RESUMO
BACKGROUND: Extracellular vesicles (EVs) have been revealed to facilitate the development of oral squamous cavity cell carcinoma (OCSCC), while its supporting role in lymph node metastases is under continuous investigation. This study aimed to examine the function of cancer-associated fibroblasts (CAF)-derived EVs (CAF-EVs) during lymph node metastasis in OCSCC and the mechanisms. METHODS: CAF were isolated from OCSCC tissues of patients, and CAF-EVs were extracted and identified. EdU, colony formation, wound healing, and Transwell assays were performed. The OCSCC cells before and after CAF-EVs treatment were injected into mice to probe the effects of CAF-EVs on tumor growth and lymph node metastasis, respectively. The effect of CAF-EVs treatment on transcriptome changes in OCSCC cells was analyzed. Clinical data of patients with OCSCC were analyzed to determine the prognostic significance of the selected genes. Finally, loss-of-function assays were conducted to corroborate the involvement of polycomb complex protein BMI-1 (BMI1) and integrin beta1 (ITGB1). RESULTS: CAF-EVs promoted the malignant behavior of OCSCC cells and accelerated tumor growth and lymph node metastasis in mice. CAF-EVs significantly increased the expression of BMI1 and ITGB1, and the expression of BMI1 and ITGB1 was negatively correlated with the overall survival and relapse-free survival of OCSCC patients. Knockdown of BMI1 or ITGB1 in OCSCC cells abated the promoting effects of CAF-EVs in vitro and in vivo. CONCLUSION: CAF-EVs elicited the metastasis-promoting properties in OCSCC by elevating BMI1 and ITGB1, suggesting that BMI1 and ITGB1 could be potential biomarkers and therapeutic targets for OCSCC.
Assuntos
Fibroblastos Associados a Câncer , Carcinoma de Células Escamosas , Vesículas Extracelulares , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Animais , Humanos , Camundongos , Neoplasias de Cabeça e Pescoço/metabolismo , Integrina beta1/genética , Metástase Linfática/genética , Neoplasias Bucais/metabolismo , Recidiva Local de Neoplasia , Complexo Repressor Polycomb 1/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismoRESUMO
Pyrotinib is a novel epidermal growth factor receptor/human epidermal growth factor receptor-2 (HER2) tyrosine kinase inhibitor that exhibited clinical efficacy in patients with HER2-positive breast cancer and HER2-mutant/amplified lung cancer. However, severe diarrhea adverse responses preclude its practical use. At present, the mechanism of pyrotinib-induced diarrhea is unknown and needs further study. First, to develop a suitable and reproducible animal model, we compared the effects of different doses of pyrotinib (20, 40, 60 and 80 mg/kg) in Wistar rats. Second, we used this model to examine the intestinal toxicity of pyrotinib. Finally, the mechanism underlying pyrotinib-induced diarrhea was fully studied using gut microbiome and host intestinal tissue metabolomics profiling. Reproducible diarrhea occurred in rats when they were given an 80 mg/kg daily dose of pyrotinib. Using the pyrotinib-induced model, we observed that Lachnospiraceae and Acidaminococcaceae decreased in the pyrotinib groups, whereas Enterobacteriaceae, Helicobacteraceae and Clostridiaceae increased at the family level by 16S rRNA gene sequence. Multiple bioinformatics methods revealed that glycocholic acid, ursodeoxycholic acid and cyclic AMP increased in the pyrotinib groups, whereas kynurenic acid decreased, which may be related to the pathogenesis of pyrotinib-induced diarrhea. Additionally, pyrotinib-induced diarrhea may be associated with a number of metabolic changes mediated by the gut microbiome, such as Primary bile acid biosynthesis. We reported the establishment of a reproducible pyrotinib-induced animal model for the first time. Furthermore, we concluded from this experiment that gut microbiome imbalance and changes in related metabolites are significant contributors to pyrotinib-induced diarrhea.
