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1.
Opt Lett ; 49(5): 1349-1352, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38427010

ABSTRACT

Due to the intrinsic polarized emission property, polarized emissive materials with anisotropic nanostructures are expected to be potential substitutes for polarizers. Herein, by the template-assisted strategy, well-aligned lead-free metal halide Cs3Cu2I5 nanowire (NW) arrays are fabricated by evaporating the precursor ink in the anodic aluminum oxide (AAO) for polarized emission. The Cs3Cu2I5/AAO composite film emits highly polarized light with a degree of polarization (DOP) of 0.50. Furthermore, by changing the molar ratio of CsI/CuI, the stability of Cs3Cu2I5 precursor inks is improved. Finally, an ultraviolet (UV) light-emitting diode (LED) is adopted to pump the composite film to achieve a blue LED device. The reported Cs3Cu2I5/AAO composite film with highly polarized light emissions will have great potential for polarized emission applications such as liquid crystal display backlights, waveguides, and lasers.

2.
Environ Res ; 256: 119268, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38815721

ABSTRACT

In this study, electrochemistry was used to enhance the advanced oxidation of Fe(Ⅱ)/PAA (EC/Fe(Ⅱ)/PAA) to disintegrate waste activated sludge, and its performance and mechanism was compared with those of EC, PAA, EC/PAA and Fe(Ⅱ)/PAA. Results showed that the EC/Fe(Ⅱ)/PAA process effectively improved sludge disintegration and the concentrations of soluble chemical oxygen demand, polysaccharides and nucleic acids increased by 62.85%, 41.15% and 12.21%, respectively, compared to the Fe(Ⅱ)/PAA process. Mechanism analysis showed that the main active species produced in the EC/Fe(Ⅱ)/PAA process were •OH, R-O• and FeIVO2+. During the reaction process, sludge flocs were disrupted and particle size was reduced by the combined effects of active species oxidation, electrochemical oxidation and PAA oxidation. Furthermore, extracellular polymeric substances (EPS) was degraded, the conversion of TB-EPS to LB-EPS and S-EPS was promoted and the total protein and polysaccharide contents of EPS were increased. After sludge cells were disrupted, intracellular substances were released, causing an increase in nucleic acids, humic acids and fulvic acids in the supernatant, and resulting in sludge reduction. EC effectively accelerated the conversion of Fe(Ⅲ) to Fe(Ⅱ), which was conducive to the activation of PAA, while also enhancing the disintegration of EPS and sludge cells. This study provided an effective approach for the release of organic matter, offering significant benefits in sludge resource utilization.


Subject(s)
Sewage , Sewage/chemistry , Waste Disposal, Fluid/methods , Oxidation-Reduction , Electrochemical Techniques/methods , Iron/chemistry , Biological Oxygen Demand Analysis
3.
Chem Res Toxicol ; 36(9): 1483-1494, 2023 09 18.
Article in English | MEDLINE | ID: mdl-37622730

ABSTRACT

Genipin (GP) is the reactive aglycone of geniposide, the main component of traditional Chinese medicine Gardeniae Fructus (GF). The covalent binding of GP to cellular proteins is suspected to be responsible for GF-induced hepatotoxicity and inhibits drug-metabolizing enzyme activity, although the mechanisms remain to be clarified. In this study, the mechanisms of GP-induced human hepatic P450 inactivation were systemically investigated. Results showed that GP inhibited all tested P450 isoforms via distinct mechanisms. CYP2C19 was directly and irreversibly inactivated without time dependency. CYP1A2, CYP2C9, CYP2D6, and CYP3A4 T (testosterone as substrate) showed time-dependent and mixed-type inactivation, while CYP2B6, CYP2C8, and CYP3A4 M (midazolam as substrate) showed time-dependent and irreversible inactivation. For CYP3A4 inactivation, the kinact/KI values in the presence or absence of NADPH were 0.26 or 0.16 min-1 mM-1 for the M site and 0.62 or 0.27 min-1 mM-1 for the T site. Ketoconazole and glutathione (GSH) both attenuated CYP3A4 inactivation, suggesting an active site occupation- and reactive metabolite-mediated inactivation mechanism. Moreover, the in vitro and in vivo formation of a P450-dependent GP-S-GSH conjugate indicated the involvement of metabolic activation and thiol residues binding in GP-induced enzyme inactivation. Lastly, molecular docking analysis simulated potential binding sites and modes of GP association with CYP2C19 and CYP3A4. We propose that direct covalent binding and metabolic activation mediate GP-induced P450 inactivation and alert readers to potential risk factors for GP-related clinical drug-drug interactions.


