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1.
Mol Med Rep ; 21(3): 1517-1526, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32016472

RESUMO

Non­small cell lung cancer (NSCLC) is prevalent worldwide. Lung squamous cell carcinoma (LUSC) is one of the main subtypes of NSCLC yet, currently, few biomarkers are available for the diagnosis of LUSC. The present study aimed to investigate the expression and role of adenosine deaminase RNA specific B1 (ADARB1) in lung squamous cell carcinoma (LUSC). Integrative bioinformatics analysis was used to identify the effects of ADARB1 expression on the occurrence and prognosis of LUSC. The expression of ADARB1 was further examined by immunohistochemistry (IHC). Bioinformatics analysis suggested that ADARB1 was downregulated in LUSC, serving as a potential tumor suppressor, and these results were verified by IHC performed on a lung cancer tissue array. Clinical studies suggested that ADARB1 expression and methylation levels were significantly associated with patient characteristics in LUSC. Moreover, ADARB1 global methylation levels were upregulated in LUSC tissues compared with normal lung tissues. Higher methylation levels of cg24063645 were associated with shorter overall survival time of patients with LUSC. A negative correlation was identified between ADARB1 and epidermal growth factor receptor (EGFR) expression in LUSC. Using the Gene Expression Omnibus database, it was suggested that the expression of ADARB1 in LUSC was significantly different compared with that in lung adenocarcinoma. Furthermore, protein­protein interactions were studied and a biological process annotation analysis was conducted. The present study suggested that ADARB1 was downregulated in LUSC; therefore, ADARB1 may serve as a specific biomarker and a potential therapeutic target for LUSC.

2.
Nat Nanotechnol ; 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31988500

RESUMO

The solid-electrolyte interphase (SEI) dictates the performance of most batteries, but the understanding of its chemistry and structure is limited by the lack of in situ experimental tools. In this work, we present a dynamic picture of the SEI formation in lithium-ion batteries using in operando liquid secondary ion mass spectrometry in combination with molecular dynamics simulations. We find that before any interphasial chemistry occurs (during the initial charging), an electric double layer forms at the electrode/electrolyte interface due to the self-assembly of solvent molecules. The formation of the double layer is directed by Li+ and the electrode surface potential. The structure of this double layer predicts the eventual interphasial chemistry; in particular, the negatively charged electrode surface repels salt anions from the inner layer and results in an inner SEI that is thin, dense and inorganic in nature. It is this dense layer that is responsible for conducting Li+ and insulating electrons, the main functions of the SEI. An electrolyte-permeable and organic-rich outer layer appears after the formation of the inner layer. In the presence of a highly concentrated, fluoride-rich electrolyte, the inner SEI layer has an elevated concentration of LiF due to the presence of anions in the double layer. These real-time nanoscale observations will be helpful in engineering better interphases for future batteries.

4.
Mol Med Rep ; 21(1): 360-370, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31939622

RESUMO

The gasdermin (GSDM) superfamily has been demonstrated to consist of several important molecules that modulate multifunctional signal processes, such as cell pyroptosis. In this research, the roles of the GSDM superfamily on the occurrence and prognosis of lung adenocarcinoma (LUAD) were evaluated using integrative bioinformatic analyses and in vitro methods. Here, data from several bioinformatic platforms revealed that GSDMC is significantly upregulated in LUAD tissues and cell lines. Real­time fluorescence quantitative PCR (qPCR) demonstrated that GSDMC was obviously upregulated in radio­resistant LUAD cells, compared with their parental cells. Moreover, upregulated GSDMC expression was confirmed to be an independent indicator of poor first progression (FP) and overall survival (OS) in LUAD patients. DNA methylation analysis showed an evidently negative correlation between GSDMC expression and methylation status of one CpG site (cg05316065) in its DNA sequence. Patients with high methylation values had significantly higher Karnofsky performance scores (KPSs) and prolonged OS rates. Together, we confirmed that overexpression of GSDMC acts as a promising predictive factor for the poor prognosis of LUAD patients.

