Tumor Exosomal ENPP1 Hydrolyzes cGAMP to Inhibit cGAS-STING Signaling.

To evade immune surveillance, tumor cells express ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) on the surface of their membrane, which degrades extracellular cyclic GMP-AMP (cGAMP), thereby inhibiting the cyclic GMP-AMP synthase (cGAS) stimulator of interferon gene (STING) DNA-sensing pathway. To fully understand this tumor stealth mechanism, it is essential to determine whether other forms of ENPP1 with hydrolytic cGAMP activity also are present in the tumor microenvironment to regulate this innate immune pathway. Herein, it is reported that various tumor-derived exosomes carry ENPP1, and can hydrolyze synthetic 2'3'-cGAMP and endogenous 2'3'-cGAMP produced by cells to inhibit cGAS-STING pathway in immune cells. Moreover, tumor exosomal ENPP1 also can hydrolyze 2'3'-cGAMP bound to LL-37 (an effective transporter of 2'3'-cGAMP) to inhibit STING signaling. Furthermore, high expression of ENPP1 in exosomes is observed isolated from human breast and lung cancer tissue, and tumor exosomal ENPP1 inhibited the immune infiltration of CD8+ T cells and CD4+ T cells. The results elucidate the essential function of tumor exosomal ENPP1 in the cGAS-STING pathway, furthering understanding of the crosstalk between the tumor cells and immune system.

Metabolic remodeling by the PD-L1 inhibitor BMS-202 significantly inhibits cell malignancy in human glioblastoma.

Recently, crystallographic studies have demonstrated that BMS-202, a small-molecule compound characterized by a methoxy-1-pyridine chemical structure, exhibits a high affinity to PD-L1 dimerization. However, its roles and mechanisms in glioblastoma (GBM) remain unclear. The objective of this study is to investigate the antitumor activity of BMS-202 and its underlying mechanisms in GBM using multi-omics and bioinformatics techniques, along with a majority of in vitro and in vivo experiments, including CCK-8 assays, flow cytometry, co-immunoprecipitation, siRNA transfection, PCR, western blotting, cell migration/invasion assays and xenografts therapeutic assays. Our findings indicate that BMS-202 apparently inhibits the proliferation of GBM cells both in vitro and in vivo. Besides, it functionally blocks cell migration and invasion in vitro. Mechanistically, it reduces the expression of PD-L1 on the surface of GBM cells and interrupts the PD-L1-AKT-BCAT1 axis independent of mTOR signaling. Taken together, we conclude that BMS-202 is a promising therapeutic candidate for patients with GBM by remodeling their cell metabolism regimen, thus leading to better survival.

Oral Delivery of Gemcitabine-Loaded Glycocholic Acid-Modified Micelles for Cancer Therapy.

The clinical utility of gemcitabine, an antimetabolite antineoplastic agent applied in various chemotherapy treatments, is limited due to the required intravenous injection. Although chemical structure modifications of gemcitabine result in enhanced oral bioavailability, these modifications compromise complex synthetic routes and cause unexpected side effects. In this study, gemcitabine-loaded glycocholic acid-modified micelles (Gem-PPG) were prepared for enhanced oral chemotherapy. The in vitro transport pathway experiments revealed that intact Gem-PPG were transported across the intestinal epithelial monolayer via an apical sodium-dependent bile acid transporter (ASBT)-mediated pathway. In mice, the pharmacokinetic analyses demonstrated that the oral bioavailability of Gem-PPG approached 81%, compared to less than 20% for unmodified micelles. In addition, the antitumor activity of oral Gem-PPG (30 mg/kg, BIW) was superior to that of free drug injection (60 mg/kg, BIW) in the xenograft model. Moreover, the assessments of hematology, blood chemistry, and histology all indicated the hypotoxicity profile of the drug-loaded micelles.

The pro-invasive factor COL6A2 serves as a novel prognostic marker of glioma.

