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OBJECTIVE: To analyze the isolation rate, prevalence trends, species distribution, and drug sensitivity of non-tuberculous mycobacteria (NTM) in Anhui Province, providing a reference for diagnosis and treatment strategies. METHODS: Specimens from suspected mycobacterial infection patients at Anhui Chest Hospital (including outpatients and inpatients) from January 2021 to December 2023 were cultured. Identified NTM strains were analyzed for species distribution and drug sensitivity. RESULTS: Of 10,519 mycobacteria strains cultured, 1,589 were NTM (15.11%). The top four species were Mycobacterium intracellulare (75.36%), Mycobacterium abscessus (11.78%), Mycobacterium kansasii (7.09%), and Mycobacterium avium (2.85%). NTM strains showed high sensitivity to amikacin and clarithromycin (≥90%) and significant sensitivity to rifabutin, moxifloxacin, and rifampicin (89.03%-79.61%). They exhibited high resistance to imipenem/cilastatin, sulfamethoxazole, minocycline, and doxycycline (≥95%). CONCLUSION: NTM isolation rates in Anhui have remained stable, with the predominant species being M. intracellulare, M. kansasii, M. abscessus, and M. avium. NTM strains are highly sensitive to amikacin, clarithromycin, rifabutin, moxifloxacin, and rifampicin. These findings can guide diagnosis, treatment strategies, and drug selection for NTM disease in Anhui Province.
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Background: Porphyromonas gingivalis (P.gingivalis) is associated with the onset of Alzheimer's disease (AD), but the underlying molecular mechanism is unclear. Neuroinflammation in the brain from the microglial immune response induces the pathological progression of AD. In this study, the roles and molecular mechanism of P.gingivalis in microglial inflammation in vitro were investigated. Methods: In this study, a P.gingivalis oral administration mouse model was generated, and microglia were stimulated with P.gingivalis in vitro. The viability of the microglia after P.gingivalis treatment was evaluated through CCK-8 and live/dead cell staining. Inflammation in brain tissue after P.gingivalis treatment and the immune response of microglia in vitro were detected by RTâPCR, Western blotting and IF. Moreover, the RNA sequence was used, and the role of the NF-κB signalling pathway in microglial activation was analysed after P.gingivalis stimulation. Results: The mRNA and protein levels of IL-6 and IL-17 were increased, and the expression of IL-10 was decreased in brain tissue after P.gingivalis oral administration. The viability of the HMC3 cells significantly decreased with 5% P.gingivalis after stimulation. The results of live/dead cell staining also showed the inhibitory effect of 5% P.gingivalis supplementation on cell viability. Moreover, 5% P.gingivalis supplementation increased the mRNA and protein levels of IL-6 and IL-17 and decreased IL-10 expression in HMC3 cells. P.gingivalis supplementation increased the mRNA and protein levels of iNOS and CD86 and decreased CD206 expression in HMC3 cells. RNA sequencing revealed that the NF-κB signalling pathway was involved in this process. Furthermore, p-P65 was upregulated and p-IKBα was downregulated in brain tissue and HMC3 cells after P.gingivalis stimulation, and an NF-κB signalling pathway inhibitor (QNZ) reversed the viability, M1 polarization and inflammatory factors of microglia in HMC3 cells in vitro. Conclusions: In conclusion, P.gingivalis induced neuroinflammation in the brain, possibly through promotion of M1 polarization of microglia via activation of the NF-κB signalling pathway during the progression of AD.
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Discovering and engineering herbicide-resistant genes is a crucial challenge in crop breeding. This study focuses on the 4-hydroxyphenylpyruvate dioxygenase Inhibitor Sensitive 1-Like (HSL) protein, prevalent in higher plants and exhibiting weak catalytic activity against many ß-triketone herbicides (ß-THs). The crystal structures of maize HSL1A complexed with ß-THs were elucidated, identifying four essential herbicide-binding residues and explaining the weak activity of HSL1A against the herbicides. Utilizing an artificial evolution approach, we developed a series of rice HSL1 mutants targeting the four residues. Then, these mutants were systematically evaluated, identifying the M10 variant as the most effective in modifying ß-THs. The initial active conformation of substrate binding in HSL1 was also revealed from these mutants. Furthermore, overexpression of M10 in rice significantly enhanced resistance to ß-THs, resulting in a notable 32-fold increase in resistance to methyl-benquitrione. In conclusion, the artificially evolved M10 gene shows great potential for the development of herbicide-resistant crops.
