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1.
J Nanobiotechnology ; 22(1): 349, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902761

RESUMO

Repeated and widespread use of single chemical pesticides raises concerns about efficiency and safety, developing multi-component synergistic pesticides provides a new route for efficient control of diseases. Most commercial compound formulations are open systems with non-adjustable released rates, resulting in a high frequency of applications. Meanwhile, although nano pesticide delivery systems constructed with different carrier materials have been extensively studied, realizing their actual scale-up production still has important practical significance due to the large-scale field application. In this study, a boscalid and pyraclostrobin dual-loaded nano pesticide system (BPDN) was constructed with industrial-grade carrier materials to facilitate the realization of large-scale production. The optimal industrial-scale preparation mechanism of BPDN was studied with surfactants as key factors. When agricultural emulsifier No.600 and polycarboxylate are used as the ratio of 1:2 in the preparation process, the BPDN has a spherical structure with an average size of 270 nm and exhibits superior physical stability. Compared with commercial formulation, BPDN maintains rate-stabilized release up to 5 times longer, exhibits better dispersion and spreading performance on foliar, has more than 20% higher deposition amounts, and reduces loss. A single application of BPDN could efficiently control tomato gray mold during the growing period of tomatoes due to extended duration and combinatory effectiveness, reducing two application times and labor costs. Toxicology tests on various objects systematically demonstrated that BPDN has improved safety for HepG2 cells, and nontarget organism earthworms. This research provides insight into creating safe, efficient, and environmentally friendly pesticide production to reduce manual operation times and labor costs. Accompanied by production strategies that can be easily scaled up industrially, this contributes to the efficient use of resources for sustainable agriculture.


Assuntos
Praguicidas , Estrobilurinas , Praguicidas/química , Humanos , Portadores de Fármacos/química , Animais , Carbamatos/química , Tensoativos/química , Nanopartículas/química , Tamanho da Partícula , Solanum lycopersicum , Compostos de Bifenilo , Niacinamida/análogos & derivados
2.
Front Microbiol ; 15: 1405039, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38894972

RESUMO

Background: Pear black spot (PBS) is caused by Alternaria alternata and causes severe damage worldwide. It is particularly important to screen for synergistic fungicide combinations to address issues associated with the low efficacy of biocontrol agents, high dosage requirements and poor sustained effectiveness of chemical fungicides. Methods: In vitro and in vivo studies were performed to determine the efficacy of a treatment for this important disease. Additionally, transcriptomic and metabolomic analyses were performed to determine the main molecular and biochemical mechanisms involved in the interaction. Results: Bacillus tequilensis 2_2a has a significant synergistic effect with difenoconazole, causing hyphal entanglement and spore lysis and inhibiting the formation of PBS lesions in vitro. In the field, the control effect of the combination was greater than 95%. The pathways associated with the synergistic effect on the mycelia of A. alternata were divided into two main types: one included glycolysis, oxidative phosphorylation, and MAPK signal transduction, while the other included glycolysis, the TCA cycle, coenzyme A biosynthesis, sterol synthesis, and fatty acid degradation. Both types of pathways jointly affect the cell cycle. The main functions of the key genes and metabolites that have been verified as being affected are glucose synthesis and oxidative respiration, as well as citric acid synthesis, acetyl-CoA synthesis, and sterol synthesis. Both functions involve intracellular pyridine nucleotide metabolism and adenine nucleotide transformation. Conclusion: This study helps to reveal the synergistic mechanisms underlying the combined efficacy of biological and chemical agents, providing a scientific basis for field applications.