Background: Glioma is an incurable malignant lesion with poor outcome characterized by easy recurrence after surgery with or without radiotherapy and chemotherapy. Studies have shown that COL6A2 is closely related to the tumorigenesis and development of a variety of tumors. However, the role of COL6A2 in glioma and the relationship between COL6A2 and tumor infiltrating immune cells remain unclear. Methods: Western blot, real-time PCR, a tissue microarray and immunohistochemistry were applied to detect COL6A2 mRNA and protein amounts in glioma, and all experiments were repeated three times. A tissue microarray of glioma samples was used for prognostic analysis. Detection of COL6A2 co-expression with immune genes using immunohistochemical methods, and tumor modeling using nude mice for prevention and treatment studies. Based on the mRNA expression of COL6A2, patients with glioma in TCGA were divided into the low and high COL6A2 expression groups, and GO and KEGG pathway analyses were performed. A PPI network was constructed using STRING, and the associations of COL6A2 with tumor-infiltrating immune cells and immune genes were analyzed in the CIBERSORT and TISIDB databases. COL6A2 mRNA and protein amounts were increased in glioma. Results: Multiple-database and tissue microarray analyses showed that COL6A2 expression in glioma was associated with poor prognosis, Tissue microarray showed that COL6A2 was the highest expressed in WHO IV and significantly higher in TCGA-GBM than in TCGA-LGG. Immunohistochemistry can well demonstrate the co-expression of COL6A2 with immune genes in a tumor model established in nude mice, showing that interference with COL6A2 expression may have an inhibitory effect on tumors. The mRNA expression of COL6A2 was involved in 22 KEGG pathways, and GSEA analysis showed that 28 and 57 gene sets were significantly enriched at nominal p values <0.01 and <0.05, respectively, protein network revealed a tight interaction between COL6A2 and SPARC. The CIBERSORT database indicated that COL6A2 was correlated with 15 types of tumor-infiltrating immune cells, including M2 macrophages, CD8 T cells, neutrophils, gamma delta T cells, activated CD4 memory T cells, follicular helper T cells, M0 macrophages, M1 macrophages, regulatory T cells (Tregs), activated NK cells, eosinophils, activated mast cells, monocytes, activated dendritic cells, and resting CD4 memory T cells. The TISIDB database indicated that COL6A2 was significantly correlated with lymphocytes such as regulatory T cell, Type 17 T helper cell, Type 1 T helper cell, and immunomodulatory genes. In addition, COL6A2-related immune regulatory genes show that most immune regulatorygenes have prognostic value for glioma, and high-risk immune genes are notconducive to the survival of glioma patients. Conclusions: COL6A2-related immune regulatory genes show that most immune regulatory genes have prognostic value for glioma, and high-risk immune genes are not conducive to the survival of glioma patients. COL6A2 may be a novel potential prognostic biomarker of glioma and associated with tumor-infiltrating immune cells in the tumor microenvironment, and interference with COL6A2 expression can inhibit tumor growth, which suggests COL6A2 as a potential target for future treatment.

Cell origin and genome profile difference of penoscrotum invasive extramammary Paget disease compared with its in situ counterpart.

Penoscrotum extramammary Paget disease (pEMPD) is a rare cutaneous carcinoma with an unknown cell origin. pEMPD always presents as a tumor in situ with an indolent process, whereas some progress into invasive forms with more aggressive behavior. The in situ and invasive cases display different morphologies and biological behavior, and thus far, a relationship between these two components has not been demonstrated. Immunohistochemistry was used to disclose the immunotype of pEMPD, and the results revealed that invasive/in situ pEMPD possessed with some identical immunophenotypes such as CK7, P63, and CK10, which inferred the clonal relatedness. The variable expressions of GCDFP-15 and carcino embryonic antigen hinted that tumor cell origin might be an epidermal sweat gland in epiderma. In our cohort, invasive pEMPD presented increased expression of androgen receptor and decreased MUC5CA expression, and these two changes might bring to the shift of invasive phenotype. To better understanding the relationship between these distinct tumor forms, we performed whole exome sequencing testing to evaluate overlapping genomic alterations of six paired invasive/in situ pEMPDs. The results showed that missense mutation was the predominant mutation type, and C>T transition accounted for 65.1% in all SNP mutation. Among the top 20 differential genes obtained from the six paired invasive/in situ pEMPD analysis, MUC4 (one missense, one in frame del, and one multi-hit), AHNAK2 (two missense and one multi-hit), DOT1L (two missense and one multi-hit), and FRG1 (two missense and one-multi hit) mutations were most enriched in invasive pEMPDs, which postulated that these genes may play roles in the disease progression.

Identification of Metabolism-Related Gene-Based Subgroup in Prostate Cancer.

