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1.
Sci Total Environ ; 856(Pt 2): 159136, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36191708

RESUMO

Soil salinization is one of the most severe environmental problems restricting biodiversity maintenance and ecosystem functioning in a coastal wetland. Recent studies have well documented how salinization affects soil microbial communities along vegetation succession of coastal wetlands. However, the salinity effect is rarely assessed in the context of plant intraspecific variation. Here, we analyzed the soil bacterial and fungal communities of Phragmites australis wetland using amplicon high-throughput sequencing at a fine scale (within 1000 m) in the Yellow River Delta. Our results revealed that microbial diversity is significantly correlated to soil salinity (assessed as electrical conductivity, EC) but not to soil nutrients (N and P content) or plant intraspecific traits (leaf length, shoot height, and neutral genetic variation). Specifically, the microbial diversity tended to decrease with increased EC, and the bacterial community was more sensitive to EC change than the fungal community. The dominant bacterial phyla were Proteobacteria, Actinobacteria, and Chloroflexi, and the dominant fungal phyla were Ascomycota, Basidiomycota, and Mortierellomycota. The relative abundance of Actinobacteria was significantly negatively correlated to EC, while Proteobacteria were positively correlated to EC. In high salinity (> 1 mS/cm), the role of the stochastic processes became more important in community assembly according to habitat niche breadth estimation, neutral community model, C-score metric, and normalized stochasticity ratio. Additional common garden and microcosm experiments provided evidence that the genotype effect of P. australis on soil microbiome might only occur between lineages from different regions but not from the same region like the Yellow River Delta. Our findings provide new insights into soil microbial community assembly processes with the intraspecific variation of host plants in the wetland ecosystem and offer a scientific reference for salinity mitigation and vegetation management of coastal wetlands under future global changes.


Assuntos
Microbiota , Áreas Alagadas , Solo , Rios , Salinidade , Plantas , Bactérias/genética , Genótipo , China
2.
J Agric Food Chem ; 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36450093

RESUMO

The roots of Piper nigrum L., a seasoning for cooking various types of broths, are renowned for their high nutritional content and potential medicinal benefits. In this study, nine pairs of novel cyclohexene-type bisamide alkaloids (1a/1b-9a/9b) were isolated from the pepper roots using molecular network analysis strategies. Their structures were determined by extensive spectroscopic data, electronic circular dichroism (ECD) calculations, and X-ray diffraction analyses. Using an intermolecular Diels-Alder reaction, a strategy for the synthesis of bisamide alkaloids from different monomeric amide alkaloids was developed. Furthermore, these compounds were chirally separated for the first time, and compounds 3a and 5a/5b showed significant anti-neuroinflammation effects in the models of lipopolysaccharide(LPS)-induced BV2 microglial cells. Meanwhile, compounds 6b and 7a displayed concentration-dependent inhibitory activities against acetylcholinesterase with IC50 values of 6.05 ± 1.10 and 3.81 ± 0.10 µM, respectively. These findings confirmed that these bisamide alkaloids could be applied in functional food formulations and pharmaceutical products as well as facilitate the further development and usage of pepper roots.

3.
Sci Total Environ ; : 160438, 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36435241

RESUMO

BACKGROUND: Ambient air pollution has been linked to gestational complications. However, the evidence on the relationship between air pollution and fetal distress is limited. OBJECTIVES: To investigate the relationship between maternal short-term air pollution exposure and fetal distress, and to identify a potential susceptible population. METHODS: This matched case-control study, involving 313 pregnancy women with fetal distress was conducted in Xi'an, the largest city in Northwest China from 2013 to 2016. Each woman with fetal distress was randomly matched with four women without fetal distress of the same age, same gestational week, and registration in the same period (n = 1252). Inverse distance-weighted (IDW) interpolation was applied to estimate maternal air pollution exposure based on the residential addresses. We employed conditional logistic regression model to evaluate the relationship between air pollutants and fetal distress. Distributed lag nonlinear model (DLNM) was performed to examine the exposure-response relationship between air pollutants and fetal distress. RESULTS: Maternal short-term exposure to PM10, PM2.5-10 (PMc), SO2, NO2, and CO was associated with increased risk of fetal distress. Each 10 µg/m3 increment in PM10, PMc, SO2 at lag 014, and NO2 at lag 010, the odds ratio (ORs) of fetal distress were 1.027 (95 % confidence interval (CI): 1.004, 1.050), 1.058 (95 % CI: 1.014, 1.105), 1.140 (95 % CI: 1.029, 1.264), and 1.158 (95 % CI: 1.046, 1.283), respectively. Similarly, with a 0.1 mg/m3 increment in CO at lag 014, the OR of fetal distress was 1.029 (95 % CI: 1.002, 1.058). Stratified analyses showed that the estimate associations of PM10, PM2.5 and CO appeared to be stronger, although not statistically significantly, among women with gestational complications. CONCLUSION: Maternal short-term exposure to ambient air pollution may increase the risk of fetal distress. Understanding the detrimental role of air pollution in fetal distress can help us better develop preventative methods in reducing its' impact on maternal and fetal health.

