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1.
Nat Immunol ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632339

RESUMO

Adaptive immunity relies on specialized effector functions elicited by lymphocytes, yet how antigen recognition activates appropriate effector responses through nonspecific signaling intermediates is unclear. Here we examined the role of chromatin priming in specifying the functional outputs of effector T cells and found that most of the cis-regulatory landscape active in effector T cells was poised early in development before the expression of the T cell antigen receptor. We identified two principal mechanisms underpinning this poised landscape: the recruitment of the nucleosome remodeler mammalian SWItch/Sucrose Non-Fermentable (mSWI/SNF) by the transcription factors RUNX1 and PU.1 to establish chromatin accessibility at T effector loci; and a 'relay' whereby the transcription factor BCL11B succeeded PU.1 to maintain occupancy of the chromatin remodeling complex mSWI/SNF together with RUNX1, after PU.1 silencing during lineage commitment. These mechanisms define modes by which T cells acquire the potential to elicit specialized effector functions early in their ontogeny and underscore the importance of integrating extrinsic cues to the developmentally specified intrinsic program.

2.
Curr Issues Mol Biol ; 46(3): 2251-2262, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38534760

RESUMO

Prostate cancer accounts for 14% of male cancer-related fatalities in the UK. Given the challenges associated with hormone-based therapies in the context of androgen-independent prostate cancer, there is an imperative need for research into anticancer drugs. N0821, a peptide belonging to the Trp-Arg dense region and derived from the homologous region of various bee species, shows substantial potential for an anticancer effect. Both MTT assays and 3D spheroid assays were conducted to substantiate its antiproliferation potential and strongly indicated the antiproliferation effect of N0820 (WWWWRWWRKI) and N0821 (YWWWWRWWRKI). Notably, the mechanism underlying this effect is related to the downregulation of CCNA2 and the upregulation of CCNE1. Cell cycle arrest results from the reduction of CCNA2 in the S/G2 phase, leading to the accumulation of CCNE1. Our peptides were predicted to make an α-helix structure. This can act as an ion channel in the cell membrane. Therefore, we analyzed genes implicated in the influx of calcium ions into the mitochondria. Trp-Arg dense-region peptides are known for their antibacterial properties in targeting cell membranes, making the development of resistance less likely. Hence, further research in this area is essential and promising.

3.
Nutrients ; 16(3)2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38337735

RESUMO

Atopic dermatitis (AD) is a persistent inflammatory skin condition resulting from an intricate interplay among genetic, immunological, and environmental factors. Erigeron annuus (EA), an annual winter plant belonging to the family Asteraceae, possesses anti-inflammatory, cytoprotective, and antioxidant activities. In this study, we hypothesized that Erigeron annuus extract (EAE) could be an effective agent for ameliorating AD-like symptoms. To confirm this hypothesis in vitro, we used H2O2-stimulated human keratinocytes (HaCaT cells) to demonstrate that pre-treatment with EAE protected against oxidative stress. HaCaT cells pretreated with EAE and stimulated with H2O2 showed decreased intracellular malondialdehyde content, increased superoxide dismutase activity, and reduced intracellular reactive oxygen species accumulation. To verify the in vivo hypothesis based on the intracellular results, an AD disease mouse model was induced with 1-chloro-2,4-dinitrobenzene (DNCB), and EAE was orally administered at a non-toxic concentration according to the toxicity evaluation results. The results showed that AD disease models in BALB/c mice exhibited reduced ear epidermal thickness, scratching behavior, and mast cell infiltration. In conclusion, our results indicate that EAE has the potential to improve AD by upregulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway.


Assuntos
Dermatite Atópica , Erigeron , Humanos , Animais , Camundongos , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Pele/metabolismo , Dinitroclorobenzeno/toxicidade , Erigeron/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Dinitrobenzenos/efeitos adversos , Dinitrobenzenos/metabolismo , Heme Oxigenase-1/metabolismo , Peróxido de Hidrogênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Camundongos Endogâmicos BALB C , Citocinas/metabolismo
4.
J Biomed Mater Res B Appl Biomater ; 112(1): e35335, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37772460