Subject(s)
Cytochrome P-450 CYP3A , Gardenia , Humans , Cytochrome P-450 CYP2C19 , Molecular Docking Simulation , Cytochrome P-450 Enzyme System
4.
J Opt Soc Am A Opt Image Sci Vis ; 40(3): 629-636, 2023 Mar 01.
Article in English | MEDLINE | ID: mdl-37133047

ABSTRACT

In order to realize colorimetric characterization for the wide-color-gamut camera, we propose using the multilayer artificial neural network (ML-ANN) with the error-backpropagation algorithm, to model the color conversion from the RGB space of camera to theX Y Z space of the CIEXYZ standard. In this paper, the architecture model, forward-calculation model, error-backpropagation model, and the training policy of the ML-ANN were introduced. Based on the spectral reflectance curves of the ColorChecker-SG blocks and the spectral sensitivity functions of the RGB channels of typical color cameras, the method of producing the wide-color-gamut samples for the training and testing of the ML-ANN was proposed. Meanwhile, the comparative experiment employing different polynomial transforms with the least-square method was conducted. The experimental results have shown that, with the increase of the hidden layers and the neurons in each hidden layer, the training and testing errors can be decreased obviously. The mean training errors and mean testing errors of the ML-ANN with optimal hidden layers have been decreased to 0.69 and 0.84 (color difference of CIELAB), respectively, which is much better than all the polynomial transforms, including quartic polynomial transform.

5.
6.
J Proteome Res ; 21(5): 1311-1320, 2022 05 06.
Article in English | MEDLINE | ID: mdl-35353507

ABSTRACT

The members of the glutathione S-transferase (GST) superfamily often exhibit functional overlap and can compensate for each other. Their concentrations in serum are considered as disease biomarkers. A global and quantitative evaluation of serum GSTs is therefore urgent, but there is a lack of efficient approaches due to technological limitations. GSH magnetic beads were examined for their affinity to enrich GSTs in serum, and the enriched GSTs were quantitatively targeted using a Q Exactive HF-X mass spectrometer in parallel reaction monitoring (PRM) mode. To optimize the quantification of GST peptides, sample types, trypsin digestion, and serum loading were carefully assessed; a biosynthetic method was employed to generate isotope-labeled GST peptides, and instrumental parameters were systematically optimized. A total of 134 clinical sera were collected for GST quantification from healthy donors and patients with four liver diseases. Using the new approach, GSTs in healthy sera were profiled: 14 GST peptides were quantified, and the abundance of five GST families was ranked GSTM > GSTP > GSTA > MGST1 > GSTT1, ranging from 0.1 to 4 pmol/L. Furthermore, combining the abundance of multiple GST peptides could effectively distinguish different types of liver diseases. Quantification of serum GSTs through targeted proteomics, therefore, has apparent clinical potential for disease diagnosis.