3.
Heliyon ; 10(11): e31676, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38845860

RESUMO

Background: Oral squamous cell carcinoma (OSCC) is one of the most prevalent kinds of cancers. Therefore, there is a pressing need to create a new risk scoring model to personalize the prognosis of OSCC patients and screen for patient-specific therapeutic agents and molecular targets. Methods: Firstly, A series of bioinformatics was performed to construct a novel ferroptosis-related prognostic model; Further, drug sensitivity analysis was used to screen for specific therapeutic agents for OSCC; Single-cell analysis was employed to investigate the enrichment of FRDEGs (ferroptosis-related differentially expressed genes) in the OSCC microenvironment; Finally, various experiments were conducted to screen and validate molecular therapeutic targets for OSCC. Results: In this study, we constructed a novel 10-FRDEGs risk scoring model. Base on the risk scoring model, we founded three potential chemotherapeutic agents for OSCC: 5Z)-7-Oxozeaenol, AT-7519, KIN001-266; In addition, FRDEGs were enriched in the epithelial cells of OSCC. Finally, we found that CA9 and CAV1 could regulate OSCC proliferation, migration and ferroptosis in vitro. Conclusion: A novel 10-FRDEGs risk scoring model can predict the prognosis of patients with OSCC.Further,5Z)-7-Oxozeaenol, AT-7519, KIN001-266 are potential chemotherapeutic agents for OSCC.Moreover, we identified CA9、CAV1 as potential molecular target for the treatment of OSCC.Our findings provide new directions for prognostic assessment and precise treatment of oral cell squamous carcinoma.

4.
Phytomedicine ; 128: 155488, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38493718

RESUMO

BACKGROUND: This research aimed to investigate the anti-tumor effects and underlying genetic mechanisms of herbal medicine Triphala (TRP) in oral squamous cell carcinoma (OSCC). METHODS: The target genes of Triphala (TRP) in oral squamous cell carcinoma (OSCC) were identified, and subsequent functional enrichment analysis was conducted to determine the enriched signaling pathways. Based on these genes, a protein-protein interaction network was constructed to identify the top 10 genes with the highest degree. Genes deregulated in OSCC tumor samples were identified to be hub genes among the top 10 genes. In vitro experiments were performed to investigate the influence of TRP extracts on the cell metabolic activity, migration, invasion, apoptosis, and proliferation of two OSCC cell lines (CAL-27 and SCC-9). The functional rescue assay was conducted to investigate the effect of applying the inhibitor and activator of an enriched pathway on the phenotypes of cancer cells. In addition, the zebrafish xenograft tumor model was established to investigate the influence of TRP extracts on tumor growth and metastasis in vivo. RESULTS: The target genes of TRP in OSCC were prominently enriched in the PI3K-Akt signaling pathway, with the identification of five hub genes (JUN, EGFR, ESR1, RELA, and AKT1). TRP extracts significantly inhibited cell metabolic activity, migration, invasion, and proliferation and promoted cell apoptosis in OSCC cells. Notably, the application of TRP extracts exhibited the capacity to downregulate mRNA and phosphorylated protein levels of AKT1 and ESR1, while concomitantly inducing upregulation of mRNA and phosphorylated protein levels in the remaining three hub genes (EGFR, JUN, and RELA). The functional rescue assay demonstrated that the co-administration of TRP and the PI3K activator 740Y-P effectively reversed the impact of TRP on the phenotypes of OSCC cells. Conversely, the combination of TRP and the PI3K inhibitor LY294002 further enhanced the effect of TRP on the phenotypes of OSCC cells. Remarkably, treatment with TRP in zebrafish xenograft models demonstrated a significant reduction in both tumor growth and metastatic spread. CONCLUSIONS: Triphala exerted significant inhibitory effects on cell metabolic activity, migration, invasion, and proliferation in OSCC cell lines, accompanied by the induction of apoptosis, which was mediated through the inactivation of the PI3K/Akt pathway.


Assuntos
Apoptose , Movimento Celular , Proliferação de Células , Simulação de Acoplamento Molecular , Neoplasias Bucais , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Peixe-Zebra , Animais , Neoplasias Bucais/tratamento farmacológico , Humanos , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Linhagem Celular Tumoral , Fosfatidilinositol 3-Quinases/metabolismo , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Extratos Vegetais/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Mapas de Interação de Proteínas , Carcinoma de Células Escamosas/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto , Cromonas/farmacologia , Morfolinas/farmacologia
5.
RSC Adv ; 14(3): 2016-2026, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38196914