RESUMO

Calcium phosphate cement (CPC) is generally used for bone repair and augmentation. Poloxamers are tri-block copolymers that are used as surfactants but have applications in drug and antibiotic delivery. However, their biological effects on bone regeneration systems remain unelucidated. Here, we aimed to understand how supplementing the prototype CPC with poloxamer would impact cellular activity and its function as a bone-grafting material. A novel CPC, modified beta-tricalcium phosphate (mß-TCP) powder, was developed through a planetary ball-milling process using a beta-tricalcium phosphate (ß-TCP). The mß-TCP dissolves rapidly and accelerates hydroxyapatite precipitation; successfully shortening the cement setting time and enhancing the strength. Furthermore, the addition of poloxamer 407 to mß-TCP could reduce the risk of leakage from bone defects and improve fracture toughness while maintaining mechanical properties. In this study, the poloxamer addition effects (0.05 and 0.1 g/mL) on the cellular activities of MC3T3-E1 cells cultured in vitro were investigated. The cell viability of mß-TCP containing poloxamer 407 was similar to that of mß-TCP. All specimens showed effective cell attachment and healthy polygonal extension of the cytoplasm firmly attached to hydroxyapatite (HA) crystals. Therefore, even with the addition of poloxamer to mß-TCP, it does not have a negative effect to osteoblast growth. These data demonstrated that the addition of poloxamer 407 to mß-TCP might be considered a potential therapeutic application for the repair and regeneration of bone defects.


Assuntos
Fosfatos de Cálcio , Poloxâmero , Poloxâmero/farmacologia , Fosfatos de Cálcio/farmacologia , Fosfatos de Cálcio/química , Cimentos Ósseos/farmacologia , Cimentos Ósseos/química , Hidroxiapatitas
5.
Biosensors (Basel) ; 13(11)2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37998145

RESUMO

In this study, an impedance biosensor capable of real-time monitoring of the growth and drug reactions using NIH/3T3 cells was fabricated through a semiconductor process. With the fabricated impedance biosensor, the cell growth and drug reaction states are monitored in real-time, showing the validness of the developed biosensor. By using the developed impedance biosensor, we have investigated the capacitance contribution of NIH/3T3 cells existing on electrodes and between electrodes. To compare the capacitance value contributions of the cells on and between electrodes, wide- and narrow-gap electrode patterns are manufactured with 3.7 and 0.3 mm electrode gap spacings, respectively. From the detailed analysis, the capacitance contributions of NIH/3T3 cells existing on electrodes are estimated around less than 20 percent compared to the cells existing between electrodes. In other words, a minimized electrode area with maximized electrode spacing is the promising impedance biosensor design guide for accurate cell capacitance measurements.


Assuntos
Técnicas Biossensoriais , Animais , Camundongos , Impedância Elétrica , Eletrodos , Capacitância Elétrica , Células 3T3
6.
Nanomicro Lett ; 16(1): 33, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38015283

RESUMO

Supported nanoparticles have attracted considerable attention as a promising catalyst for achieving unique properties in numerous applications, including fuel cells, chemical conversion, and batteries. Nanocatalysts demonstrate high activity by expanding the number of active sites, but they also intensify deactivation issues, such as agglomeration and poisoning, simultaneously. Exsolution for bottom-up synthesis of supported nanoparticles has emerged as a breakthrough technique to overcome limitations associated with conventional nanomaterials. Nanoparticles are uniformly exsolved from perovskite oxide supports and socketed into the oxide support by a one-step reduction process. Their uniformity and stability, resulting from the socketed structure, play a crucial role in the development of novel nanocatalysts. Recently, tremendous research efforts have been dedicated to further controlling exsolution particles. To effectively address exsolution at a more precise level, understanding the underlying mechanism is essential. This review presents a comprehensive overview of the exsolution mechanism, with a focus on its driving force, processes, properties, and synergetic strategies, as well as new pathways for optimizing nanocatalysts in diverse applications.

