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1.
Apoptosis ; 29(3-4): 393-411, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37950848

RESUMO

Identification of molecular biomarkers associated with neutrophilic asthma (NA) phenotype may inform the discovery of novel pathobiological mechanisms and the development of diagnostic markers. Three mRNA transcriptome datasets extracted from induced sputum of asthma patients with various inflammatory types were used to screen for macrophage-related molecular mechanisms and targets in NA. Furthermore, the predicted targets were also validated on an independent dataset (N = 3) and animal model (N = 5). A significant increase in total cells, neutrophils and macrophages was observed in bronchoalveolar lavage (BAL) fluid of NA mice induced by ovalbumin/freund's adjuvant, complete (OVA/CFA). And we also found elevated levels of neutrophil and macrophage infiltration in NA subtype in external datasets. NA mice had increased secretion of IgE, IL-1ß, TNF-α and IL-6 in serum and BAL fluid. MPO, an enzyme present in neutrophils, was also highly expressed in NA mice. Then, weighted gene co-expression network analysis (WGCNA) identified 684 targets with the strongest correlation with NA, and we obtained 609 macrophage-related specific differentially expressed genes (DEGs) in NA by integrating macrophage-related genes. The top 10 genes with high degree values were obtained and their mRNA levels and diagnostic performance were then determined by RT-qPCR and receiver operator characteristic (ROC) analysis. Statistically significant correlations were found between macrophages and all key targets, with the strongest correlation between ITGAM and macrophages in NA. Double-Immunofluorescence staining further confirmed the co-localization of ITGAM and F4/80 in NA. ITGAM was identified as a critical target to distinguish NA from healthy/non-NA individuals, which may provide a novel avenue to further uncover the mechanisms and therapy of NA.


Assuntos
Apoptose , Asma , Humanos , Animais , Camundongos , Asma/tratamento farmacológico , Asma/genética , Asma/induzido quimicamente , Neutrófilos , Macrófagos , RNA Mensageiro/genética , Antígeno CD11b
2.
Small ; : e2403267, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38982953

RESUMO

Carbon-based perovskite solar cells (PSCs) coupled with solution-processed hole transport layers (HTLs) have shown potential owing to their combination of low cost and high performance. However, the commonly used poly(3-hexylthiophene) (P3HT) semicrystalline-polymer HTL dominantly shows edge-on molecular orientation, in which the alkyl side chains directly contact the perovskite layer, resulting in an electronically poor contact at the perovskite/P3HT interface. The study adopts a synergetic strategy comprising of additive and solvent engineering to transfer the edge-on molecular orientation of P3HT HTL into 3D molecular orientation. The target P3HT HTL possesses improved charge transport as well as enhanced moisture-repelling capability. Moreover, energy level alignment between target P3HT HTL and perovskite layer is realized. As a result, the champion devices with small (0.04 cm2) and larger areas (1 cm2) deliver notable efficiencies of 20.55% and 18.32%, respectively, which are among the highest efficiency of carbon-electrode PSCs.

3.
J Cardiovasc Pharmacol ; 80(6): 869-876, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36027599

RESUMO

ABSTRACT: This retrospective study investigated factors influencing the steady-state trough concentrations (C trough ) of rivaroxaban in patients with nonvalvular atrial fibrillation (NVAF). We retrieved data from patients with NAVF who first started rivaroxaban anticoagulation at the Fujian Provincial Hospital from October 2017 to October 2020 through the electronic medical record system. Patients were followed for 1 year after the first dose of rivaroxaban, and the primary efficacy and safety end points were recorded. All follow-up visits were completed by October 2021. A C trough of <12 ng/mL was defined as C trough deficiency. Factors that influenced rivaroxaban C trough deficiency were investigated using multivariate binary logistic regression analysis. Kaplan-Meier survival curve analysis was used to determine differences between C trough deficiency and event-free survival. A total of 167 patients with NVAF were enrolled in the study, including 113 men and 54 women, with an average (± SD) age of 70.40 ± 12.46 years. High albumin levels were an independent protective factor against C trough deficiency (odds ratio, 0.932; P = 0.031). C trough deficiency was associated with the probability of freedom from thrombotic events ( P = 0.004); however, there were no significant differences in the probability of freedom from bleeding events ( P > 0.05). In conclusion, among the variables studied, a low albumin level was the main contributor to C trough deficiency. Rivaroxaban C trough deficiency also increased thrombotic events, but this was not associated with hemorrhagic events in Chinese patients with NVAF.


