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The recent theory-driven discovery of a class of clathrate hydrides (e.g., CaH6, YH6, YH9, and LaH10) with superconducting critical temperatures (Tc) well above 200 K has opened the prospects for "hot" superconductivity above room temperature under pressure. Recent efforts focus on the search for superconductors among ternary hydrides that accommodate more diverse material types and configurations compared to binary hydrides. Through extensive computational searches, we report the prediction of a unique class of thermodynamically stable clathrate hydrides structures consisting of two previously unreported H24 and H30 hydrogen clathrate cages at megabar pressures. Among these phases, LaSc2H24 shows potential hot superconductivity at the thermodynamically stable pressure range of 167 to 300 GPa, with calculated Tcs up to 331 K at 250 GPa and 316 K at 167 GPa when the important effects of anharmonicity are included. The very high critical temperatures are attributed to an unusually large hydrogen-derived density of states at the Fermi level arising from the newly reported peculiar H30 as well as H24 cages in the structure. Our predicted introduction of Sc in the La-H system is expected to facilitate future design and realization of hot superconductors in ternary clathrate superhydrides.
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The discovery of novel antitumor agents derived from natural plants is a principal objective of anticancer drug research. Frankincense, a widely recognized natural antitumor medicine, has undergone a systematic review encompassing its species, chemical constituents, and diverse pharmacological activities and mechanisms. The different species of frankincense include Boswellia serrata, Somali frankincense, Boswellia frereana, and Boswellia arabica. Various frankincense extracts and compounds exhibit antitumor, anti-inflammatory, and hepatoprotective properties and antioxidation, memory enhancement, and immunological regulation capabilities. They also have comprehensive effects on regulating flora. Frankincense and its principal chemical constituents have demonstrated promising chemoprophylactic and therapeutic abilities against tumors. This review provides a systematic summary of the mechanism of action underlying the antitumor effects of frankincense and its major constituents, thus laying the foundations for developing effective tumor-combating targets.
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Franquincenso , Humanos , Franquincenso/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/químicaRESUMO
Hydrides are promising candidates for achieving room-temperature superconductivity, but a formidable challenge remains in reducing the stabilization pressure below a megabar. In this study, we successfully synthesized a ternary lanthanum borohydride by introducing the nonmetallic element B into the La-H system, forming robust B-H covalent bonds that lower the pressure required to stabilize the superconducting phase. Electrical transport measurements confirm the presence of superconductivity with a critical temperature (Tc) of up to 106 K at 90 GPa, as evidenced by zero resistance and Tc shift under an external magnetic field. X-ray diffraction and transport measurements identify the superconducting compound as LaB2H8, a nonclathrate hydride, whose crystal structure remains stable at pressures as low as â¼ half megabar (59 GPa). Stabilizing superconductive stoichiometric LaB2H8 in a submegabar pressure regime marks a substantial advancement in the quest for high-Tc superconductivity in polynary hydrides, bringing us closer to the ambient pressure conditions.
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OBJECTIVES: The high prevalence of antibiotic-resistant bacteria poses a threat to the global public health. The appropriate use of adjuvants to restore the antimicrobial activity of antibiotics against resistant bacteria could be an effective strategy for combating antibiotic resistance. In this study, we investigated the counteraction of Triton X-100 (TX-100) and the mechanisms underlying the antibiotic resistance of Enterococcus faecalis (E. faecalis). METHODS: Standard, wild-type (WT), and induced antibiotic-resistant E. faecalis strains were used in this study. In vitro antibacterial experiments were conducted to evaluate the antimicrobial activities of gentamicin sulfate and ciprofloxacin hydrochloride in the presence and absence of 0.02 % TX-100 against both planktonic and biofilm bacteria. Transcriptomic and untargeted metabolomic analyses were performed to explore the molecular mechanisms of TX-100 as an antibiotic adjuvant. Additionally, membrane permeability, membrane potential, glycolysis-related enzyme activity, intracellular adenosine triphosphate (ATP), and expression levels of virulence genes were assessed. The biocompatibility of different drug combinations was also evaluated. RESULTS: A substantially low TX-100 concentration improved the antimicrobial effects of gentamicin sulfate or ciprofloxacin hydrochloride against antibiotic-resistant E. faecalis. Mechanistic studies demonstrated that TX-100 increased cell membrane permeability and dissipated membrane potential. Moreover, antibiotic resistance and pathogenicity of E. faecalis were attenuated by TX-100 via downregulation of the ABC transporter, phosphotransferase system (PTS), and ATP supply. CONCLUSIONS: TX-100 enhanced the antimicrobial activity of gentamicin sulfate and ciprofloxacin hydrochloride at a low concentration by improving antibiotic susceptibility and attenuating antibiotic resistance and pathogenicity of E. faecalis. CLINICAL SIGNIFICANCE: These findings provide a theoretical basis for developing new root canal disinfectants that can reduce antibiotic resistance.
