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1.
Front Chem ; 9: 755836, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568290

RESUMO

In this study, a kind of graphene oxide-cuprous oxide (GO-Cu2O) nanocomposites was fabricated with different morphologies to serve as a photocatalytic material for the degradation of organic/inorganic dyes under visible light and the bactericidal effect against pathogenic bacteria. The GO-Cu2O was prepared with solid cube and hollow dodecahedra morphologies through in-situ synthesis, and characterized by scanning electron microscopy (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD), Raman, Ultraviolet and visible spectrophotometry (UV/vis), and Fourier transform infrared spectroscopy. In comparison with cubic GO-Cu2O, the absorption and degradation efficiency of the GO-Cu2O dodecahedra (GCD) composite in Methyl orange (MO), Rhodamine B (RhB), and phenol was higher owning to the more active sites for the simultaneous dye and light absorption of hollow structure. The antibacterial effect of the GO-Cu2O dodecahedra was examined by the flat colony counting method with an excellent bactericidal effect against pathogenic bacteria. The possible mechanism for the preparation of GCD possessing the enhancement of the visible-light photocatalytic and antibacterial efficiencies were also investigated.

2.
BMC Med ; 19(1): 190, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34465315

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) is a clinically aggressive disease with abundant variants that cause homologous recombination repair deficiency (HRD). Whether TNBC patients with HRD are sensitive to anthracycline, cyclophosphamide and taxane (ACT), and whether the combination of HRD and tumour immunity can improve the recognition of ACT responders are still unknown. METHODS: Data from 83 TNBC patients in The Cancer Genome Atlas (TCGA) was used as a discovery cohort to analyse the association between HRD and ACT chemotherapy benefits. The combined effects of HRD and immune activation on ACT chemotherapy were explored at both the genome and the transcriptome levels. Independent cohorts from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and Gene Expression Omnibus (GEO) were adopted to validate our findings. RESULTS: HRD was associated with a longer ACT chemotherapy failure-free interval (FFI) with a hazard ratio of 0.16 (P = 0.004) and improved patient prognosis (P = 0.0063). By analysing both HRD status and ACT response, we identified patients with a distinct TNBC subtype (ACT-S&HR-P) that showed higher tumour lymphocyte infiltration, IFN-γ activity and NK cell levels. Patients with ACT-S&HR-P had significantly elevated immune inhibitor levels and presented immune activation associated with the increased activities of both innate immune cells and adaptive immune cells, which suggested treatment with immune checkpoint blockade as an option for this subtype. Our analysis revealed that the combination of HRD and immune activation enhanced the efficiency of identifying responders to ACT chemotherapy (AUC = 0.91, P = 1.06e-04) and synergistically contributed to the clinical benefits of TNBC patients. A transcriptional HRD signature of ACT response-related prognostic factors was identified and independently validated to be significantly associated with improved survival in the GEO cohort (P = 0.0038) and the METABRIC dataset (P < 0.0001). CONCLUSIONS: These findings highlight that HR deficiency prolongs FFI and predicts intensified responses in TNBC patients by combining HRD and immune activation, which provides a molecular basis for identifying ACT responders.


Assuntos
Neoplasias de Mama Triplo Negativas , Antraciclinas , Ciclofosfamida , Humanos , Reparo de DNA por Recombinação , Taxoides , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética
3.
Aging (Albany NY) ; 13(13): 17830-17846, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34254950