Assuntos
Fibrilação Atrial , Rivaroxabana , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Rivaroxabana/efeitos adversos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Estudos Retrospectivos
4.
BMC Infect Dis ; 22(1): 651, 2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-35902828

RESUMO

BACKGROUND: At present, skeletal tuberculosis (TB) diagnosis is mostly by histopathology, but the positivity rate is low. There is a need to develop new methods for the molecular identification of this disorder. Therefore, we aimed to investigate the clinical utility of quantitative PCR (qPCR)-based diagnosis of skeletal TB from formalin-fixed paraffin-embedded (FFPE) tissues and its comparative evaluation with acid-fast bacillus staining (AFS). METHODS: We detected Mycobacterium tuberculosis (M. tuberculosis/MTB) DNA using qPCR and AFS in FFPE tissue samples from 129 patients suspected of having skeletal TB. The sensitivity, specificity as well as area under the curve (AUC) of qPCR and AFS were calculated. Meanwhile, some factors potentially affecting qPCR and AFS results were investigated. RESULTS: Overall, qPCR outperformed AFS in detecting M. tuberculosis. The AUC of qPCR was higher than that of AFS (0.744 vs.0.561, p < 0.001). Furthermore, decalcification of bone tissues did not affect the sensitivity and specificity of qPCR tests. Whereas it impacted the performance of AFS, decalcification increased AFS's specificity and decreased its sensitivity (p < 0.05). Moreover, qPCR had a significantly larger AUC than AFS in decalcified and non-decalcified groups (0.735/0.756 vs. 0.582/0.534, p < 0.001) respectively. Similarly, the AUC of PCR was more extensive than that of AFS regardless of skeletal TB patients with concomitant pulmonary TB or not (0.929 vs. 0.762; 0.688 vs. 0.524, p < 0.01). CONCLUSIONS: Our data demonstrate that qPCR offers superior accuracy for the detection of mycobacteria in FFPE tissues compared to traditional AFS, indicating its clinical value in osteoarticular TB diagnosis.


Assuntos
Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Formaldeído , Humanos , Mycobacterium tuberculosis/genética , Inclusão em Parafina , Reação em Cadeia da Polimerase em Tempo Real/métodos , Sensibilidade e Especificidade
5.
Int J Med Sci ; 18(2): 335-346, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33390802

RESUMO

Aims: We aimed to explore the crucial miRNA-mRNA axis through bioinformatics analysis and provide evidences for the development of pathophysiological mechanisms and new therapies for HBV-related HCC. Methods: MiRNA (GSE76903) and mRNA (GSE77509) dataset were used to screen differentially expressed miRNAs (DE-miRNAs) and differentially expressed mRNAs (DE-mRNAs) using R software. Overlapping genes between DE-mRNAs and target genes of DE-miRNAs were identified as candidate genes. Hub genes were obtained via cytohubba analysis. The expression at protein and mRNA levels and prognostic value of hub genes were evaluated based on The Cancer Genome Atlas (TCGA) data. Key miRNA-mRNA axes were constructed according to predicted miRNA-mRNA pairs. MiRNA expression and prognostic role were respectively identified using starBase v3.0 and Kaplan-Meier plotter database. Real-time PCR was performed to verify the expression of crucial miRNAs and mRNAs. Coexpression of crucial miRNA and mRNA were analyzed using starBase v3.0. Results: CDK1, CCNB1, CKS2 and CCNE1 were screened as hub genes, which were significantly upregulated at protein and mRNA levels. These up-regulated hub genes were also significantly associated with poor prognosis. Hsa-mir-195-5p/CDK1, hsa-mir-5589-3p/CCNB1 and hsa-let-7c-3p/CKS2 were screened as critical miRNA-mRNA axes. Critical miRNAs were decreased in HCC, which indicates unfavourable prognosis. QPCR results showed that crucial miRNAs were decreased, whereas critical mRNAs were increased in HBV-related HCC. A reverse relationship between miRNA and mRNA in crucial axis was further verified. Conclusion: This study identified several miRNA-mRNA axes in HBV-related HCC. Hsa-mir-195-5p/CDK1, hsa-mir-5589-3p/CCNB1 and hsa-let-7c-3p/CKS2 might serve as potential prognostic biomarkers and therapeutic targets for HBV-related HCC.