Assuntos
Neoplasias da Mama , Microbioma Gastrointestinal , Humanos , Ratos , Animais , Feminino , RNA Ribossômico 16S , Ratos Wistar , Receptor ErbB-2/metabolismo , Neoplasias da Mama/patologia , Aminoquinolinas/efeitos adversos , Metabolômica , Diarreia/induzido quimicamente , Íleo/metabolismo , Íleo/patologiaRESUMO
Histone deacetylase 8 (HDAC8) is overexpressed in multiple cancers and lack of effective chemical probes which could detect and visualize HDAC8 in tumor cells and tissues remains unsolved. In this work, three novel turn-on HDAC8 fluorescent probes 17-19 derived from solvatochromic fluorophore 4-sulfamonyl-7-aminobenzoxadiazole (SBD) conjugating with a potent HDAC8 inhibitor PCI-34051 (IC50 = 10 nM) as the recognition group were fabricated. The probes exhibited much stronger fluorescence when they transfer from hydrophilic environment (Φ < 8%) to hydrophobic environment (Φ > 46%). Compared with PCI-34051 (KD = 9.16 × 10-6 M), probes 17 (KD = 5.37 × 10-6 M), 18 (KD = 3.57 × 10-6 M) and 19 (KD = 8.89 × 10-6 M) possessed slightly better affinity for HDAC8. Probe 19 was selected for cell imaging and it showed significantly enhanced fluorescence only after binding into the cavity of HDAC8 in SH-SY5Y and MDA-MB-231 tumor cells. Co-localization results demonstrated that HDAC8 is expressed in cytoplasm and nucleus. Furthermore, probe 19 was successfully utilized to distinguish the expression level of HDAC8 in SH-SY5Y tumor and normal tissue slices.
Assuntos
Neuroblastoma , Intervenção Coronária Percutânea , Corantes Fluorescentes , Inibidores de Histona Desacetilases/química , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Humanos , Proteínas RepressorasRESUMO
Piezoelectric vibration energy harvester (PVEH) is a promising device for sustainable power supply of wireless sensor nodes (WSNs). PVEH is resonant and generates power under constant frequency vibration excitation of mechanical equipment. However, it cannot output high power through off-resonance if it has frequency offset in manufacturing, assembly and use. To address this issue, this paper designs and optimizes a PVEH to harvest power specifically from grid transformer vibration at 100 Hz with high power density of 5.28 µWmm-3g-2. Some resonant frequency modulation methods of PVEH are discussed by theoretical analysis and experiment, such as load impedance, additional mass, glue filling, axial and transverse magnetic force frequency modulation. Finally, efficient energy harvesting of 6.1 V output in 0.0226 g acceleration is tested in grid transformer reactor field application. This research has practical value for the design and optimization process of tunable PVEH for a specific vibration source.
Assuntos
Modalidades de Fisioterapia , Vibração , Fenômenos Físicos , Aceleração , ComércioRESUMO
Glypican-3 (GPC3) is a serological biomarker for the diagnosis of Hepatocellular carcinoma (HCC), but it is a challenging task to develop a bioassay for determination of the trace GPC3 in serum. In this study, Bioluminescense immunoassay based on bifunctional nanobody-nanoluciferase fusion was developed with the ultra-sensitive feature to achieve this goal. First, nanobodies special against GPC-3 binder as biological recognition element were generated by immunization and phage display technology. Second, The best clone GPN2 was fused with nanoluciferase as a dual-functional immunoreagent to establish an ultra-sensitive bioluminescence enzyme immunoassay (BLEIA), which is 30 and 5 times more sensitive than the traditional colorimetric assay and fluorescent assay, respectively. The cross-reactivity analysis of BLEIA showed that there was no cross-reactivity with HCC related tumor markers AFP, CEA, CA19-9 and GPC1/GPC2. The limit of detection (LOD) of developed BLEIA was 1.5 ng/mL, which assured its application in the diagnosis of GPC3 in 94 serum samples. This study indicates that BLEIA based on nanobody-nanoluciferase fusion could be used as a useful tool for the diagnosis of HCC patients.