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Antibacterianos , Biofilmes , Ciprofloxacina , Farmacorresistência Bacteriana , Enterococcus faecalis , Gentamicinas , Testes de Sensibilidade Microbiana , Octoxinol , Enterococcus faecalis/efeitos dos fármacos , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Ciprofloxacina/farmacologia , Gentamicinas/farmacologia , Octoxinol/farmacologia , Permeabilidade da Membrana Celular/efeitos dos fármacos , Humanos , Trifosfato de Adenosina/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Glicólise/efeitos dos fármacosRESUMO
Profiting from the sustained clinical improvement and prolonged patient survival, immune checkpoint blockade of programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis has emerged as a revolutionary cancer therapy approach. However, the anti-PD-1/PD-L1 antibodies only achieve a clinical response rate of approximately 20%. Herein, we identified a novel combination strategy that Chinese medicine ginseng-derived ginsenoside Rh2 (Rh2) markedly improved the anti-cancer efficacy of anti-PD-L1 antibody in mice bearing MC38 tumor. Rh2 combined with anti-PD-L1 antibody (combo treatment) further triggered the infiltration, proliferation and activation of CD8+ T cells in the tumor microenvironment (TME). Depletion of CD8+ T cells by mouse CD8 blocking antibody abolished the anti-cancer effect of combo treatment totally. Mechanistically, combo treatment further increased the expression of CXCL10 through activating TBK1-IRF3 signaling pathway, explaining the increased infiltration of T cells. Employing anti- CXC chemokine receptor 3 (CXCR3) blocking antibody prevented the T cells infiltration and abolished the anti-cancer effect of combo treatment. Meanwhile, combo treatment increased the percentage of M1-like macrophages and raised the ratio of M1/M2 macrophages in TME. By comparing the anti-cancer effect of combo treatment among MC38, CT26 and 4T1 tumors, resident T cells were considered as a prerequisite for the effectiveness of combo treatment. These findings demonstrated that Rh2 potentiated the anti-cancer effect of PD-L1 blockade via promoting the T cells infiltration and activation, which shed a new light on the combination strategy to enhance anti-PD-L1 immunotherapy by using natural product Rh2.
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Antígeno B7-H1 , Linfócitos T CD8-Positivos , Humanos , Animais , Camundongos , Linhagem Celular Tumoral , Imunoterapia , Microambiente Tumoral , Quimiocina CXCL10/farmacologiaRESUMO
Traditional Chinese medicine (TCM) has been widely used for cancer treatment. Identification of anti-cancer targets of TCM is the first and principal step in discovering molecular mechanisms of TCM as well as obtaining novel targets for cancer therapy. In this study, glycogen phosphorylase L (PYGL) was identified as one of the targeted proteins for several TCMs and was upregulated in various cancer types. The expression level of PYGL was positively correlated with the stage of lung cancer and the poor prognosis of patients. Meanwhile, knockdown of PYGL significantly inhibited proliferation and migration in lung cancer cells. In addition, PYGL was associated with spindle, kinetochore, and microtubule, the cellular components that are closely related to mitosis, in lung cancer. Moreover, PYGL was more susceptible to be upregulated by 144 mutated genes. Taken together, PYGL is a potential target for lung cancer treatment and its molecular mechanism probably influences the mitotic function of cells by regulating energy metabolism.