7.
Adv Sci (Weinh) ; 10(30): e2302380, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37712147

RESUMO

Neuromorphic hardware with a spiking neural network (SNN) can significantly enhance the energy efficiency for artificial intelligence (AI) functions owing to its event-driven and spatiotemporally sparse operations. However, an artificial neuron and synapse based on complex complementary metal-oxide-semiconductor (CMOS) circuits limit the scalability and energy efficiency of neuromorphic hardware. In this work, a neuromorphic module is demonstrated composed of synapses over neurons realized by monolithic vertical integration. The synapse at top is a single thin-film transistor (1TFT-synapse) made of poly-crystalline silicon film and the neuron at bottom is another single transistor (1T-neuron) made of single-crystalline silicon. Excimer laser annealing (ELA) is applied to activate dopants for the 1TFT-synapse at the top and rapid thermal annealing (RTA) is applied to do so for the 1T-neuron at the bottom. Internal electro-thermal annealing (ETA) via the generation of Joule heat is also used to enhance the endurance of the 1TFT-synapse without transferring heat to the 1T-neuron at the bottom. As neuromorphic vision sensing, classification of American Sign Language (ASL) is conducted with the fabricated neuromorphic module. Its classification accuracy on ASL is ≈92.3% even after 204 800 update pulses.

8.
Microbiol Immunol ; 67(10): 456-467, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37525428

RESUMO

Defensins and inflammation are innate immune barriers of the body against infectious pathogens. Searching for a compound that can inhibit infectious diseases by affecting human ß-defensin (HBD) and proinflammatory cytokines is the new trend in research to control bacterial infection. The aim of this study is to provide a natural compound, Filipendula glaberrima Nakai extract (FGE), which is able to induce the expression of an antimicrobial defensin as well as reduce inflammation. FGE induced the expression of HBD2 and HBD3 through activating both p38 and NF-κB signaling pathways. Furthermore, FGE inhibited the expression of TNF-α and IL-6 via p38 and NF-κB pathways in Staphylococcus aureus-stimulated THP1 cells. Injection of FGE alleviated cutaneous erythema and swelling caused by S. aureus injection in mice ears. Taken together, FGE could reduce bacterial infection by inducing the expression of defensin and anti-inflammatory activity.


Assuntos
Infecções Bacterianas , Filipendula , beta-Defensinas , Animais , Camundongos , Humanos , NF-kappa B/metabolismo , Células Cultivadas , Staphylococcus aureus , beta-Defensinas/metabolismo , Inflamação/tratamento farmacológico
9.
Curr Issues Mol Biol ; 45(7): 5950-5966, 2023 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-37504292

RESUMO

Saussurea neoserrata Nakai offers a reliable and efficient source of antioxidants that can help alleviate adverse skin reactions triggered by air pollutants. Air pollutants, such as particulate matter (PM), have the ability to infiltrate the skin and contribute to the higher occurrence of cardiovascular, cerebrovascular, and respiratory ailments. Individuals with compromised skin barriers are particularly susceptible to the impact of PM since it can be absorbed more readily through the skin. This study investigated the impact of protocatechuic acid and syringin, obtained from the n-BuOH extract of S. neoserrata Nakai, on the release of PGE2 and PGD2 induced by PM10. Additionally, it examined the gene expression of the synthesis of PGE2 and PGD2 in human keratinocytes. The findings of this research highlight the potential of utilizing safe and efficient plant-derived antioxidants in dermatological and cosmetic applications to mitigate the negative skin reactions caused by exposure to air pollution.

10.
Curr Opin Immunol ; 82: 102323, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37028221

RESUMO

Single-cell technologies have revealed the extensive heterogeneity and complexity of the immune system. Systems biology approaches in immunology have taken advantage of the high-parameter, high-throughput data and analyzed immune cell types in a 'bottom-up' data-driven method. This approach has discovered previously unrecognized cell types and functions. Especially for human immunology, in which experimental manipulations are challenging, systems approach has become a successful means to investigate physiologically relevant contexts. This review focuses on the recent findings in lymphocyte biology, from their development, differentiation into subsets, and heterogeneity in their functions, enabled by these systems approaches. Furthermore, we review examples of the application of findings from systems approach studies and discuss how now to leave the rich dataset in the curse of high dimensionality.