Assuntos
Carcinoma Hepatocelular/genética , Hepatite B Crônica/genética , Neoplasias Hepáticas/genética , MicroRNAs/metabolismo , RNA Mensageiro/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Biologia Computacional , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Hepatite B Crônica/mortalidade , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Prognóstico
6.
Biochem Biophys Res Commun ; 521(4): 887-893, 2020 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-31711642

RESUMO

Gastric cancer (GC) is the fourth most frequent malignancy worldwide. Recently, long noncoding RNA (lncRNA) LINC00470 has been demonstrated to play an oncogenic role in human cancer. However, the clinical significance and functional role of LINC00470 in the progression of GC is largely unknown. In this study, our findings showed that LINC00470 was significantly upregulated in GC tissues and cell lines, and correlated with distant metastasis, TNM stage and poor prognosis. Overexpression and knockdown experiments revealed its oncogenic functions on GC cell proliferation, migration and invasion. Mechanistically, LINC00470 associated with PTEN mRNA and suppressed its stability through interaction with the N6-methyladenosine (m6A) writer METTL3. We also showed that LINC00470-METTL3-mediated PTEN mRNA degradation relied on the m6A reader protein YTHDF2-dependent pathway. Taken together, LINC00470 might serve as a therapeutic target for GC patients.


Assuntos
PTEN Fosfo-Hidrolase/genética , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Adenosina/análogos & derivados , Adenosina/genética , Adenosina/metabolismo , Idoso , Linhagem Celular Tumoral , Movimento Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Metiltransferases/genética , Metiltransferases/metabolismo , Pessoa de Meia-Idade , PTEN Fosfo-Hidrolase/metabolismo , Estabilidade de RNA , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
7.
Pestic Biochem Physiol ; 160: 79-86, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31519260

RESUMO

Peptidoglycan recognition proteins (PGRPs) are important recognition receptors which play a critical role in signal identification and transmission in Toll or immune deficiency (IMD) pathways, particularly when pathogens evade and circumvent reactive oxygen species. Antimicrobial peptides (AMPs) synthesis can be activated by these signals to further eliminate pathogens. In this study, we cloned and characterized three different PGRP genes in Plutella xylostella strains, DBM1Ac-S, DBM1Ac-R and a field strain (DBMF). The results showed that PGRP1 belongs to the PGRP-SA family, PGRP2 to PGRP-LB, and PGRP3 to PGRP-LF. Moreover, PGRP1 expressed the highest transcript level, followed by PGRP3 and PGRP2, in two tissues including the gut and the larval carcass tissues of the DBM1Ac-S strain. Furthermore, altered expression levels of PGRP1-3 genes were detected in both gut and carcass tissues. Moreover, the DBM1Ac-R strain had the highest phenol oxidase (PO) activity among these three strains. The characterization of PGRP gene expression and PO activity in DBM1Ac-S, DBM1Ac-R and DBM-F provides insights into their important physiological roles in the immune system of P. xylostella exposed to Bt Cry1Ac toxin.


Assuntos
Proteínas de Bactérias/farmacologia , Proteínas de Transporte/genética , Citocinas/genética , Endotoxinas/farmacologia , Expressão Gênica , Proteínas Hemolisinas/farmacologia , Monofenol Mono-Oxigenase/metabolismo , Sequência de Aminoácidos , Animais , Bacillus thuringiensis/metabolismo , Toxinas de Bacillus thuringiensis , Proteínas de Transporte/química , Clonagem Molecular , Lepidópteros , Homologia de Sequência de Aminoácidos
8.
J Cardiovasc Nurs ; 32(2): 196-203, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-26646596

RESUMO

BACKGROUND: Anxiety is the most common negative emotion among the patients awaiting coronary angiography. The increased anxiety may exacerbate coronary heart disease symptoms and possibly contribute to complications during the procedure. Chinese hand massage is a nonpharmaceutical intervention that has been used in several clinical situations in China and might have beneficial effects on reducing anxiety before coronary angiography. OBJECTIVE: The aim of this study was to evaluate the effectiveness and safety of Chinese hand massage care on anxiety among patients awaiting coronary angiography. METHODS: One hundred eighty-five subjects awaiting coronary angiography in a single hospital in Fuzhou, China, between May 2012 and September 2012 were screened. One hundred eligible participants were recruited and randomly assigned into the control or Chinese hand massage group. The control group received the conventional therapies and care according to the guidelines, and those in the Chinese hand massage group received additional Chinese hand massage care in conjunction with the same conventional therapies and care as the control group. The anxiety scores (evaluated by using the Hamilton Anxiety Rating Scale), heart rate, blood pressure, quality of life (Short-Form Health Survey), and the adverse events were recorded at the baseline and after coronary angiography, respectively. RESULTS: The scores of Hamilton Anxiety Rating Scale in the Chinese hand massage group (11.78 [SD, 2.9]) had a statistically significant decrease compared with those in the control group (15.96 [SD, 3.4]) at post-procedure (P < .01). There was no statistically significant difference on blood pressure, heart rate, and Short-Form Health Survey at postangiography between the Chinese hand massage group and the control group. No adverse event was reported during the intervention period. CONCLUSIONS: Chinese hand massage effectively alleviated anxiety without any adverse effects among patients awaiting coronary angiography. Therefore, it might be recommended as a nonpharmacological nursing intervention. However, future study with a larger sample size is needed to further confirm the efficacy of Chinese hand massage intervention.