RESUMO
In this paper, we investigate the coverage performance and energy efficiency of multi-tier heterogeneous cellular networks (HetNets) which are composed of macrocells and different types of small cells, i.e., picocells and femtocells. By virtue of stochastic geometry tools, we model the multi-tier HetNets based on a Poisson point process (PPP) and analyze the Signal to Interference Ratio (SIR) via studying the cumulative interference from pico-tier and femto-tier. We then derive the analytical expressions of coverage probabilities in order to evaluate coverage performance in different tiers and investigate how it varies with the small cells' deployment density. By taking the fairness and user experience into consideration, we propose a disjoint channel allocation scheme and derive the system channel throughput for various tiers. Further, we formulate the energy efficiency optimization problem for multi-tier HetNets in terms of throughput performance and resource allocation fairness. To solve this problem, we devise a linear programming based approach to obtain the available area of the feasible solutions. System-level simulations demonstrate that the small cells' deployment density has a significant effect on the coverage performance and energy efficiency. Simulation results also reveal that there exits an optimal small cell base station (SBS) density ratio between pico-tier and femto-tier which can be applied to maximize the energy efficiency and at the same time enhance the system performance. Our findings provide guidance for the design of multi-tier HetNets for improving the coverage performance as well as the energy efficiency.
RESUMO
Polyimide polymer membranes have become critical materials in gas separation and storage applications due to their high selectivity and excellent permeability. However, with over 107 known types of polyimides, relying solely on experimental research means potential high-performance candidates are likely to be overlooked. This study employs a deep learning method optimized by negative correlation ensemble techniques to predict the gas permeability and selectivity of polyimide structures, enabling rapid and efficient material screening. We propose a deep neural network model based on negative correlation deep ensemble methods (DNN-NCL), using Morgan molecular fingerprints as input. The DNN-NCL model achieves an R2 value of approximately 0.95 on the test set, which is a 4% improvement over recent model performance, and effectively mitigates overfitting with a maximum discrepancy of less than 0.03 between the training and test sets. High-throughput screening of over 8 million hypothetical polymers identified hundreds of promising candidates for gas separation membranes, with 14 structures exceeding the Robeson upper bound for CO2/N2 separation. Visualization of high-throughput predictions shows that although the Robeson upper bound was never explicitly used as a model constraint, the majority of predictions are compressed below this limit, demonstrating the deep learning model's ability to reflect real-world physical conditions. Reverse analysis of model predictions using SHAP analysis achieved interpretability of the deep learning model's predictions and identified three key functional groups deemed important by the deep neural network for gas permeability: carbonyl, thiophene, and ester groups. This established a bridge between the structure and properties of polyimide materials. Additionally, we confirmed that two polyimide structures predicted by the model to have excellent CO2/N2 selectivity, namely 6-methylpyrimidin-5-amine and 1,4,5,6-tetrahydropyrimidin-2-amine, have been experimentally validated in previous studies. This research demonstrates the feasibility of using deep learning methods to explore the vast chemical space of polyimides, providing a powerful tool for discovering high-performance gas separation membranes.
RESUMO
NAD(P)H:quinone oxidoreductase 1 (NQO1) is a potential biomarker for breast cancer (BC) diagnosis and prognosis. However, existing fluorescent probes for NQO1 detection have limitations such as short emission wavelength, weak fluorescence response, or large background interference. Here, we developed two novel near-infrared (NIR) fluorescent probes, DCl-Q and DCl2-Q, that selectively detect NQO1 activity in BC cells and tissues. They consist of a trimethyl-locked quinone as the recognition group and a donor-π-acceptor structure with halogen atoms as the reporter group. They exhibit strong fluorescence emission at around 660 nm upon binding to NQO1. We demonstrated that they can distinguish BC cells with different NQO1 expression levels and image endogenous NQO1 in tumor-bearing mice. Our probes provide a convenient and highly sensitive tool for BC diagnosis and prognosis based on NQO1 detection.