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Resistência a Herbicidas , Herbicidas , Oryza , Proteínas de Plantas , Oryza/genética , Oryza/metabolismo , Resistência a Herbicidas/genética , Herbicidas/farmacologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Melhoramento Vegetal/métodos , Plantas Geneticamente Modificadas/genética , MutaçãoRESUMO
BACKGROUND: The increasing prevalence of tuberculosis (TB) and diabetes on a global scale poses a significant health challenge, particularly due to their co-occurrence, which amplifies the severity, recurrence and mortality rates associated with both conditions. This highlights the need for further investigation into their inter-relationship. AIM: To explore the computed tomography (CT) imaging and clinical significance of bacterium-positive pulmonary TB (PTB) combined with diabetes. METHODS: There were 50 patients with bacterium-positive PTB and diabetes, and 50 with only bacterium-positive PTB. The latter were designated as the control group. The CT imaging of the two groups of patients was compared, including lesion range, shape, density and calcification. RESULTS: No significant differences were observed in age, gender, smoking and drinking history, high blood pressure, hyperlipidemia and family genetic factors between the groups. However, compared to the patients diagnosed solely with simple bacterium-positive PTB, those with concurrent diabetes showed a wider range of lesions and more complex and diverse morphology on CT images. Among them, intrapulmonary tuberculosis lesions were often accompanied by manifestations of pulmonary infection, such as cavity formation and bronchiectasis. At the same time, diabetes-related signs were often seen on CT images, such as pulmonary infection combined with diabetic pulmonary lesions. Logistic regression analysis identified age and medical history as significant factors influencing the degree of pulmonary infection and CT imaging outcomes in patients with both TB and diabetes. This suggests that older age and specific medical histories may increase the risk or severity of pulmonary damage in these patients. CONCLUSION: CT imaging reveals more complex lesions in PTB patients with diabetes, emphasizing the need for careful evaluation and comprehensive analysis to enhance diagnostic accuracy.
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The natural healing process of extraction socket and traditional socket plug material could not prevent buccal bone wall resorption and down growth of epithelium from the socket orifice. A multiphase bioactive socket plug (BP) is designed to overcome the natural healing process by maintaining the three-dimensional (3D) volume of extraction sockets, particularly in sockets with wall defects, and later provide sufficient alveolar bone volume for implant placement. The study aimed to fabricate and evaluate the physical, chemical, and biological performance of BPin vitro. The BP was fabricated through freeze-drying and layer-by-layer assembly, comprised of a base serving as a scaffold, a central portion for promoting bone regeneration, an upper buccal portion for maintaining alveolar socket dimension with a covering collagen membrane (Memb) on the top and upper buccal surface to prevent soft tissue infiltration. The BP as the experimental group and a pure collagen plug (CP) as the control group were investigated and compared. Radiograph, scanning electron microscopy, and energy-dispersive spectroscopy mapping confirmed that the four-part BP was successfully assembled and fabricated. Swelling rate analysis indicated that BP, CP, and Memb reached swelling equilibrium within 1 hour. BP exhibited a high remaining weight percentage in collagenase solution (68.81 ± 2.21% on day 90) and sustained calcium ion release, reaching the maximum 0.13 ± 0.04 mmol l-1on day 14. In biological assays, BP exhibited excellent cell proliferation (The OD value increased from 0.02 on day 1 to 0.23 on day 21.). The BP group exhibited higher alkaline phosphatase activity and osteocalcin content than the CP group within 21 days. Memb and BP exhibited outstanding barrier function, as evidenced by Hematoxylin and eosin staining. In summary, the multiphase bioactive socket plug represents a promising scaffold for alveolar ridge preservation application.