5.
J Cell Commun Signal ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31933275

RESUMO

Pembrolizumab monotherapy has been demonstrated as a first-line therapy for non-small-cell lung cancer (NSCLC) patients with a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of ≥50%; however, the clinical efficacy is limited by the unreasonable threshold of the TPS. A recent study published by Mok et al. (Lancet 393:1819-1830, 2019) showed that pembrolizumab monotherapy could also be extended as an effective first-line therapeutic strategy for NSCLC patients with low TPS. However, this needs to be further evaluated in detail after considering the following issues. In Mok's report, the survival curves were much lower in a pembrolizumab-treated group in the first 6 months of treatment compared with a chemotherapy group. These contradictory findings might have been due to anecdotal occurrences of rapid progression, especially hyperprogressive disease.

6.
J Phys Condens Matter ; 32(5): 055301, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31600737

RESUMO

Using density functional theory and nonequilibrium Green's function method, the spin-dependent electronic transport properties of six transition metal porphyrin molecules (VP, CrP, MnP, FeP, CoP, and NiP), which are linked to gold electrodes through the thiolated ethynyl groups, are investigated. Two different linkage modes (beta linkage and meso linkage) of the substituted ethynyl groups on the porphyrin macrocycle are considered. The results show that the linkage mode of ethynyl groups plays an important role on the spin transport properties of the molecular junctions and the beta linkage is more favorable for the spin filtering efficiency of current than the meso linkages. The spin-up and spin-down energy levels show the different evolutions which is responsible for the difference of spin filtering efficiency between the two linkage modes. The computational results of total current show that the meso-linked molecular junctions have the better conductive performances than the beta-linked ones which may be caused by the different electronic transport paths.

8.
Ann Transl Med ; 7(20): 541, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31807523

RESUMO

Background: Gliomas are the most frequently occurring malignant brain cancers. Recently, isocitrate dehydrogenase (IDH) mutations, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, and 1p/19q co-deletion have been suggested to indicate a favorable prognosis in gliomas. However, the clinical prognostic value of these genetic tests in human gliomas is not fully understood. Methods: We included glioma patients who accepted genetic testing including IDH, MGMT and 1p/19q at Xiangya Hospital, Central South University in China (Jan 2015 to Jun 2017) and further analyzed the effect of the above gene states in high-grade gliomas. Results: In 103 high-grade glioma patients, IDH mutation, MGMT promoter methylation, and 1p/19q co-deletion had better progression-free survival (PFS) than IDH wild-type (P=0.005), MGMT unmethylated promoter (P=0.002), and without 1p19q co-deletion (P=0.008), respectively. Additionally, we classified the above gliomas into 5 molecular groups, triple-positive, IDH mutation and MGMT methylation, methylation in MGMT only, mutation in IDH only, and triple-negative, according to characteristics of recruited patients. We found that triple-positive gliomas had better PFS than triple-negative cases in high-grade patients (P=0.016). Moreover, the IDH mutation and MGMT methylation groups had prolonged PFS compared to triple-negative (P=0.029). Conclusions: Our study reinforced the clinical value of biomarkers, including 1p/19q co-deletion, IDH mutation, and the most prominent MGMT methylation, as previously described in glioma prognosis. Further, triple-negative patients have poorer PFS, indicating that the states of these genes can be divided into subgroups as a potential prognostic marker for clinical treatment, which requires a larger, multicenter study to testify.

9.
Infect Drug Resist ; 12: 2683-2691, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695444

RESUMO

Purpose: To describe trends and correlation between antibacterial exposure and bacterial resistance from hospitalized patients in a hospital in southern China. Patients and methods: This study used hospital-wide data regarding antimicrobial resistance and consumption between January 1, 2014 and December 31, 2018. Antibacterial consumption was expressed as antimicrobial use density (AUD). The changes in trends and associations between antibacterial utilization and resistance were analyzed using linear regression and time series analysis. Results: The total AUD of all antimicrobials decreased year by year (50.66 in 2014 vs 44.28 in 2018, P=0.03). The annual use of antimicrobials, such as penicillins, monobactams, aminoglycosides, macrolides, and lincosamides, significantly decreased (P<0.05), while the annual use of quinolones and tetracyclines significantly increased (P<0.05). Among the top ten isolated bacteria, antimicrobial resistance trends of Escherichia coli, Pseudomonas aeruginosa, Candida albicans, Staphylococcus aureus, and Staphylococcus epidermidis significantly decreased (P<0.05). Significant positive correlation was found between AUD of carbapenems and resistance rate of Acinetobacter baumannii to imipenem (ß=32.87, P<0.01), as well as the correlation between AUD of quinolones and resistance rate of Enterococcus faecium to levofloxacin (ß=104.40, P<0.01). Conclusion: The consumption of antibiotics and antibiotic resistance has been significantly improved in this tertiary hospital. Additionally, the efforts of China's antibiotic management may be suggested by the relationship between indicated antibiotic resistance and consumption. However, overall AUD levels and poor control of the use of antibiotics, such as quinolones and tetracyclines, still require strengthened management.