RESUMO

Due to persistent inflammation and limited osteogenesis, jawbone defects present a considerable challenge in regenerative medicine. Amelogenin, a major protein constituent of the developing enamel matrix, demonstrates promising capabilities in inducing regeneration of periodontal supporting tissues and exerting immunomodulatory effects. These properties render it a potential therapeutic agent for enhancing jawbone osteogenesis. Nevertheless, its clinical application is hindered by the limitations of monotherapy and its rapid release characteristics, which compromise its efficacy and delivery efficiency. In this context, calcium alginate hydrogel, recognized for its superior physicochemical properties and biocompatibility, emerges as a candidate for developing a synergistic bioengineered drug delivery system. This study describes the synthesis of an injectable calcium amelogenin/calcium alginate hydrogel using calcium alginate loaded with amelogenin. We comprehensively investigated its physical properties, its role in modulating the immunological environment conducive to bone healing, and its osteogenic efficacy in areas of jawbone defects. Our experimental findings indicate that this synthesized composite hydrogel possesses desirable mechanical properties such as injectability, biocompatibility, and biodegradability. Furthermore, it facilitates jawbone formation by regulating the bone-healing microenvironment and directly inducing osteogenesis. This research provides novel insights into the development of bone-tissue regeneration materials, potentially advancing their clinical application.

6.
Biomol Biomed ; 24(1): 73-81, 2024 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-37435641

RESUMO

The aim of this study was to screen potential susceptibility genes using whole-exome sequencing (WES) in 15 Han Chinese patients with stage III or IV periodontitis and to evaluate the quantity and quality of genomic DNA extracted from saliva. DNA was extracted from saliva epithelial cells, quality-tested, and then subjected to WES and bioinformatics analyses. All variation loci were analyzed and interpreted following the American College of Medical Genetics and Genomics (ACMG) criteria. Candidate pathogenic variation loci were identified and verified using Sanger sequencing. Correlation and functional analyses of the candidate genes were used to identify potential susceptibility genes in patients with severe periodontitis. LFNG, LENG8, NPHS1, HFE, ILDR1, and DMXL2 genes were identified in over two cases each with shared mutations. Following these analyses, the DMXL2 gene was identified as being associated with stage III and IV periodontitis. These results suggest a potential pathophysiological risk mechanism for periodontitis, but need to be verified through larger clinical studies and mechanistic experiments to determine the pathogenicity of these gene mutations and their generalizability to a wider population of periodontitis patients. By screening candidate pathogenic variation loci using WES in 15 Han Chinese patients with stage III or IV periodontitis, our study could provide a pipeline and feasibility support for the identification of susceptibility genes in patients with stage III and IV periodontitis.


Assuntos
DNA , Exoma , Humanos , Projetos Piloto , Sequenciamento do Exoma , Exoma/genética , Mutação/genética
7.
Biol Direct ; 18(1): 81, 2023 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-38017487

RESUMO

The human bone marrow mesenchymal stem cells (hBMSCs) undergo intense osteogenic differentiation, a crucial bone formation mechanism. Evidence from prior studies suggested an association between long noncoding RNAs (lncRNAs) and the osteogenic differentiation of hBMSCs. However, precise roles and molecular mechanisms are still largely unknown. In this work, we report for the first time that lncRNA KCNMA1 antisense RNA 1 (KCNMA1-AS1) plays a vital role in regulating hBMSCs' osteogenic differentiation. Here, it was observed that the KCNMA1-AS1 expression levels were significantly upregulated during osteogenic differentiation. In addition, KCNMA1-AS1 overexpression enhanced in vitro osteogenic differentiation of hBMSCs and in vivo bone formation, whereas knockdown of KCNMA1-AS1 resulted in the opposite result. Additionally, the interaction between KCNMA1-AS1 and mothers against decapentaplegic homolog 9 (SMAD9) was confirmed by an RNA pull-down experiment, mass spectrometry, and RIP assay. This interaction regulated the activation of the SMAD9 signaling pathway. Moreover, rescue assays demonstrated that the inhibitor of the SMAD9 signaling pathway reversed the stimulative effects on osteogenic differentiation of hBMSCs by KCNMA1-AS1 overexpression. Altogether, our results stipulate that KCNMA1-AS1 promotes osteogenic differentiation of hBMSCs via activating the SMAD9 signaling pathway and can serve as a biomarker and therapeutic target in treating bone defects.