Assuntos
NAD(P)H Desidrogenase (Quinona) , Neoplasias , Animais , Camundongos , NAD(P)H Desidrogenase (Quinona)/química , Corantes Fluorescentes/química , Fluorescência , QuinonasRESUMO
Currently, SARS-CoV-2 has evolved into various variants, including the numerous highly mutated Omicron sub-lineages, significantly increasing immune evasion ability. The development raises concerns about the possibly diminished effectiveness of available vaccines and antibody-based therapeutics. Here, we describe those representative categories of broadly neutralizing antibodies (bnAbs) that retain prominent effectiveness against emerging variants including Omicron sub-lineages. The molecular characteristics, epitope conservation, and resistance mechanisms of these antibodies are further detailed, aiming to offer suggestion or direction for the development of therapeutic antibodies, and facilitate the design of vaccines with broad-spectrum potential.
Assuntos
Anticorpos Antivirais , Anticorpos Amplamente Neutralizantes , COVID-19 , Epitopos , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , SARS-CoV-2/imunologia , Humanos , Anticorpos Antivirais/imunologia , COVID-19/imunologia , COVID-19/virologia , Anticorpos Amplamente Neutralizantes/imunologia , Epitopos/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Anticorpos Neutralizantes/imunologia , Evasão da Resposta Imune , Vacinas contra COVID-19/imunologiaRESUMO
The micro thermoelectric device (m-TED) boasts features such as adjustable volume, straightforward structure, and precise, rapid temperature control, positioning it as the only current solution for managing the temperature of microelectronic systems. It is extensively utilized in 5G optical modules, laser lidars, and infrared detection. Nevertheless, as the size of the m-TED diminishes, the growing proportion of interface damages the device's operational reliability, constraining the advancement of the m-TED. In this study, we used commercially available bismuth telluride materials to construct the m-TED. The device's reliability was tested under various temperatures: -40, 85, 125, and 150 °C. By deconstructing and analyzing the devices that failed during the tests, we discovered that the primary cause of device failure was the degradation of the solder layer. Moreover, we demonstrated that encapsulating the device with polydimethylsiloxane (PDMS) could effectively delay the deterioration of its performance. This study sparks new insights into the service reliability of m-TEDs and paves the way for further optimizing device interface design and enhancing the device manufacturing process.
RESUMO
RATIONALE: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease. However, the misdiagnosis of ALS always occurs because of atypical clinical manifestations. Since mutations in Cu/Zn superoxide dismutase 1 (SOD1) have been implicated as causative and account for 20% of fALS cases, early genetic sequencing of suspected individuals in ALS pedigrees could be helpful. PATIENT CONCERNS: Here we report a Chinese family spanning three generations with fALS. A heterozygous c.125G>A (p.Gly42Asp) missense mutation in exon 2 of SOD1 gene was detected in our proband as well as her 2 siblings and next generation. Phenotypic diversity was also reported among symptomatic individuals. DIAGNOSES: Peripheral blood samples from the proband were collected and sent for polymerase chain reaction (PCR) and Sanger sequencing of the SOD1 gene at Sanvalley Diagnostics. The other 11 members in the studied family then underwent locus verification. INTERVENTIONS: Butylphthalide, Vitamin B12, Coenzyme Q10 and mouse nerve growth factor is given to the symptomatic members. OUTCOMES: The symptoms of our proband was not improved by treatments at a late stage. She passed away the fourth year of the disease due to respiratory failure. Two siblings of the proband were given active treatments once verified as carrier. Their symptoms are still limited to limb weakness. LESSONS: This study suggests genetic sequencing is a powerful tool for the diagnosis of familial ALS. Phenotypic heterogeneity exists among G41D-mutated individuals, which further highlights the importance of genomic strategies for early diagnosis.
