in spinal dorsal horn neurons was 2.94 ± 0.28 µM. In three pain models, the analgesic effect of SchB was comparable to that of indomethacin at the same dose. Besides, SchB rescued PGE2-induced suppression of α3 GlyR activity and alleviated persistent pain. Notably, SchB could also potently decrease the frequency of action potentials and inhibit sodium and calcium channels in DRG neurons. Consistent with the data from DRG neurons, SchB was also found to significantly block Nav1.7 sodium channels and Cav2.2 channels in recombinant cells. CONCLUSION: Our results demonstrated that, Schisandrin B, the primary lignan component of Schisandra chinensis, may exert its analgesic effect by acting on multiple ion channels, including glycine receptors, Nav1.7 channels, and Cav2.2 channels.


Assuntos
Lignanas , Compostos Policíclicos , Schisandra , Receptores de Glicina , Lignanas/farmacologia , Dor , Canais de Cálcio Tipo N , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Canais de Sódio , Ciclo-Octanos
6.
Nature ; 626(8000): 772-778, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38383625

RESUMO

High-capacity storage technologies are needed to meet our ever-growing data demands1,2. However, data centres based on major storage technologies such as semiconductor flash devices and hard disk drives have high energy burdens, high operation costs and short lifespans2,3. Optical data storage (ODS) presents a promising solution for cost-effective long-term archival data storage. Nonetheless, ODS has been limited by its low capacity and the challenge of increasing its areal density4,5. Here, to address these issues, we increase the capacity of ODS to the petabit level by extending the planar recording architecture to three dimensions with hundreds of layers, meanwhile breaking the optical diffraction limit barrier of the recorded spots. We develop an optical recording medium based on a photoresist film doped with aggregation-induced emission dye, which can be optically stimulated by femtosecond laser beams. This film is highly transparent and uniform, and the aggregation-induced emission phenomenon provides the storage mechanism. It can also be inhibited by another deactivating beam, resulting in a recording spot with a super-resolution scale. This technology makes it possible to achieve exabit-level storage by stacking nanoscale disks into arrays, which is essential in big data centres with limited space.

7.
Sci Adv ; 10(5): eadk6643, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38306426

RESUMO

Conductive hydrogels have a remarkable potential for applications in soft electronics and robotics, owing to their noteworthy attributes, including electrical conductivity, stretchability, biocompatibility, etc. However, the limited strength and toughness of these hydrogels have traditionally impeded their practical implementation. Inspired by the hierarchical architecture of high-performance biological composites found in nature, we successfully fabricate a robust and sensitive conductive nanocomposite hydrogel through self-assembly-induced bridge cross-linking of MgB2 nanosheets and polyvinyl alcohol hydrogels. By combining the hierarchical lamellar microstructure with robust molecular B─O─C covalent bonds, the resulting conductive hydrogel exhibits an exceptional strength and toughness. Moreover, the hydrogel demonstrates exceptional sensitivity (response/relaxation time, 20 milliseconds; detection lower limit, ~1 Pascal) under external deformation. Such characteristics enable the conductive hydrogel to exhibit superior performance in soft sensing applications. This study introduces a high-performance conductive hydrogel and opens up exciting possibilities for the development of soft electronics.

8.
World J Gastroenterol ; 30(1): 112-114, 2024 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-38293328

RESUMO

This letter to the editor is a commentary on a study titled "Liver metastases: The role of magnetic resonance imaging." Exploring a noninvasive imaging evaluation system for the biological behavior of hepatocellular carcinoma (HCC) is the key to achieving precise diagnosis and treatment and improving prognosis. This review summarizes the role of magnetic resonance imaging in the detection and evaluation of liver metastases, describes its main imaging features, and focuses on the added value of the latest imaging tools (such as T1 weighted in phase imaging, T1 weighted out of phase imaging; diffusion-weighted imaging, T2 weighted imaging). In this study, I investigated the necessity and benefits of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid for HCC diagnostic testing and prognostic evaluation.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/patologia , Meios de Contraste , Gadolínio DTPA , Imageamento por Ressonância Magnética/métodos , Imagem de Difusão por Ressonância Magnética , Estudos Retrospectivos
9.
Appl Biochem Biotechnol ; 196(1): 68-84, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37099125

