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1.
Neuroscience ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32059985

RESUMO

The application of Resting State functional MRI (RS-fMRI) in Parkinson's disease was widely performed using standard statistical tests, however, the machine learning approach has not yet been investigated in PD using RS-fMRI. In current study, we utilized the mean regional amplitude values as the features in patients with PD (n = 72) and in healthy controls (HC, n = 89). The t-test and linear support vector machine were employed to select the features and make prediction, respectively. Three frequency bins (Slow-5: 0.0107 - 0.0286 Hz; Slow-4: 0.0286 - 0.0821 Hz; Conventional: 0.01 - 0.08 Hz) were analyzed. Our results showed that the Slow-4 may provide important information than Slow-5 in PD, and it had almost identical classification performance compared with the Combined (Slow-5 and Slow-4) and Conventional frequency bands. Similar with previous neuroimaging studies in PD, the discriminative regions were mainly included the disrupted motor system, aberrant visual cortex, dysfunction of paralimbic/limbic and basal ganglia networks. The lateral parietal lobe, such as right IPL and SMG, was detected as the discriminative features exclusively in Slow-4. Our findings, at the first time, indicated that the machine learning approach is a promising choice for detecting abnormal regions in PD, and a multi-frequency scheme would provide us more specific information.

2.
Bioresour Technol ; 301: 122758, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31986373

RESUMO

Cultivating sand-consolidating cyanobacteria using wastewater has unique advantages on both nutrients recycling and ecological restoration by transferring excessive nutrients from wastewaters to desert areas. Although previous study showed that sand-consolidating cyanobacterium well adapted to synthetic domestic wastewater, no study has been carried out on actual wastewater. This study aims to investigate the sand-consolidating cyanobacterial biomass production and nutrients removal by cultivating Scytonema hyalinum in the municipal wastewater under different temperatures. The results showed that biomass accumulation increased with temperature from 20 â„ƒ to 30 â„ƒ, while severely depressed at 35 â„ƒ. More than 81.63% sCOD, 90.64% TDN and 97.08% TDP were removed by day 30 under each temperature except for 35℃. The inoculation of S. hyalinum strongly regulated the native wastewater bacterial community. These results indicated that sand-consolidating cyanobacterium S. hyalinum well adapted to municipal wastewater and temperature had remarkable effects on cyanobacterial biomass accumulation, nutrients removal and wastewater native bacterial community dynamics.


Assuntos
Cianobactérias , Águas Residuárias , Biomassa , Nitrogênio , Nutrientes , Areia , Temperatura Ambiente
3.
Brain Imaging Behav ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31909443

RESUMO

Depression is the most common non-motor symptom accompanying Parkinson's disease (PD) with high prevalence but unclear pathophysiological mechanism. Relatively little is known about the topological patterns of white matter structural networks in depressed patients with PD. In this study, we used diffusion-tensor imaging (DTI) and graph theory approaches to explore the brain structural connectome in non-depressed patients with PD (n = 47), depressed patients with PD (n = 20) and healthy controls (n = 46). All three groups exhibited small-world topology. Compared with healthy controls, non-depressed patients with PD and depressed patients with PD showed a significant reduction of network efficiency in the cortico-subcortical circuits. Moreover, depressed patients with PD exhibited higher network efficiency in fronto-limbic system, compared to non-depressed patients with PD. To sum up, our data indicated a disrupted integrity in the large-scale brain systems in depressed patients with PD patients. The structural connectome provided a basis for functional alterations in depressed patients with PD that may advance our current understanding of pathophysiological mechanism underlying Parkinson's disease.

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.
Surg Innov ; 27(1): 88-100, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31514682

RESUMO

Purpose. We analyzed the literature to determine (1) the surgically relevant applications for which head-mounted display (HMD) use is reported; (2) the types of HMD most commonly reported; and (3) the surgical specialties in which HMD use is reported. Methods. The PubMed, Embase, Cochrane Library, and Web of Science databases were searched through August 27, 2017, for publications describing HMD use during surgically relevant applications. We identified 120 relevant English-language, non-opinion publications for inclusion. HMD types were categorized as "heads-up" (nontransparent HMD display and direct visualization of the real environment), "see-through" (visualization of the HMD display overlaid on the real environment), or "non-see-through" (visualization of only the nontransparent HMD display). Results. HMDs were used for image guidance and augmented reality (70 publications), data display (63 publications), communication (34 publications), and education/training (18 publications). See-through HMDs were described in 55 publications, heads-up HMDs in 41 publications, and non-see-through HMDs in 27 publications. Google Glass, a see-through HMD, was the most frequently used model, reported in 32 publications. The specialties with the highest frequency of published HMD use were urology (20 publications), neurosurgery (17 publications), and unspecified surgical specialty (20 publications). Conclusion. Image guidance and augmented reality were the most commonly reported applications for which HMDs were used. See-through HMDs were the most commonly reported type used in surgically relevant applications. Urology and neurosurgery were the specialties with greatest published HMD use.