Assuntos
Ansiedade/etiologia , Ansiedade/prevenção & controle , Angiografia Coronária/psicologia , Mãos , Massagem , Medicina Tradicional Chinesa , Idoso , Pressão Sanguínea , China , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde
9.
Zhonghua Yi Xue Za Zhi ; 95(35): 2875-9, 2015 Sep 15.
Artigo em Zh | MEDLINE | ID: mdl-26815194

RESUMO

OBJECTIVE: To study effect of tumor suppressor p14ARF on cisplatin-induced apoptosis in human osteosarcoma cells with its molecular mechanisms to provide evidences for increasing chemosensitivity of osteosarcoma. METHODS: pcDNA3.1-p14ARF plasmid was stable transfected into MG63 cells lack of p14ARF expression. Expression of p14ARF on mRNA and protein level was evaluated with RT-PCR and Western blot. MG63, MG63-vec and MG63-ARF cells were treated with cisplatin. Cell growth inhibition and IC50 were determined through MTT assay. Apoptosis was detected using fluorescence-activated cell sorting and Hoechst33258 staining. The expression of p53, Bax, p21, Mdm2, Fas, Caspase-3, caspase-9 and PARP was detected with Western blot. RNAi was used to silence p53. Cells were pre-treated with Caspase-9 specific inhibitor Z-LEHD-FMK to determine whether the effect was Caspase-9-dependent. RESULTS: There was no expression of p14ARF in MG63 and MG63-vec cells but obvious expression in MG63-ARF cells on mRNA and protein level. Cell viability was 84.2%±4.3%, 80.8%±4.3% and 58.9%±5.4% in MG63, MG63-vec, and MG63-ARF cells after treatment of cisplatin for 72 h. IC50 was (11.1±0.6), (10.7±0.9) and (7.2±0.7) µmol/L. The apoptotic rate was 13.6%, 18.5% and 35.9% in groups, There were more obvious apoptotic more changes in MG63-ARF cells than MG63 and MG63-vec cells, and activation of Caspase-3, 9 and PARP on higher level in U2OS-ARF cells after stimulation with cisplatin for 72 h. The expression of p53, Bax, p21, Mdm2 and Fas, in MG63-vec and MG63-ARF cells did not changed (P>0.05). The expression of p53 was effectively and continuously suppressed by p53-siRNA in U2OS-vec and U2OS-ARF cells. The p53 silencing did not alter the cytotoxicity mediated by cisplatin treatment for 72 h (P>0.05). Cell viability was 96.8%±3.6%, 54.1%±5.7% and 89.5%±5.1% in Z-LEHD-FMK, cisplatin and Z-LEHD-FMK+cisplatin groups. CONCLUSION: p14ARF enhances cisplatin-induced apoptosis in human osteosarcoma MG63 cells in p53-independent caspase-9-dependent pathway, in which the intrinsic mitochondrial apoptotic pathway is involved.


Assuntos
Apoptose , Caspase 3 , Caspase 9 , Linhagem Celular Tumoral , Cisplatino , Humanos , Oligopeptídeos , Osteossarcoma , Proteínas Proto-Oncogênicas c-mdm2 , Proteína Supressora de Tumor p14ARF , Proteína Supressora de Tumor p53
10.
Zhonghua Yi Xue Za Zhi ; 94(43): 3443-6, 2014 Nov 25.
Artigo em Zh | MEDLINE | ID: mdl-25622680