RESUMO

Alginate lyase can degrade alginate into oligosaccharides through ß-elimination for various biological, biorefinery, and agricultural purposes. Here, we report a novel PL7 family exolytic alginate lyase VwAlg7A from marine bacteria Vibrio sp. W13 and achieve the heterologous expression in E. coli BL21 (DE3). VwAlg7A is 348aa with a calculated molecular weight of 36 kDa, containing an alginate lyase 2 domain. VwAlg7A exhibits specificity towards poly-guluronate. The optimal temperature and pH of VwAlg7A are 30 °C and 7.0, respectively. The activity of VwAlg7A can be significantly inhibited by the Ni2+, Zn2+, and NaCl. The Km and Vmax of VwAlg7A are 36.9 mg/ml and 395.6 µM/min, respectively. The ESI and HPAEC-PAD results indicate that VwAlg7A cleaves the sugar bond in an exolytic mode. Based on the molecular docking and mutagenesis results, we further confirmed that R98, H169, and Y303 are important catalytic residues.


Assuntos
Escherichia coli , Sulfonamidas , Vibrio , Sequência de Aminoácidos , Simulação de Acoplamento Molecular , Escherichia coli/genética , Escherichia coli/metabolismo , Polissacarídeo-Liases/química , Vibrio/genética , Alginatos/metabolismo , Especificidade por Substrato , Concentração de Íons de Hidrogênio , Proteínas de Bactérias/química
10.
Microbiol Spectr ; 12(1): e0224623, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38047697

RESUMO

IMPORTANCE: Tuberculous meningitis is a life-threatening infection with high mortality and disability rates. Current diagnostic methods using cerebrospinal fluid (CSF) samples have limited sensitivity and lack predictive biomarkers for evaluating prognosis. This study's findings reveal excessive activation of the immune response during tuberculous meningitis (TBM) infection. Notably, a strong negative correlation was observed between CSF levels of monokine induced by interferon-γ (MIG) and the CSF/blood glucose ratio in TBM patients. MIG also exhibited the highest area under the curve with high sensitivity and specificity. This study suggests that MIG may serve as a novel biomarker for differentiating TBM infection in CSF or serum, potentially leading to improved diagnostic accuracy and better patient outcomes.


Assuntos
Tuberculose Meníngea , Humanos , Tuberculose Meníngea/diagnóstico , Tuberculose Meníngea/tratamento farmacológico , Curva ROC , Interferon gama , Soro , Biomarcadores , Líquido Cefalorraquidiano
11.
Adv Sci (Weinh) ; 11(4): e2305232, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37997188

RESUMO

The reduction of noises, achieved through absorption, is of paramount importance to the well-being of both humans and machines. Lattice structures, defined as architectured porous solids arranged in repeating patterns, are emerging as advanced sound-absorbing materials. Their immense design freedom allows for customizable pore morphology and interconnectivity, enabling the design of specific absorption properties. Thus far, the sound absorption performance of various types of lattice structures are studied and they demonstrated favorable properties compared to conventional materials. Herein, this review gives a thorough overview on the current research status, and characterizations for lattice structures in terms of acoustics is proposed. Till date, there are four main sound absorption mechanisms associated with lattice structures. Despite their complexity, lattice structures can be accurately modelled using acoustical impedance models that focus on critical acoustical geometries. Four defining features: morphology, relative density, cell size, and number of cells, have significant influences on the acoustical geometries and hence sound wave dissipation within the lattice. Drawing upon their structural-property relationships, a classification of lattice structures into three distinct types in terms of acoustics is proposed. It is proposed that future attentions can be placed on new design concepts, advanced materials selections, and multifunctionalities.

12.
mSystems ; 9(1): e0100423, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38078741