RESUMO

Esophageal squamous cell carcinoma (ESCC) represents one of the most common malignancies and is the fifth leading cause of cancer-related deaths. Long intergenic non-coding RNAs (lincRNAs) have been suggested to be dysregulated in various types of cancers, and a growing number of lincRNAs have been implicated to be functional in the ESCC progression. In this study, we examined the role of linc00941 in the ESCC progression and explored the underlying molecular mechanisms. The bioinformatics analysis identified the up-regulation of linc00941 in the ESCC tissues. Further in vitro studies showed that linc00941 was up-regulated in ESCC cell lines. The loss-of-function studies demonstrated that linc00941 knockdown suppressed ESCC cell proliferation, invasion and migration, and also suppressed the in vivo tumor growth. Furthermore, bioinformatics prediction along with luciferase reporter assay and RNA immunoprecipitation assay implied that linc00941 acted as a competing endogenous RNA for miR-877-3p, and linc00941 regulated ESCC cell progression via at least targeting miR-877-3p. Subsequently, miR-877-3p targeted prostate transmembrane protein, androgen induced 1 (PMEPA1) 3' untranslated region and repressed PMEPA1 expression in ESCC cells; overexpression of PMEPA1 attenuated the inhibitory effects of linc00941 knockdown on the ESCC cell progression. Linc00941 knockdown suppressed epithelial-mesenchymal transition (EMT) via targeting miR-877-3p/PMEPA1 axis in ESCC cells. In conclusion, our results indicated the oncogenic role of linc00941 in ESCC, and knockdown of linc00941 suppressed ESCC cell proliferation, invasion, migration and EMT via interacting with miR-877-3p/PMEPA1 axis.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Proteínas de Membrana/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Biologia Computacional , Progressão da Doença , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Front Microbiol ; 12: 616937, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33841348

RESUMO

The present manuscript highlights the potential role of Streptomyces roseoverticillatus 63 (Sr-63) against Xanthomonas oryzae pv. oryzae (Xoo), which is the cause of a disastrous bacterial leaf blight disease with rice worldwide. The disease suppression was achieved under greenhouse conditions. A foliar spray of the fermentation broth of Sr-63 significantly reduced the leaf blight symptoms with rice in Xoo inoculated rice plants. Furthermore, we observed that the carbazomycin B, isolated from the fermentation broth of Sr-63, was demonstrated to have antibacterial activity against Xoo with a minimum inhibitory concentration (MIC) of 8 µg mL-1. The results indicated that carbzomycin B hampered the membrane formation of Xoo, reduced the production of xanthomonadin and extracellular polymeric substance (EPS). The fourier transform infrared spectroscopic (FT-IR) indicated that carbazomycin B changed the components of the cell membrane, then caused a change of the cell surface hydrophobicity of Xoo. Scanning electron microscopy revealed that the Xoo cells treated with carbazomycin B exhibited apparent structural deformation. The results also indicated that carbazomycin B had a negative impact on the metabolism of Xoo, carbazomycin B reduced the activity of malate dehydrogenase (MDH) activity and suppressed the protein expression of Xoo. Overall, our data suggests that Streptomyces roseoverticillatus 63 is a promising biocontrol agent that could be used to combat the bacterial leaf blight diseases of rice.

5.
Cancers (Basel) ; 13(7)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33915876

RESUMO

BACKGROUND: Immune checkpoint blockade (ICB) therapy has yielded successful clinical responses in treatment of a minority of patients in certain cancer types. Substantial efforts were made to establish biomarkers for predicting responsiveness to ICB. However, the systematic assessment of these ICB response biomarkers remains insufficient. METHODS: We collected 22 transcriptome-based biomarkers for ICB response and constructed multiple benchmark datasets to evaluate the associations with clinical response, predictive performance, and clinical efficacy of them in pre-treatment patients with distinct ICB agents in diverse cancers. RESULTS: Overall, "Immune-checkpoint molecule" biomarkers PD-L1, PD-L2, CTLA-4 and IMPRES and the "Effector molecule" biomarker CYT showed significant associations with ICB response and clinical outcomes. These immune-checkpoint biomarkers and another immune effector IFN-gamma presented predictive ability in melanoma, urothelial cancer (UC) and clear cell renal-cell cancer (ccRCC). In non-small cell lung cancer (NSCLC), only PD-L2 and CTLA-4 showed preferable correlation with clinical response. Under different ICB therapies, the top-performing biomarkers were usually mutually exclusive in patients with anti-PD-1 and anti-CTLA-4 therapy, and most of biomarkers presented outstanding predictive power in patients with combined anti-PD-1 and anti-CTLA-4 therapy. CONCLUSIONS: Our results show these biomarkers had different performance in predicting ICB response across distinct ICB agents in diverse cancers.