4.
Fitoterapia ; 163: 105327, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36208855

RESUMO

Seven triterpenoids (1-7), two prenylated coumarins (8 and 9), and one diphenylpropane (10), including five previously undescribed compounds (1-3, 8, and 10), were obtained from the stem and root barks of Daphne giraldii. The structures and absolute configurations of the new triterpenoids were established by NMR, HRESIMS, ECD calculations, and single-crystal X-ray diffraction analysis. All identified compounds were tested for cytotoxicities (human tumour cell line Hep3B) and inhibitory effects on AChE in vitro. Notably, prenylated coumarins (8 and 9) exhibited moderate cytotoxic activities and 3-hydroxy-substituted triterpenoids (2 and 4) showed mild inhibitory effects on AChE. Furthermore, compounds 2 and 4 have also been subjected to molecular docking studies to investigate the inhibitory mechanism.

5.
Artigo em Inglês | MEDLINE | ID: mdl-36194329

RESUMO

Evidence of the short-term effects of ambient sulfur dioxide (SO2) exposure on the economic burden of ischemic stroke is limited. This study aimed to explore the association between short-term ambient SO2 exposure and hospitalization costs for ischemic stroke in Chongqing, the most populous city in China. The hospital-based study included 7271 ischemic stroke inpatients. Multiple linear regression models were used to estimate the association between SO2 concentration and hospitalization costs. Propensity score matching was used to compare the patients' characteristics when exposed to SO2 concentrations above and below 20 µg/m3. It is found that short-term SO2 exposure was positively correlated with the hospitalization costs of ischemic stroke. The association was more evident in males, people younger than 65, and people hospitalized in the cool seasons. Besides, among the components of hospitalization costs, medicine costs were most significantly associated with SO2. More interesting, the lower concentration of SO2, the higher costs associated with 1 µg/m3 SO2 change. Above all, SO2 was positively associated with hospitalization costs of ischemic stroke, even at its low levels. The measures to reduce the level of SO2 can help reduce the burden of ischemic stroke.

6.
J Nat Prod ; 85(10): 2433-2444, 2022 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-36223633

RESUMO

Highly oxidized germacranolides are mainly found in the genus Elephantopus, contain a characteristic ten-membered molecular core that is highly flexible, and exhibit potential cytotoxic properties. However, their configurations were assigned ambiguously in previous reports due to spectroscopic observation of macrocyclic systems. Herein, 17 highly oxidized germacranolides, including 12 new germacranolides (1-12), were isolated from Elephantopus tomentosus. Their structures were characterized by spectroscopic data analysis combined with X-ray crystallography and ECD calculations, and it was possible to propose configurational revisions of five previously reported analogues (13-17). Cytotoxic activities for 1-17 against two hepatocellular carcinoma cell lines (HepG2 and Hep3B) were tested, and compounds 1-10 and 13-16 generated IC50 values of 2.2-9.8 µM. Furthermore, the observed cytotoxic activity of 1 was determined as being mediated by inducing the apoptosis of HepG2 and Hep3B cells via mitochondrial dysfunction.


Assuntos
Antineoplásicos Fitogênicos , Antineoplásicos , Asteraceae , Estrutura Molecular , Antineoplásicos Fitogênicos/química , Sesquiterpenos de Germacrano/química , Asteraceae/química
7.
Anal Bioanal Chem ; 414(29-30): 8223-8232, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36301330

RESUMO

Hemin with functions such as oxygen carrying, oxygen storing, promoting redox, and performing electron transfer is important for the health of organisms. In this paper, green synthetic silicon nanoparticles (Si-NPs) were synthesized and used for free hemin detection in serum (a low limit of detection (LOD), 29.5 nM). The quenching mechanism was investigated by UV-vis absorption spectra, time-resolved luminescence decay curve, and circular dichroism (CD) spectra. It was confirmed that multiple redox centers of hemin led to intensified effective collision and increased the electron transfer rate, therefore enhancing the dynamic quenching, and it was undeniable that the inner filter effect (IFE) also played a role in the quenching.