10.
Front Cell Dev Biol ; 7: 217, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632968

RESUMO

Background: LncRNAs have been shown to play essential roles in cancer therapeutic response. However, the detailed mechanism of lncRNAs in temozolomide (TMZ) resistance in glioblastoma (GBM) remain to be elucidated. Methods: To elucidate the mechanism maintaining TMZ resistance, we constructed two TMZ-resistant GBM cell lines (T98G-R/U118-R). LncRNAs from four public datasets were reanalyzed, and the candidate lncRNA ADAMTS9-AS2 was evaluated in TMZ-treated GBM patients and in vitro cell lines. Results: Reanalysis of lncRNA expression profiles identified ADAMTS9-AS2 as significantly overexpressed in TMZ-resistant GBM cells and as positively associated with the IC50 of TMZ in GBM cells. Overexpression of ADAMTS9-AS2 was also significantly associated with poor TMZ response and shorter progression-free survival (PFS) in TMZ-treated GBM patients. Knockdown of ADAMTS9-AS2 inhibited proliferation and attenuated the IC50 of TMZ, as well as mitigating invasion and migration in TMZ-resistant GBM cells. Subsequent investigations indicated that reduced expression of ADAMTS9-AS2 significantly suppressed expression of the FUS protein, which was predicted as a direct substrate of ADAMTS9-AS2. Expression trends of FUS were directly correlated with those of ADAMTS9-AS2, as shown by increasing concentrations and prolonged treatment with TMZ. RNA pull-down and RIP assays indicated that both endogenous and exogenous ADAMTS9-AS2 directly binds to the RRM and Znf_RanBP2 domains of FUS, consequently increasing FUS protein expression. Knockdown of ADAMTS9-AS2 reduced the half-life of FUS and decreased FUS protein stability via K48 ubiquitin degradation. Moreover, the E3 ubiquitin-protein ligase MDM2 interacts with and down regulates FUS, while the RRM and Znf_RanBP2 domains of FUS facilitate its binding with MDM2. ADAMTS9-AS2 decreased the interaction between MDM2 and FUS, which mediates FUS K48 ubiquitination. Additionally, knockdown of the ADAMTS9-AS2/FUS signaling axis significantly alleviated progression and metastasis in TMZ-resistant cells. Conclusion: ADAMTS9-AS2 possessed a novel function that promotes TMZ resistance via upregulating the FUS/MDM2 axis in GBM cells. The RRM or Znf_RanBP2 domains of FUS facilitate the combination of ADAMTS9-AS2 and FUS, competitively inhibiting MDM2-dependent FUS K48 ubiquitination and resulting in enhanced FUS stability and TMZ resistance. Our results suggest that the ADAMTS9-AS2/FUS/MDM2 axis may represent a suitable prognostic biomarker and a potential target in TMZ-resistant GBM therapy.

11.
Microsyst Nanoeng ; 5: 48, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31645998

RESUMO

Raman spectroscopy plays a crucial role in biochemical analysis. Recently, superhydrophobic surface-enhanced Raman scattering (SERS) substrates have enhanced detection limits by concentrating target molecules into small areas. However, due to the wet transition phenomenon, further reduction of the droplet contact area is prevented, and the detection limit is restricted. This paper proposes a simple method involving femtosecond laser-induced forward transfer for preparing a hybrid superhydrophilic-superhydrophobic SERS (HS-SERS) substrate by introducing a superhydrophilic pattern to promote the target molecules to concentrate on it for ultratrace detection. Furthermore, the HS-SERS substrate is heated to promote a smaller concentrated area. The water vapor film formed by the contact of the solution with the substrate overcomes droplet collapse, and the target molecules are completely concentrated into the superhydrophilic region without loss during evaporation. Finally, the concentrated region is successfully reduced, and the detection limit is enhanced. The HS-SERS substrate achieved a final contact area of 0.013 mm2, a 12.1-fold decrease from the unheated case. The reduction of the contact area led to a detection limit concentration as low as 10-16 M for a Rhodamine 6G solution. In addition, the HS-SERS substrate accurately controlled the size of the concentrated areas through the superhydrophilic pattern, which can be attributed to the favorable repeatability of the droplet concentration results. In addition, the preparation method is flexible and has the potential for fluid mixing, fluid transport, and biochemical sensors, etc.