Assuntos
Células-Tronco Mesenquimais , RNA Longo não Codificante , Humanos , Osteogênese/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Diferenciação Celular/genética , Transdução de Sinais/genética , Células-Tronco Mesenquimais/metabolismo , Proteína Smad8/metabolismo , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo
8.
Plant Dis ; 107(11): 3531-3541, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37882825

RESUMO

Pear powdery mildew (PPM), caused by Phyllactinia pyri, is one of the most serious diseases affecting production in the Hebei pear-growing region of China. Iminoctadine trialbesilate and trifloxystrobin are known to have broad-spectrum activity against a wide range of plant pathogens, including P. pyri. A total of 105 P. pyri strains were isolated from 11 cities in Hebei Province from 2017 to 2019. Iminoctadine trialbesilate and trifloxystrobin significantly inhibited P. pyri growth. Microscopic observation showed that P. pyri mycelia had different degrees of desiccation and that the conidial cell contents had been released. The sensitivities of 60 P. pyri strains to iminoctadine trialbesilate and trifloxystrobin were determined in vitro, and the average EC50 values were 0.5773 ± 0.0014 and 1.2038 ± 0.0010 µg/ml, respectively. The average EC50 values for 85 and 75% of the strains with continuous single peak frequency distributions were 0.4534 ± 0.0012 and 0.8124 ± 0.0039 µg/ml, respectively. These data could be used as the baseline sensitivities of P. pyri to these two fungicides. The maximum difference multiples of the sensitivities of P. pyri strains from the different cities to iminoctadine trialbesilate and trifloxystrobin were 13.5- and 17.2-fold, respectively. Cluster analysis showed that there was no significant correlation between P. pyri sensitivity and geographical origin. The field efficacies in controlling PPM were higher than 85%. These findings can improve how we monitor iminoctadine trialbesilate and trifloxystrobin resistance and improve application efficiency.


Assuntos
Pyrus , Estrobilurinas/farmacologia , Erysiphe
9.
Heliyon ; 9(10): e20659, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37842569

RESUMO

Background: Head and neck squamous cell carcinoma (HNSCC) represents a predominant type of cancer found in the head and neck region, characterized by a high incidence and unfavorable prognosis. The IGF2BPs gene family, which belongs to the RNA-binding protein class, has been critically implicated in several cancers, and its involvement in HNSCC necessitates further exploration. Objective: To explore the clinical significance and potential biological functions of the IGF2BPs gene family in HNSCC. Methods: A bioinformatic methodology was employed to examine the expression profile, diagnostic and prognostic significance, and biological mechanisms of the IGF2BPs gene family in HNSCC, with a particular emphasis on its involvement in the immune function of HNSCC. This was followed by in vitro investigations to unravel the biological roles of the IGF2BPs gene family in HNSCC. Results: This investigation has demonstrated that, in contrast with normal control tissue, HNSCC has a substantial elevation in the expression level of the IGF2BPs gene family. Patients with a high level of IGF2BPs gene family expression demonstrated higher prediction accuracy for HNSCC. Furthermore, patients with HNSCC and elevated IGF2BPs gene family expression levels exhibited poor survival outcomes. The IGF2BPs gene family displayed a significant association with a variety of immune infiltrating cells and immune genes in HNSCC. Studies conducted in vitro have confirmed that IGF2BP2 silencing suppressed the migration, proliferation, and invasion of HNSCC cells. Conclusions: It has been determined that the IGF2BPs gene family plays a crucial part in the onset and progression of HNSCC, and its association with tumor immunity has been established. The IGF2BPs gene family holds promising potential as a diagnostic and prognostic biomarker for HNSCC.