Assuntos
Esclerose Lateral Amiotrófica/diagnóstico , Superóxido Dismutase-1/genética , Superóxido Dismutase/genética , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/mortalidade , Análise Mutacional de DNA , Evolução Fatal , Feminino , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Mutação , Mutação de Sentido Incorreto , Linhagem , Superóxido Dismutase/metabolismoRESUMO
Carboxylesterases (CESs) and Histone deacetylases (HDACs) are regarded as important signaling enzymes highly associated with the development and progression of multiple cancers, including hepatocellular carcinoma (HCC). In this work, a near-infrared (NIR) fluorescent probe named Lys-HXPI was designed and synthesized, which linked a hemicyanine dye and 6-acetamidohexanoic acid via an ester bond. Lys-HXPI displayed a remarkable increase with a NIR emission at 720 nm, a low detection limit (<10 nM) for HDAC1, HDAC 6, CES1 and CES2, as well as a high selectivity for the target enzymes over other relevant analytes. Furthermore, Lys-HXPI was used to image endogenous target enzymes in living cells, tumor-bearing nude mice and tissue slices. The ability of Lys-HXPI to simultaneous image CESs and HDACs was demonstrated with RT-qPCR and the confocal imaging in Hep G2 and MDA-MB-231. Taking advantage of NIR emission, the probe was also successfully applied to imaging Hep G2 tumor mice and tissue slices. Lys-HXPI is expected to be useful for the effective detecting of CESs and HDACs in complex biosystems.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Carbocianinas , Hidrolases de Éster Carboxílico , Carcinoma Hepatocelular/diagnóstico por imagem , Corantes Fluorescentes/química , Histona Desacetilases , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Camundongos , Camundongos NusRESUMO
BACKGROUND: Shenling Baizhu Powder (SBP) is a traditional Chinese medicine (TCM) prescription, which has the good efficacy on gastrointestinal toxicity. In this study, we used gut microbiota analysis, metabonomics and network pharmacology to investigate the therapeutic effect of SBP on pyrotinib-induced diarrhea. METHODS: 24 Rats were randomly divided into 4 groups: control group, SBP group (3.6 g/kg /bid SBP for 10 days), pyrotinib model group (80 mg/kg/qd pyrotinib) and pyrotinib + SBP treatment group. A 16S rRNA sequencing was used to detect the microbiome of rat fecal bowel. Metabolic profiles were collected by non-targeted metabolomics and key metabolic pathways were identified using MetaboAnalyst 5.0. The antitumor effect of SBP on cells treated with pyrotinib was measured using a CCK-8 assay. Network pharmacology was used to predict the target and action pathway of SBP in treating pyrotinib-related diarrhea. RESULTS: In vivo study indicated that SBP could significantly alleviate pyrotinib-induced diarrhea, reaching a therapeutic effect of 66.7%. SBP could regulate pyrotinib-induced microbiota disorder. LEfSe research revealed that the SBP could potentially decrease the relative abundance of Escherichia, Helicobacter and Enterobacteriaceae and increase the relative abundance of Lachnospiraceae, Bacilli, Lactobacillales etc. In addition, 25-Hydroxycholesterol, Guanidinosuccinic acid, 5-Hydroxyindolepyruvate and cAMP were selected as potential biomarkers of SBP for pyrotinib-induced diarrhea. Moreover, Spearman's analysis showed a correlation between gut microbiota and metabolite: the decreased 25-hydroxycholesterol in the pyrotinib + SBP treatment group was negatively correlated with Lachnospiraceae while positively correlated with Escherichia and Helicobacter. Meanwhile, SBP did not affect the inhibitory effect of pyrotinib on BT-474 cells and Calu-3 cells in vitro. Also, the network analysis further revealed that SBP treated pyrotinib-induced diarrhea through multiple pathways, including inflammatory bowel disease, IL-17 signaling pathway, pathogenic Escherichia coli infection and cAMP signaling pathway. CONCLUSIONS: SBP could effectively relieve pyrotinib-induced diarrhea, revealing that intestinal flora and its metabolites may be involved in this process.