Assuntos
Hemina , Nanopartículas , Silício , Limite de Detecção , Oxigênio
8.
Environ Res ; 215(Pt 2): 114395, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36150443

RESUMO

Type 2 diabetes (T2DM) as a non-communicable disease imposes heavy disease burdens on society. Limited studies have been conducted to assess the effects of short-term air pollution exposure on T2DM, especially in Asian regions. Our research aimed to determine the association between short-term exposure to ambient nitrogen dioxide (NO2) and outpatient visits for T2DM in Chongqing, the largest city in western China, based on the data collected from November 28, 2013 to December 31, 2019. A generalized additive model (GAM) was applied, and stratified analyses were performed to investigate the potential modifying effects by age, gender, and season. Meanwhile, the disease burden was revealed from attributable risk. Positive associations between short-term NO2 and daily T2DM outpatient visits were observed. The strongest association was observed at lag 04, with per 10 µg/m3 increase of NO2 corresponded to increased T2DM outpatient visits at 1.57% [95% confidence interval (CI): 0.48%, 2.65%]. Stronger associations were presented in middle-aged group (35-64 years old), male group, and cool seasons (October to March). Moreover, there were 1.553% (8664.535 cases) of T2DM outpatient visits attributable to NO2. Middle-aged adults, males, and patients who visited in cool seasons suffered heavier burdens. Conclusively, short-term exposure to NO2 was associated with increased outpatient visits for T2DM. Attention should be paid to the impact of NO2 on the burden of T2DM, especially for those vulnerable groups.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Diabetes Mellitus Tipo 2 , Adulto , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , China/epidemiologia , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/epidemiologia , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Dióxido de Nitrogênio/análise , Dióxido de Nitrogênio/toxicidade , Pacientes Ambulatoriais , Material Particulado/análise , Material Particulado/toxicidade
9.
Comput Intell Neurosci ; 2022: 9811905, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36082356

RESUMO

Objective: To investigate hypoxia-induced Nestin regulates lung cancer viability and metabolism by targeting transcription factors Nrf2, STAT3, and SOX2. Methods: Eighty-four cases of nonsmall cell lung cancer (nonsmall cell lung cancer, NSCLC), which had been treated from June 2020 to February 2021, were randomly selected from our clinicopathology database. Immunohistochemical staining of collected tissue cells was performed to assess the expression patterns of Nestin, STAT3, Nrf2, and SOX2. Data were quantified and statistically analyzed using one-way and two-way ANOVA tests with P < 0.05. Results: Clinicopathological findings showed significant differences in lymph node metastasis, tissue differentiation, and histology on induction of Nestin expression; Nestin expression correlated with STAT3, Nrf2, and SOX2 expression.Nestin/STAT3/SOX2/Nrf2 are involved in angiogenesis and lung cancer development. Conclusion: Hypoxia-induced Nestin promotes the progression of nonsmall lung cancer cells by targeting the downstream transcription factors STAT3, Nrf2, and SOX2.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Hipóxia , Fator 2 Relacionado a NF-E2/metabolismo , Nestina/genética , Nestina/metabolismo , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Fator de Transcrição STAT3/metabolismo
10.
Fitoterapia ; 162: 105259, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35931288

RESUMO

Four undescribed compounds including one germacrane-type sesquiterpene lactones (1), alkaloid (2) along with two neolignans (3-4) were isolated from Elephantopus scaber L. Their structures and absolute configurations were elucidated unambiguously by means of 1D and 2D NMR spectroscopic data analysis, and quantum chemical electronic circular dichroism calculations, as well as single-crystal X-ray crystallography. Their anti-tyrosinase activities have been evaluated in vitro and compound 2 exhibited significant inhibitory activity. Furthermore, molecular docking was performed to study the interaction patterns between 2 and the tyrosinase.