15.
Front Oncol ; 9: 852, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31552177

RESUMO

Nafamostat mesylate (NM), a synthetic serine protease inhibitor first placed on the market by Japan Tobacco in 1986, has been approved to treat inflammatory-related diseases, such as pancreatitis. Recently, an increasing number of studies have highlighted the promising effects of NM in inhibiting cancer progression. Alone or in combination treatments, studies have shown that NM attenuates various malignant tumors, including pancreatic, colorectal, gastric, gallbladder, and hepatocellular cancers. In this review, based on several activating pathways, including the canonical Nuclear factor-κB (NF-κB) signaling pathway, tumor necrosis factor receptor-1 (TNFR1) signaling pathway, and tumorigenesis-related tryptase secreted by mast cells, we summarize the anticancer properties of NM in existing studies both in vitro and in vivo. In addition, the efficacy and side effects of NM in cancer patients are summarized in detail. To further clarify NM's antitumor activities, clinical trials devoted to validating the clinical applications and underlying mechanisms are needed in the future.

16.
PLoS One ; 14(9): e0222298, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31491024

RESUMO

Adenosine deaminase RNA-specific B1 (ADARB1), an adenosine-to-inosine (A-to-I) RNA-editing enzyme, has been found to play an essential role in the development of cancer. However, the specific function of ADARB1 in lung cancer, especially in lung adenocarcinoma (LUAD), is still not fully understood and requires further study. In our study, integrative bioinformatics were used to analyze the detailed function of ADARB1 in LUAD. By conducting bioinformatics analyses of several public databases, such as Gene Expression Profiling Interactive Analysis (GEPIA), GE-mini, and Oncomine, we found significantly decreased ADARB1 expression in LUAD cells and tissues. Moreover, RT-PCR and Western blot showed lower ADARB1 expression in H358 and A549 LUAD cells compared to human bronchial epithelial Beas-2B cells. Wound Healing Assay indicated that knockdown ADARB1 could promote LUAD cell metastasis. By using the Kaplan-Meier Plotter tool, we found that downregulation of ADARB1 was related to shorter first progression (FP), overall survival time (OS) and post-progression survival time (PPS). The relevant clinical data acquired from the Wanderer database indicated that the expression and methylation values of ADARB1 were significantly associated with the clinical characteristics of LUAD. Using DNA methylation inhibitor, we found DNMT inhibitor 5-aza-2-deoxycytidine (5-azaD) could promote the expression of ADARB1 and reverse the inhibition effect of ADARB1 in migration. In addition, functional enrichment analysis of ADARB1-associated coexpression genes was further conducted. Our investigation demonstrated that low levels of ADARB1 were specifically found in LUAD, and this gene might be a potential target in the diagnostic and prognostic evaluation of LUAD patients.

17.
PeerJ ; 7: e7652, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534865

RESUMO

Objective: Aloperine (ALO), an alkaloid isolated from the leaves of Sophora alopecuroides, has been suggested to exhibit anti-inflammatory and anti-tumor properties and is traditionally used to treat various human diseases, including cancer. However, limited information is available about the mechanisms that determine the anti-tumor activities of ALO. Methods: Herein, through comprehensive bioinformatics methods and in vitro functional analyses, we evaluated the detailed anti-tumor mechanisms of ALO. Results: Using the databases Bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine and PubChem Project, we identified the potential targets of ALO. A protein-protein interaction network was constructed to determine the relationship among these probable targets. Functional enrichment analysis revealed that ALO is potentially involved in the induction of apoptosis. In addition, molecular docking demonstrated that ALO expectedly docks into the active pocket of the Bcl2 protein, suggesting Bcl2 as a direct target of ALO. Moreover, western blot and qPCR analysis showed that ALO downregulated Bcl2 expression in human glioma cell lines, SK-N-AS and U118. Using flow cytometry methods, we further confirmed that ALO significantly promotes apoptosis in SK-N-AS and U118 cell lines, similar to the effect induced by ABT-737, a well-known Bcl2 inhibitor. In addition, Bcl-2 overexpression could rescue ALO-induced Bcl-2 inhibition and suppress pro-apoptotic effects in glioma cells. Conclusion: Taken together, these findings suggest that the natural agent ALO effectively enhances apoptosis by acting as a potential Bcl2 inhibitor in human glioma cells.