RESUMO
Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder affecting branched-chain amino acids. Mutations in the BCKDHA, BCKDHB, and DBT gene impair the branched-chain alpha-ketoacid dehydrogenase (BCKD) complex, resulting in the accumulation of branched-chain amino acids and branched-chain alpha-ketoacid in tissues and plasma. This leads to mental and physical retardation, feeding problems, and a maple syrup odor in the urine. In this study, we describe the clinical and biochemical manifestations of a sporadic mutation in a neonate with classic MSUD. Analysis of the BCKDHA gene revealed a compound heterozygous mutation consisting of two novel missense mutations (p.L103P and p.R265P). Viewing the protein with PyMOL indicated that the p.L103P and p.R265P mutations were, respectively, located in the helical region and core domains of the BCKD's Ela component. The p.L103P mutation affected the hydrophobic cores and is predicted to shorten the helix; the p.R265P mutation can predictably affect the cofactor binding site by ligating the associated manganese ion. In conclusion, we identified two novel missense mutations in the BCKDHA gene in a Chinese patient with MSUD.
Assuntos
3-Metil-2-Oxobutanoato Desidrogenase (Lipoamida)/genética , Povo Asiático/genética , Doença da Urina de Xarope de Bordo/genética , Mutação Puntual , Sequência de Aminoácidos , Feminino , Humanos , Recém-Nascido , Dados de Sequência MolecularRESUMO
Oral squamous cell carcinoma (OSCC) is a frequent malignant tumor worldwide. Long noncoding RNAs (lncRNAs) are known to play key roles in different types of cancer, including OSCC. It was previously reported that lncRNA deleted in lymphocytic leukemia 1 (DLEU1) is notably upregulated in OSCC; however, the role of DLEU1 in OSCC remains unclear. Gene and protein expression levels in OSCC cells were detected by reverse transcriptionquantitative PCR and western blotting, respectively, in the present study. A Transwell assay was performed to measure cell migration and invasion. Flow cytometry was used to detect cell apoptosis, and the dualluciferase reporter assay was applied to confirm the interaction between DLEU1, microRNA (miR)1495p and CDK6 in OSCC cells. DLEU1 expression was negatively associated with the survival rate of patients with OSCC. In addition, silencing of DLEU1 notably inhibited the proliferation of OSCC cells by inducing apoptosis. Meanwhile, DLEU1 directly bound to miR1495p, and CDK6 was found to be the direct target of miR1495p. Furthermore, DLEU1 knockdowninduced inhibition of OSCC cell proliferation was significantly reversed by the miR1495p antagomir. Knockdown of lncRNA DLEU1 reversed the proliferation of OSCC cells via regulation of the miR1495p/CDK6 axis. Thus, DLEU1 may serve as a novel target for treating OSCC.
Assuntos
Carcinogênese/efeitos dos fármacos , Carcinogênese/genética , Carcinoma de Células Escamosas/tratamento farmacológico , Quinase 6 Dependente de Ciclina/metabolismo , MicroRNAs/metabolismo , Neoplasias Bucais/tratamento farmacológico , RNA Longo não Codificante/genética , RNA Longo não Codificante/farmacologia , Apoptose , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular , Transformação Celular Neoplásica/genética , China , Quinase 6 Dependente de Ciclina/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Neoplasias Bucais/patologiaRESUMO
BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most comment types of oral malignancies. SET-domain-containing protein 6 (SETD6) was recently identified as an important regulator of multiple signaling pathways through methylating protein substrates. Meanwhile, SETD6 is known to participate in multiple cancers. However, the role of SETD6 in OSCC remains unclear. METHODS: Gene and protein expressions in OSCC cells or tissues were detected by RT-qPCR and western blot, respectively. In addition, CCK-8 assay was used to test the cell viability. A transwell assay was performed to measure cell migration and invasion. Flow cytometry was used to test cell apoptosis and cycle. Meanwhile, methylation-specific PCR (MSP) was used to detect the status of promoter methylation. RESULTS: SETD6 was significantly upregulated in OSCC tissues. In addition, knockdown of SETD6 notably inhibited the proliferation and induced the apoptosis of OSCC cells. Furthermore, silencing of SETD6 notably suppressed the migration and invasion of OSCC cells. Meanwhile, SETD6 siRNA significantly inhibited the promoter methylation of RelA (NF-κB p65) and PAK4. Furthermore, SETD6 siRNA induced G1 arrest in OSCC cells. CONCLUSION: Knockdown of SETD6 inhibits the tumorigenesis of OSCC by suppressing promoter methylation of PAK4 and RelA. Therefore, our study might shed new light on exploring strategies for the treatment of OSCC.