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Glicogênio Fosforilase , Neoplasias Pulmonares , Humanos , Glicogênio Fosforilase/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genéticaRESUMO
OBJECTIVES: N6-methyladenosine (m6A) and long non-coding RNAs (lncRNAs) significantly impact the prognosis and the response to immunotherapy in head and neck squamous cell carcinoma (HNSCC). Therefore, this study aimed to develop an m6A-related lncRNA (m6AlncRNA) model for predicting the prognosis and the immunotherapeutic response in HNSCC. METHODS: We identified the m6AlncRNAs and constructed a risk assessment signature by using univariable Cox, Least Absolute Shrinkage and Selection Operator (LASSO), and multivariate Cox regression analyses. The Kaplan-Meier analysis, receiver-operating characteristic (ROC) curves, principal component analysis (PCA), decision curve analysis (DCA), consistency index (C-index), and nomogram were applied to assess the risk model. Finally, we investigated the predictability of this model in prognosis and response to immunotherapy and evaluated various novel compounds for the clinical treatment of HNSCC. RESULTS: HNSCC patients were assigned to high- and low-risk groups based on the median risk scores, and the high- and low-risk groups had different clinical features, tumor immune infiltration status, tumor immune dysfunction and exclusion (TIDE), tumor mutational burden (TMB), sensitivity to novel potential compounds, and immunotherapeutic response. CONCLUSIONS: The model we developed was accurate and efficient in predicting the prognosis of patients with HNSCC. It was also sensitive in stratifying HNSCC patients with good response to immunotherapy. Therefore, our study provided insight into elucidating the processes and mechanisms of m6AlncRNAs.
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Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous malignancy with poor prognosis. This article aims to explore the clinical significance of cell differentiation trajectory in HNSCC, identify different molecular subtypes by consensus clustering analysis, and develop a prognostic risk model on the basis of differentiation-related genes (DRGs) for predicting the prognosis of HNSCC patients. Firstly, cell trajectory analysis was performed on single-cell RNA sequencing (scRNA-seq) data, four molecular subtypes were identified from bulk RNA-seq data, and the molecular subtypes were predictive of patient survival, clinical features, immune infiltration status, and expression of immune checkpoint genes (ICGs)s. Secondly, we developed a 10-DRG signature for predicting the prognosis of HNSCC patients by using weighted correlation network analysis (WGCNA), differential expression analysis, univariate Cox regression analysis, and multivariate Cox regression analysis. Then, a nomogram integrating the risk assessment model and clinical features can successfully predict prognosis with favorable predictive performance and superior accuracy. We projected the response to immunotherapy and the sensitivity of commonly used antitumor drugs between the different groups. Finally, we used the quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) analysis and western blot to verify the signature. In conclusion, we identified distinct molecular subtypes by cell differentiation trajectory and constructed a novel signature based on differentially expressed prognostic DRGs, which could predict the prognosis and response to immunotherapy for patients and may provide valuable clinical applications in the treatment of HNSCC.