6.
Biol Trace Elem Res ; 193(2): 508-516, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31025241

RESUMO

Selenium (Se) has been well recognized as an immune-enhancing agent with antioxidant and anti-tumor properties. The commonly used chemotherapy drug, cyclophosphamide (CTX), induces liver injury by increasing the reactive oxygen species (ROS) level. However, little is known about how Se alleviates CTX-induced liver injury in geese. In this study, 90 male Magang geese (3 days old) were randomly allocated into three groups (control, CTX, and Se + CTX group) with three replicates per group and ten geese per replicate. The control and CTX groups were fed a basal diet (Se content was 0.03 mg/kg). The Se + CTX group was fed a basal diet containing 0.44 mg/kg sodium selenite (Se content was 0.2 + 0.03 mg/kg). The control group was injected with 0.5 mL saline, while the CTX and Se + CTX groups were injected with CTX at 40 mg/kg body weight per day on days 21-23. The liver index, liver histology, and ultra-micromorphology detected antioxidant enzyme activity in the liver and serum. In addition, we detected the liver marker enzymes and protein levels in serum, and hepatocyte DNA damage. Se could alleviate liver development dysregulation, hepatocyte structural damage, the disturbances in antioxidant enzyme (GPx, CAT, and SOD) activity, and malondialdehyde (MDA) levels in the serum and liver. Besides, Se could alleviate the dysregulation of liver marker enzyme (ALT and AST) activity and protein (ALB and TP) levels in the serum, and DNA migration induced by CTX. In conclusion, Se may inhibit hepatocyte necrosis and DNA damage by inhibiting CTX-induced oxidative stress.

7.
Int J Cancer ; 146(6): 1730-1740, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31840816

RESUMO

Immune checkpoint blockade (ICB) has shown long-term survival benefits, but only in a small fraction of cancer patients. Recent studies suggest that improved vessel perfusion by ICB positively correlates with its therapeutic outcomes. However, the underlying mechanism of such a process remains unclear. Here, we show that anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) treatment-induced tumor vessel normalization was accompanied by an increased infiltration of eosinophils into breast tumors. Eosinophil accumulation was positively correlated with the responsiveness of a breast tumor to anti-CTLA4 therapy. Depletion of eosinophils subsequently negated vessel normalization, reduced antitumor immunity and attenuated tumor growth inhibition by anti-CTLA4 therapy. Moreover, intratumoral accumulation of eosinophils relied on T lymphocytes and interferon γ production. Together, these results suggest that eosinophils partially mediate the antitumor effects of CTLA4 blockade through vascular remodeling. Our findings uncover an unidentified role of eosinophils in anti-CTLA4 therapy, providing a potential new target to improve ICB therapy and to predict its efficacy.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Antígeno CTLA-4/antagonistas & inibidores , Eosinófilos/efeitos dos fármacos , Eosinófilos/metabolismo , Neoplasias/etiologia , Neoplasias/metabolismo , Neovascularização Patológica/metabolismo , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores , Linhagem Celular Tumoral , Eosinófilos/imunologia , Feminino , Humanos , Imunidade , Imunomodulação/efeitos dos fármacos , Imunofenotipagem , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Depleção Linfocítica , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neovascularização Patológica/tratamento farmacológico , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
8.
Br J Radiol ; 93(1105): 20190562, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31603347