Subject(s)
Glutathione Transferase , Tandem Mass Spectrometry , Chromatography, Liquid , Glutathione , Glutathione Transferase/analysis , Humans , Liver , Peptides , Proteomics/methods
7.
Antimicrob Agents Chemother ; 66(10): e0081122, 2022 10 18.
Article in English | MEDLINE | ID: mdl-36106884

ABSTRACT

Bedaquiline has been widely used as a part of combination dosage regimens for the treatment of multidrug-resistant tuberculosis (MDR-TB) patients with limited options. Although the effectiveness and safety of bedaquiline have been demonstrated in clinical trials, limited studies have investigated the significant pharmacokinetics and the impact of genotype on bedaquiline disposition. Here, we developed a population pharmacokinetic model of bedaquiline to describe the concentration-time data from Chinese adult patients diagnosed with MDR-TB. A total of 246 observations were collected from 99 subjects receiving the standard recommended dosage. Bedaquiline disposition was well described by a one-compartment model with first-order absorption. Covariate modeling identified that gamma-glutamyl transferase (GGT) and the single-nucleotide polymorphism (SNP) rs319952 in the AGBL4 gene were significantly associated with the apparent clearance of bedaquiline. The clearance (CL/F) was found to be 1.4 L/h lower for subjects with allele GG in SNP rs319952 than for subjects with alleles AG and AA and to decrease by 30% with a doubling in GGT. The model-based simulations were designed to assess the impact of GGT/SNP rs319952 on bedaquiline exposure and showed that patients with genotype GG in SNP rs319952 and GGT ranging from 10 to 50 U/L achieved the targeted maximum serum concentration at steady state (Cmax,ss). However, when GGT was increased to 100 U/L, Cmax,ss was 1.68-fold higher than the highest concentration pursued. The model developed provides the consideration of genetic polymorphism and hepatic function for bedaquiline dosage in MDR-TB adult patients.


Subject(s)
Tuberculosis, Multidrug-Resistant , Tuberculosis, Pulmonary , Adult , Humans , Antitubercular Agents/pharmacokinetics , Diarylquinolines/pharmacokinetics , Transferases , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/genetics , Tuberculosis, Multidrug-Resistant/complications , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/complications , Polymorphism, Single Nucleotide
8.
Opt Express ; 30(15): 27539-27559, 2022 Jul 18.
Article in English | MEDLINE | ID: mdl-36236923

ABSTRACT

Accurate three-dimensional (3D) morphological computational models of cells are important in a number of biological studies. This study proposes a precise depth-varying point spread function (PDV-PSF) method for reconstructing 3D computational models of suspended cells from two-dimensional (2D) confocal image stacks. Our approach deblurs the 2D images in horizontal plane and corrects the deformation in vertical direction to overcome the refractive index mismatch problem caused by suspended cells imaging through stratified media. Standard fluorescent polystyrene spheres and Jurkat T-lymphocytes are selected to evaluate the validity and accuracy of this PDV-PSF method. Qualitative and quantitative results demonstrate that our approach has superior performance in 3D morphological computational models reconstruction of suspended cells.


Subject(s)
Imaging, Three-Dimensional , Polystyrenes , Algorithms , Computer Simulation , Imaging, Three-Dimensional/methods
9.
Chemistry ; 28(38): e202104591, 2022 Jul 06.
Article in English | MEDLINE | ID: mdl-35394659

ABSTRACT

Though numerous nanomaterials with enzyme-like activities have been utilized as probes and sensors for detecting biological molecules, it is still challenging to construct highly sensitive detectors for biomarkers using polymeric materials. Benefiting from the π-d delocalization effect of electrons, excellent metal-chelating property, high electron transferability, and good chemical stability of π-conjugated phthalocyanine, the design of the copper phthalocyanine-based conjugated polymer nanoparticles (Cu-PcCP NPs) as a colorimetric sensor for a variety of biomarkers is reported. The Cu-PcCP NPs are synthesized through a simple microwave-assisted polymerization, and their chemical structures are thoroughly characterized. The colorimetric results of Cu-PcCP NPs demonstrate excellent peroxidase-like detecting activity and also great substrate selectivity than most of the reported Cu-based nanomaterials. The Cu-PcCP NPs can achieve a detection limit of 4.88 µM for the H2 O2 , 4.27 µM for the L-cysteine, and 21.10 µM for the glucose via a cascade catalytic system, which shows comparable detecting sensitivity as that of many earlier reported enzyme-like nanomaterials. Moreover, Cu-PcCP NPs present remarkable resistance to harsh conditions, including high temperature, low pH, and excessive salts. These highly specific π-conjugated copper-phthalocyanine nanoparticles not only overcome the current limitation of polymeric material-based sensors but also provide a new direction for designing next-generation enzyme-like nanomaterial-based colorimetric biosensors.