RESUMO

OBJECTIVE: To explore the effects of tumor suppressor p14ARF on chemosensitivity of human osteosarcoma U2OS cells to cisplatin and elucidate its molecular mechanism. METHODS: U2OS cells expressing no p14ARF and U2OS-ARF cells expressing p14ARF stably through stable transfection were treated with cisplatin. Cell viability and IC50 were assayed with methyl thiazolyl tetrazolium (MTT). Apoptosis was examined by fluorescence-activated cell sorting and Hoechst33258 staining. The expressions of p53, Bax, p21, Mdm2 and Fas were detected by Western blot. And colorimetry was used to determine the activities of caspase-3, caspase-8 and caspase-9. RESULTS: The viability was 84.8% ± 4.4%, 86.9% ± 5.0% and 66.7% ± 4.6% respectively in U2OS, U2OS-vec and U2OS-ARF cells. The values of IC50 were (15.8 ± 0.9) µmol/L, (16.3 ± 0.6) and (8.9 ± 0.8) µmol/L respectively in U2OS, U2OS-vec and U2OS-ARF cells. The levels of viability and IC50 obviously decreased in U2OS-ARF cells in response to cisplatin (P < 0.05). There were higher apoptotic rate and more obvious apoptotic morphological changes in U2OS-ARF cells than U2OS and U2OS-vec cells. The basal levels of p53, Mdm2 and p21 in U2OS-ARF cells were slightly higher than those in U2OS-vec cells. Cisplatin up-regulated p53, Mdm2 and p21 in both cell lines. However, the up-regulation was more pronounced in U2OS-ARF cells. Cisplatin did not change the levels of Bax and Fas in U2OS-vec cells. Bax protein was up-regulated in U2OS-ARF cells while the level of Fas remained constant. p14ARF also enhanced the activities of caspase-9 and caspase-3 in response to cisplatin. CONCLUSION: p14ARF enhances the chemosensitivity to cisplatin in human osteosarcoma U2OS cells through p53 apoptotic pathway. And intrinsic mitochondrial apoptosis is involved.


Assuntos
Osteossarcoma , Apoptose , Caspases , Linhagem Celular Tumoral , Sobrevivência Celular , Cisplatino , Genes Supressores de Tumor , Humanos , Proteínas Oncogênicas , Proteínas Proto-Oncogênicas c-mdm2 , Proteína Supressora de Tumor p53 , Regulação para Cima , Proteína X Associada a bcl-2
11.
J Ethnopharmacol ; 330: 118102, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-38561057

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoqinglong Decotion (XQLD) is a commonly used Chinese herbal formula in clinical practice, especially for allergic diseases such as asthma. However, its intrinsic mechanism for the treatment of neutrophilic asthma (NA) remains unclear. AIM OF THE STUDY: The aim of this study was to evaluate the efficacy and potential mechanisms of XQLD on NA using network pharmacology and in vivo experiments. MATERIALS AND METHODS: First, the active compounds, potential targets and mechanisms of XQLD against NA were initially elucidated by network pharmacology. Then, OVA/CFA-induced NA mice were treated with XQLD to assess its efficacy. Proteins were then analyzed and quantified using a Tandem Mass Tags approach for differentially expressed proteins (DEPs) to further reveal the mechanisms of NA treatment by XQLD. Finally, the hub genes, critical DEPs and potential pathways were validated. RESULTS: 176 active compounds and 180 targets against NA were identified in XQLD. Protein-protein interaction (PPI) network revealed CXCL10, CX3CR1, TLR7, NCF1 and FABP4 as hub genes. In vivo experiments showed that XQLD attenuated inflammatory infiltrates, airway mucus secretion and remodeling in the lungs of NA mice. Moreover, XQLD significantly alleviated airway neutrophil inflammation in NA mice by decreasing the expression of IL-8, MPO and NE. XQLD also reduced the levels of CXCL10, CX3CR1, TLR7, NCF1 and FABP4, which are closely associated with neutrophil inflammation. Proteomics analysis identified 28 overlapping DEPs in the control, NA and XQLD groups, and we found that XQLD inhibited ferroptosis signal pathway (elevated GPX4 and decreased ASCL3) as well as the expression of ARG1, MMP12 and SPP1, while activating the Rap1 signaling pathway. CONCLUSION: This study revealed that inhibition of ARG1, MMP12 and SPP1 expression as well as ferroptosis pathways, and activation of the Rap1 signaling pathway contribute to the therapeutic effect of XQLD on NA.


Assuntos
Asma , Medicamentos de Ervas Chinesas , Farmacologia em Rede , Proteômica , Animais , Asma/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Camundongos , Mapas de Interação de Proteínas , Feminino , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Camundongos Endogâmicos BALB C , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Antiasmáticos/farmacologia , Modelos Animais de Doenças , Ovalbumina , Masculino
12.
Artigo em Inglês | MEDLINE | ID: mdl-38920066