10.
J Oncol ; 2022: 4867730, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35693982

RESUMO

Objective: To investigate the function and regulatory mechanisms of methylenetetrahydrofolate dehydrogenase (MTHFD) family genes in oral squamous cell carcinoma (OSCC), especially focus on their regulating role in tumor immunity. Methods: The publicly available data from the TCGA database were used to investigate the expression pattern and regulatory role of MTHFD family genes in OSCC. More importantly, the involvement of MTHFD family genes in tumor immunity was investigated in terms of immune and stromal cell infiltration in tumor microenvironment, tumor-infiltrating immune cells, and immunomodulatory genes (e.g., immunoinhibitory genes and immunostimulatory genes). Statistical analysis was performed using R software packages and public web servers. Results: MTHFD family genes were considerably upregulated in OSCC as compared with normal oral tissue. Patients with high MTHFD2 expression presented worse survival outcomes than those with low MTHFD2 expression. Functional enrichment analysis showed that the top 100 positively and negatively correlated genes of the MTHFD family genes were significantly enriched in several KEGG pathways, including cell cycle, spliceosome, DNA replication, and Th17 cell differentiation. As a result of tumor immunity analysis, MTHFD2L expression was found to be negatively related to the Estimate-Stromal-Immune score in OSCC; however, there was no statistical significance between the Estimate-Stromal-Immune score and MTHFD1, MTHFD1L, or MTHFD2 in OSCC. Additionally, MTHFD family genes were found to be significantly positively correlated with tumor-infiltrating immune cells, including Treg and Th17 cells. Moreover, MTHFD family genes were significantly correlated with several immune inhibitory genes such as CD274 and CTLA4 and several immune-stimulatory genes such as CXCL12, CXCR4, and TMIGD2. Conclusion: Given the expression pattern, prognostic value, biological functions, and involvement in tumor immunity, MTHFD family genes could serve as potential therapeutic biomarkers in targeting tumor immunity in oral cancer.

11.
Front Endocrinol (Lausanne) ; 13: 846154, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35663324

RESUMO

Objective: To investigate the mechanisms of super-enhancer-associated LINC01485/miR-619-5p/RUNX2 signaling axis involvement in osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). Methods: Osteogenic differentiation of hBMSCs was induced in vitro. The expression levels of LINC01485 and miR-619-5p during osteogenesis were measured using quantitative real-time polymerase chain reaction (qRT-PCR). Osteogenic differentiation was examined by qRT-PCR, western blot, alkaline phosphatase (ALP) staining, ALP activity measurement, and Alizarin Red S (ARS) staining assays. Thereafter, the effects of LINC01485 and miR-619-5p on osteogenic differentiation of hBMSCs were evaluated by performing loss- and gain-of-function experiments. Subsequently, a fluorescence in situ hybridization (FISH) assay was employed to determine the cellular localization of LINC01485. Bioinformatics analysis, RNA antisense purification (RAP) assay, and dual-luciferase reporter assays were conducted to analyze the interactions of LINC01485, miR-619-5p, and RUNX2. Rescue experiments were performed to further delineate the role of the competitive endogenous RNA (ceRNA) signaling axis consisting of LINC01485/miR-619-5p/RUNX2 in osteogenic differentiation of hBMSCs. Results: The expression of LINC01485 was up-regulated during osteogenic differentiation of hBMSCs. The overexpression of LINC01485 promoted osteogenic differentiation of hBMSCs by up-regulating the expression of osteogenesis-related genes [e.g., runt-related transcription factor 2 (RUNX2), osterix (OSX), collagen type 1 alpha 1 (COL1A1), osteocalcin (OCN), and osteopontin (OPN)], and increasing the activity of ALP. ALP staining and ARS staining were also found to be increased upon overexpression of LINC01485. The opposing results were obtained upon LINC01485 interference in hBMSCs. miR-619-5p was found to inhibit osteogenic differentiation. FISH assay displayed that LINC01485 was mainly localized in the cytoplasm. RAP assay results showed that LINC01485 bound to miR-619-5p, and dual-luciferase reporter assay verified that LINC01485 bound to miR-619-5p, while miR-619-5p and RUNX2 bound to each other. Rescue experiments illustrated that LINC01485 could promote osteogenesis by increasing RUNX2 expression by sponging miR-619-5p. Conclusion: LINC01485 could influence RUNX2 expression by acting as a ceRNA of miR-619-5p, thereby promoting osteogenic differentiation of hBMSCs. The LINC01485/miR-619-5p/RUNX2 axis might comprise a novel target in the bone tissue engineering field.