Assuntos
Carcinogênese , Carcinoma de Células Escamosas/metabolismo , Inativação Gênica , Neoplasias Bucais/metabolismo , Proteínas Metiltransferases/genética , Fator de Transcrição RelA/metabolismo , Quinases Ativadas por p21/metabolismo , Apoptose , Carcinoma de Células Escamosas/genética , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Genoma Humano , Humanos , Imuno-Histoquímica , Neoplasias Bucais/genética , Neoplasias/metabolismo , Reação em Cadeia da Polimerase , Domínios Proteicos , Proteínas Metiltransferases/metabolismo , RNA Interferente Pequeno/metabolismo , Transdução de SinaisRESUMO
In order to increase CO2/N2 selectivity of polyimide (PI) dense membranes, task-specific ionic liquid (TSIL), 1-aminoethyl-3-buthylimidazolium hexafluorophosphate ([NH2ebim][PF6]), has been grafted to polymer chains as large side groups by forming the structure of Schiff base for the first time. The modified membranes were characterized by Fourier transform infrared spectroscopy (FT-IR), elemental analysis, thermogravimetric analysis (TGA), X-ray diffraction (XRD), dynamic thermomechanical analysis (DMA), and stress-strain testing. The results showed that TSIL had been successfully linked to PI chains by forming "C=N." The modified membranes had more free volume, which was favorable to the improvement of CO2 permeability. The reduction of spin degree of freedom means the rigidity increment of polymer chains, which indicated that the selectivity of CO2/N2 can be enhanced. As a result, CO2 permeability of the modified membrane (TSIL-0.8 wt%) was increased from 5.28 to 10.2 Barrer, and CO2/N2 selectivity was increased from 21.9 to 92.8 at 30 °C and 0.1 MPa. Meanwhile, the effects of different feed pressures (0.1-0.6 MPa) and different operating temperatures (30-60 °C) on CO2/N2 transport properties were also investigated, and it was found that the separation performances of the modified membranes had already exceeded Robeson's upper bound.
Assuntos
Líquidos Iônicos , Dióxido de Carbono , Polímeros , Bases de Schiff , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
The immune checkpoint blockade is an effective strategy to enhance the antitumor T cell effector activity, thus becoming one of the most promising immunotherapeutic strategies in the history of cancer treatment. Several immune checkpoint inhibitor have been approved by the FDA, such as antiCTLA4, antiPD1, antiPDL1 monoclonal antibodies. Most tumor patients benefitted from these antibodies, but some of the patients did not respond to them. To increase the effectiveness of immunotherapy, including immune checkpoint blockade therapies, miniaturization of antibodies has been introduced. A singledomain antibody, also known as nanobody, is an attractive reagent for immunotherapy and immunoimaging thanks to its unique structural characteristic consisting of a variable region of a single heavy chain antibody. This structure confers to the nanobody a light molecular weight, making it smaller than conventional antibodies, although remaining able to bind to a specific antigen. Therefore, this review summarizes the production of nanobodies targeting immune checkpoint molecules and the application of nanobodies targeting immune checkpoint molecules in immunotherapy and immunoimaging.