6.
Biomed Pharmacother ; 137: 111373, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33761599

RESUMO

Psoriasis is a chronic, inflammatory autoimmune disease mediated by T cells, and characterized with abnormal proliferation and differentiation of keratinocytes, and inflammatory infiltration. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway has been identified to play essential roles in mediating various of biological processes, and is closely related to autoimmune diseases. Dendritic cells (DCs) are important antigen presenting cells and play an important regulatory role in T cells. The proliferation, differentiation and function of DCs are regulated by JAK and FMS-like tyrosine kinase 3 (FLT3) signal pathways. Flonoltinib maleate (FM), a high selectivity dual JAK2/FLT3 inhibitor with IC50 values of 0.8 nM and 15 nM for JAK2 and FLT3, respectively, was developed by our laboratory. Moreover, FM was a potent JAK2 inhibitor with 863-fold and 696-fold selectivity over JAK1 and JAK3, respectively. In this study, the anti-psoriasis activity of FM was evaluated both in vitro and in vivo. FM effectively inhibited the proliferation of HaCaT, the inflammatory keratinocyte induced by M5 and markedly suppressed the generation and differentiation of DCs from bone marrow (BM), and inhibited the expression of FLT3 in DCs in vitro. FM effectively inhibited the ear thickening and improved the pathological changes of the ear in interleukin (IL)-23-induced psoriasis-like acanthosis mouse model. Further in keratin 14-vascular endothelial growth factor (K14-VEGF) transgenic homozygous mice model, FM could obviously improve the psoriatic symptom and pathological changes, significantly inhibit the generations of Th1 and Th17 cells in the spleen, and the accumulations of DCs in the ears. FM could also significantly reduce the expression of various inflammatory factors both in C57BL/6 and K14-VEGF mice ears, and the serum of K14-VEGF mice. Mechanism revealed that FM effectively suppressed the phosphorylation of JAK2, STAT3 and STAT5 in inflammatory keratinocytes and the mice ears of C57BL/6 and K14-VEGF, as well as the phosphorylation of FLT3 in K14-VEGF mice ears. In conclusion, FM plays an excellent anti-psoriasis activity, including inhibiting keratinocyte proliferation and regulating inflammatory response through inhibiting JAK2 and FLT3 signaling pathway.


Assuntos
Janus Quinase 2/antagonistas & inibidores , Psoríase/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidores , Animais , Células da Medula Óssea/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Orelha Externa/efeitos dos fármacos , Humanos , Queratinócitos/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Inibidores de Proteínas Quinases/farmacologia , Fatores de Transcrição STAT/efeitos dos fármacos , Fatores de Transcrição STAT/genética
7.
Environ Pollut ; 270: 116079, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33234379

RESUMO

The mechanisms of soot's photochemistry are still unclear, especially, how the microstructure and composition of soot influence its photoactivity. In the current study, we started with the exploration of the microstructure of soot particles and gained new insights. The elemental-carbon fraction of soot (E-soot), considered the core component of soot and can reflect the intrinsic characteristics of soot, was extracted by organic solvents and characterized in terms of structure and chemical reactivity. The intrinsic structure of E-soot was found to be more analogous to reduced graphene oxide than to graphene, in terms of containing similar levels of defective sites such as oxygen-containing functional groups and environmentally persistent free radicals, as well as exhibiting similar optoelectronic performance. The generation of reactive oxygen species via an electron transfer pathway under visible light suggests that reduced graphene oxide-like E-soot can serve as a potential carbo-photocatalyst, which facilitates elucidating the mechanism of E-soot's role during soot's photochemical aging. Our study reveals the intrinsic structure of soot and its role in photo-triggered reactive oxygen species production, which is vital for atmospheric and health effects.