Assuntos
Células-Tronco Mesenquimais , MicroRNAs , RNA Longo não Codificante , Diferenciação Celular/genética , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Humanos , Hibridização in Situ Fluorescente , MicroRNAs/metabolismo , Osteogênese/genética , RNA Longo não Codificante/genética
13.
Front Cardiovasc Med ; 9: 830732, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35299983

RESUMO

Background: Periodontal disease has been associated with gestational complications and both conditions have a high prevalence in rural populations from developing regions. A cross-sectional study was carried out to explore the relationship between periodontal inflamed surface area (PISA), blood pressure (BP), and, serum uric acid levels (UA) in a group of rural North Chinese pregnant women in the third trimester of pregnancy. Methods: Three hundred and thirty-five rural women aged 20-34 years, with normal body mass index (BMI) were examined in a cross-sectional study during their third trimester of gestation. Exclusion criteria were history of pregnancy complications, multiple pregnancy, smoking habits, diabetes, hypertension or any known infectious disease. Socio-demographic variables, including age and socioeconomic status (SES), systolic blood pressure (SBP) and diastolic blood pressure (DBP) readings, serum UA levels, and PISA values were recorded. A structural equation model was implemented with two constructed latent variables including "Dem" (comprising of age and SES category to represent unobserved demographic variables) and, "BP" (comprising of SBP and DBP to account for measurement error and lack of multiple BP readings). The model accounted for co-variance of BP and UA, and implemented simultaneous regressions for BP and UA as outcomes, upon Dem and PISA values as exogenous variables. Results: The median PISA score was 1,081.7 (IQR = 835.01), reflecting high levels of periodontal inflammation in the sample. SEM showed a significant association of PISA with BP (estimate = 0.011, 95% CI = 0.009-0.012 p < 0.001) and UA (estimate = 0.001, 95% CI = 0.001-0.001, p < 0.001). Conclusion: Higher PISA values were significantly associated with higher blood pressure and uric acid levels among rural pregnant women in a cross-sectional sample from a center in North China after accounting for a latent demographic construct derived from age and SES.

14.
Front Cell Infect Microbiol ; 12: 815318, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35186795

RESUMO

Fusobacterium nucleatum is a common oral opportunistic bacterium that can cause different infections. In recent years, studies have shown that F. nucleatum is enriched in lesions in periodontal diseases, halitosis, dental pulp infection, oral cancer, and systemic diseases. Hence, it can promote the development and/or progression of these conditions. The current study aimed to assess research progress in the epidemiological evidence, possible pathogenic mechanisms, and treatment methods of F. nucleatum in oral and systemic diseases. Novel viewpoints obtained in recent studies can provide knowledge about the role of F. nucleatum in hosts and a basis for identifying new methods for the diagnosis and treatment of F. nucleatum-related diseases.


Assuntos
Infecções por Fusobacterium , Neoplasias Bucais , Doenças Periodontais , Infecções por Fusobacterium/diagnóstico , Infecções por Fusobacterium/microbiologia , Fusobacterium nucleatum , Humanos
15.
Front Cell Dev Biol ; 9: 765859, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34912804

RESUMO

Regulatory cell death has been a major focus area of cancer therapy research to improve conventional clinical cancer treatment (e.g. chemotherapy and radiotherapy). Ferroptosis, a novel form of regulated cell death mediated by iron-dependent lipid peroxidation, has been receiving increasing attention since its discovery in 2012. Owing to the highly iron-dependent physiological properties of cancer cells, targeting ferroptosis is a promising approach in cancer therapy. In this review, we summarised the characteristics of ferroptotic cells, associated mechanisms of ferroptosis occurrence and regulation and application of the ferroptotic pathway in cancer therapy, including the use of ferroptosis in combination with other therapeutic modalities. In addition, we presented the challenges of using ferroptosis in cancer therapy and future perspectives that may provide a basis for further research.