18.
Mol Med Rep ; 20(4): 3642-3648, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485643

RESUMO

There is increasing evidence that human complement factor H­related protein 1 (CFHR1) plays a crucial role in the development of malignant diseases. However, few studies have identified the roles of CFHR1 in the occurrence and prognosis of lung adenocarcinoma (LADC). In the present study, comprehensive bioinformatic analyses of data obtained from the Oncomine platform, UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) demonstrated that CFHR1 expression is significantly reduced in both LADC tissues and cancer cells. The patients presenting with downregulation of CFHR1 had significantly lower overall survival (OS) and post progression survival (PPS) times. Through analysis of the datasets from Gene Expression Omnibus database, we found that the compound actinomycin D promoted CFHR1 expression, further displaying the cytotoxic effect in the LADC cell line A549. In addition, the expression level of CFHR1 in the cisplatin­resistant LADC cell line CDDP­R (derived from H460) was also significantly reduced. Our research demonstrated that low levels of CFHR1 are specifically found in LADC samples, and CFHR1 could serve as a potential therapeutic target for this subset of lung cancers. Determination of the detailed roles of CFHR1 in LADC biology could provide insightful information for further investigations.

19.
Curr Res Transl Med ; 67(4): 123-128, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31492588

RESUMO

Carbamoyl phosphate synthetase-1 (CPS1), the first rate-limiting mitochondrial enzyme in the urea cycle, regulates proliferation and differentiation during tumor progression. However, the detailed function of CPS1 in glioblastoma Multiforme (GBM) is still unclear. Here, we highlight mechanisms for CPS1 upregulation and the effects of upregulated CPS1 on GBM tumorigenesis. The transcriptome data from several public databases, such as Oncomine and GEPIA, revealed that CPS1 transcriptional level was significantly upregulated in GBM tissues and cells. Moreover, CPS1 was hypomethylated in GBM tissues. The Wanderer database, linked to the Cancer Genome Atlas (TCGA), showed the association between CPS1 expression or its methylation values and the clinicopathological parameters in GBM patients. Our work fully demonstrated that CPS1 expression was upregulated in GBM and this gene could be used as a potential diagnostic and prognosis indicator for GBM.

20.
Front Oncol ; 9: 683, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31403034

RESUMO

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (EBV+ DLBCL) is a rare type of lymphoma with a high incidence in elderly patients, poor drug response, and unfavorable prognosis. Despite advances in genomic profiling and precision medicine in DLBCL, EBV+ DLBCL remain poorly characterized and understood. We include 236 DLBCL patients for EBV-encoded mRNA (EBER) in situ hybridization detection and analyzed 9 EBV+ and 6 EBV negative cases by next-generation sequencing (NGS). We then performed fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) to analyze chromosome rearrangements and gene expressions in 22 EBV+ and 30 EBV negative cases. The EBER results showed a 9.3% (22/236) positive rate. The NGS results revealed recurrent alterations in MYC and RHOA, components of apoptosis and NF-κB pathways. The most frequently mutated genes in EBV+ DLBCL were MYC (3/9; 33.3%), RHOA (3/9; 33.3%), PIM1 (2/9; 22.2%), MEF2B (2/9; 22.2%), MYD88 (2/9; 22.2%), and CD79B (2/9; 22.2%) compared with KMT2D (4/6; 66.7%), CREBBP (3/6; 50.0%), PIM1 (2/6; 33.3%), TNFAIP3 (2/6; 33.3%), and BCL2 (2/6; 33.3%) in EBV-negative DLBCL. MYC and KMT2D alterations stood out the most differently mutated genes between the two groups. FISH detection displayed a lower rearrangement rate in EBV+ cohort. Furthermore, KMT2D expression was highly expressed and associated with poor survival in both cohorts. MYC was only overexpressed and related to an inferior prognosis in the EBV+ DLBCL cohort. In summary, we depicted a distinct mutation profile for EBV+ and EBV-negative DLBCL and validated the differential expression of KMT2D and MYC with potential prognostic influence, thereby providing new perspectives into the pathogenesis and precision medicine of DLBCL.

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