RESUMO

Oomycetes are fungus-like eukaryotic microorganisms which can cause catastrophic diseases in many plants. Successful infection of oomycetes depends highly on their effector proteins that are secreted into plant cells to subvert plant immunity. Thus, systematic identification of effectors from the oomycete proteomes remains an initial but crucial step in understanding plant-pathogen relationships. However, the number of experimentally identified oomycete effectors is still limited. Currently, only a few bioinformatics predictors exist to detect potential effectors, and their prediction performance needs to be improved. Here, we used the sequence embeddings from a pre-trained large protein language model (ProtTrans) as input and developed a support vector machine-based method called POOE for predicting oomycete effectors. POOE could achieve a highly accurate performance with an area under the precision-recall curve of 0.804 (area under the receiver operating characteristic curve = 0.893, accuracy = 0.874, precision = 0.777, recall = 0.684, and specificity = 0.936) in the fivefold cross-validation, considerably outperforming various combinations of popular machine learning algorithms and other commonly used sequence encoding schemes. A similar prediction performance was also observed in the independent test. Compared with the existing oomycete effector prediction methods, POOE provided very competitive and promising performance, suggesting that ProtTrans effectively captures rich protein semantic information and dramatically improves the prediction task. We anticipate that POOE can accelerate the identification of oomycete effectors and provide new hints to systematically understand the functional roles of effectors in plant-pathogen interactions. The web server of POOE is freely accessible at http://zzdlab.com/pooe/index.php. The corresponding source codes and data sets are also available at https://github.com/zzdlabzm/POOE.IMPORTANCEIn this work, we use the sequence representations from a pre-trained large protein language model (ProtTrans) as input and develop a Support Vector Machine-based method called POOE for predicting oomycete effectors. POOE could achieve a highly accurate performance in the independent test set, considerably outperforming existing oomycete effector prediction methods. We expect that this new bioinformatics tool will accelerate the identification of oomycete effectors and further guide the experimental efforts to interrogate the functional roles of effectors in plant-pathogen interaction.


Assuntos
Oomicetos , Oomicetos/metabolismo , Proteínas Fúngicas/genética , Software , Plantas/metabolismo , Idioma
13.
J Proteome Res ; 23(1): 494-499, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38069805

RESUMO

Plant-pathogen protein-protein interactions (PPIs) play crucial roles in the arm race between plants and pathogens. Therefore, the identification of these interspecies PPIs is very important for the mechanistic understanding of pathogen infection and plant immunity. Computational prediction methods can complement experimental efforts, but their predictive performance still needs to be improved. Motivated by the rapid development of natural language processing and its successful applications in the field of protein bioinformatics, here we present an improved XGBoost-based plant-pathogen PPI predictor (i.e., AraPathogen2.0), in which sequence encodings from the pretrained protein language model ESM2 and Arabidopsis PPI network-related node representations from the graph embedding technique struc2vec are used as input. Stringent benchmark experiments showed that AraPathogen2.0 could achieve a better performance than its precedent version, especially for processing the test data set with novel proteins unseen in the training data.


Assuntos
Arabidopsis , Mapeamento de Interação de Proteínas , Mapeamento de Interação de Proteínas/métodos , Processamento de Linguagem Natural , Plantas , Proteínas/metabolismo , Arabidopsis/metabolismo
14.
Acta Pharmacol Sin ; 45(3): 465-479, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38017298

RESUMO

Epilepsy is a prevalent and severe neurological disorder and approximately 30% of patients are resistant to existing medications. It is of utmost importance to develop alternative therapies to treat epilepsy. Schisandrin B (SchB) is a major bioactive constituent of Schisandra chinensis (Turcz.) Baill and has multiple neuroprotective effects, sedative and hypnotic activities. In this study, we investigated the antiseizure effect of SchB in various mouse models of seizure and explored the underlying mechanisms. Pentylenetetrazole (PTZ), strychnine (STR), and pilocarpine-induced mouse seizure models were established. We showed that injection of SchB (10, 30, 60 mg/kg, i.p.) dose-dependently delayed the onset of generalized tonic-clonic seizures (GTCS), reduced the incidence of GTCS and mortality in PTZ and STR models. Meanwhile, injection of SchB (30 mg/kg, i.p.) exhibited therapeutic potential in pilocarpine-induced status epilepticus model, which was considered as a drug-resistant model. In whole-cell recording from CHO/HEK-239 cells stably expressing recombinant human GABAA receptors (GABAARs) and glycine receptors (GlyRs) and cultured hippocampal neurons, co-application of SchB dose-dependently enhanced GABA or glycine-induced current with EC50 values at around 5 µM, and application of SchB (10 µM) alone did not activate the channels in the absence of GABA or glycine. Furthermore, SchB (10 µM) eliminated both PTZ-induced inhibition on GABA-induced current (IGABA) and strychnine (STR)-induced inhibition on glycine-induced current (Iglycine). Moreover, SchB (10 µM) efficiently rescued the impaired GABAARs associated with genetic epilepsies. In addition, the homologous mutants in both GlyRs-α1(S267Q) and GABAARs-α1(S297Q)ß2(N289S)γ2L receptors by site-directed mutagenesis tests abolished SchB-induced potentiation of IGABA and Iglycine. In conclusion, we have identified SchB as a natural positive allosteric modulator of GABAARs and GlyRs, supporting its potential as alternative therapies for epilepsy.