16.
Front Cell Dev Biol ; 9: 687245, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422810

RESUMO

Background: The mechanisms through which immunosuppressed patients bear increased risk and worse survival in oral squamous cell carcinoma (OSCC) are unclear. Here, we used deep learning to investigate the genetic mechanisms underlying immunosuppression in the survival of OSCC patients, especially from the aspect of various survival-related subtypes. Materials and methods: OSCC samples data were obtained from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and OSCC-related genetic datasets with survival data in the National Center for Biotechnology Information (NCBI). Immunosuppression genes (ISGs) were obtained from the HisgAtlas and DisGeNET databases. Survival analyses were performed to identify the ISGs with significant prognostic values in OSCC. A deep learning (DL)-based model was established for robustly differentiating the survival subpopulations of OSCC samples. In order to understand the characteristics of the different survival-risk subtypes of OSCC samples, differential expression analysis and functional enrichment analysis were performed. Results: A total of 317 OSCC samples were divided into one inferring cohort (TCGA) and four confirmation cohorts (ICGC set, GSE41613, GSE42743, and GSE75538). Eleven ISGs (i.e., BGLAP, CALCA, CTLA4, CXCL8, FGFR3, HPRT1, IL22, ORMDL3, TLR3, SPHK1, and INHBB) showed prognostic value in OSCC. The DL-based model provided two optimal subgroups of TCGA-OSCC samples with significant differences (p = 4.91E-22) and good model fitness [concordance index (C-index) = 0.77]. The DL model was validated by using four external confirmation cohorts: ICGC cohort (n = 40, C-index = 0.39), GSE41613 dataset (n = 97, C-index = 0.86), GSE42743 dataset (n = 71, C-index = 0.87), and GSE75538 dataset (n = 14, C-index = 0.48). Importantly, subtype Sub1 demonstrated a lower probability of survival and thus a more aggressive nature compared with subtype Sub2. ISGs in subtype Sub1 were enriched in the tumor-infiltrating immune cells-related pathways and cancer progression-related pathways, while those in subtype Sub2 were enriched in the metabolism-related pathways. Conclusion: The two survival subtypes of OSCC identified by deep learning can benefit clinical practitioners to divide immunocompromised patients with oral cancer into two subpopulations and give them target drugs and thus might be helpful for improving the survival of these patients and providing novel therapeutic strategies in the precision medicine area.

17.
J Clin Lab Anal ; 35(8): e23872, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34407267

RESUMO

BACKGROUND: Nanodiamonds (NDs) have been demonstrated to have bactericidal activity on several microorganisms and can be used in various kinds of dental materials. NDs are potential candidates for antibacterial dental materials. However, the possible inhibitory effect of NDs on oral pathogenic bacteria is largely unknown. This study was performed to investigate the inhibitory effects of carboxylated nanodiamond (cND) on Streptococcus mutans. METHODS: Fourier transform infrared spectroscopy was used to confirm carboxyl groups on the surface of commercial cND. The inhibitory effect of serially diluted cND on S. mutans was evaluated by spectrophotometry and plating methods. Escherichia coli was treated as a positive control in spectrophotometry. Chlorhexidine was used as a positive control in plating methods. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were employed to confirm the antibacterial activity of cND. RESULTS: The results showed that cND exhibited a significant inhibitory effect on S. mutans. For S. mutans, the minimum inhibitory concentration was 4 µg/ml and the minimum bactericidal concentration was 16 µg/ml. SEM and TEM results indicated that cND functioned as an antibacterial agent, likely due to its ability to disrupt the cell membrane of S. mutans. CONCLUSION: In conclusion, these findings demonstrated an inhibitory effect of cND on S. mutans and suggest its use as a potential antibacterial dental material.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Nanodiamantes , Streptococcus mutans/efeitos dos fármacos , Antibacterianos/administração & dosagem , Membrana Celular/efeitos dos fármacos , Placa Dentária/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Nanodiamantes/química , Espectroscopia de Infravermelho com Transformada de Fourier , Streptococcus mutans/citologia , Streptococcus mutans/isolamento & purificação
18.
Eur Radiol ; 31(12): 9110-9119, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34047848