Subject(s)
Metal Nanoparticles , Nanoparticles , Biomarkers , Colorimetry/methods , Copper/chemistry , Indoles , Metal Nanoparticles/chemistry , Nanoparticles/chemistry , Organometallic Compounds
10.
BMC Public Health ; 22(1): 2068, 2022 11 12.
Article in English | MEDLINE | ID: mdl-36369026

ABSTRACT

BACKGROUND: To evaluate the global burden of cataracts by year, age, region, gender, and socioeconomic status using disability-adjusted life years (DALYs) and prevalence from the Global Burden of Disease (GBD) study 2019. METHODS: Global, regional, or national DALY numbers, crude DALY rates, and age-standardized DALY rates caused by cataracts, by year, age, and gender, were obtained from the Global Burden of Disease Study 2019. Socio-demographic Index (SDI) as a comprehensive indicator of the national or regional development status of GBD countries in 2019 was obtained from the GBD official website. Kruskal-Wallis test, linear regression, and Pearson correlation analysis were performed to explore the associations between the health burden with socioeconomic levels, Wilcoxon Signed-Rank Test was used to investigate the gender disparity. RESULTS: From 1990 to 2019, global DALY numbers caused by cataracts rose by 91.2%, crude rates increased by 32.2%, while age-standardized rates fell by 11.0%. Globally, age-standardized prevalence and DALYs rates of cataracts peaked in 2017 and 2000, with the prevalence rate of 1283.53 [95% uncertainty interval (UI) 1134.46-1442.93] and DALYs rate of 94.52 (95% UI 67.09-127.24) per 100,000 population, respectively. The burden was expected to decrease to 1232.33 (95% UI 942.33-1522.33) and 91.52 (95% UI 87.11-95.94) by 2050. Southeast Asia had the highest blindness rate caused by cataracts in terms of age-standardized DALY rates (99.87, 95% UI: 67.18-144.25) in 2019. Gender disparity has existed since 1990, with the female being more heavily impacted. This pattern remained with aging among different stages of vision impairments and varied through GBD super regions. Gender difference (females minus males) of age-standardized DALYs (equation: Y = -53.2*X + 50.0, P < 0.001) and prevalence rates (equation: Y = - 492.8*X + 521.6, P < 0.001) was negatively correlated with SDI in linear regression. CONCLUSION: The global health of cataracts is improving but the steady growth in crude DALY rates suggested that health progress does not mean fewer demands for cataracts. Globally, older age, females, and lower socioeconomic status are associated with higher cataract burden. The findings of this study highlight the importance to make gender-sensitive health policies to manage global vision loss caused by cataracts, especially in low SDI regions.


Subject(s)
Cataract , Global Burden of Disease , Male , Humans , Female , Quality-Adjusted Life Years , Global Health , Prevalence , Cataract/epidemiology , Blindness/epidemiology , Blindness/etiology
11.
PLoS Genet ; 15(2): e1007888, 2019 02.
Article in English | MEDLINE | ID: mdl-30707694