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Colágeno , Alicerces Teciduais , Alvéolo Dental , Alvéolo Dental/cirurgia , Animais , Colágeno/química , Alicerces Teciduais/química , Materiais Biocompatíveis/química , Regeneração Óssea/efeitos dos fármacos , Processo Alveolar , Proliferação de Células , Microscopia Eletrônica de Varredura , Humanos , Teste de Materiais , Aumento do Rebordo Alveolar/métodos , Extração Dentária , Osteoblastos/citologia , Substitutos Ósseos/química , Substitutos Ósseos/farmacologia , Cicatrização , Cálcio/metabolismo , Cálcio/química , Osteocalcina/metabolismoRESUMO
The rapid development of the battery industry has brought about a large amount of waste battery pollution. How to realize the high-value utilization of waste batteries is an urgent problem to be solved. Herein, cobalt and titanium compounds (LTCO) were firstly recovered from spent lithium-ion batteries (LIBs) using the carbon thermal reduction approach, and plasmonic attapulgite/Co(Ti)Ox (H-ATP/Co(Ti)Ox) nanocomposites were prepared by the microwave hydrothermal technique. H-ATP had a large specific surface area and enough active sites to capture CO2 molecules. The biochar not only reduced the spinel phase of waste LIBs into metal oxides including Co3O4 and TiO2 but also increased the separation and transmission of the carriers, thereby accelerating the adsorption and reduction of CO2. In addition, H-ATP/Co(Ti)Ox exhibited a localized surface plasmon resonance effect (LSPR) in the visible to near-infrared region and released high-energy hot electrons, enhancing the surface temperature of the catalyst and further improving the catalytic reduction of CO2 with a high CO yield of 14.7 µmol·g-1·h-1. The current work demonstrates the potential for CO2 reduction by taking advantage of natural mineral and spent batteries.
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BACKGROUND: Ovarian carcinoma (OC) is a fatal malignancy, with most patients experiencing recurrence and resistance to chemotherapy. In contrast to hematogenous metastasizing tumors, ovarian cancer cells disseminate within the peritoneal cavity, especially the omentum. Previously, we reported omental crown-like structure (CLS) number is associated with poor prognosis of advanced-stage OC. CLS that have pathologic features of a dead or dying adipocyte was surrounded by several macrophages is well known a histologic hallmark for inflammatory adipose tissue. In this study, we attempted to clarify the interaction between metastatic ovarian cancer cells and omental CLS, and to formulate a therapeutic strategy for advanced-stage ovarian cancer. METHODS: A three-cell (including OC cells, adipocytes and macrophages) coculture model was established to mimic the omental tumor microenvironment (TME) of ovarian cancer. Caspase-1 activity, ATP and free fatty acids (FFA) levels were detected by commercial kits. An adipocyte organoid model was established to assess macrophages migration and infiltration. In vitro and in vivo experiments were performed for functional assays and therapeutic effect evaluations. Clinical OC tissue samples were collected for immunochemistry stain and statistics analysis. RESULTS: In three-cell coculture model, OC cells-derived IL-6 and IL-8 could induce the occurrence of pyroptosis in omental adipocytes. The pyroptotic adipocytes release ATP to increase macrophage infiltration, release FFA into TME, uptake by OC cells to increase chemoresistance. From OC tumor samples study, we demonstrated patients with high gasdermin D (GSDMD) expression in omental adipocytes is highly correlated with chemoresistance and poor outcome in advanced-stage OC. In animal model, by pyroptosis inhibitor, DSF, effectively retarded tumor growth and prolonged mice survival. CONCLUSIONS: Omental adipocyte pyroptosis may contribute the chemoresistance in advanced stage OC. Omental adipocytes could release FFA and ATP through the GSDMD-mediate pyroptosis to induce chemoresistance and macrophages infiltration resulting the poor prognosis in advanced-stage OC. Inhibition of adipocyte pyroptosis may be a potential therapeutic modality in advanced-stage OC with omentum metastasis.