Assuntos
Grafite , Fuligem , Luz , Espécies Reativas de Oxigênio , Esqueleto
8.
Mol Immunol ; 125: 15-22, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32619930

RESUMO

PIM1 is serine/threonine protein kinase that is involved in numerous biological processes. Pulmonary fibrosis (PF) is a chronic pathological result of the dysfunctional repair of lung injury without effective therapeutic treatments. In the current study, we investigated whether PIM1 inhibition would improve bleomycin (BLM)-induced pulmonary fibrosis. In a BLM-induced pulmonary fibrosis model, PIM1 was persistently upregulated in fibrotic lung tissues. Furthermore, PIM1 inhibition by the PIM1-specific inhibitor SMI-4a showed protective effects against BLM-induced mortality. Furthermore, SMI-4a suppressed hydroxyproline deposition and reversed epithelial-mesenchymal transition (EMT) formation, which was characterized by E-cadherin and α-SMA expression in vivo. More importantly, the ZEB1/E-cadherin pathway was found to be closely associated with BLM-induced pulmonary fibrosis. After the in vitro treatment of A549 cells, PIM1 regulated E-cadherin expression by dependently modulating the activity of the transcription factor ZEB1. These findings were verified in vivo after SMI-4a administration. Finally, an shPIM1-expressing adeno-associated virus was delivered via intratracheal injection to induce a long-term PIM1 deficiency in the alveolar epithelium. AAV-mediated PIM1 knockdown in the lung tissues alleviated BLM-induced pulmonary fibrosis, as indicated by collagen accumulation reduction, pulmonary histopathological mitigation and EMT reversion. These findings enhance our understanding of the roles of PIM1 in BLM-induced pulmonary fibrosis and suggest PIM1 inhibition as a potential therapeutic strategy in chronic pulmonary injuries.


Assuntos
Células Epiteliais Alveolares/metabolismo , Caderinas/metabolismo , Proteínas Fúngicas/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fibrose Pulmonar/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Células A549 , Células Epiteliais Alveolares/patologia , Animais , Antibióticos Antineoplásicos/toxicidade , Bleomicina/toxicidade , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal/fisiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/patologia
9.
J Transl Med ; 18(1): 226, 2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32513288

RESUMO

BACKGROUND: Docetaxel (DTX) is a widely used anti-tumour drug, and its dosage is solely determined by body surface area (BSA). Adverse events, such as neutropenia or unsatisfied efficacy, likely occur because of differences in the pharmacokinetics (PK) and pharmacodynamics of patients. Thus, a feasible dosage adjustment method is needed. METHODS: A total of 209 eligible patients who provided consent were enrolled and randomised into two groups to receive the BSA- and PK-guided dosage adjustments of DTX-based chemotherapy (3 weeks per cycle). The AUC of DTX was detected, and the therapeutic window for Chinese patients was determined. The proportion of patients within the therapeutic window was evaluated. Neutropenia was examined in accordance with the toxicity grading standard suggested by the World Health Organisation. Tumour response was assessed in accordance with Response Evaluation Criteria in Solid Tumors version 1.1. The primary endpoint was the incidence of neutropenia, and the secondary endpoints were disease control rate (DCR) and 3-year survival rate. RESULTS: The therapeutic window for Chinese patients was 1.7-2.5 mg·h/L. The proportion of patients within the therapeutic window was 63.89% versus 28.33% (P < 0.0001), and the incidence of neutropenia was 68.33% versus 38.89% (P = 0.001) in the experimental group versus the control group in the sixth cycle, respectively. DCR was 72% versus 85% (P = 0.018) in the control group versus the experimental group. The 3-year survival rate of the PK group was significantly higher than that of the BSA group (P = 0.034). CONCLUSIONS: The PK-guided dosage adjustment of DTX could significantly increase the proportion of patients within the therapeutic window, decrease the incidence of neutropenia and increase the DCR and the 3-year survival rate. The PK-guided dosage adjustment based on the dynamic monitoring of AUC could be a useful method for oncologists to improve individualised treatment options, optimise drug efficacy and reduce drug toxicity.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Área Sob a Curva , Docetaxel/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Estudos Prospectivos
10.
Environ Sci Technol ; 54(14): 8558-8567, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32589839