ABSTRACT

Brain metastasis (BM) is a major complication of lung adenocarcinoma (LAD). An investigation of the pathogenic mechanisms of BM, as well as the identification of appropriate molecular markers, is necessary. The aim of this study was to determine the expression patterns of microRNAs (miRNAs) in LAD with BM, and to investigate the biological role of these miRNAs during tumorigenesis. miRNA array profiles were used to identify BM-associated miRNAs. These miRNAs were independently validated in 155 LAD patients. Several in vivo and in vitro assays were performed to verify the effects of miRNAs on BM. We identified six miRNAs differentially expressed in patients with BM as compared to patients with BM. Of these, miR-4270 and miR-423-3p were further investigated. miR-4270 and miR-423-3p directly targeted MMP19 and P21, respectively, to influence cell viability, migration, and colony formation in vitro. miR-4270 downregulation and miR-423-3p upregulation was associated with an increased risk of BM in LAD patients. Thus, our results suggested that miR-4270 and miR-423-3p might play an important role in BM pathogenesis in LAD patients, and that these miRNAs might be useful prognostic and clinical treatment targets.


Subject(s)
Adenocarcinoma of Lung/genetics , Brain Neoplasms/genetics , Lung Neoplasms/genetics , MicroRNAs/genetics , Adenocarcinoma of Lung/pathology , Biomarkers, Tumor/genetics , Brain Neoplasms/pathology , Carcinogenesis/genetics , Carcinogenesis/pathology , Cell Movement/genetics , Cell Proliferation/genetics , Cell Survival/genetics , Down-Regulation/genetics , Female , Gene Expression Regulation, Neoplastic/genetics , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Up-Regulation/genetics
12.
Molecules ; 27(9)2022 Apr 24.
Article in English | MEDLINE | ID: mdl-35566087

ABSTRACT

Rapid and highly sensitive determination of clozapine (CLZ), a psychotropic drug for the treatment of refractory schizophrenia, in patients is of great significance to reduce the risk of disease recurrence. However, direct electroanalysis of CLZ in human whole blood remains a great challenge owing to the remarkable fouling that occurs in a complex matrix. In this work, a miniaturized, integrated, disposable electrochemical sensing platform based on the integration of nanochannel arrays on the surface of screen-printed carbon electrodes (SPCE) is demonstrated. The device achieves high determination sensitivity while also offering the electrode anti-fouling and anti-interference capabilities. To enhance the electrochemical performance of SPCE, simple electrochemical polarization including anodic oxidation and cathodic reduction is applied to pretreat SPCE. The electrochemically polarized SPCE (p-SPCE) exhibits an enhanced electrochemical peak signal toward CLZ compared with bare SPCE. An electrochemically assisted self-assembly method (EASA) is utilized to conveniently electrodeposit a vertically ordered mesoporous silica nanomembrane film (VMSF) on the p-SPCE, which could further enrich CLZ through electrostatic interactions. Owing to the dual signal amplification based on the p-SPCE and VMSF nanochannels, the developed VMSF/SPCE sensor enables determination of CLZ in the range from 50 nM to 20 µM with a low limit of detection (LOD) of 28 nM (S/N = 3). Combined with the excellent anti-fouling and anti-interference abilities of VMSF, direct and sensitive determination of CLZ in human blood is also achieved.


Subject(s)
Clozapine , Carbon , Electrochemical Techniques/methods , Electrodes , Humans , Limit of Detection , Silicon Dioxide
13.
Molecules ; 27(24)2022 Dec 07.
Article in English | MEDLINE | ID: mdl-36557774

ABSTRACT

A disposable and portable electrochemical sensor was fabricated by integrating vertically-ordered silica mesoporous films (VMSF) and electrochemically reduced graphene (ErGO) on a screen-printed carbon electrode (SPCE). Such VMSF/ErGO/SPCEs could be prepared by a simple and controllable electrochemical method. Stable growth of VMSF on SPCE could be accomplished by the introduction of an adhesive ErGO nanolayer owing to its oxygen-containing groups and two-dimensional (2D) planar structure. An outer VMSF layer acting as a protective coating is able to prevent the leakage of the inner ErGO layer from the SPCE surface. Thanks to the electrostatic permselectivity and anti-fouling capacity of VMSF and to the good electroactive activity of ErGO, binary nanocomposites of VMSF and ErGO endow the SPCE with excellent analytical performance, which could be used to quantitatively detect doxorubicin (DOX) in biological samples (human serum and urine) with high sensitivity, good long-term stability, and low sample amounts.