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Adipócitos , Resistencia a Medicamentos Antineoplásicos , Omento , Neoplasias Ovarianas , Piroptose , Microambiente Tumoral , Feminino , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Omento/metabolismo , Humanos , Adipócitos/metabolismo , Camundongos , Animais , Linhagem Celular Tumoral , Técnicas de CoculturaRESUMO
Tumor-infiltrating lymphocyte (TIL) deficiency is the most conspicuous obstacle to limit the cancer immunotherapy. Immune checkpoint inhibitors (ICIs), such as anti-PD-1 antibody, have achieved great success in clinical practice. However, due to the limitation of response rates of ICIs, some patients fail to benefit from monotherapy. Thus, novel combination therapy that could improve the response rates emerges as new strategies for cancer treatment. Here, we reported that the natural product rocaglamide (RocA) increased tumor-infiltrating T cells and promoted Th17 differentiation of CD4+ TILs. Despite RocA monotherapy upregulated PD-1 expression of TILs, which was considered as the consequence of T cell activation, combining RocA with anti-PD-1 antibody significantly downregulated the expression of PD-1 and promoted proliferation of TILs. Taken together, these findings demonstrated that RocA could fuel the T cell anti-tumor immunity and revealed the remarkable potential of RocA as a therapeutic candidate when combining with the ICIs.
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Benzofuranos , Diferenciação Celular , Inibidores de Checkpoint Imunológico , Linfócitos do Interstício Tumoral , Receptor de Morte Celular Programada 1 , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/metabolismo , Camundongos , Animais , Benzofuranos/farmacologia , Benzofuranos/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Humanos , Diferenciação Celular/efeitos dos fármacos , Neoplasias/imunologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Feminino , Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Linhagem Celular TumoralRESUMO
Background: Exploring potential biomarkers for predicting clinical outcomes and developing targeted therapies for acute myeloid leukemia (AML) is of utmost importance. This study aimed to investigate the expression pattern of the thioredoxin-interacting protein (TXNIP)/nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) pathway and its role in the prognosis of AML patients. Methods: In this study, we examined the prognostic value of TXNIP/NLRP3 pathway in AML patients using microarray data from Gene Expression Omnibus (GEO) and transcriptome data from the Cancer Genome Atlas (TCGA) to develop a prognostic model and validated the results by quantitative real-time PCR (qRT-PCR) in a validation cohort of 26 AML patients and 18 healthy individuals from Jinan University (JNU) database. Results: Analysis of the GSE13159 database revealed that TXNIP, interleukin 1 beta (IL1B) within the TXNIP/NLRP3 pathway were significantly upregulated and caspase1 (CASP1) was downregulated in AML patients (TXNIP, P = 0.031; IL1B, P = 0.042; CASP1, P = 0.038). Compared to high NLRP3 expression, AML patients with low NLRP3 expression had a longer overall survival (OS) in the GSE12417 dataset (P = 0.004). Moreover, both the training and validation results indicated that lower TXNIP, NLRP3, and IL1B expression were associated with favorable prognosis (GSE12417, P = 0.009; TCGA, P = 0.050; JNU, P = 0.026). According to the receiver operating characteristic curve analysis, this model demonstrated a sensitivity of 84% for predicting three-year survival. These data might provide novel predictors for AML outcome and direction for further investigation of the possibility of using TXNIP/NLRP3/IL1B genes in novel targeted therapies for AML.