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Neoplasias de Cabeça e Pescoço , Imunoterapia , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Prognóstico , Fatores Imunológicos , Diferenciação Celular/genética , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/terapiaRESUMO
Background: Rheumatoid arthritis (RA) is recognized as a chronic inflammatory disease featured by pathological synovial inflammation. Currently, the underlying pathophysiological mechanisms of RA remain unclear. In the study, we attempted to explore the underlying mechanisms of RA and provide potential targets for the therapy of RA via bioinformatics analysis. Methods: We downloaded four microarray datasets (GSE77298, GSE55235, GSE12021, and GSE55457) from the GEO database. Firstly, GSE77298 and GSE55457 were identified DEGs by the "limma" and "sva" packages of R software. Then, we performed GO, KEGG, and GSEA enrichment analyses to further analyze the function of DEGs. Hub genes were screened using LASSO analysis and SVM-RFE analysis. To further explore the differences of the expression of hub genes in healthy control and RA patient synovial tissues, we calculated the ROC curves and AUC. The expression levels of hub genes were verified in synovial tissues of normal and RA rats by qRT-PCR and western blot. Furthermore, the CIBERSORTx was implemented to assess the differences of infiltration in 22 immune cells between normal and RA synovial tissues. We explored the association between hub genes and infiltrating immune cells. Results: CRTAM, CXCL13, and LRRC15 were identified as RA's potential hub genes by machine learning and LASSO algorithms. In addition, we verified the expression levels of three hub genes in the synovial tissue of normal and RA rats by PCR and western blot. Moreover, immune cell infiltration analysis showed that plasma cells, T follicular helper cells, M0 macrophages, M1 macrophages, and gamma delta T cells may be engaged in the development and progression of RA. Conclusions: In brief, our study identified and validated that three hub genes CRTAM, CXCL13, and LRRC15 might involve in the pathological development of RA, which could provide novel perspectives for the diagnosis and treatment with RA.
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Artrite Reumatoide , Redes Reguladoras de Genes , Ratos , Animais , Ontologia Genética , Redes Reguladoras de Genes/genética , Perfilação da Expressão Gênica , Transcriptoma/genética , Artrite Reumatoide/metabolismo , Biologia ComputacionalRESUMO
OBJECTIVE: Rheumatoid arthritis (RA) is considered to be a chronic immune disease pathologically characterized by synovial inflammation and bone destruction. At present, the potential pathogenesis of RA is still unclear. Hub genes are recognized to play a pivotal role in the occurrence and progression of RA. METHODS: Firstly, we attempted to screen hub genes that are associated with RA, to clarify the underlying pathological mechanisms of RA, and to offer potential treatment methods for RA. We acquired these datasets (GSE12021, GSE55235, and GSE55457) of RA patients and healthy samples from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were recognized via R software. Then, Gene ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were utilized to deeply explore the underlying biological functions and pathways closely associated with RA. In addition, a protein-protein interaction (PPI) network was built to further evaluate and screen for hub genes. Finally, on the basis of the results of PPI analysis, we confirmed the mRNA expression levels of five hub genes in the synovial tissue of rats modeled with RA. RESULTS: In the human microarray datasets, LCK, JAK2, SOCS3, STAT1, and EGFR were identified as hub genes associated with RA by bioinformatics analysis. Furthermore, we verified the differential expression levels of hub genes in rat synovial tissues via qRT-PCR (P < 0.05). CONCLUSIONS: Our findings suggest that the hub genes LCK, JAK2, SOCS3, STAT1, and EGFR might have vital roles in the progression of RA and may offer novel therapeutic treatments for RA.
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BACKGROUND: Rheumatoid arthritis (RA) is a chronic disease which is characterized by a circadian variation of key clinical symptoms and findings, with prominent joint swelling, stiffness and pain occurring in the early morning and light clinical symptoms during the day. Chrono-moxibustion is carried out at different time, which could result in dissimilar therapeutic effects. However, its efficacy has seldom been systematically demonstrated and few studies have reported that Chrono-moxibustion may regulate the circadian rhythm of RA. We therefore designed a randomized trial to explore the effective difference of Chrono-moxibustion in RA treatment, as well as to study its influence on circadian rhythm of RA patients. METHODS: This study is a randomized controlled trial involving 120 participants, and a total of 90 eligible RA patients will be randomly allocated to three groups in a 1:1:1 ratio as moxibustion at 7 to 9 am, moxibustion at 5 to 7 pm, and waiting list group, meanwhile, 30 healthy people will be divided into the control group. Patients in moxibustion groups will be treated for 30 minutes per session, 3 times a week, lasting 6 weeks. All of RA patients will be evaluated with questionnaires and laboratory tests before treatment, as well as 3 weeks, 6 weeks, and 3 months after treatment. One way analysis of variance (ANOVA) with multiple comparisons will be applied to identify differences more than two groups. Halberg cosiner software will be used to analysis the circadian rhythm. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: This study will provide evidence-based evidence for the effective difference of Chrono-moxibustion in RA treatment and its influence on circadian rhythm of RA patients.