Assuntos
Antineoplásicos Imunológicos , Inibidores de Checkpoint Imunológico , Imunoterapia , Neoplasias , Anticorpos de Domínio Único , Animais , Antineoplásicos Imunológicos/imunologia , Antineoplásicos Imunológicos/uso terapêutico , Humanos , Inibidores de Checkpoint Imunológico/imunologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/imunologia , Neoplasias/imunologia , Neoplasias/terapia , Anticorpos de Domínio Único/imunologia , Anticorpos de Domínio Único/uso terapêuticoRESUMO
This study aimed to evaluate the antioxidant effect of Lactobacillus plantarum SCS2 (L. plantarum SCS2). After 1 week of acclimation, 120 male KM mice were divided into normal group (NG), model group (MG), solvent control group (KG), and different test groups (TG1, TG2, TG3) (n = 20/group) randomly. In the second week, except NG mice, other mice were given 0.2 ml 50 mg/kg (body weight) streptozocin (STZ) through intraperitoneal injection for 5 days. After successful modeling, NG and MG mice were fed normally, KG mice was given 0.5 ml 0.1 mol/L phosphate buffer saline (PBS) per day, TG1, TG2, and TG3 mice were given 0.5 ml suspension, intracellular content and heat-killed intracellular content of L. plantarum SCS2 per day for 9 weeks. Body weight and blood glucose were observed and recorded during intragastric administration. Glucose tolerance levels were measured at the twelfth week, then mice were sacrificed and the serum was collected to measure insulin (INS), glycosylated hemoglobin (HbA1c), malondialdehyde (MDA), reactive oxygen species (ROS) and antioxidant enzymes. The results showed that the reduction of weight loss in TG1 and TG2 mice was observed, which was consistent with the blood glucose. At the same time, the INS level of TG1, TG2, and TG3 mice were increased and the HbA1c levels were decreased. Otherwise, the MDA and ROS content in the serum of TG1, TG2, and TG3 mice were decreased and the level of antioxidant enzymes was increased. Interestingly, the activity and content of antioxidant enzymes in TG2 group was the highest in the three test groups. PRACTICAL APPLICATIONS: The results of this study showed that L. plantarum SCS2 could effectively reduce blood glucose, relieve weight loss, improve INS deficiency, and also improve oxidative stress by increasing the activity of antioxidant enzymes. The findings suggest that L. plantarum SCS2 could improve diabetes-related symptoms by alleviating oxidative stress. In the future, people could promote the application of lactic acid bacteria (LAB) which is found in traditional foods with the ability of improving oxidative damage in food nutrition and related fields, so as to guide residents to form good dietary habits, and effectively prevent type 2 diabetes. Meanwhile, it also can enhance the edible value of traditional foods.
RESUMO
BACKGROUND: Secretory carrier membrane proteins 3 (SCAMP3) is an endocytosis-associated protein involved in regulating endosomal pathways and the trafficking of vital signaling receptors. This study aimed to comprehensively assess the role of SCAMP3 in hepatocellular carcinoma (HCC) by integrated bioinformatics analysis. METHODS: In this study, bioinformatics databases were used to explore the differential expression status and prognostic value of SCAMP3 gene in HCC, and bioinformatics analyses of survival data and interactors of SCAMP3 were conducted to predict the prognostic value of SCAMP3 in HCC. RESULTS: Using the TCGA data, our data shows that SCAMP3 mRNA expression is most significantly different between liver and hepatocellular carcinoma tissues and higher expression of SCAMP3 has unfavorable prognostic significance in HCC. Tumor grade, stage, and gender also showed a significant relevance with SCAMP3 expression. High SCAMP3 expression of males revealed significantly poorer survival and progression compared with low SCAMP3 expression of males. BioGRID statistics explores 79 unique interactions with SCAMP3 and multiple post translational modifications. Further analysis finds that SOCS2 may negatively correlate with SCAMP3, while GBA, MX1, and DDOST positively correlate with SCAMP3. Moreover, ncRNA analysis shows that SCAMP3 gene expression is positively associated with lncRNA SBF2-AS1 and negatively related with Has-miR-145. The expressions of SBF2-AS1 and Has-miR-145 are also significantly related with survival in HCC. DISCUSSION: SCAMP3 expression can be affected by multiple genes or ncRNAs expression that are associated with survival, thus suggesting that SCAMP3 can be used as a clinical diagnosis and prognostic biomarker in HCC.