RESUMO

INTRODUCTION: Most COVID-19 survivors are troubled with chronic persistent symptoms, which have currently no definitive treatments. Bufei Huoxue (BFHX) capsule exerts clinical benefit, while the material basis and molecular mechanism remain unclear. AIM: The study aimed to elucidate the protective mechanisms of BFHX capsules against COVID-19 convalescence. UHPLC-HRMS and various databases were employed to explore potential compounds and targets. PPI, MCODE, transcription factor (TF), and miRNA analyses were conducted to receive hub targets and corresponding upstream regulators. METHOD: Molecular docking was applied to verify the binding activity of compound and target. Further, GO, KEGG, WIKI, and Reactome analyses were performed, and compound-targetsymptom and gene-disease networks were constructed. A total of 127 compounds and 313 targets were acquired. A sum of 10 hub targets were screened and showed good binding affinities with critical compounds. RESULT: MLLT1, CBFB, and EZH2 were identified as key TFs, and hsa-mir-146a-5p, hsa-mir- 26b-5p, and hsa-mir-24-3p were predicted to be important miRNAs. BFHX capsule may alleviate the symptoms by targeting TNF, IL-6, IFNG, and TGF-ß1. Besides, BFHX capsule may exert a therapeutic effect on respiratory disease (especially pulmonary fibrosis and lung infection) and multi-system damage during COVID-19 convalescence by regulating cytokine-cytokine receptor interaction, as well as TGF-ß, TNF, and Toll-like receptor signaling pathways. CONCLUSION: In summary, BFHX capsule may exert a therapeutic effect on multi-system damages during COVID-19 convalescence through multiple compounds (such as albiflorin, isopsoralen, and neobavaisoflavone), multiple targets (such as TNF, IL-6, and EGF) and multiple pathways (TGF-ß, TNF, and Toll-like receptor signaling pathways).

13.
Commun Biol ; 7(1): 181, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38351296

RESUMO

Airway epithelial transcriptome analysis of asthma patients with different severity was used to disentangle the immune infiltration mechanisms affecting asthma exacerbation, which may be advantageous to asthma treatment. Here we introduce various bioinformatics methods and develop two models: an OVA/CFA-induced neutrophil asthma mouse model and an LPS-induced human bronchial epithelial cell damage model. Our objective is to investigate the molecular mechanisms, potential targets, and therapeutic strategies associated with asthma severity. Multiple bioinformatics methods identify meaningful differences in the degree of neutrophil infiltration in asthma patients with different severity. Then, PTPRC, TLR2, MMP9, FCGR3B, TYROBP, CXCR1, S100A12, FPR1, CCR1 and CXCR2 are identified as the hub genes. Furthermore, the mRNA expression of 10 hub genes is determined in vivo and in vitro models. Reperixin is identified as a pivotal drug targeting CXCR1, CXCR2 and MMP9. We further test the potential efficiency of Reperixin in 16HBE cells, and conclude that Reperixin can attenuate LPS-induced cellular damage and inhibit the expression of them. In this study, we successfully identify and validate several neutrophilic signatures and targets associated with asthma severity. Notably, Reperixin displays the ability to target CXCR1, CXCR2, and MMP9, suggesting its potential therapeutic value for managing deteriorating asthma.


Assuntos
Asma , Metaloproteinase 9 da Matriz , Animais , Camundongos , Humanos , Metaloproteinase 9 da Matriz/genética , Lipopolissacarídeos , Asma/tratamento farmacológico , Asma/genética , Brônquios , Perfilação da Expressão Gênica
14.
Eur J Pharmacol ; 966: 176378, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38309679

RESUMO

Heart failure (HF) is a complex chronic condition characterized by structural and functional impairments. The differentiation of endothelial cells into myofibroblasts (EndoMT) in response to cardiac fibrosis is controversial, and the relative contribution of endothelial plasticity remains to be explored. Single-cell RNA sequencing was used to identify endothelial cells undergoing fibrotic differentiation within 2 weeks of transverse aortic constriction (TAC). This subset of endothelial cells transiently expressed fibrotic genes but had low expression of alpha-smooth muscle actin, indicating a non-canonical EndoMT, which we named a transient fibrotic-like phenotype (EndoFP). The role of EndoFP in pathological cardiac remodeling may be correlated with increased levels of osteopontin. Cardiomyocytes and fibroblasts co-cultured with EndoFP exhibited heightened pro-hypertrophic and pro-fibrotic effects. Mechanistically, we found that the upregulated expression of insulin-like growth factor-binding protein 5 may be a key mediator of EndoFP-induced cardiac dysfunction. Furthermore, our findings suggested that Rab5a is a novel regulatory gene involved in the EndoFP process. Our study suggests that the specific endothelial subset identified in TAC-induced pressure overload plays a critical role in the cellular interactions that lead to cardiac fibrosis and hypertrophy. Additionally, our findings provide insight into the mechanisms underlying EndoFP, making it a potential therapeutic target for early heart failure.