Subject(s)
Biofouling , Graphite , Nanocomposites , Humans , Graphite/chemistry , Silicon Dioxide , Biofouling/prevention & control , Carbon , Nanocomposites/chemistry , Electrochemical Techniques/methods , Electrodes
14.
Cancer Cell Int ; 21(1): 396, 2021 Jul 27.
Article in English | MEDLINE | ID: mdl-34315493

ABSTRACT

BACKGROUND: Protopine is an isoquinoline alkaloid that possesses various biological activities including the anti-tumour activity. However, the effects of protopine on liver carcinoma cells are still elusive. The aim of this study is to examine the effects of protopine on liver carcinoma cells both in vitro and in vivo. METHODS: MTT assay was performed to measure the cell viability. Wound healing and transwell assays were conducted to assess the motility of cells. Cellular apoptosis and ROS levels were measured by the flow cytometry. Western blotting assay was used to measure the change of proteins. The cytotoxicity of protopine was also evaluated in xenograft mice. RESULTS: Protopine inhibited viabilities and triggered apoptosis via the intrinsic pathway in a caspase-dependent manner in liver carcinoma cells. Furthermore, protopine also induced accumulation of intracellular ROS which further led to the inhibition of PI3K/Akt signalling pathway. Finally, in vivo study showed that protopine also repressed tumour growth in xenograft mice without noticeable toxicity. CONCLUSIONS: Protopine might be used as a potential therapeutic agent for the treatment of liver carcinoma.

15.
Cardiology ; 146(5): 607-615, 2021.
Article in English | MEDLINE | ID: mdl-34237718

ABSTRACT

BACKGROUND: Thyroid function is increasingly recognized as an important modifiable factor for atrial fibrillation (AF); however, it is unclear if the changes in thyroid hormones, even within the normal range, are associated with AF recurrence after catheter ablation. METHODS: Consecutive paroxysmal AF patients who underwent catheter ablation were enrolled. Patients with abnormal thyroid hormones or previous thyroid illnesses were excluded. Patients were followed for 12 months or until they presented with the first episode of atrial tachyarrhythmia after a blanking period. RESULTS: The study included 448 patients with a mean age of 61 (14) years, and 46% were women. After a 1-year follow-up, 104 (23.2%) patients experienced atrial tachyarrhythmia recurrences after an ablation procedure. Recurrence was significantly different among quartile groups of thyroid function, with highest FT4 and FT3 levels associated with the greatest risk of recurrence (p < 0.001 and p = 0.024, respectively). FT4 and FT3 levels were independent predictors of atrial tachyarrhythmia recurrence (hazard ratio 1.07 per 1 pmol/L increase in FT4, 95% confidence interval [CI] 1.01-1.15, p = 0.036 and 1.31 per 1 pmol/L increase in FT3, 95% CI 1.01-1.71, p = 0.032). CONCLUSIONS: High-normal FT3 and FT4 levels are associated with AF recurrence after catheter ablation in this Chinese population. Attention to thyroid hormones could be valuable to assist in the management of AF.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Atrial Fibrillation/surgery , Humans , Middle Aged , Prospective Studies , Thyroid Gland/surgery
16.
J Radiol Prot ; 41(2)2021 06 01.
Article in English | MEDLINE | ID: mdl-33873158

ABSTRACT

There is currently general concern over low-level radioactive wastewater from the development of nuclear industry. In this paper, a method based on an ultralow-level liquid scintillation spectrometer for measuring uranium radioactivity in low-level radioactive wastewater is proposed. This method can easily and quickly measure the radioactivity level of uranium in samples and can even distinguish the main isotopes of uranium. The liquid scintillation method directly provides results in units of radioactivity activity concentration, which are more convenient for comparison with relevant national standards to determine whether the emission standards are met. The lowest limit of detection of this method is 0.014 Bq l-1within 600 min.