RESUMO

OBJECTIVE: Patients with diabetes mellitus, diabetic nephropathy (DN) and healthy donor were analyzed to test whether the early DN patients can be detected using both blood oxygenation level dependent (BOLD) and diffusion tensor imaging. METHODS: This study was approved by the Ethics Committee of our hospital. MR images were acquired on a 3.0-Tesla MR system (Discovery MR750, General Electric, Milwaukee, WI). 30 diabetic patients were divided into NAU (normal to mildly increased albuminuria, N = 15) and MAU (moderately increased albuminuria, N = 15) group based on the absence or presence of microalbuminuria. 15 controls with sex- and age-matched were enrolled in the study. Prior to MRI scan, all participants were instructed to collect their fresh morning urine samples for quantitative measurement of urinary microalbumin and urinary creatinine. Then, the estimations of serum creatinine, serum uric acid, HbAlc and fasting plasma glucose as well as fundus examinations were performed in all subjects. Then, the values of albumin-creatinine ratio (ACR) and estimated glomerular filtration rate were also calculated. All subjects underwent renal diffusion tensor imaging (DTI) and BOLD acquisition after fasting for 4 h. Regions of interest were placed in renal medulla and cortex for evaluating apparent diffusion coefficient (ADC), fractional anisotropy (FA) and R2* values by two experienced radiologists. The consistency between the two observations was estimated using intragroup correlation coefficients. To test differences in ADC, FA and R2* values across the three groups, the data were analyzed using separate one-way ANOVAs. Post-hoc pair wise comparisons were then performed using t-test. To investigate the clinical relevance of imaging parameters in both regions across the three groups, the correlations of values of the ACR/estimated glomerular filtration rate and of the ADC/FA/R2* were calculated. RESULTS: There was a high level of consistency of those ADC, FA and R2* values across the three groups on both renal cortex and medulla measured by the two doctors. The FA value of medulla in MAU group was lower than that in control (p < 0.01). The R2* value of medulla in the NAU group was higher than that in the control (p < 0.01), and the R2* value of medulla in the MAU group was lower than that in the control (p = 0.009) . Moreover, the current study revealed a decreasing trend in FA values of the renal medulla from the control group to NAU and MAU groups. Finally, a weak negatively correlation between medullary R2* and ACR was found in current study. CONCLUSION: Medullary R2* value might be a new more sensitive predictor of early DN. Meanwhile, BOLD imaging detected the medullary hypoxia at the simply diabetic stage, while DTI didn't identify the medullary directional diffusion changes at this stage. Based on our assumption mentioned above, it's presumable that BOLD imaging may be more sensitive for assessment of the early renal function changes than DTI. These imaging techniques are more accurate and practical than conventional tests. ADVANCES IN KNOWLEDGE: Non-invasive MRI was used to detect renal function changes at early DN stage.


Assuntos
Nefropatias Diabéticas/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Anisotropia , Biomarcadores/análise , Imagem de Tensor de Difusão , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Testes de Função Renal , Masculino , Pessoa de Meia-Idade
10.
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.

11.
Leuk Lymphoma ; : 1-7, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31795794

RESUMO

18F-FDG PET/CT is recommended for staging and response assessment in FDG-avid lymphomas, such as HL and DLBCL. But evidence of PET/CT regarding T-cell lymphomas (TCLs) was limited. In this retrospective study, we conducted survival analysis using interim PET/CT in 51 TCLs patients. PET/CT were reported using the Deauville 5-point score (DS) and the ΔSUVmax. In univariate analysis, I-PET/CT had a significant prognostic value of survival outcomes based on DS (p < .001 for progression-free survival (PFS), p = .010 for overall survival (OS)) and ΔSUVmax (p < .001 for PFS, p = .023 for OS). In multivariate analysis, DS remained a statistically independent predictor of PFS (p < .001) and OS (p = .017). ΔSUVmax remained a statistically independent predictor of PFS (p = .008), but not of OS (p = 0.311). Therefore, DS on I-PET/CT had a remarkable value of predicting survival outcomes in TCLs.

12.
Mikrochim Acta ; 187(1): 61, 2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31853650

RESUMO

An ultra-sensitive method is described here for the determination of HIF-1α (an early biomarker for myocardial infarction) in circulating exosomes in serum. Gold nanospheres were functionalized with a HIF-1α-binding aptamer via sulfydryl chemistry. The apt-AuNP-coated gold seeds were grown by seed-mediated growth, and this significantly increased the peroxidase-mimicking property the nanoparticles. A chromogenic system composed of 3,3'5,5'-tetramethylbenzidine and hydrogen peroxide was used. Absorbance at 652 nm increases linearly in the 0.3 to 200 ng L-1 HIF-1α concentration range, and the limit of detection is 0.2 ng L-1. The method was tested by analyzing rat serum from isoproterenol (ISO)-induced myocardial infarction. It allows HIF-1α to be directly determined in a 25 µL sample without preconcentration. The assay is not interfered by the polydispersity of exosomes released under either health and disease conditions. Graphical abstractGold nanospheres were functionalized with a HIF-1α-binding aptamer via sulfydryl chemistry. Nanosized gold seed particles were then modified with the functionalized gold nanospheres, and this strongly increases the peroxidase-mimicking activity of the nanomaterial. By using the tetramethylbenzidine/H2O2 chromogenic system, the absorbance at 652 nm increases linearly in the 0.3 to 200 ng L-1 HIF-1α concentration range.

13.
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.