Assuntos
Cardiomiopatias , Cardiopatias , Insuficiência Cardíaca , Animais , Camundongos , Miócitos Cardíacos , Células Endoteliais/patologia , Cardiopatias/metabolismo , Insuficiência Cardíaca/patologia , Cardiomiopatias/metabolismo , Fibrose , Fibroblastos/metabolismo , Remodelação Ventricular , Camundongos Endogâmicos C57BL
15.
Biosensors (Basel) ; 13(5)2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37232881

RESUMO

It is still challenging to achieve simultaneous and sensitive detection of multiple organophosphorus pesticides (OPs). Herein, we optimized the ssDNA templates for the synthesis of silver nanoclusters (Ag NCs). For the first time, we found that the fluorescence intensity of T base-extended DNA-templated Ag NCs was over three times higher than the original C-riched DNA-templated Ag NCs. Moreover, a "turn-off" fluorescence sensor based on the brightest DNA-Ag NCs was constructed for the sensitive detection of dimethoate, ethion and phorate. Under strong alkaline conditions, the P-S bonds in three pesticides were broken, and the corresponding hydrolysates were obtained. The sulfhydryl groups in the hydrolyzed products formed Ag-S bonds with the silver atoms on the surface of Ag NCs, which resulted in the aggregation of Ag NCs, following the fluorescence quenching. The fluorescence sensor showed that the linear ranges were 0.1-4 ng/mL for dimethoate with a limit of detection (LOD) of 0.05 ng/mL, 0.3-2 µg/mL for ethion with a LOD of 30 ng/mL, and 0.03-0.25 µg/mL for phorate with a LOD of 3 ng/mL. Moreover, the developed method was successfully applied to the detection of dimethoate, ethion and phorate in lake water samples, indicating a potential application in OP detection.


Assuntos
Nanopartículas Metálicas , Praguicidas , Prata/química , Compostos Organofosforados , Fluorescência , Dimetoato , Forato , Nanopartículas Metálicas/química , DNA/química , Espectrometria de Fluorescência
16.
Microbiol Resour Announc ; 12(1): e0100722, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36468866

RESUMO

Rhodococcus qingshengii PM1 was isolated from selenium-rich carbonaceous mudstones in Enshi, Hubei, China. Here, we report the complete genome sequence of this strain, which was obtained by combining Illumina and Nanopore sequencing.

17.
Front Endocrinol (Lausanne) ; 14: 1187882, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37347115

RESUMO

Background: Coronavirus disease 2019 (COVID-19) is a highly contagious respiratory disease that has posed a serious threat to people's daily lives and caused an unprecedented challenge to public health and people's health worldwide. Lung squamous cell carcinoma (LUSC) is a common type of lung malignancy with a highly aggressive nature and poor prognosis. Patients with LUSC could be at risk for COVID-19, We conducted this study to examine the potential for naringenin to develop into an ideal medicine and investigate the underlying action mechanisms of naringenin in COVID-19 and LUSC due to the anti-viral, anti-tumor, and anti-inflammatory activities of naringenin. Methods: LUSC related genes were obtained from TCGA, PharmGKB, TTD,GeneCards and NCBI, and then the transcriptome data for COVID-19 was downloaded from GEO, DisGeNET, CTD, DrugBank, PubChem, TTD, NCBI Gene, OMIM. The drug targets of Naringenin were revealed through CTD, BATMAN, TCMIP, SymMap, Chemical Association Networks, SwissTargetPrediction, PharmMapper, ECTM, and DGIdb. The genes related to susceptibility to COVID-19 in LUSC patients were obtained through differential analysis. The interaction of COVID-19/LUSC related genes was evaluated and demonstrated using STRING to develop a a COX risk regression model to screen and evaluate the association of genes with clinical characteristics. To investigate the related functional and pathway analysis of the common targets of COVID-19/LUSC and Naringenin, KEGG and GO enrichment analysis were employed to perform the functional analysis of the target genes. Finally, The Hub Gene was screened and visualized using Cytoscape, and molecular docking between the drug and the target was performed using Autodock. Results: We discovered numerous COVID-19/LUSC target genes and examined their prognostic value in LUSC patients utilizing a variety of bioinformatics and network pharmacology methods. Furthermore, a risk score model with strong predictive performance was developed based on these target genes to assess the prognosis of LUSC patients with COVID-19. We intersected the therapeutic target genes of naringenin with the LUSC, COVID-19-related targets, and identified 354 common targets, which could be used as potential target genes for naringenin to treat COVID-19/LUSC. The treatment of COVID-19/LUSC with naringenin may involve oxidative stress, anti-inflammatory, antiviral, antiviral, apoptosis, immunological, and multiple pathways containing PI3K-Akt, HIF-1, and VEGF, according to the results of the GO and KEGG enrichment analysis of these 354 common targets. By constructing a PPI network, we ascertained AKT1, TP53, SRC, MAPK1, MAPK3, and HSP90AA1 as possible hub targets of naringenin for the treatment of COVID-19/LUSC. Last but not least, molecular docking investigations showed that naringenin has strong binding activity in COVID-19/LUSC. Conclusion: We revealed for the first time the pharmacological targets and potential molecular processes of naringenin for the treatment of COVID-19/LUSC. However, these results need to be confirmed by additional research and validation in real LUSC patients with COVID-19.