Assuntos
Alcaloides , Asteraceae , Lignanas , Sesquiterpenos , Asteraceae/química , Lactonas , Simulação de Acoplamento Molecular , Estrutura Molecular , Sesquiterpenos de Germacrano
11.
Chem Biodivers ; 19(10): e202200558, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36036517

RESUMO

Nine coumarins including a pair of new enantiomers (1a/1b) and seven known compounds (2-8) were isolated from Sarcandra glabra (Thunb.) Nakai. Among them, compounds 1a and 1b were naturally occurring coumarin-phenylpropanoid conjugate enantiomers. Their structures were identified by NMR and ECD calculations. Compounds 1-8 were tested for acetylcholinesterase (AchE) inhibiting activity. The results of the enzymology experiment showed that compound 3 demonstrated obvious AchE inhibitory activity which showed the IC50 value of 1.982±0.003 µM, and the binding sites were predicted by molecular docking.


Assuntos
Acetilcolinesterase , Magnoliopsida , Acetilcolinesterase/metabolismo , Magnoliopsida/química , Simulação de Acoplamento Molecular , Cumarínicos/farmacologia , Cumarínicos/química , Sementes/metabolismo , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/química
12.
Plant Foods Hum Nutr ; 77(4): 538-544, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35986175

RESUMO

Recent epidemiologic studies have demonstrated a link between the consumption of daily functional fruits rich in phenols and the prevention of disease for neurodegenerative disorders. Hawthorn products are derived from the functional fruit hawthorn, which is rich in phenols and has been used around the world for centuries. In order to explore the phenolic components in hawthorn, the investigation of the ethanol extract led to the separation of five new phenol compounds (1a/1b, 2-4), including one pair of enantiomers (1a/1b), along with seven disclosed analogs (5-11). Their structures were elucidated based on extensive spectroscopic analyses and electronic circular dichroism (ECD). The compounds (1-11) were tested for antioxidant activities by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonicacid) (ABTS), and ferric reducing antioxidant power (FRAP) methods. Apart from that, monomeric compounds 2, 4, and 6 exhibited more potent protective capabilities against H2O2 (hydrogen peroxide)-induced SH-SY5Y cells. Meanwhile, electronic analyses were performed using the highest occupied molecular orbital (HOMO), and the lowest unoccupied molecular orbital (LUMO) to analyze compounds 2, 4, and 6. Furthermore, compounds (1-11) measured acetylcholinesterase (AChE) inhibitory activities, and 2, 4, and 6 possessed greater AChE inhibitory activity than donepezil. At the same time, molecular docking was used to investigate the possible mechanism of the interaction between active compounds (2, 4, and 6) and AChE.


Assuntos
Crataegus , Neuroblastoma , Humanos , Crataegus/química , Antioxidantes/análise , Peróxido de Hidrogênio , Acetilcolinesterase , Donepezila , Simulação de Acoplamento Molecular , Fenol , Extratos Vegetais/química , Fenóis/farmacologia , Fenóis/análise , Etanol
13.
Front Oncol ; 12: 930589, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35832540

RESUMO

Background: Immune checkpoint inhibitors (ICIs) induce durable responses, but only a minority of patients achieve clinical benefits. The development of gene expression profiling of tumor transcriptomes has enabled identifying prognostic gene expression signatures and patient selection with targeted therapies. Methods: Immune exclusion score (IES) was built by elastic net-penalized Cox proportional hazards (PHs) model in the discovery cohort and validated via four independent cohorts. The survival differences between the two groups were compared using Kaplan-Meier analysis. Both GO and KEGG analyses were performed for functional annotation. CIBERSORTx was also performed to estimate the relative proportion of immune-cell types. Results: A fifteen-genes immune exclusion score (IES) was developed in the discovery cohort of 65 patients treated with anti-PD-(L)1 therapy. The ROC efficiencies of 1- and 3- year prognosis were 0.842 and 0.82, respectively. Patients with low IES showed a longer PFS (p=0.003) and better response rate (ORR: 43.8% vs 18.2%, p=0.03). We found that patients with low IES enriched with high expression of immune eliminated cell genes, such as CD8+ T cells, CD4+ T cells, NK cells and B cells. IES was positively correlated with other immune exclusion signatures. Furthermore, IES was successfully validated in four independent cohorts (Riaz's SKCM, Liu's SKCM, Nathanson's SKCM and Braun's ccRCC, n = 367). IES was also negatively correlated with T cell-inflamed signature and independent of TMB. Conclusions: This novel IES model encompassing immune-related biomarkers might serve as a promising tool for the prognostic prediction of immunotherapy.