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Artrite Reumatoide , Moxibustão , Artrite Reumatoide/etiologia , Artrite Reumatoide/terapia , Doença Crônica , Ritmo Circadiano , Humanos , Moxibustão/métodos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: The clinical symptoms of rheumatoid arthritis (RA) have significant circadian rhythms, with morning stiffness and joint pain. Moxibustion is effective in the treatment of RA, while the underlying therapeutic mechanisms remain limited. Thus, we explored whether moxibustion could adjust the circadian rhythm of RA by modulating the core clock genes CLOCK and BMAL1 at the molecular level. METHODS: 144 Sprague Dawley rats were randomly divided into four groups: control group (group A), model group (group B), 7-9 am moxibustion treatment group (group C), and 5-7 pm moxibustion treatment group (group D). Each group was divided into 6 time points (0 am, 4 am, 8 am, 12 N, 6 pm, and 8 pm) with an equal number of rats at each time point. Except for group A, all rats were injected with Freund's Complete Adjuvant (FCA) 0.15 ml on the right foot pad to establish the RA model. The rats of the two moxibustion treatment groups were respectively subjected to moxibustion at 7-9 am and 5-7 pm. After 3 weeks of treatment, the tissues were collected at 6 time points during the next 24 hours. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to test the mRNA expression of CLOCK and BMAL1 in the hypothalamus and synovial tissues. CLOCK and BMAL1 protein expression in synovial tissues were detected with western blot. RESULTS: Compared to group A, group B showed significantly down-regulated expression levels of CLOCK and BMLA1 at synovial tissue (P < 0.05), while no statistically significant difference was found in the hypothalamus (P > 0.05). The expression levels of CLOCK and BMLA1 were up-regulated in the moxibustion treatment groups in different tissues, especially in synovial tissue (P < 0.05) compared to group B. Nevertheless, no difference was observed between groups C and D (P > 0.05). CONCLUSIONS: Moxibustion could treat RA by modulating clock core genes CLOCK and BMAL1 to regulate the circadian rhythm. However, there was no significant difference between the 7-9 am moxibustion treatment group and the 5-7 pm moxibustion treatment group. This study provides a basis for research on moxibustion in the treatment of RA.
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BACKGROUND: Non-tumor tissue has a significant impact on the prognosis of head and neck squamous cell carcinoma (HNSCC). Previous studies for HNSCC have mainly focused on tumor tissue, greatly neglecting the role of non-tumor tissue. This study aimed to identify HNSCC subtypes and prognostic gene sets based on activity changes of immunologic and hallmark gene sets in tumor and adjacent non-tumor tissues to improve patient prognosis. METHODS: In the study, we used gene set variation analysis (GSVA) to estimate the relative enrichment of gene sets over the sample population, and identified relevant subtypes of HNSCC by Cox regression analysis and the non-negative matrix factorization (NMF) method. The representative gene sets were identified by calculating the differential enrichment score of gene sets between each of the two subgroups, intersecting them, and screening them using univariate Cox regression analysis. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to screen out potential prognostic gene sets and establish a risk model. Finally, genes encompassed in each prognostic gene set were obtained and subjected to enrichment analysis and protein-protein interaction (PPI) in tumor and non-tumor tissues. RESULTS: We identified three subtypes of HNSCC based on gene sets in tumor and non-tumor tissues, and patients with subtype 1 had a higher survival rate than subtypes 2 and 3. The subtypes were related to the survival status, pathological stage, and T stage of HNSCC patients. In total 450 differentially gene sets and 39 representative gene sets were obtained by calculating the differential enrichment score of gene sets between each of the two subgroups, intersecting them, and screening them using univariate Cox regression analysis. The prognostic model was constructed by LASSO regression analysis, including five prognostic gene sets. Kaplan-Meier analysis indicated that different risk groups and the five prognostic gene sets were associated with survival status in the model. Finally, enrichment analysis and PPI indicated that non-tumor and tumor tissues affect the prognosis of HNSCC patients in different ways. CONCLUSION: In conclusion, we provide a novel insight for rational treatment strategies and precise prognostic assessments based on tumor and adjacent non-tumor tissues, suggesting that more emphasis should be placed on changes in adjacent non-tumor and tumor tissues, rather than just the tumor itself.