Subject(s)
Radiation Monitoring , Radioactivity , Water Pollutants, Radioactive , Scintillation Counting , Wastewater , Water Pollutants, Radioactive/analysis
17.
Int J Cancer ; 146(7): 1963-1978, 2020 04 01.
Article in English | MEDLINE | ID: mdl-31390487

ABSTRACT

E3 ubiquitin ligases primarily determine the substrate specificity of the ubiquitin-proteasome system and play an essential role in the resistance to bortezomib in multiple myeloma (MM). Neural precursor cell-expressed developmentally downregulated gene 4-1 (NEDD4-1, also known as NEDD4) is a founding member of the NEDD4 family of E3 ligases and is involved in the proliferation, migration, invasion and drug sensitivity of cancer cells. In the present study, we investigated the role of NEDD4-1 in MM cells and explored its underlying mechanism. Clinically, low NEDD4-1 expression has been linked to poor prognosis in patients with MM. Functionally, NEDD4-1 knockdown (KD) resulted in bortezomib resistance in MM cells in vitro and in vivo. The overexpression (OE) of NEDD4-1, but not an enzyme-dead NEDD4-1-C867S mutant, had the opposite effect. Furthermore, the overexpression of NEDD4-1 in NEDD4-1 KD cells resensitized the cells to bortezomib in an add-back rescue experiment. Mechanistically, pAkt-Ser473 levels and Akt signaling were elevated and decreased by NEDD4-1 KD and OE, respectively. NEDD4-1 ubiquitinated Akt and targeted pAkt-Ser473 for proteasomal degradation. More importantly, the NEDD4-1 KD-induced upregulation of Akt expression sensitized MM cells to growth inhibition after treatment with an Akt inhibitor. Collectively, our results suggest that high NEDD4-1 levels may be a potential new therapeutic target in MM.


Subject(s)
Bortezomib/pharmacology , Drug Resistance, Neoplasm , Multiple Myeloma/pathology , Nedd4 Ubiquitin Protein Ligases/metabolism , Animals , Bortezomib/therapeutic use , Cell Line, Tumor , Gene Knockdown Techniques , Humans , Male , Mice , Multiple Myeloma/drug therapy , Multiple Myeloma/mortality , Nedd4 Ubiquitin Protein Ligases/genetics , Primary Cell Culture , Prognosis , Proteolysis , Proto-Oncogene Proteins c-akt/metabolism , Ubiquitination , Xenograft Model Antitumor Assays
18.
Cytometry A ; 97(1): 78-90, 2020 01.
Article in English | MEDLINE | ID: mdl-31876079

ABSTRACT

Light scattering detection in microfluidic chips provides an important tool to identify cancer cells without any label processes. However, forward small-angle scattering signals of cells, which are related to their sizes and morphologies, are hard to be detected accurately when scattering angle is less than 11° in microfluidic chips by traditional lighting design due to the influence of incident beam. Therefore, cell's size and morphology being the golden standard for clinical detection may lose their efficacy in recognizing cancer cells from healthy ones. In this article, a novel lighting design in microfluidic chips is put forward in which traditional incident Gaussian beam can be modulated into quasi-Bessel beam by a microprism and waveguide. The quasi-Bessel beam's advantages of nondiffraction theoretically make forward scattering (FS) detection less than 11° possibly. Our experimental results for peripheral blood lymphocytes of human beings and cultured HeLa cells show that the detection rates increase by 47.87% and 46.79%, respectively, by the novel designed microfluidic chip compared to traditional Gaussian lighting method in microfluidic chips. © 2019 International Society for Advancement of Cytometry.