Assuntos
Sistema Imunitário , Biologia de Sistemas , Humanos , Subpopulações de Linfócitos , Diferenciação Celular , Contagem de Linfócitos
11.
Nano Lett ; 23(8): 3334-3343, 2023 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-37068052

RESUMO

Obtaining the heterogeneous conformation of small proteins is important for understanding their biological role, but it is still challenging. Here, we developed a multi-tilt nanoparticle-aided cryo-electron microscopy sampling (MT-NACS) technique that enables the observation of heterogeneous conformations of small proteins and applied it to calmodulin. By imaging the proteins labeled by two gold nanoparticles at multiple tilt angles and analyzing the projected positions of the nanoparticles, the distributions of 3D interparticle distances were obtained. From the measured distance distributions, the conformational changes associated with Ca2+ binding and salt concentration were determined. MT-NACS was also used to track the structural change accompanied by the interaction between amyloid-beta and calmodulin, which has never been observed experimentally. This work offers an alternative platform for studying the functional flexibility of small proteins.


Assuntos
Calmodulina , Nanopartículas Metálicas , Microscopia Crioeletrônica/métodos , Ouro/química , Nanopartículas Metálicas/química , Conformação Proteica
12.
Molecules ; 28(6)2023 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-36985716

RESUMO

Both defensin and inflammation are part of the human innate immune system that responds rapidly to pathogens. The combination of defensins with pro- or anti-inflammatory effects can be a potential research direction for the treatment of infection by pathogens. This study aimed to identify whether MSF (Miracle Synergy material made using Filipendula glaberrima), a probiotic lysate of Filipendula glaberrima extracts fermented with Lactiplantibacillus plantarum K8, activates the expression of human ß-defensin (HBD2 and HBD3) to protect the host against pathogens and inhibit inflammation caused by S. aureus, in vitro with Western blot analysis, qRT-PCR and in vivo studies with a mouse model were used to evaluate the effects of MSF. The MSF treatment induced HBD2 and HBD3 expression via the p38 and NF-κB pathways. Furthermore, MSF treatment significantly reduced the expression of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6, and IL-8), also through p38 and NF-κB in S. aureus-induced inflammatory condition. MSF treatment remarkably reduced erythema in mice ears caused by the injection of S. aureus, while K8 lysate treatment did not initiate a strong recovery. Taken together, MSF induced the expression of HBD2 and HDB3 and activated anti-inflammatory activity more than the probiotic lysates of L. plantarum K8. These findings show that MSF is a potential defensin inducer and anti-inflammatory agent.


Assuntos
NF-kappa B , beta-Defensinas , Animais , Camundongos , Humanos , NF-kappa B/metabolismo , beta-Defensinas/metabolismo , Peptídeos Antimicrobianos , Staphylococcus aureus , Células Cultivadas , Transdução de Sinais , Inflamação/tratamento farmacológico
13.
J Korean Acad Nurs ; 53(1): 87-100, 2023 Feb.
Artigo em Coreano | MEDLINE | ID: mdl-36898687

RESUMO

PURPOSE: This study aimed to develop a nursing simulation learning module for coronavirus disease 2019 (COVID-19) patient-care and examine its effects on clinical reasoning competence, clinical competence, performance confidence, and anxiety in COVID-19 patient care for nursing students. METHODS: A non-equivalent control group pre- and post-test design was employed. The study participants included 47 nursing students (23 in the experimental group and 24 in the control group) from G City. A simulation learning module for COVID-19 patient-care was developed based on the Jeffries simulation model. The module consisted of a briefing, simulation practice, and debriefing. The effects of the simulation module were measured using clinical reasoning competence, clinical competence, performance confidence, and anxiety in COVID-19 patient-care. Data were analyzed using χ²-test, Fisher's exact test, t-test, Wilcoxon signed-rank test, and Mann-Whitney U test. RESULTS: The levels of clinical reasoning competence, clinical competence, and performance confidence of the experimental group were significantly higher than that of the control group, and the level of anxiety was significantly low after simulation learning. CONCLUSION: The nursing simulation learning module for COVID-19 patient-care is more effective than the traditional method in terms of improving students' clinical reasoning competence, clinical competence, and performance confidence, and reducing their anxiety. The module is expected to be useful for educational and clinical environments as an effective teaching and learning strategy to empower nursing competency and contribute to nursing education and clinical changes.