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Biomarcadores Tumorais , Proteínas de Transporte , Inflamassomos , Interleucina-1beta , Leucemia Mieloide Aguda , Proteína 3 que Contém Domínio de Pirina da Família NLR , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Feminino , Masculino , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Pessoa de Meia-Idade , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Inflamassomos/metabolismo , Inflamassomos/genética , Transdução de Sinais/genética , Adulto , Idoso , Regulação Leucêmica da Expressão Gênica , Tiorredoxinas/genética , Tiorredoxinas/metabolismoRESUMO
BACKGROUND: The mechanism of mitochondria-related genes (MRGs) in childhood allergic asthma (CAS) was unclear. The aim of this study was to find new biomarkers related to MRGs in CAS. METHODS: This research utilized two CAS-related datasets (GSE40888 and GSE40732) and extracted 40 MRGs from the MitoCarta3.0 Database. Initially, differential expression analysis was performed on CAS and control samples in the GSE40888 dataset to obtain the differentially expressed genes (DEGs). Differentially expressed MRGs (DE-MRGs) were obtained by overlapping the DEGs and MRGs. Protein protein interactions (PPI) network of DE-MRGs was created and the top 10 genes in the degree ranking of Maximal Clique Centrality (MCC) algorithm were defined as feature genes. Hub genes were obtained from the intersection genes from the Least absolute shrinkage and selection operator (LASSO) and EXtreme Gradient Boosting (XGBoost) algorithms. Additionally, the expression validation was conducted, functional enrichment analysis, immune infiltration analysis were finished, and transcription factors (TFs)-miRNA-mRNA regulatory network was constructed. RESULTS: A total of 1505 DEGs were obtained from the GSE40888, and 44 DE-MRGs were obtained. A PPI network based on these 44 DE-MRGs was created and revealed strong interactions between ADCK5 and MFN1, BNIP3 and NBR1. Four hub genes (NDUFAF7, MTIF3, MRPS26, and NDUFAF1) were obtained by taking the intersection of genes from the LASSO and XGBoost algorithms based on 10 signature genes which obtained from PPI. In addition, hub genes-based alignment diagram showed good diagnostic performance. The results of Gene Set Enrichment Analysis (GSEA) suggested that hub genes were closely related to mismatch repair. The B cells naive cells were significantly expressed between CAS and control groups, and MTIF3 was most strongly negatively correlated with B cells naive. In addition, the expression of MTIF3 and MRPS26 may have influenced the inflammatory response in CAS patients by affecting mitochondria-related functions. The quantitative real-time polymerase chain reaction (qRTâPCR) results showed that four hub genes were all down-regulated in the CAS samples. CONCLUSION: NDUFAF7, MTIF3, MRPS26, and NDUFAF1 were identified as an MRGs-related biomarkers in CAS, which provides some reference for further research on CAS.
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Asma , Biomarcadores , Mitocôndrias , Mapas de Interação de Proteínas , Humanos , Asma/genética , Criança , Biomarcadores/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Redes Reguladoras de Genes , Perfilação da Expressão Gênica , MicroRNAs/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Mitocondriais/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Introduction: γδ T cells recognize and exert cytotoxicity against tumor cells. They are also considered potential immune cells for immunotherapy. Our previous study revealed that the altered expression of immune checkpoint T-cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) on γδ T cells may result in immunosuppression and is possibly associated with a poor overall survival in acute myeloid leukemia (AML). However, whether γδ T-cell memory subsets are predominantly involved and whether they have a relationship with clinical outcomes in patients with AML under the age of 65 remain unclear. Methods: In this study, we developed a multicolor flow cytometry-based assay to monitor the frequency and distribution of γδ T-cell subsets, including central memory γδ T cells (TCM γδ), effector memory γδ T cells (TEM γδ), and TEM expressing CD45RA (TEMRA γδ), in peripheral blood from 30 young (≤65 years old) patients with newly diagnosed non-acute promyelocytic leukemia (also known as M3) AML (AMLy-DN), 14 young patients with AML in complete remission (AMLy-CR), and 30 healthy individuals (HIs). Results: Compared with HIs, patients with AMLy-DN exhibited a significantly higher differentiation of γδ T cells, which was characterized by decreased TCM γδ cells and increased TEMRA γδ cells. A generally higher TIGIT expression was observed in γδ T cells and relative subsets in patients with AMLy-DN, which was partially recovered in patients with AMLy-CR. Furthermore, 17 paired bone marrow from patients with AMLy-DN contained higher percentages of γδ and TIGIT+ γδ T cells and a lower percentage of TCM γδ T cells. Multivariate logistic regression analyses revealed the association of high percentage of TIGIT+ TCM γδ T cells with an increased risk of poor induction chemotherapy response. Conclusions: In this study, we investigated the distribution of γδ T cells and their memory subsets in patients with non-M3 AML and suggested TIGIT+ TCM γδ T cells as potential predictive markers of induction chemotherapy response.