Subject(s)
Light , Microfluidics , Neoplasms/pathology , HeLa Cells/cytology , Humans , Leukocytes, Mononuclear/cytology , Lighting/methods , Microfluidics/methods
19.
BMC Cancer ; 20(1): 816, 2020 Aug 27.
Article in English | MEDLINE | ID: mdl-32854650

ABSTRACT

BACKGROUND: Recently, copy number alteration (CNA) of 9p24.1 were demonstrated in 10% of diffuse large b-cell lymphoma (DLBCL), with gene expression and mutation profiles that were similar to those of primary mediastinal large B-cell lymphoma (PMBCL). However, their CNA-based profile and clinical impact still remain unclear. METHODS: Multiplex ligation-dependent probe amplification were employed to investigate the prevalence of JAK2/PD-L2 amplification in DLBCL and their CNA-based pattern of driver genes. The clinical outcome and characteristics were also analyzed. RESULTS: Using unsupervised hierarchical clustering, a small group of DLBCL (10.5%, 8/76) was clustered together with PMBCL as Cluster_2, demonstrating amplification of JAK2 (100%,8/8) and PD-L2 (75.0%,6/8). This subgroups of DLBCL demonstrated significant higher expression of PD-L1 than those with MYD88 L265P mutation(p = 0.024). And they exhibited dismal OS and PFS as compared with DLBCL_others(p = 0.003 and 0.001, respectively), which is similar to DLBCL with MYD88 L265P mutation. CONCLUSIONS: DLBCL with amplification of JAK2/PD-L2 exhibits CNA pattern that is similar to PMBCL, and demonstrates unfavorable clinical outcome that resembles those with MYD88 L265P mutation. It is essential to identify this subgroup of DLBCL who may acquire more benefits from the JAK2 and PD-L1 signaling inhibition.


Subject(s)
DNA Copy Number Variations , Gene Amplification , Gene Expression Regulation, Neoplastic , Janus Kinase 2/genetics , Lymphoma, Large B-Cell, Diffuse/genetics , Mediastinal Neoplasms/genetics , Myeloid Differentiation Factor 88/genetics , Programmed Cell Death 1 Ligand 2 Protein/genetics , Adult , Aged , Biomarkers, Tumor/genetics , Female , Gene Expression , Humans , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Mediastinal Neoplasms/pathology , Middle Aged , Prognosis , Progression-Free Survival , Retrospective Studies , Young Adult
20.
Analyst ; 145(2): 385-392, 2020 Jan 21.
Article in English | MEDLINE | ID: mdl-31844853

ABSTRACT

Patient survival remains poor even after diagnosis in lung cancer cases, and the molecular events resulting from lung cancer progression remain unclear. Raman spectroscopy could be used to noninvasively and accurately reveal the biochemical properties of biological tissues on the basis of their pathological status. This study aimed at probing biomolecular changes in lung cancer, using Raman spectroscopy as a potential diagnostic tool. Herein, biochemical alterations were evident in the Raman spectra (region of 600-1800 cm-1) in normal and cancerous lung tissues. The levels of saturated and unsaturated lipids and the protein-to-lipid, nucleic acid-to-lipid, and protein-to-nucleic acid ratios were significantly altered among malignant tissues compared to normal lung tissues. These biochemical alterations in tissues during neoplastic transformation have profound implications in not only the biochemical landscape of lung cancer progression but also cytopathological classification. Based on this spectroscopic approach, classification methods including k-nearest neighbour (kNN) and support vector machine (SVM) were successfully applied to cytopathologically diagnose lung cancer with an accuracy approaching 99%. The present results indicate that Raman spectroscopy is an excellent tool to biochemically interrogate and diagnose lung cancer.


Subject(s)
Lipids/analysis , Lung Neoplasms/diagnosis , Nucleic Acids/analysis , Proteins/analysis , Adenocarcinoma/diagnosis , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Disease Progression , Female , Humans , Lipid Metabolism/physiology , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Male , Middle Aged , Nucleic Acids/metabolism , Proteins/metabolism , Spectrum Analysis, Raman , Support Vector Machine
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