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Programmed death ligand-1 (PD-L1) and indoleamine 2, 3-dioxygenase 1 (IDO1) are immune checkpoints induced by interferon-γ (IFN-γ) in the tumor microenvironment, leading to immune escape of tumors. Myricetin (MY) is a flavonoid distributed in many edible and medicinal plants. In this study, MY was identified to inhibit IFN-γ-induced PD-L1 expression in human lung cancer cells. It also reduced the expression of IDO1 and the production of kynurenine which is the product catalyzed by IDO1, while didn't show obvious effect on the expression of major histocompatibility complex-I (MHC-I), a crucial molecule for antigen presentation. In addition, the function of T cells was evaluated using a co-culture system consist of lung cancer cells and the Jurkat-PD-1 T cell line overexpressing PD-1. MY restored the survival, proliferation, CD69 expression and interleukin-2 (IL-2) secretion of Jurkat-PD-1 T cells suppressed by IFN-γ-treated lung cancer cells. Mechanistically, IFN-γ up-regulated PD-L1 and IDO1 at the transcriptional level through the JAK-STAT-IRF1 axis, which was targeted and inhibited by MY. Together, our research revealed a new mechanism of MY mediated anti-tumor activity and highlighted the potential implications of MY in tumor immunotherapy.
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Antígeno B7-H1/antagonistas & inibidores , Flavonoides/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Interferon gama/farmacologia , Neoplasias Pulmonares/metabolismo , Células A549 , Antígeno B7-H1/biossíntese , Antígeno B7-H1/genética , Técnicas de Cocultura , Relação Dose-Resposta a Droga , Regulação Neoplásica da Expressão Gênica/fisiologia , Células HCT116 , Células HEK293 , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/biossíntese , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Células Jurkat , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/fisiologiaRESUMO
The prevention and treatment of oral diseases is more difficult in diabetic patients with poorly controlled blood glucose levels. This study aims to explore an effective, low-cytotoxicity medication for root canal treatment in diabetic patients. The antibacterial effect of the combination of Triton X-100 (TX-100) and metformin (Met) on Enterococcus faecalis (E. faecalis) was evaluated by determining the minimum inhibitory concentration (MIC), minimum bactericidal concentration required to kill 99% bacteria (MBC99) and by conducting dynamic time-killing assays. While the antibiofilm activity was measured by crystal violet (CV) assay, field emission scanning electron microscope (FE-SEM), confocal laser scanning microscope (CLSM) and colony-forming unit (CFU) counting assays. The expression of relative genes was evaluated by real-time quantitative polymerase chain reaction (RT-qPCR), and the cytotoxicity of the new combination on MC3T3-E1 cell was also tested. Results showed that the antibacterial and antibiofilm activities of Met could be significantly enhanced by very low concentrations of TX-100 in both normal and high-glucose conditions, with a much lower cytotoxicity than 2% chlorhexidine (CHX). Thus, the TX-100 + Met combination may be developed as a promising and effective root canal disinfectant for patients with diabetes.