RESUMO

OBJECTIVES: To evaluate whether amide proton transfer (APT) MRI can be used to characterize gliomas in pediatric patients and whether it provides added value beyond relaxation times. METHODS: In this prospective study, APT imaging and relaxation time mapping were performed in 203 pediatric patients suspected of gliomas from February 2018 to December 2019. The region of interest (ROI) in the tumor was automatically generated with artifact detection and ROI-shrinking algorithms. Several APT-related metrics (CESTR, CESTRnr, MTRRex, AREX, and APT#) and quantitative T1 and T2 were compared between low-grade and high-grade gliomas using the student's t-test or Mann-Whitney U-test. The performance of these parameters was assessed using the receiver operating characteristic (ROC) analysis. A stepwise multivariate logistic regression model was used to combine the imaging parameters. RESULTS: Forty-eight patients (mean age: 6 ± 4 years; 23 males and 25 females) were included in the final analysis. All the APT-related metrics except APT# had significantly (p < 0.05) higher values in the high-grade group than the low-grade group. Under different ROI-shrinking cutoffs, the quantitative T1 (p = 0.045-0.200) and T2 (p = 0.037-0.171) values of high-grade gliomas were typically lower than those of low-grade ones. The stepwise multivariate logistic regression revealed that CESTRnr and APT# were combined significant predictors of glioma grades (p < 0.05), with an area under the ROC curve (AUC) of 0.86 substantially larger than those of T1 (AUC = 0.69) and T2 (AUC = 0.68). CONCLUSIONS: APT imaging can be used to differentiate high-grade and low-grade gliomas in pediatric patients and provide added value beyond quantitative relaxation times. KEY POINTS: • Amide proton transfer (APT) MRI showed significantly (p < 0.05) higher values in pediatric patients with high-grade gliomas than those with low-grade ones. • The area under the curve was 0.86 for APT MRI to differentiate low-grade and high-grade gliomas in pediatric patients, which was substantially higher than that for quantitative T1 (0.69) and T2 (0.68). • APT MRI demonstrated added value beyond quantitative T1 and T2 mapping in characterizing pediatric gliomas.


Assuntos
Neoplasias Encefálicas , Glioma , Amidas , Neoplasias Encefálicas/diagnóstico por imagem , Criança , Pré-Escolar , Feminino , Glioma/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Gradação de Tumores , Estudos Prospectivos , Prótons
19.
Int J Mol Med ; 47(5)2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33760127

RESUMO

Oral tongue squamous cell carcinoma (OTSCC) is one of the most aggressive pathological types of head and neck squamous cell carcinoma, and presents with rapid local invasion and metastasis. The present study confirmed that the long non­coding (lnc) RNA MIR4713HG was markedly upregulated in both OTSCC tissues and cell lines and associated with poor survival. The present study performed a series of experiments to investigate the impact of MIR4713HG on OTSCC and revealed that upregulation of MIR4713HG had a crucial role in promoting cell proliferation and metastasis of OTSCC cell lines both in vitro and in vivo. By applying bioinformatics analyses, micro RNA let­7c­5p was observed to physically bind with MIR4713HG, and the knockdown of let­7c­5p could counteract the influence of MIR4713HG on OTSCC. Furthermore, the present study demonstrated that let­7c­5p performed its regulating role in OTSCC via affecting the expression level of transmembrane channel like 7 (TMC7). In conclusion, the present study demonstrated that lncRNA MIR4713HG acted as a pro­tumor factor facilitating cell proliferation and metastasis of OTSCC via affecting the let­7c­5p/TMC7 signaling pathway, which presents as a promising therapeutic target in OTSCC.


Assuntos
MicroRNAs/metabolismo , RNA Longo não Codificante/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Neoplasias da Língua/patologia , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/secundário , Masculino , Proteínas de Membrana/genética , Camundongos Endogâmicos BALB C , MicroRNAs/genética , RNA Longo não Codificante/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Neoplasias da Língua/genética , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Small ; 17(48): e2007025, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33682331

RESUMO

Transformation of CO2 into value-added products via photothermal catalysis has become an increasingly popular route to help ameliorate the energy and environmental crisis derived from the continuing use of fossil fuels, as it can integrate light into well-established thermocatalysis processes. The question however remains whether negative CO2 emission could be achieved through photothermal catalytic reactions performed in facilities driven by electricity mainly derived from fossil energy. Herein, we propose universal equations that describe net CO2 emissions generated from operating thermocatalysis and photothermal reverse water-gas shift (RWGS) and Sabatier processes for batch and flow reactors. With these reactions as archetype model systems, the factors that will determine the final amount of effluent CO2 can be determined. The results of this study could provide useful guidelines for the future development of photothermal catalytic systems for CO2 reduction.

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