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Receptores de Antígenos de Linfócitos T gama-delta , Receptores Imunológicos , Humanos , Receptores Imunológicos/metabolismo , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Prognóstico , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Adulto Jovem , Idoso , Células T de Memória/imunologia , Células T de Memória/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/diagnóstico , Memória Imunológica , Leucemia Promielocítica Aguda/imunologia , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/mortalidade , ImunofenotipagemRESUMO
Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver disorders of varying severity, ultimately leading to fibrosis. This spectrum primarily consists of NAFL and non-alcoholic steatohepatitis. The pathogenesis of NAFLD is closely associated with disturbances in the gut microbiota and impairment of the intestinal barrier. Non-gut commensal flora, particularly bacteria, play a pivotal role in the progression of NAFLD. Notably, Porphyromonas gingivalis, a principal bacterium involved in periodontitis, is known to facilitate lipid accumulation, augment immune responses, and induce insulin resistance, thereby exacerbating fibrosis in cases of periodontitis-associated NAFLD. The influence of oral microbiota on NAFLD via the "oral-gut-liver" axis is gaining recognition, offering a novel perspective for NAFLD management through microbial imbalance correction. This review endeavors to encapsulate the intricate roles of oral bacteria in NAFLD and explore underlying mechanisms, emphasizing microbial control strategies as a viable therapeutic avenue for NAFLD.
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The anemia of inflammation (AI) is characterized by the presence of inflammation and abnormal elevation of hepcidin. Accumulating evidence has proved that Rocaglamide (RocA) was involved in inflammation regulation. Nevertheless, the role of RocA in AI, especially in iron metabolism, has not been investigated, and its underlying mechanism remains elusive. Here, we demonstrated that RocA dramatically suppressed the elevation of hepcidin and ferritin in LPS-treated mice cell line RAW264.7 and peritoneal macrophages. In vivo study showed that RocA can restrain the depletion of serum iron (SI) and transferrin (Tf) saturation caused by LPS. Further investigation showed that RocA suppressed the upregulation of hepcidin mRNA and downregulation of Fpn1 protein expression in the spleen and liver of LPS-treated mice. Mechanistically, this effect was attributed to RocA's ability to inhibit the IL-6/STAT3 pathway, resulting in the suppression of hepcidin mRNA and subsequent increase in Fpn1 and TfR1 expression in LPS-treated macrophages. Moreover, RocA inhibited the elevation of the cellular labile iron pool (LIP) and reactive oxygen species (ROS) induced by LPS in RAW264.7 cells. These findings reveal a pivotal mechanism underlying the roles of RocA in modulating iron homeostasis and also provide a candidate natural product on alleviating AI.