14.
Per Med ; 19(4): 307-314, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35762314

RESUMO

Aim: To observe the difference in the risk of polymyxin B (PMB)-induced acute kidney injury (AKI) with or without dose adjustment based on the patients renal function. Materials & methods: This retrospective cohort analysis was carried out in 115 patients treated with PMB from November 2018 to October 2019. Results: No significant difference in the incidence of AKI as well as secondary outcomes was observed between these two groups (47.5 vs 37.14%; p = 0.304). Conclusion: Dosing adjustment based on renal function does not significantly lower the risk of PMB-induced AKI. A non adjusted dosing strategy for PMB is recommended in patients exhibiting various levels of renal impairment.


Assuntos
Injúria Renal Aguda , Polimixina B , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/epidemiologia , Antibacterianos/efeitos adversos , Humanos , Rim/fisiologia , Polimixina B/efeitos adversos , Estudos Retrospectivos
15.
Acta Biochim Biophys Sin (Shanghai) ; 54(3): 378-387, 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35538035

RESUMO

Long non-coding RNA (lncRNA) LINC00891 knockdown is associated with poor prognosis of lung adenocarcinoma, but the underlying mechanism remains to be further explored. Here, we found that LINC00891 expression is downregulated in lung cancer tissues and cell lines compared with that in adjacent normal tissues and normal lung epithelial cells. LINC00891 overexpression impedes cell proliferation, invasion, migration and epithelial-to-mesenchymal transition (EMT) process in lung cancer cells. Mechanistic research showed that GATA2 directly binds to LINC00891 promoter and transcriptionally regulates LINC00891 expression. Meanwhile, GATA2 was identified as a target of miR-128-3p, and it is negatively regulated by miR-128-3p. Moreover, overexpression of GATA2 suppresses lung cancer cell proliferation, invasion, migration, and EMT process. Furthermore, LINC00891 restrains the RhoA pathway activity, and treatment with CCG-1423 (a specific RhoA pathway inhibitor) antagonizes the promoting effect of LINC00891 knockdown on cell malignant behaviors. Additionally, silencing of LINC00891 promotes xenograft tumor growth, which can be reversed by administration with CCG-1423. In summary, LINC00891 regulated by the miR-128-3p/GATA2 axis restrains lung cancer cell malignant progression and hinders xenograft tumor growth by suppressing the RhoA pathway.


Assuntos
Fator de Transcrição GATA2 , Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Fator de Transcrição GATA2/genética , Fator de Transcrição GATA2/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Proteína rhoA de Ligação ao GTP/genética , Proteína rhoA de Ligação ao GTP/metabolismo
16.
Int J Mol Sci ; 23(10)2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35628537

RESUMO

In salt-sensitive plants, root hydraulic conductivity is severely inhibited by NaCl, rapidly leading to the loss of water balance. However, halophytic plants appear to effectively control plant water flow under salinity conditions. In this study, we tested the hypothesis that Na+ is the principal salt factor responsible for the enhancement of aquaporin-mediated water transport in the roots of halophytic grasses, and this enhancement plays a significant role in the maintenance of water balance, gas exchange, and the growth of halophytic plants exposed to salinity. We examined the effects of treatments with 150 mM of NaCl, KCl, and Na2SO4 to separate the factors that affect water relations and, consequently, physiological and growth responses in three related grass species varying in salt tolerance. The grasses included relatively salt-sensitive Poa pratensis, moderately salt-tolerant Poa juncifolia, and the salt-loving halophytic grass Puccinellia nuttalliana. Our study demonstrated that sustained growth, chlorophyll concentrations, gas exchange, and water transport in Puccinellia nuttalliana were associated with the presence of Na in the applied salt treatments. Contrary to the other examined grasses, the root cell hydraulic conductivity in Puccinellia nuttalliana was enhanced by the 150 mM NaCl and 150 mM Na2SO4 treatments. This enhancement was abolished by the 50 µM HgCl2 treatment, demonstrating that Na was the factor responsible for the increase in mercury-sensitive, aquaporin-mediated water transport. The observed increases in root Ca and K concentrations likely played a role in the transcriptional and (or) posttranslational regulation of aquaporins that enhanced root water transport capacity in Puccinellia nuttalliana. The study demonstrates that Na plays a key role in the aquaporin-mediated root water transport of the halophytic grass Puccinellia nuttalliana, contributing to its salinity tolerance.