Assuntos
COVID-19 , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , COVID-19/epidemiologia , COVID-19/genética , Antivirais
18.
Health Sci Rep ; 5(5): e834, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36177398

RESUMO

Background and Aims: It is well known that public health emergencies can affect the mental health of medical personnel, and many studies have focused on cross-sectional studies with short-term benefits. The present study aimed to investigate the long-term influence of infectious disease outbreak about the mental health of hospital staff. Methods: The demographic characteristics and mental health status of staff in Fuzhou, China, were analyzed by using the Generalized Anxiety Disorder (GAD-7) Scale and Depression Screening Scale (9-item Patient Health Questionnaire [PHQ-9]) in February and December 2020. Results: There were no significant differences in anxiety levels during different time periods (p > 0.05), but there were significant differences among anxiety level and total score of GAD-7 scale (p < 0.001). There were significant differences among the number of people with depression, depression level, and total score on the PHQ-9 scale (p < 0.001). As the pandemic progressed, total scores of anxiety in medical staff with different titles decreased (p < 0.05), but depression scores in professionals with intermediate and senior titles increased significantly (p < 0.05). changes in anxiety and depression scores during different time periods also changed according to hospital worker specialty. Total scores of anxiety in doctors, nurses, medical technicians, and other staff members all decreased (p < 0.05), while total scores of depression in doctors, nurses, and other staff members significantly increased (p < 0.05). There were no significant differences in total depression score among medical technicians (p > 0.05). Conclusions: Since the outbreak of an infectious disease public health emergency, the anxiety of hospital staff has decreased over time, but the depression has increased. The management and psychological support personnel in medical institutions should continue to pay attention to the mental health of medical staff, and it is necessary to take different intervention measures in different periods when implementing the psychological crisis prevention mechanism.

19.
Biosensors (Basel) ; 12(10)2022 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-36290969

RESUMO

In this work, a label-free fluorescent detection method for glyphosate, based on DNA-templated silver nanoclusters (DNA-Ag NCs) and a Cu2+-ion-modulated strategy, was developed. In the presence of Cu2+, the fluorescence of the DNA-Ag NCs was quenched. Glyphosate can restore the fluorescence of DNA-Ag NCs. By analyzing the storage stability of the obtained DNA-Ag NCs using different DNA templates, specific DNA-Ag NCs were selected for the construction of the glyphosate sensor. The ultrasensitive detection of glyphosate was achieved by optimizing the buffer pH and Cu2+ concentration. The sensing of glyphosate demonstrated a linear response in the range of 1.0-50 ng/mL. The limit of detection (LOD) was 0.2 ng/mL. The proposed method was successfully applied in the detection of glyphosate in a real sample, indicating its high application potential for glyphosate detection.


Assuntos
Nanopartículas Metálicas , Prata , Espectrometria de Fluorescência , DNA , Corantes Fluorescentes
20.
Bioengineered ; 13(5): 12475-12488, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35593105

RESUMO

Root-related or endophytic microbes in halophytes play an important role in adaptation to extreme saline environments. However, there have been few comparisons of microbial distribution patterns in different tissues associated with halophytes. Here, we analyzed the bacterial communities and distribution patterns of the rhizospheres and tissue endosphere in two Suaeda species (S. salsa and S. corniculata Bunge) using the 16S rRNA gene sequencing. The results showed that the bacterial abundance and diversity in the rhizosphere were significantly higher than that of endophytic, but lower than that of bulk soil. Microbial-diversity analysis showed that the dominant phyla of all samples were Proteobacteria, Actinobacteria, Bacteroidetes, Acidobacteria and Firmicutes, among which Proteobacteria were extremely abundant in all the tissue endosphere. Heatmap and Linear discriminant analysis Effect Size (LEfSe) results showed that there were notable differences in microbial community composition related to plant compartments. Different networks based on plant compartments exhibited distinct topological features. Additionally, the bulk soil and rhizosphere networks were more complex and showed higher centrality and connectedness than the three endosphere networks. These results strongly suggested that plant compartments, and not species, affect microbiome composition.


Assuntos
Chenopodiaceae , Microbiota , Bactérias/genética , Chenopodiaceae/genética , Chenopodiaceae/microbiologia , Microbiota/genética , Raízes de Plantas/microbiologia , RNA Ribossômico 16S/genética , Rizosfera , Plantas Tolerantes a Sal/genética , Solo , Microbiologia do Solo
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