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Benzofuranos , Hepcidinas , Homeostase , Interleucina-6 , Ferro , Animais , Camundongos , Anemia/metabolismo , Anemia/genética , Anemia/tratamento farmacológico , Anemia/patologia , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Ferritinas/metabolismo , Ferritinas/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Hepcidinas/efeitos dos fármacos , Hepcidinas/genética , Hepcidinas/metabolismo , Homeostase/efeitos dos fármacos , Inflamação/metabolismo , Inflamação/genética , Inflamação/patologia , Interleucina-6/metabolismo , Interleucina-6/genética , Ferro/metabolismo , Lipopolissacarídeos/farmacologia , Fígado/metabolismo , Fígado/patologia , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Receptores da Transferrina/metabolismo , Receptores da Transferrina/genética , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Benzofuranos/farmacologiaRESUMO
The construction of efficient methods for highly sensitive and rapid detection of disease markers is essential for the early diagnosis of serious diseases. In this paper, taking advantage of the UiO-66-NH2 signal molecule in combination with a waste-free entropy-driven DNA machine, a novel homogeneous electrochemical ratiometric platform is developed to detect MircoRNA (miRNA). Metal-organic framework materials (UiO-66-NH2 MOF) and ferrocene were utilized as electrochemical signal tags and reference probes, respectively. The target-initiated waste-free three-dimensional (3D) entropy-driven DNA nanomachine is activated in the presence of miRNA, resulting in DNA-labeled-UiO-66-NH2 falling off from the electrode, leading to a decrease in the signal of UiO-66-NH2 at 0.83V. Our strategy can mitigate false positive responses induced by the DNA probes immobilized on electrodes in traditional distance-dependent signal adjustment ratiometric strategies. The proposed ratiometric platform demonstrates superior sensitivity (a detection limit of 9.8 fM), simplified operation, high selectivity, and high repeatability. The ratiometric biosensor is also applied to detect miRNA content in spiked serum samples.
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Técnicas Biossensoriais , Técnicas Eletroquímicas , Entropia , Estruturas Metalorgânicas , MicroRNAs , MicroRNAs/sangue , MicroRNAs/análise , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Humanos , Estruturas Metalorgânicas/química , DNA/química , Limite de Detecção , Eletrodos , Sondas de DNA/química , Sondas de DNA/genética , Compostos Ferrosos/química , Metalocenos/químicaRESUMO
Immune evasion by cancer cells poses a significant challenge for natural killer (NK) cell-based immunotherapy. Pyroptosis, a newly discovered form of programmed cell death, has shown great potential for enhancing the antitumor immunity of NK cells. Consequently, targeting pyroptosis has become an attractive strategy for boosting NK cell activity against cancer. In this study, various assays were conducted, including NK cell cytotoxicity assays, flow cytometry, xenograft tumor models, real-time PCR, and ELISA to assess NK cell-mediated cell killing, as well as gene and protein expressions. The results indicated that Euphohelioscopin A (Eupho-A), a potential pyroptosis activator, enhances NK cell-mediated lysis of tumor cells, resulting in inhibiting tumor growth that could be reversed by NK cell depletion. Furthermore, we found that Eupho-A significantly enhanced IFN-γ production in NK cells and synergistically up-regulated GSDME with IFN-γ in cancer cells. Eupho-A also increased the cleavage of GSDME, promoting GZMB-induced pyroptosis, which could be reversed by GSDME knockdown and IFN-γ blockade. Overall, the findings suggested that Eupho-A enhanced NK cell-mediated killing of cancer cells by triggering pyroptosis, making Eupho-A a promising pyroptosis activator with great potential for using in NK cell-based cancer immunotherapy.
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In this research, a sustainable substrate, termed green and long-lasting substrate (GLS), featuring a blend of emulsified substrate (ES) and modified rice husk ash (m-RHA) was devised. The primary objective was to facilitate the bioremediation of groundwater contaminated with trichloroethylene (TCE) using innovative GLS for slow carbon release and pH control. The GLS was concocted by homogenizing a mixture of soybean oil, surfactants (Simple Green™ and soya lecithin), and m-RHA, ensuring a gradual release of carbon sources. The hydrothermal synthesis was applied for the production of m-RHA production. The analyses demonstrate that m-RHA were uniform sphere-shape granules with diameters in micro-scale ranges. Results from the microcosm study show that approximately 83% of TCE could be removed (initial TCE concentration = 7.6 mg/L) with GLS supplement after 60 days of operation. Compared to other substrates without RHA addition, higher TCE removal efficiency was obtained, and higher Dehalococcoides sp. (DHC) population and hydA gene (hydrogen-producing gene) copy number were also detected in microcosms with GLS addition. Higher hydrogen concentrations enhanced the DHC growth, which corresponded to the increased DHC populations. The addition of the GLS could provide alkalinity at the initial stage to neutralize the acidified groundwater caused by the produced organic acids after substrate biodegradation, which was advantageous to DHC growth and TCE dechlorination. The addition of m-RHA reached an increased TCE removal efficiency, which was due to the fact that the m-RHA had the zeolite-like structure with a higher surface area and lower granular diameter, and thus, it resulted in a more effective initial adsorption effect. Therefore, a significant amount of TCE could be adsorbed onto the surface of m-RHA, which caused a rapid TCE removal through adsorption. The carbon substrates released from m-RHA could then enhance the subsequent dechlorination. The developed GLS is an environmentally-friendly and green substrate.