RESUMO

Modifications of the physicochemical properties and oxidative potential (OP) of soot due to visible-light irradiation and its underlying mechanisms during atmospheric aging have not been elucidated. In this study, two types of soot obtained using different air/fuel ratios (A/F) were aged under visible light with or without ozone (O3) at an atmospherically relevant level in an environmental chamber. Physicochemical characteristics and OP of aged soot were systematically measured using the dithiothreitol (DTT) assay (OPDTT). Regardless of the presence of O3, visible light markedly promoted oxidation of soot, which led to consumption of polycyclic aromatic hydrocarbons, formation of oxygen-containing functional groups, and enhancement of OPDTT values. Compared to low-A/F soot, high-A/F soot contained more elemental carbon but less organic carbon and was more sensitive to visible light by exhibiting greater changes. It was proposed that elemental carbon in soot under visible-light irradiation initiated an inside-to-outside oxidation pathway, where reactive oxygen species played an important role. This study clarified the solar irradiation-triggered self-oxidation process in soot, which is important to its atmospheric and health effects.


Assuntos
Ozônio , Fuligem , Oxirredução , Estresse Oxidativo , Espécies Reativas de Oxigênio
11.
Cell Mol Biol (Noisy-le-grand) ; 66(1): 109-113, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32359393

RESUMO

To explore the effects of Qing Qiao Capsule in the treatment of chronic secretory otitis media and the levels of serum inflammatory factors, a total of 50 chronic secretory otitis media patients in the control group were subjected to caefaclor capsule, while the total of 50 cases in the observation group were treated with Qing Qiao Capsule. The traditional Chinese medicine (TCM) syndrome scores, therapeutic effects, and the levels of inflammatory factors were evaluated. After treatment, the scores of deafness, hearing loss, dizziness, soreness and weakness of the waist and knees, and fever is hens in palms and soles were significantly decreased in both groups (all P value <0.05). However, each score in the observation group was markedly less than that of the control group (all P value <0.05). Moreover, the C-reactive protein (CRP), procalcitonin (PCT) and tumor necrosis factor-α (TNF-α) levels measured after treatment were significantly lowered than those before treatment (all P value <0.05). Also, the levels of CRP, PCT and TNF-α in the observation group were obviously less than that of the control group (all P value <0.05). And the total therapeutic efficacy of the observation group was significantly higher than that of the control group (P<0.05). But no significant difference was observed in the rates of adverse reactions between both groups (P>0.05). Application of Qing Qiao Capsule in the treatment of chronic secretory otitis media yields better results, lowers TCM syndrome scores, and alleviates the body's inflammatory response, which is a safe drug in clinical use.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Mediadores da Inflamação/sangue , Otite Média com Derrame/sangue , Otite Média com Derrame/tratamento farmacológico , Adulto , Idoso , Cápsulas , Doença Crônica , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Humanos , Masculino , Medicina Tradicional Chinesa , Pessoa de Meia-Idade , Síndrome , Resultado do Tratamento
12.
Gynecol Oncol ; 158(1): 66-76, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32402633

RESUMO

OBJECTIVE: Platinum-based chemotherapy remains the first-line treatment for ovarian carcinoma by inducing DNA damage. The therapeutic impact of clonal and subclonal somatic mutations in DNA damage repair (DDR) pathways remains unexplored. METHODS: We performed an integrated analysis to infer the clonality of somatic deleterious mutations in 385 ovarian carcinomas treated with platinum-based chemotherapy. The Kaplan-Meier method was performed for visualization and the differences between survival curves were calculated by log-rank test. Proportional hazards models were used to estimate relative hazards for platinum-free interval (PFI), progression-free survival (PFS) and overall survival (OS). RESULTS: We found that somatic deleterious mutations in DDR pathways exhibited widespread clonal heterogeneity, and that patients with DDR clonal mutations exhibited a "hypermutator phenotype". Clonal somatic mutations in homologous recombination repair (HRR) pathway were significantly associated with better OS (HR = 0.19 (95% CI, 0.06-0.59), P = 0.0044) and PFS (HR = 0.20 (95% CI, 0.08-0.49), P = 0.0005) than HRR wild-type, while HRR subclonal mutations were not associated with prognosis. Moreover, HRR clonal mutations were associated with significantly higher chemotherapy sensitive rate (P = 0.0027) and longer PFI (HR = 0.20 (95% CI, 0.08-0.49), P = 0.0005) than HRR wild-type, while HRR subclonal mutations were not. We validated our findings using an independent cohort of 93 ovarian cancer patients that received platinum-based chemotherapy. CONCLUSIONS: HRR clonal mutations, but not subclonal mutations, were associated with improved survival, chemotherapy response, and genome instability compared with HRR wild-type.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mutação , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Reparo do DNA , Feminino , Instabilidade Genômica , Recombinação Homóloga , Humanos , Estimativa de Kaplan-Meier , Compostos Organoplatínicos/administração & dosagem , Neoplasias Ovarianas/cirurgia , Valor Preditivo dos Testes , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Resultado do Tratamento
14.
Proc Natl Acad Sci U S A ; 117(11): 6237-6245, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32123075