Assuntos
Epilepsia , Lignanas , Compostos Policíclicos , Receptores de Glicina , Camundongos , Animais , Humanos , Pilocarpina/efeitos adversos , Estricnina/farmacologia , Estricnina/uso terapêutico , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Receptores de GABA-A , Glicina/farmacologia , Hipnóticos e Sedativos , Ácido gama-Aminobutírico , Ciclo-Octanos
15.
Phys Chem Chem Phys ; 25(48): 33130-33140, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38047441

RESUMO

In recent years, α-In2Se3 has attracted great attention in miniaturizing nonvolatile random memory devices because of its room temperature ferroelectricity and atomic thickness. In this work, we construct two-dimensional (2D) van der Waals (vdW) heterostructures α-In2Se3/MoS2 with different ferroelectric polarization and design a 2D graphene (Gr)/In2Se3/MoS2/Gr ferroelectric tunnel junction (FTJ) with the symmetric electrodes. Our calculations show that the band alignment of the heterostructures can be changed from type-I to type-II accompanied by the reversal of the ferroelectric polarization of In2Se3. Furthermore, the ferroelectricity persists in Gr/In2Se3/MoS2/Gr vdW FTJs, and the presence of dielectric layer MoS2 in the FTJs enables the effective modulation of the tunneling barrier by altering the ferroelectric polarization of α-In2Se3, which results in two distinct conducting states denoted as "ON" and "OFF" with a large tunneling electroresistance (TER) ratio exceeding 105%. These findings suggest the importance of ferroelectric vdW heterostructures in the design of FTJs and propose a promising route for applying the 2D ferroelectric/semiconductor heterostructures with out-of-plane polarization in high-density ferroelectric memory devices.

16.
BMC Complement Med Ther ; 23(1): 400, 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37936097

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC), abbreviated as liver cancer, is one of the most common cancers in clinics. HCC has a wider spread and higher incidence due to its high malignancy and metastasis. In HCC, effective strategies to block cancer cell migration, invasion, and neovascularization need to be further studied. Consumption of flavonoid-rich Oroxylum indicum (OI) has been associated with multiple beneficial effects, including anti-inflammatory and anticancer properties, but the potential effects on HCC have not been thoroughly investigated. OBJECTIVE: In this study, we aimed to reveal the effect of OI on HCC and its potential mechanism through microfluidic technology. METHODS: We designed microfluidic chips for cell migration, invasion, and neovascularization to evaluate the effect of OI on HepG2 cells. To further explore the mechanism of its anti-liver cancer action, the relevant signaling pathways were studied by microfluidic chips, RT‒qPCR and immunofluorescence techniques. Compared to the control group, cell migration, invasion, and angiogenesis were significantly reduced in each administration group. According to the P53 and VEGF pathways predicted by network pharmacology, RT‒qPCR and immunofluorescence staining experiments were conducted. RESULTS: The results showed that OI upregulated the expression of Bax, P53 and Caspase-3 and downregulated the expression of Bcl-2 and MDM2. It has been speculated that OI may directly or indirectly induce apoptosis of HepG2 cells by regulating apoptosis-related genes. OI blocks the VEGF signaling pathway by downregulating the expression levels of VEGF, HIF-1α and EGFR and inhibits the migration and invasion of HepG2 cells and the formation of new blood vessels. CONCLUSION: Our findings suggest that OI may inhibit the migration, invasion, and neovascularization of HepG2 cells, and its regulatory mechanism may be related to the regulation of the P53 and VEGF pathways.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Microfluídica
17.
Front Immunol ; 14: 1269097, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38022513