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BACKGROUND: As one of the effective pharmacological constituents of Ginseng Radix et Rhizoma, ginsenoside Rh2 (Rh2) exerts a remarkable anticancer effect on various cancer cell lines in vitro and strongly inhibits tumor growth in vivo without severe toxicity. OBJECTIVE: This article reviewed existing evidence supporting the anticancer effects of Rh2 to classify and conclude previous and current knowledge on the mechanisms and therapeutic effects of Rh2, as well as to promote the clinical application of this natural product. CONCLUSION: This article reviewed the anticancer efficacies and mechanisms of Rh2, including the induction of cell cycle arrest and programmed cell death, repression of metastasis, alleviation of drug resistance, and regulation of the immune system. Finally, this paper discussed the research and application prospects of Rh2.
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Ginsenosídeos , Panax , Apoptose , Pontos de Checagem do Ciclo Celular , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêuticoRESUMO
BACKGROUND: Gastric cancer (GC) is a considerable health burden around the world. Circular RNA Nance-Horan syndrome-like 1 (circNHSL1) is reported to be highly expressed in GC. Nevertheless, the function and molecule mechanism of circNHSL1 are still unclear. METHODS: The expression levels of circNHSL1, microRNA-149-5p (miR-149-5p) and YWHAZ were detected by real-time quantitative polymerase chain reaction (RT-qPCR). The subcellular fractionation identified the remarkable cytoplasmic localization of circNHSL1. Cell migration and invasion were measured by transwell assays. The levels of glutamine, glutamate and α-ketoglutarate (α-KG) were assessed by the corresponding kit. The protein levels of CD63, CD9, CD81, alanine, serine, cysteine-preferring transporter 2 (ASCT2), glutaminase 1 (GLS1), and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) were detected by Western blot assay. The binding relationship between miR-149-5p and circNHSL1 or YWHAZ was predicted by starBase 3.0 and then verified by RNA pull-down and dual-luciferase reporter assays. Xenograft tumor model examined the biological role of circNHSL1 in vivo. Exosomes were examined by a transmission electron microscope and nanoparticle tracking analysis (NTA). RESULTS: CircNHSL1 was highly expressed in GC cell-derived exosomes, GC tissues, and cells. Its knockdown impeded GC cell migration, invasion, and glutaminolysis. Mechanism analysis showed that circNHSL1 could affect YWHAZ expression by sponging miR-149-5p, thereby regulating GC progression. CircNHSL1 downregulation blocked GC tumor growth in vivo. CONCLUSION: Our studies disclosed that circNHSL1 knockdown repressed migration, invasion, and glutaminolysis in vitro and inhibited tumor growth in vivo by miR-149-5p/YWHAZ axis in GC, implying an underlying circRNA-targeted therapy for GC treatment.
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Polarization singularities have topological properties, because they can maintain their features invariably during propagation. The topological property can be destroyed by shifting the polarization singularities away from the central axis, and this destruction originates from the space separation of spin angular momentum components. We find that paired centrosymmetric off-axis polarization singularities can recover the topological property in the Fourier plane (reciprocal space), which belongs to the pseudo-topological property. We reveal that the pseudo-topological property is related to the invisible redistribution of both spin and orbital angular momentum states. We experimentally generate a series of Julia fractal vector optical fields with the pseudo-topological property. They may have potential applications in optical encryption and quantum information.
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Despite many decades of research of diodes, which are fundamental components of electronic and photoelectronic devices with p-n or Schottky junctions using bulk or 2D materials, stereotyped architectures and complex technological processing (doping and multiple material operations) have limited future development. Here, a novel rectification device, an orientation-induced diode, assembled using only few-layered black phosphorus (BP) is investigated. The key to its realization is to utilize the remarkable anisotropy of BP in low dimensions and change the charge-transport conditions abruptly along the different crystal orientations. Rectification ratios of 6.8, 22, and 115 can be achieved in cruciform BP, cross-stacked BP junctions, and BP junctions stacked with vertical orientations, respectively. The underlying physical processes and mechanisms can be explained using "orientation barrier" band theory. The theoretical results are experimentally confirmed using localized scanning photocurrent imaging. These orientation-induced optoelectronic devices open possibilities for 2D anisotropic materials with a new degree of freedom to improve modulation in diodes.