Assuntos
Aquaporinas , Poa , Íons/farmacologia , Raízes de Plantas/metabolismo , Poa/metabolismo , Tolerância ao Sal , Plantas Tolerantes a Sal/metabolismo , Sódio/metabolismo , Cloreto de Sódio/farmacologia , Água/metabolismo
17.
Sci Rep ; 12(1): 6946, 2022 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-35484177

RESUMO

Colorectal cancer (CRC) is the third most common malignant tumor. DNA damage plays a crucial role in tumorigenesis, and abnormal DNA repair pathways affect the occurrence and progression of CRC. In the current study, we aimed to construct a DNA repair-related gene (DRG) signature to predict the overall survival (OS) of patients with CRC patients. The differentially expressed DRGs (DE-DRGs) were analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The prognostic gene signature was identified by univariate Cox regression and least absolute shrinkage and selection operator (LASSO)-penalized Cox proportional hazards regression analysis. The predictive ability of the model was evaluated using the Kaplan-Meier curves and time-dependent receiver operating characteristic (ROC) curves. The gene set enrichment analysis (GSEA) was performed to explore the underlying biological processes and signaling pathways. ESTIMATE and CIBERSORT were implemented to estimate the tumor immune score and immune cell infiltration status between the different risk group. The half-maximal inhibitory concentration (IC50) was evaluated to representing the drug response of this signature. Nine DE-DRGs (ESCO2, AXIN2, PLK1, CDC25C, IGF1, TREX2, ALKBH2, ESR1 and MC1R) signatures was constructed to classify patients into high- and low-risk groups. The risk score was an independent prognostic indicator of OS (hazard ratio > 1, P < 0.001). The genetic alteration analysis indicated that the nine DE-DRGs in the signature were changed in 63 required samples (100%), and the major alteration was missense mutation. Function enrichment analysis revealed that the immune response and mtotic sister chromatid segregation were the main biological processes. The high-risk group had higher immune score than the low-risk group. What's more, low-risk patients were more sensitive to selumetinib and dasatinib. The nine DE-DRGs signature was significantly associated with OS and provided a new insight for the diagnosis and treatment of CRC.


Assuntos
Biomarcadores Tumorais , Neoplasias Colorretais , Acetiltransferases/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Neoplasias Colorretais/diagnóstico , Reparo do DNA/genética , Humanos , Estimativa de Kaplan-Meier , Prognóstico
18.
J Pharmacol Exp Ther ; 381(3): 247-256, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35383125

RESUMO

Acute lung injury (ALI) is a serious inflammatory lung disease. Imbalances in the polarization of classically activated (M1) and alternatively activated (M2) macrophages are closely related to ALI. Anisodamine has a promising therapeutic effect for septic shock. Nevertheless, the role of anisodamine in progression of ALI remains to be investigated. Our results showed that anisodamine significantly reduced lung damage, myeloperoxidase (MPO) activity, lung wet/dry ratio, total cell number, and protein concentrations in bronchoalveolar lavage fluid and decreased interleukin (IL)-6 level and the levels of M1 phenotypic markers, whereas it increased IL-10 level and the levels of M2 phenotypic markers in mice with a nasal instillation of lipopolysaccharide (LPS). Bone marrow-derived macrophages (BMDMs) were stimulated or transfected with LPS plus anisodamine or LPS plus G9a short hairpin RNA. Anisodamine and downregulation of G9a both promoted BMDM M2 polarization caused by IL-4 treatment and inhibited M1 polarization resulting from LPS treatment. Chromatin immunoprecipitation assay revealed that anisodamine inhibited G9a-mediated methylation and expression suppression on interferon regulatory factory 4 (IRF4). Overexpression of G9a or silence of IRF4 reversed the improvement effect of anisodamine on lung tissue injury, evidenced by an increase of MPO activity and the restoration of LPS-induced alterations of M1 and M2 polarization. In conclusion, anisodamine protected against LPS-induced ALI, during which anisodamine suppressed the LPS-stimulated alterations of macrophage M1 and M2 polarization through inhibiting G9a-mediated methylation of IRF4, suggesting that anisodamine was a potential therapeutic drug to alleviate ALI. SIGNIFICANCE STATEMENT: Anisodamine treatment was able to attenuate lung injury and pulmonary edema caused by lipopolysaccharide (LPS) stimulation, and the specific mechanism was that anisodamine reversed the LPS-induced alterations of M1 and M2 polarization by inhibiting G9a-mediated methylation and expression suppression of interferon regulatory factor 4, which suggests that anisodamine has the potential to alleviate acute lung injury.