RESUMO

Urothelial carcinoma (UC) with deficient mismatch repair (dMMR) is a specific subtype of UC characterized by the loss of mismatch repair (MMR) proteins and its association with Lynch syndrome (LS). However, comprehensive real-world data on the incidence, clinicopathological characteristics, molecular landscape, and biomarker landscape for predicting the efficacy of PD-1/PD-L1 inhibitors in the Chinese patients with dMMR UC remains unknown. We analyzed 374 patients with bladder urothelial carcinoma (BUC) and 232 patients with upper tract urothelial carcinoma (UTUC) using tissue microarrays, immunohistochemistry, and targeted next-generation sequencing. Results showed the incidence of dMMR UC was higher in the upper urinary tract than in the bladder. Genomic analysis identified frequent mutations in KMT2D and KMT2C genes and LS was confirmed in 53.8% of dMMR UC cases. dMMR UC cases displayed microsatellite instability-high (MSI-H) (PCR method) in 91.7% and tumor mutational burden-high (TMB-H) in 40% of cases. The density of intratumoral CD8+ T cells correlated with better overall survival in dMMR UC patients. Positive PD-L1 expression was found in 20% cases, but some patients positively responded to immunotherapy despite negative PD-L1 expression. Our findings provide valuable insights into the characteristics of dMMR UC in the Chinese population and highlights the relevance of genetic testing and immunotherapy biomarkers for treatment decisions.


Assuntos
Carcinoma de Células de Transição , Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias da Bexiga Urinária , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/genética , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Receptor de Morte Celular Programada 1/genética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Reparo de Erro de Pareamento de DNA/genética , População do Leste Asiático , Neoplasias Colorretais Hereditárias sem Polipose/genética
18.
Regul Toxicol Pharmacol ; 145: 105520, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37884076

RESUMO

The genetically modified (GM) maize GG2 contains gr79-epsps and gat genes, conferring glyphosate tolerance. The present study aimed to investigate potential effects of maize GG2 in a 90-day subchronic feeding study on Wistar Han RCC rats. Maize grains from GG2 or non-GM maize were incorporated into diets at concentrations of 25% and 50% and administered to Wistar Han RCC rats (n = 10/sex/group) for 90 days. The basal-diet group of rats (n = 10/sex/group) were fed with common commercialized rodent diet. Compared with rats fed with the corresponding non-GM maize and the basal-diet, no biologically relevant differences were observed in rats fed with the maize GG2, according to the results of body weight/gain, feed consumption/utilization, clinical signs, mortality, ophthalmology, clinical pathology (hematology, prothrombin time, urinalysis, serum chemistry), organ weights, and gross and microscopic pathology. Under the conditions of this study, these results indicated that maize GG2 is as safe as the non-GM maize in this 90-day feeding study.


Assuntos
Carcinoma de Células Renais , Alimentos Geneticamente Modificados , Neoplasias Renais , Ratos , Animais , Ratos Wistar , Ratos Sprague-Dawley , Plantas Geneticamente Modificadas/genética , Zea mays/genética , Ração Animal/análise
19.
Cell Death Dis ; 14(10): 676, 2023 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-37833290

RESUMO

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of death in the world. In most cases, drug resistance and tumor recurrence are ultimately inevitable. One obstacle is the presence of chemotherapy-insensitive quiescent cancer cells (QCCs). Identification of unique features of QCCs may facilitate the development of new targeted therapeutic strategies to eliminate tumor cells and thereby delay tumor recurrence. Here, using single-cell RNA sequencing, we classified proliferating and quiescent cancer cell populations in the human colorectal cancer spheroid model and identified ATF3 as a novel signature of QCCs that could support cells living in a metabolically restricted microenvironment. RNA velocity further showed a shift from the QCC group to the PCC group indicating the regenerative capacity of the QCCs. Our further results of epigenetic analysis, STING analysis, and evaluation of TCGA COAD datasets build a conclusion that ATF3 can interact with DDIT4 and TRIB3 at the transcriptional level. In addition, decreasing the expression level of ATF3 could enhance the efficacy of 5-FU on CRC MCTS models. In conclusion, ATF3 was identified as a novel marker of QCCs, and combining conventional drugs targeting PCCs with an option to target QCCs by reducing ATF3 expression levels may be a promising strategy for more efficient removal of tumor cells.


Assuntos
Neoplasias Colorretais , Recidiva Local de Neoplasia , Humanos , Recidiva Local de Neoplasia/genética , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Regiões Promotoras Genéticas , Microambiente Tumoral , Fator 3 Ativador da Transcrição/genética , Fator 3 Ativador da Transcrição/metabolismo
20.
Artigo em Inglês | MEDLINE | ID: mdl-37733797

RESUMO

KEY POINTS: Nasal secretions of allergic rhinitis patients were analyzed by Olink proteomics. Fifteen differentially expressed proteins (DEPs) were identified. The DEPs were significantly correlated with the total nasal symptom scores of patients with allergic rhinitis.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...