Assuntos
COVID-19 , Bacharelado em Enfermagem , Estudantes de Enfermagem , Humanos , Competência Clínica , Ansiedade , Assistência ao Paciente , Bacharelado em Enfermagem/métodos
14.
J Environ Manage ; 335: 117493, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-36822047

RESUMO

Despite the identification of numerous bioplastic-degrading bacteria, the inconsistent rate of bioplastic degradation under differing cultivation conditions limits the intercomparison of results on biodegradation kinetics. In this study, we isolated a poly (Ɛ-caprolactone) (PCL)-degrading bacterium from a plastic-contaminated landfill and determined the principle-based biodegradation kinetics in a confined model system of varying cultivation conditions. Bacterial degradation of PCL films synthesized by different polymer number average molecular weights (Mn) and concentrations (% w/v) was investigated using both solid and liquid media at various temperatures. As a result, the most active gram-negative bacterial strain at ambient temperature (28 °C), designated CY2-9, was identified as Aquabacterium sp. Based on 16 S rRNA gene analysis. A clear zone around the bacterial colony was apparently exhibited during solid cultivation, and the diameter sizes increased with incubation time. During biodegradation processes in the PCL film, the thermal stability declined (determined by TGA; weight changes at critical temperature), whereas the crystalline proportion increased (determined by DSC; phase transition with temperature increment), implying preferential degradation of the amorphous region in the polymer structure. The surface morphologies (determined by SEM; electron optical system) were gradually hydrolyzed, creating destruction patterns as well as alterations in functional groups on film surfaces (determined by FT-IR; infrared spectrum of absorption or emission). In the kinetic study based on the weight loss of the PCL film (4.5 × 104 Da, 1% w/v), ∼1.5 (>±0.1) × 10-1 day-1 was obtained from linear regression for both solid and liquid media cultivation at 28 °C. The biodegradation efficiencies increased proportionally by a factor of 2.6-7.9, depending on the lower polymer number average molecular weight and lower concentration. Overall, our results are useful for measuring and/or predicting the degradation rates of PCL films by microorganisms in natural environments.


Assuntos
Plásticos , Poliésteres , Poliésteres/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Cinética , Polímeros , Bactérias/metabolismo
15.
Sci Rep ; 13(1): 530, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-36631494

RESUMO

Glaucoma is a multifactorial disease where various systemic features are involved in the progression of the disease. Based on initial systemic profiles in electronic medical records, this study aimed to develop a model predicting factors of long-term rapid retinal nerve fiber layer (RNFL) thinning over 5 years in 505 patients with primary open-angle glaucoma. Eyes with faster or slower RNFL thinning were stratified using a decision tree model, and systemic and ophthalmic data were incorporated into the models based on random forest and permutation methods, with the models interpreted by Shapley additive explanation plots (SHAP). According to the decision tree, a higher lymphocyte ratio (> 34.65%) was the most important systemic variable discriminating faster or slower RNFL thinning. Higher mean corpuscular hemoglobin (> 32.05 pg) and alkaline phosphatase (> 88.0 IU/L) concentrations were distinguishing factors in the eyes with lymphocyte ratios > 34.65% and < 34.65%, respectively. SHAP demonstrated larger baseline RNFL thickness, greater fluctuation of intraocular pressure (IOP), and higher maximum IOP as the strongest ophthalmic factors, while higher lymphocyte ratio and higher platelet count as the strongest systemic factors associated with faster RNFL thinning. Machine learning-based modeling identified several systemic factors as well as previously acknowledged ophthalmic risk factors associated with long-term rapid RNFL thinning.


Assuntos
Glaucoma de Ângulo Aberto , Glaucoma , Disco Óptico , Humanos , Glaucoma de Ângulo Aberto/epidemiologia , Glaucoma de Ângulo Aberto/complicações , Registros Eletrônicos de Saúde , Campos Visuais , Tomografia de Coerência Óptica/métodos , Células Ganglionares da Retina , Glaucoma/complicações , Pressão Intraocular , República da Coreia/epidemiologia , Progressão da Doença
16.
Neoplasia ; 35: 100862, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36508876