RESUMO

Stomata in the plant epidermis play a critical role in growth and survival by controlling gas exchange, transpiration, and immunity to pathogens. Plants modulate stomatal cell fate and patterning through key transcriptional factors and signaling pathways. MicroRNAs (miRNAs) are known to contribute to developmental plasticity in multicellular organisms; however, no miRNAs appear to target the known regulators of stomatal development. It remains unclear as to whether miRNAs are involved in stomatal development. Here, we report highly dynamic, developmentally stage-specific miRNA expression profiles from stomatal lineage cells. We demonstrate that stomatal lineage miRNAs positively and negatively regulate stomatal formation and patterning to avoid clustered stomata. Target prediction of stomatal lineage miRNAs implicates potential cellular processes in stomatal development. We show that miR399-mediated PHO2 regulation, involved in phosphate homeostasis, contributes to the control of stomatal development. Our study demonstrates that miRNAs constitute a critical component in the regulatory mechanisms controlling stomatal development.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/fisiologia , Regulação da Expressão Gênica de Plantas/fisiologia , MicroRNAs/metabolismo , Estômatos de Plantas/crescimento & desenvolvimento , Enzimas de Conjugação de Ubiquitina/genética , MicroRNAs/genética , Plantas Geneticamente Modificadas , RNA-Seq
15.
Microb Pathog ; 142: 104077, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32084579

RESUMO

Alpha-linolenic acid (ALA), an important component of polyunsaturated fatty acids (PUFAs), possesses potent anti-inflammatory properties. To date, the effects of ALA on acute lung injury (ALI) remains unknown. This study was designed to investigate the potential protective effects of ALA on LPS-induced ALI and the underpinning mechanisms. An animal model of ALI was established via intratracheally injection of lipopolysaccharide (LPS, 1 mg/kg). We found that lung wet/dry weight ratio and protein concentration in Bronchoalveolar lavage fluid (BALF) were dramatically decreased by ALA pretreatment. Treatment with ALA significantly alleviated the infiltration of total cells and neutrophils, while increased the number of the macrophages. ALA significantly inhibited the secretion of proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) and increased anti-inflammatory cytokine. Moreover, we found that the levels of myeloperoxidase (MPO) and malondialdehyde (MDA) were highly increased in LPS-induced ALI, while the activities of glutathione (GSH) and superoxide dismutase (SOD) were decreased, which were reversed by ALA. ALA attenuated LPS-induced histopathological changes and apoptosis. Furthermore, ALA significantly inhibited the phosphorylation of IκBα and NF-κB (p65) activation in ALI. ALA showed anti-inflammatory effects in mice with LPS-induced ALI. NF-κB pathway may be involved in ALA mediated protective effects.