14.
Quant Imaging Med Surg ; 9(10): 1747-1766, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31728316

RESUMO

Chemical exchange saturation transfer (CEST) imaging is a novel contrast mechanism, relying on the exchange between mobile protons in amide (-NH), amine (-NH2) and hydroxyl (-OH) groups and bulk water. Due to the targeted protons present in endogenous molecules or exogenous compounds applied externally, CEST imaging can respectively, generate endogenous or exogenous contrast. Nowadays, CEST imaging for endogenous contrast has been explored in pre-clinical and clinical studies. Amide CEST, also called amide proton transfer weighted (APT) imaging, generates CEST effect at 3.5 ppm away from the water signal and has been widely investigated. Given the sensitivity to amide proton concentration and pH level, APT imaging has shown robust performance in the assessment of ischemia, brain tumors, breast and prostate cancer as well as neurodegenerative diseases. With advanced methods proposed, pure APT and Nuclear Overhauser Effect (NOE) mediated CEST effects were separately fitted from original APT signal. Using both effects, early but promising results were obtained for glioma patients in the evaluation of tumor response to therapy and patient survival. Compared to amide CEST, amine CEST is also mobile proton concentration and pH dependent, but has a faster exchange rate between amine protons and water. The resultant CEST effect is usually introduced at 1.8-3 ppm. Glutamate and creatine, as two main metabolites with amine groups for CEST imaging, have been applied to quantitatively assess diseases in the central nervous system and muscle system, respectively. Glycosaminoglycan (Gag) as a representative metabolite with hydroxyl groups has also been measured to evaluate the cartilage of knee or intervertebral discs in CEST MRI. Due to limited frequency difference between hydroxyl protons and water, 7T for better spectral separation is preferred over 3T for GagCEST measurement. The applications of CEST MRI with exogenous contrast agents are still quite limited in clinic. While certain diamagnetic CEST agents, such as dynamic-glucose, have been tried in human for brain tumor or neck cancer assessment, most exogenous agents, i.e., paramagnetic CEST agents, are still tested in the pre-clinical stage, mainly due to potential toxicity. Engineered tissues for tissue regeneration and drug delivery have also shown a great potential in CEST imaging, as many of them, such as hydrogel and polyamide materials, contain mobile protons or can be incorporated with CEST specific chemical compounds. These engineered tissues can thus generate CEST effect in vivo, allowing a possibility to understand the fate of them in vivo longitudinally. Although the CEST MRI with engineered tissues has only been established in early stage, the obtained first evidence is crucial for further optimizing these biomaterials and finally accomplishing the translation into clinical use.

15.
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.

16.
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.

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.

19.
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.

20.
J Magn Reson Imaging ; 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31430008

RESUMO

BACKGROUND: MRI is one of the most important techniques to assess the treatment response of gliomas. However, differentiating tumor recurrence (TuR) from treatment effects (TrE) remains challenging. PURPOSE: To compare the diagnostic performance of MR diffusion-weighted imaging (DWI), arterial spin labeling (ASL), proton MR spectroscopy (MRS), and amide proton transfer (APT) imaging in differentiating between TuR and TrE in posttreatment glioma patients. STUDY TYPE: Prospective. POPULATION: Thirty patients with suspected tumor progression. FIELD STRENGTH/SEQUENCE: DWI, ASL, proton MRS, and APT imaging were performed at 3T MR. ASSESSMENT: MR indices, including ADC, relative cerebral blood flow (rCBF), ratios of Cho/Cr, Cho/NAA, and NAA/Cr and APT-weighted (APTw) effect were obtained from DWI, ASL, proton MRS, and APT imaging, respectively. Indices were measured in the contralateral normal-appearing white matter and lesions defined on the Gd-enhanced T1 w image. TuR or TrE was either determined histologically or clinically from longitudinal MRI follow-up for at least 6 months. STATISTICAL TESTS: The diagnostic performance of the indices was evaluated using Student's t-test, receiver operating characteristic (ROC) curve, and multivariate logistic regression analyses. RESULTS: Among the 30 patients, 16 were diagnosed as having TuR and the rest having TrE. The recurrent tumors showed a significantly higher APTw effect (1.56 ± 1.14%) and rCBF (1.44 ± 0.61) compared with lesions representing treatment effects (-0.44 ± 1.34% and 0.72 ± 0.25, respectively, with P < 0.001). The areas under the curve (AUCs) were 0.87 and 0.90 for APTw and rCBF, respectively, in differentiating between TuR and TrE. Combining APTw and rCBF achieved a higher AUC of 0.93. MRS index ratios of Cho/Cr (P = 0.25), Cho/NAA (P = 0.16), and NAA/Cr (P = 0.86) and ADC (P = 0.37) showed no significant differences between TuR and TrE lesions, with AUCs lower than 0.70. DATA CONCLUSION: Compared with DWI and MRS, ASL and APT imaging techniques showed better diagnostic capability in distinguishing TuR from TrE. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2019.

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