RESUMO

Intrinsic or acquired radioresistance often limits the efficacy of radiation therapy (RT), thereby leading to local control failure. Cancerous cells have abnormal pH dynamics due to high metabolic demands, but it is unclear how pH dynamics contribute to radioresistance. In this study, we investigated the role of Na-H exchange 1 (NHE1), the major intracellular pH (pHi) regulator, in RT response. We observed that RT increased NHE1 expression and modulated pHi in MDA-MB-231 human breast cancer cells. When combined with RT, pharmacological NHE1 inhibition by 5-(N-Ethyl-N-isopropyl)amiloride (EIPA) reduced pHi and clonogenic survival. EIPA attenuated radiation-damaged DNA repair, increasing G2/M cell cycle arrest. The combination of EIPA and RT increased apoptotic cell death while decreasing phosphorylation of NF-κB p65. Similarly, the knockdown of NHE1 increased radiosensitivity with lower pHi and increased apoptosis. Consistent with in vitro data, the EIPA plus RT inhibited the growth of MDA-MB-231 xenograft tumors in mice to a greater extent than either EIPA or RT alone. EIPA abrogated the RT-induced increase in NHE1 and phospho-NF-κB p65 expression in tumor tissues. Such coincidence of increased NHE1 level, pHi, and NF-κB activation was also found in radioresistant MDA-MB-231 cells, which were reversed by EIPA treatment. Bioinformatics analysis of RNA sequencing data revealed that inhibiting NHE1 reversed three core gene networks that were up-regulated in radioresistant cells and correlated with high NHE1 expression in patient samples: NF-κB, senescence, and extracellular matrix. Taken together, our findings suggest that NHE1 contributes to RT resistance via NF-κB-mediated signaling networks, and NHE1 may be a promising target for improving RT outcomes.


Assuntos
Neoplasias da Mama , NF-kappa B , Humanos , Camundongos , Animais , Feminino , NF-kappa B/metabolismo , Trocadores de Sódio-Hidrogênio/genética , Trocadores de Sódio-Hidrogênio/metabolismo , Trocador 1 de Sódio-Hidrogênio/genética , Trocador 1 de Sódio-Hidrogênio/metabolismo , Amilorida/farmacologia , Apoptose , Neoplasias da Mama/genética , Neoplasias da Mama/radioterapia , Concentração de Íons de Hidrogênio
17.
Int J Mol Sci ; 23(24)2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36555180

RESUMO

Although the combination of radiotherapy and immunotherapy has proven to be effective in lung cancer treatment, it may not be sufficient to fully activate the antitumor immune response. Here, we investigated whether entinostat, a histone deacetylase inhibitor, could improve the efficacy of radiotherapy and anti-PD-1 in a murine syngeneic LL/2 tumor model. A total of 12 Gy of X-rays administered in two fractions significantly delayed tumor growth in mice, which was further enhanced by oral entinostat administration. Flow cytometry-aided immune cell profiling revealed that entinostat increased radiation-induced infiltration of myeloid-derived suppressor cells and CD8+ T cells with decreased regulatory T-cells (Tregs). Transcriptomics-based immune phenotype prediction showed that entinostat potentiated radiation-activated pathways, such as JAK/STAT3/interferon-gamma (IFN-γ) and PD-1/PD-L1 signaling. Entinostat augmented the antitumor efficacy of radiation and anti-PD-1, which may be related to an increase in IFN-γ-producing CD8+ T-cells with a decrease in Treg cells. Comparative transcriptomic profiling predicted that entinostat increased the number of dendritic cells, B cells, and T cells in tumors treated with radiation and anti-PD-1 by inducing MHC-II genes. In conclusion, our findings provided insights into how entinostat improves the efficacy of ionizing radiation plus anti-PD-1 therapy and offered clues for developing new strategies for clinical trials.


Assuntos
Carcinoma Pulmonar de Lewis , Inibidores de Histona Desacetilases , Animais , Camundongos , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Linfócitos T CD8-Positivos , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Imunomodulação , Imunidade , Interferon gama/farmacologia , Linhagem Celular Tumoral , Microambiente Tumoral
18.
Curr Microbiol ; 79(11): 340, 2022 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-36209171