Assuntos
Lesão Pulmonar Aguda , Lipopolissacarídeos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Animais , Fatores Reguladores de Interferon/genética , Fatores Reguladores de Interferon/metabolismo , Lipopolissacarídeos/farmacologia , Pulmão , Macrófagos/metabolismo , Camundongos , Alcaloides de Solanáceas
19.
Biomed Pharmacother ; 147: 112672, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35104698

RESUMO

Novel functions and involvement of circFARSA have not been reported in pancreatic cancer; in addition, its inhibitor screening has not yet been conducted. The purpose of this study was to (1) verify circFARSA as a novel anti-cancer target for pancreatic cancer and (2) to prepare a novel anti-pancreatic cancer agent targeting circFARSA. In this study, we designed and synthesized a small interfering RNA (siRNA, named siRNA-circFARSA), which specifically inhibits circFARSA expression. Using liposomes and porous silicon nanoparticles (pSiNPs) as siRNA delivery system, we prepared liposome-siRNA-circFARSA and pSiNP-PEI-siRNA-circFARSA and investigated their anti-cancer mechanism by quantitative real-time PCR and western blotting. Cell proliferation curves and transwell migration assays were performed to investigate the effect of siRNAs proliferation and migration capabilities of cancer cells. Patient-derived tumor xenograft mouse models were used to investigate the anti-cancer effects in vivo. The data showed that both liposome-siRNA-circFARSA and pSiNP-PEI-siRNA-circFARSA (Si: 0.7 µg/mL) significantly inhibited the proliferation and migration of pancreatic cancer cells in vitro. However, the biological safety and in vivo anti-cancer effects of pSiNP-PEI-siRNA-circFARSA (Si: 22.4 µg/mL) were higher than those of liposome-siRNA-circFARSA. The results showed that siRNA-circFARSA could inhibit the expression of circFARSA and then BCL-2 protein expression, thereby leading to pancreatic cancer cell apoptosis after transportation into pancreatic cancer cells. Therefore, this study provides tools for pancreatic cancer treatment in the future, as it (1) verified circFARSA as a novel target for pancreatic cancer treatment, and (2) prepared a novel anti-pancreatic cancer agent (pSiNP-PEI-siRNA-circFARSA).


Assuntos
Nanopartículas/química , Neoplasias Pancreáticas/patologia , RNA Circular/antagonistas & inibidores , RNA Interferente Pequeno/farmacologia , Silício/química , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Inativação Gênica , Humanos , Lipossomos/química , Masculino , Camundongos , Camundongos Nus , RNA Interferente Pequeno/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto
20.
ACS Appl Mater Interfaces ; 14(8): 10308-10318, 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35175030

RESUMO

Silicon/carbon (Si/C) composites have rightfully earned the attention as anode candidates for high-energy-density lithium-ion batteries (LIBs) owing to their advantageous capacity and superior cycling stability, yet their practical application remains a significant challenge. In this study, we report the large-scale synthesis of an intriguing micro/nanostructured pore-rich Si/C microsphere consisting of Si nanoparticles tightly immobilized onto a micron-sized cross-linked C matrix that is coated by a thin C layer (denoted P-Si/C@C) using a low-cost spray-drying approach and a chemical vapor deposition process with inorganic salts as pore-forming agents. The as-obtained P-Si/C@C composite has high porosity that provides sufficient inner voids to alleviate the huge volume expansion of Si. The outer smooth and robust C shells strengthen the stability of the entire structure and the solid-electrolyte interphase. Si nanoparticles embedded in a microsized cross-linked C matrix show excellent electrical conductivity and superior structural stability. By virtue of structural advantages, the as-fabricated P-Si/C@C anode displays a high initial Coulombic efficiency of 89.8%, a high reversible capacity of 1269.6 mAh g-1 at 100 mA g-1, and excellent cycle performance with a capacity of 708.6 mAh g-1 and 87.1% capacity retention after 820 cycles at 1000 mA g-1, outperforming the reported results of Si/C composite anodes. Furthermore, a low electrode swelling of 18.1% at a high areal capacity of 3.8 mAh cm-2 can be obtained. When assembled into a practical 3.2 Ah cylindrical cell, extraordinary long cycling life with a capacity retention of 81.4% even after 1200 cycles at 1C (3.2 A) and excellent rate performance are achieved, indicating significant advantages for long-life power batteries in electric vehicles.

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