16.
J Environ Sci (China) ; 87: 184-193, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31791491

RESUMO

Soot particles, mainly coming from fuel combustion, affect climate forcing through absorbing light and also result in adverse human health outcomes. Though biodiesel or additives blending with diesel was considered environmentally friendly, the understanding on absorbing and oxidative capacity of soot emitted from them are still unclear. The water-soluble organic carbon (WSOC) content, surface chemical structure, light absorption and oxidative potential (OPDTT) of soot from biodiesel/diesel and chemicals/diesel blends were investigated utilizing total organic carbon analyzer, X-ray photoelectron spectrometer, ultraviolet-visible spectrophotometry and dithiothreitol (DTT) assay. The differences and correlations between soot properties were statistically analyzed. Chemicals/diesel blends soot owned significantly higher WSOC content, ratio of mass absorbing efficiency (MAE) in 250 and 365 nm (E2/E3), OPDTT, and higher surface carbonyl content. Coconut biodiesel/diesel blends soot contained evidently higher aromatic carbon-oxygen single bond (Ar_C-O) content, and higher MAE365. The individual comparison of biodiesel/diesel blends showed 20% coconut biodiesel blend owned the lowest WSOC, E2/E3 and OPDTT, while highest Ar_C-O and MAE365, representing strongest absorbing properties. Association analysis showed OPDTT was significantly positively correlated with WSOC. Further, the evident negative correlation between MAE365 and OPDTT was observed. Our results showed coconut biodiesel/diesel blends soot induced lower levels of oxidative potential, whereas absorption of light was higher, which have far reaching consequences on climate forcing. Therefore, it is important to evaluate the balance point between light-absorbing properties and oxidative potential, under the wide use of biodiesel.


Assuntos
Poluentes Atmosféricos/análise , Biocombustíveis , Material Particulado/análise , Emissões de Veículos/análise , Fuligem/química
17.
Aging Cell ; 19(1): e13056, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31743583

RESUMO

Transient plasma membrane disruptions (PMD) occur in osteocytes with in vitro and in vivo loading, initiating mechanotransduction. The goal here was to determine whether osteocyte PMD formation or repair is affected by aging. Osteocytes from old (24 months) mice developed fewer PMD (-76% females, -54% males) from fluid shear than young (3 months) mice, and old mice developed fewer osteocyte PMD (-51%) during treadmill running. This was due at least in part to decreased pericellular matrix production, as studies revealed that pericellular matrix is integral to formation of osteocyte PMD, and aged osteocytes produced less pericellular matrix (-55%). Surprisingly, osteocyte PMD repair rate was faster (+25% females, +26% males) in osteocytes from old mice, and calcium wave propagation to adjacent nonwounded osteocytes was blunted, consistent with impaired mechanotransduction downstream of PMD in osteocytes with fast PMD repair in previous studies. Inducing PMD via fluid flow in young osteocytes in the presence of oxidative stress decreased postwounding cell survival and promoted accelerated PMD repair in surviving cells, suggesting selective loss of slower-repairing osteocytes. Therefore, as oxidative stress increases during aging, slower-repairing osteocytes may be unable to successfully repair PMD, leading to slower-repairing osteocyte death in favor of faster-repairing osteocyte survival. Since PMD are an important initiator of mechanotransduction, age-related decreases in pericellular matrix and loss of slower-repairing osteocytes may impair the ability of bone to properly respond to mechanical loading with bone formation. These data suggest that PMD formation and repair mechanisms represent new targets for improving bone mechanosensitivity with aging.


Assuntos
Membrana Celular/metabolismo , Mecanotransdução Celular/fisiologia , Osteócitos/metabolismo , Envelhecimento , Animais , Feminino , Humanos , Masculino , Camundongos
18.
Eur J Med Chem ; 185: 111790, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31699535

RESUMO

Idiopathic pulmonary fibrosis, characterized by excess accumulation of extracellular matrix, involved in many chronic diseases or injuries, threatens human health greatly. We have reported a series of compounds bearing coumarin scaffold which potently inhibited TGF-ß-induced total collagen accumulation in NRK-49F cell line and migration of macrophages. Compound 9d also suppressed the TGF-ß-induced protein expression of COL1A1, α-SMA, and p-Smad3 in vitro. Meanwhile, 9d at a dose of 100 mg/kg/day through oral administrations for 4 weeks effectively alleviated infiltration of inflammatory cells in lung tissue and fibrotic degree in bleomycin-induced pulmonary fibrosis model, which may related to its inhibition of TGF-ß/Smad3 pathway and anti-inflammation efficacy. In addition, 9d demonstrated decent bioavailability (F = 39.88%) and suitable eliminated half-life time (T1/2 = 13.09 h), suggesting that 9d could be a potential drug candidate for the treatment of fibrotic diseases.