RESUMO

Strain KSB-15 T was isolated from an orchard soil that had been contaminated with the insecticide dichlorodiphenyltrichloroethane for about 60 years. The 16S rRNA gene sequence of this strain showed the highest sequence similarities with those of Oleiharenicola alkalitolerans NVTT (95.3%), Opitutus terrae PB90-1 T (94.8%), and Oleiharenicola lentus TWA-58 T (94.7%) among type strains, which are members of the family Opitutaceae within the phylum Verrucomicrobia. Strain KSB-15 T was an obligate aerobe, Gram-negative, non-motile, coccoid or short rod with the cellular dimensions of 0.37-0.62 µm width and 0.43-0.72 µm length. The strain grew at temperatures between 15-37 °C (optimum, 25 °C), at a pH range of 5.0-11.0 (optimum, pH 6.0), and at a NaCl concentration of 0-3% (w/v) (optimum, 0%). It contained menaquinone-7 (MK-7) as the major isoprenoid quinone (94.1%), and iso-C15:0 (34.9%) and anteiso-C15:0 (29.0%) as the two major fatty acids. The genome of strain KSB-15 T was composed of one chromosome with a total size of 4,320,198 bp, a G + C content of 64.3%, 3,393 coding genes (CDS), 14 pseudogenes, and 52 RNA genes. The OrthoANIu values, In silico DDH values and average amino acid identities between strain KSB-15 T and the members of the family Opitutaceae were 71.6 ~ 73.0%, 19.0 ~ 19.9%, and 55.9 ~ 62.0%, respectively. On the basis of our polyphasic taxonomic study, we conclude that strain KSB-15 T should be classified as a novel genus of the family Opitutaceae, for which the name Horticcoccus luteus gen. nov., sp. nov. is proposed.The type strain is KSB-15 T (= KACC 22271 T = DSM 113638 T).


Assuntos
DDT , Inseticidas , Aminoácidos , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , Ácidos Graxos/química , Filogenia , Quinonas , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Cloreto de Sódio , Solo , Terpenos , Verrucomicrobia/genética , Vitamina K 2/química
19.
Sensors (Basel) ; 22(10)2022 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-35632228

RESUMO

The 5G networks aim to realize a massive Internet of Things (IoT) environment with low latency. IoT devices with weak security can cause Tbps-level Distributed Denial of Service (DDoS) attacks on 5G mobile networks. Therefore, interest in automatic network intrusion detection using machine learning (ML) technology in 5G networks is increasing. ML-based DDoS attack detection in a 5G environment should provide ultra-low latency. To this end, utilizing a feature-selection process that reduces computational complexity and improves performance by identifying features important for learning in large datasets is possible. Existing ML-based DDoS detection technology mostly focuses on DDoS detection learning models on the wired Internet. In addition, studies on feature engineering related to 5G traffic are relatively insufficient. Therefore, this study performed feature selection experiments to reduce the time complexity of detecting and analyzing large-capacity DDoS attacks in real time based on ML in a 5G core network environment. The results of the experiment showed that the performance was maintained and improved when the feature selection process was used. In particular, as the size of the dataset increased, the difference in time complexity increased rapidly. The experiments show that the real-time detection of large-scale DDoS attacks in 5G core networks is possible using the feature selection process. This demonstrates the importance of the feature selection process for removing noisy features before training and detection. As this study conducted a feature study to detect network traffic passing through the 5G core with low latency using ML, it is expected to contribute to improving the performance of the 5G network DDoS attack automation detection technology using AI technology.


Assuntos
Internet das Coisas , Aprendizado de Máquina
20.
Arch Virol ; 167(5): 1381-1385, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35397684

RESUMO

Porcine hemagglutinating encephalomyelitis virus (PHEV) is a member of the subgenus Embecovirus of the genus Betacoronavirus, and it is ubiquitously distributed in most pig-farming countries worldwide with low clinical incidence. Here, we report the full-length genome sequence and molecular characterization of a novel PHEV strain identified in diarrheic neonates in South Korea. The complete genome of the Korean PHEV strain GNU-2113 was sequenced and analyzed to characterize PHEV circulating in South Korea. The GNU-2113 genome was determined to be 29,982 nucleotides in length, with large unique deletions in the regions encoding nonstructural protein 3 and NS2. It was found to share 95.1-96.9% sequence identity with other global strains. Genetic and phylogenetic analysis indicated that the GNU-2113 strain is distantly related to the existing PHEV genotypes, implying that the virus appears to undergo substantial evolution under endemic pressure. This study provides important information about the genetic diversity of PHEV circulating subclinically in swine herds, which may ensure viral fitness in the enzootic environment.


Assuntos
Betacoronavirus 1 , Doenças dos Suínos , Animais , Betacoronavirus 1/genética , Genoma Viral , Genótipo , Filogenia , República da Coreia , Análise de Sequência de DNA , Suínos
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