Prostate cancer is still the main male health problem in the world. The role of metabolism in the occurrence and development of prostate cancer is becoming more and more obvious, but it is not clear. Here we firstly identified a metabolism-related gene-based subgroup in prostate cancer. We used metabolism-related genes to divide prostate cancer patients from The Cancer Genome Atlas into different clinical benefit populations, which was verified in the International Cancer Genome Consortium. After that, we analyzed the metabolic and immunological mechanisms of clinical beneficiaries from the aspects of functional analysis of differentially expressed genes, gene set variation analysis, tumor purity, tumor microenvironment, copy number variations, single-nucleotide polymorphism, and tumor-specific neoantigens. We identified 56 significant genes for non-negative matrix factorization after survival-related univariate regression analysis and identified three subgroups. Patients in subgroup 2 had better overall survival, disease-free interval, progression-free interval, and disease-specific survival. Functional analysis indicated that differentially expressed genes in subgroup 2 were enriched in the xenobiotic metabolic process and regulation of cell development. Moreover, the metabolism and tumor purity of subgroup 2 were higher than those of subgroup 1 and subgroup 3, whereas the composition of immune cells of subgroup 2 was lower than that of subgroup 1 and subgroup 3. The expression of major immune genes, such as CCL2, CD274, CD276, CD4, CTLA4, CXCR4, IL1A, IL6, LAG3, TGFB1, TNFRSF4, TNFRSF9, and PDCD1LG2, in subgroup 2 was almost significantly lower than that in subgroup 1 and subgroup 3, which is consistent with the results of tumor purity analysis. Finally, we identified that subgroup 2 had lower copy number variations, single-nucleotide polymorphism, and neoantigen mutation. Our systematic study established a metabolism-related gene-based subgroup to predict outcomes of prostate cancer patients, which may contribute to individual prevention and treatment.

DNase I-assisted 2'-O-methyl molecular beacon for amplified detection of tumor exosomal microRNA-21.

An end-modified 2'-O-methyl molecular beacon (eMB) with unique nuclease resistance was designed and prepared. The eMB can resist the enzymatic digestion by DNase I, which would otherwise occur upon the hybridization of the eMB with a complementary sequence. As a result, the coupling use of eMBs and DNase I allows highly sensitive detection of miRNA with a limit of detection (LOD) of 2.5 pM. The analytical strategy was further used for detection of tumor exosomal microRNA-21, and down to 0.86 µg mL-1 A375 exosomes were detected. Overall, the present method can effectively quantify tumor-derived exosomes for cancer diagnosis.

P4HA1 as an unfavorable prognostic marker promotes cell migration and invasion of glioblastoma via inducing EMT process under hypoxia microenvironment.

This study aims to explore the mechanism of glioblastoma multiforme (GBM) in hypoxia through metabolomic and proteomic analysis. We showed that the migration and invasiveness of LN18 cells was significantly enhanced after 24 h of hypoxia treatment. The metabolomic and proteomic profiling were conducted in LN18 cells cultured under hypoxia condition. Correlation analysis between significant differential metabolites and proteins revealed seven proteins and ten metabolites, of which metabolite L-Arg was negatively correlated with P4HA1 protein. Meanwhile, the expression of HIF1α, nNOS and P4HA1 was up-regulated, and the concentration of L-Arg and NO was decreased and increased respectively. Knockdown of HIF1α reduced the expression of nNOS and P4HA1, the concentration of NO and the invasiveness of cells, while increased the concentration of L-Arg. Similar changes on P4HA1 expression, the concentration of L-Arg and NO were observed when the expression of nNOS was disrupted. Lastly, knockdown of P4HA1 impaired the invasion of LN18 and T98G cells, probably through regulating the expression of Vimentin, MMP2, MMP9, Snail and E-cadherin. Consistent trends on both the overexpression of these relevant genes, as well as the concentration of L-Arg and NO were also observed in all our overexpression experiments. Besides, we investigated the relationship between P4HA1 expression and prognosis by MTA, CGGA and TCGA databases. Increased P4HA1 level was correlated poor prognosis with advanced histological grade. In summary, we found that hypoxia promotes the migration and invasion of GBM via the L-Arg/P4HA1 axis which maybe an effective molecular marker or predictor of clinical outcome in GBM patients.