Assuntos
Cumarínicos/uso terapêutico , Descoberta de Drogas , Fibrose Pulmonar/tratamento farmacológico , Animais , Bleomicina , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cumarínicos/síntese química , Cumarínicos/química , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/patologia , Células RAW 264.7 , Relação Estrutura-Atividade
19.
ACS Omega ; 4(25): 20948-20954, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31867485

RESUMO

A graphene-based or carbon-based aerogel is a three-dimensional (3D) solid material in which the carbon atoms are arranged in a sheet-like nanostructure. In this study, we report the synthesis of low-density polymer-modified aerogel monoliths by 3D macroassemblies of graphene oxide sheets that exhibit significant internal surface areas (982 m2/g) and high electrical conductivity (∼0.1 to 1 × 102 S/cm). Different types of materials were prepared to obtain a single monolithic solid starting from a suspension of single-layer graphene oxide (GO) sheets and a polymer, made from the precursors 4-carboxybenzaldehyde and poly(vinyl alcohol). These materials were used to cross-link the individual sheets by covalent bonds, resulting in wet-gels that were supercritically dried and then, in some cases, thermally reduced to yield graphene aerogel composites. The average densities were approaching 15-20 mg/cm3. This approach allowed for the modulation of the distance between the sheets, pore dimension, surface area, and related properties. This specific GO/polymer ratio has suitable malleability, making it a viable conductive material for use in 3D printing; it also has other properties suitable for energy storage, catalysis, sensing and biosensing applications, bioelectronics, and superconductors.

20.
Biomed Pharmacother ; 120: 109446, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31542617

RESUMO

BACKGROUND AND AIMS: Usnea diff ;racta Vain. (U. diffracta) belonging to the Usnea genus, is widely used as a folk medicine for the treatment of ulcer, abdominal pain, diarrhea, malaria and so on. However, the antiatherogenic effect of U. diffracta has not yet been reported. This study aims to investigate the antiatherogenic effects of the ethanol extract of U. diffracta and its mechanism. METHOD: A high fat diet and VD3 were used to establish the atherosclerotic rat model, with 0.004 g/kg/d of simvastatin as a positive control, fed with 0.7, 1.4, and 2.8 g/kg/d of Usnea ethanol extract for 21 days. The blood, liver, and aorta samples from each rat were collected after the last administration. Pharmacodynamic effects were evaluated. The inflammation related factors, the gene expressions of Toll-like receptor 5 (TLR5), myeloid differentiating factor 88 (MyD88), and nuclear factor-κB (NF-κB) were detected. RESULTS AND CONCLUSIONS: Compared with the model group, simvastatin and ethanol extract of U. diffracta can significantly reduce the serum levels of triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), Ca2+, AST, ALT, the liver contents of total cholesterol (TC), TG, AI and liver index, as well as significantly increase the contents of high-density lipoprotein cholesterol (HDL-C) both in serum and liver (p < 0.01 or p < 0.05). The serum level of ox-LDL can be significantly reduced by simvastatin, low and medium U. diffracta ethanol extract doses (p < 0.01). In addition, simvastatin and low dosage of U. diffracta ethanol extract can significantly reduce the liver content of LDL-C (p < 0.01). U. diffracta ethanol extract shows a positive antiatherogenic effect. Furthermore, the mechanism may be related to promoting the expression of serum IL-10 and inhibition of TLR5/NF-κB signaling pathway.


Assuntos
Aorta/efeitos dos fármacos , Aterosclerose/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Fígado/efeitos dos fármacos , Usnea/química , Animais , Aterosclerose/induzido quimicamente , Cálcio/sangue , Citocinas/efeitos dos fármacos , Dieta Hiperlipídica , Lipídeos/sangue , Modelos Animais , Ratos , Ratos Sprague-Dawley , Sinvastatina/farmacologia
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