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Água Subterrânea , Tricloroetileno , Poluentes Químicos da Água , Tricloroetileno/metabolismo , Biodegradação Ambiental , Carbono , Poluentes Químicos da Água/análise , Água Subterrânea/química , Hidrogênio , Concentração de Íons de HidrogênioRESUMO
Efficient detection of cancer-related nucleic acids is pivotal for early cancer diagnosis. This study introduces a target induced three-dimensional DNA biomimetic networks (B-3D Net)-based ratiometric fluorescence platform using manganese dioxide nanosheets (MnO2 NS)/o-phenylenediamine in combination with hybridization chain reaction to detect cancer-related genes (p53 gene). The incorporation of multiple signals within the B-3D networks can significantly enhance catalytic activity and amplify the output signals, enabling a high sensitivity. Compared with traditional ratio fluorescence platforms, there is no demand to synthesize fluorescent nanoprobes due to the in-situ formation of fluorescence species, which is simple and cost-effective. The corresponding assay demonstrated exceptional sensitivity (with a detection limit as low as 2 fM), selectivity, reproducibility, and accuracy, which mitigates disturbances caused by instrument errors, an inaccurate probe count, and the microenvironment. Furthermore, the ease and straightforwardness of discerning changes in fluorescent brightness and colour by the naked eye are evident. Using the relevant software, a linear relationship between fluorescent images using a smartphone and target concentration was obtained. Hence, the novel ratiometric sensing system will demonstrate new opportunities on determination of target DNA samples in complex biological environments.
Assuntos
Neoplasias , Óxidos , Compostos de Manganês , Corantes Fluorescentes , Reprodutibilidade dos Testes , Biomimética , DNA/genética , Limite de DetecçãoRESUMO
One strategy to correct alveolar bone defects is use of bioactive bone substitutes to maintain the structure of defect site and facilitate cells and vessels' ingrowth. This study aimed to fabricate and characterize the freeze-dried bone regeneration scaffolds composed of polymeric Type I collagen, nano Beta-tricalcium phosphate (ß-TCP), and gelatin. The stable structures of scaffolds were obtained by thermal crosslinking and EDC/NHS ((1-ethyl-3-(3-dimethylaminopropyl) carbodiimide)/(N-hydroxysuccinimide)) chemical crosslinking processes. Subsequently, the physicochemical and biological properties of the scaffolds were characterized and assessed. The results indicated the bioactive composite scaffolds containing 10% and 20% (w/v) nano ß-TCP exhibited suitable porosity (84.45 ± 25.43 nm, and 94.51 ± 14.69 nm respectively), a rapid swelling property (reaching the maximum swelling rate at 1 h), excellent degradation resistance (residual mass percentage of scaffolds higher than 80% on day 90 in PBS and Type I collagenase solution respectively), and sustained calcium release capabilities. Moreover, they displayed outstanding biological properties, including superior cell viability, cell adhesion, and cell proliferation. Additionally, the scaffolds containing 10% and 20% (w/v) nano ß-TCP could promote the osteogenic differentiation of MC3T3-E1. Therefore, the bioactive composite scaffolds containing 10% and 20% (w/v) nano ß-TCP could be further studied for being used to treat alveolar bone defects in vivo.