A New Method for the Sputum Cytology Test Without Direct Contact to Specimens During COVID-19 Pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic continues to spread across the world. Specimens of blood, body fluids and excreta received in the department of pathology undoubtedly increased the risk of infection, especially in some hospitals that are short of professional protection capability. Here we provided a new simple way for the sputum cytology test during the COVID-19 pandemic. METHODS: Sputum samples from 30 patients with lung cancer were collected and divided into two groups, including the control group and the experimental group. Samples of the control group were processed in the biological safety cabinet, while the experimental group was put into the sealed specimen bag directly and pretreated with 75% medical alcohol. Then the cell morphology and tumor cell identification were analyzed by cell smears and liquid-based cell staining. The expression of cell antigens was determined by immunohistochemical staining. RESULT: Our result showed that both sputum samples in two groups exhibited complete cell structure and clear morphology according to the cell smear and liquid-based cell staining. In addition, the immunohistochemical result showed that cell antigens, including cytokeratin (CK), leukocyte common antigen (LCA), and thyroid transcription factor-1 (TTF1), were specifically expressed in the cell membrane, cytoplasm, and nucleus, respectively. The tumor cells were distributed diffusely, and cell antigens were located accurately after pretreatment with 75% medical alcohol and were consistent with that of the control group. CONCLUSION: Using 75% medical alcohol to pretreat sputum specimens has no obvious impact on cell morphology and antigens expression. Our study provided a new method for the sputum cytology test with no direct contact so as to protect medical staff against the virus during COVID-19 outbreak.

Rivaroxaban ameliorates angiotensin II-induced cardiac remodeling by attenuating TXNIP/Trx2 interaction in KKAy mice.

As an anticoagulant, Rivaroxaban has recently been reported to be protective in cardiac injury. Based on those previous research results, we detected the roles of Rivaroxaban in Angiotensin II (AngII)-induced cardiac remodeling with KKAy mice and unraveled the underlying mechanisms. Rivaroxaban inhibited cardiac fibrosis and hypertrophy in AngII-infused KKAy mice. In addition, it also inhibited mitochondrial dysfunction. Noteworthily, Rivaroxaban altered the expression of many genes associated with mitochondrial function. Rivaroxaban inhibited the expression of thioredoxin binding protein (TXNIP) as well as the activation of apoptosis stimulating kinase 1 (ASK1). In H9c2 cells treated with AngII and high glucose, Rivaroxaban inhibited TXNIP/thioredoxin2 (Trx2) interaction. Moreover, TXNIP knockout abolished AngII-induced cardiac fibrosis and hypertrophy. Thus, Rivaroxaban ameliorates AngII-induced cardiac remodeling via the suppression of TXNIP signaling in KKAy mice, providing novel mechanism underlying the protective roles of Rivaroxaban against cardiac damage.

Sirtuin 7 promotes glioma proliferation and invasion through activation of the ERK/STAT3 signaling pathway.

Sirtuin7 (Sirt7) is a member of the Sir2 histone deacetylase family that functions in a number of physiological processes, including cellular metabolism, ageing and apoptosis. Several studies have indicated that Sirt7 may serve a vital role in promoting the development of cancer. However, to the best of our knowledge, its function in glioma progression has not been demonstrated. The present study revealed that Sirt7 expression was upregulated in human glioma tissues and that the high expression level of Sirt7 was positively associated with glioma malignancy. Further results indicated that the suppression of Sirt7 expression could inhibit the activation of phosphorylated extracellular signal-regulated kinase (p-ERK) concomitantly with decreased expression of cyclin-dependent kinase 2 in glioma cells. Phosphorylation of signal transducer and activator of transcription 3 (STAT3) inhibited when Sirt7 was downregulated by siRNA interference in glioma cell lines. The findings of the present study indicated that Sirt7 affects the malignancy of glioma cells mainly in promoting glioma proliferation and invasion through ERK and STAT3 signaling. Thus, Sirt7 may function as a valuable target for the treatment of human glioma.

Detection of IDH1 and IDH2 Mutation in Formalin-fixed Paraffin-embedded Gliomas Using Allele-specific COLD-PCR and Probe Melting Curve Analysis.

Many tumors, especially gliomas, contain an isocitrate dehydrogenase (IDH) mutation that can be used for clinical diagnosis and prognosis. Our study aimed to develop a new reliable detection assay for IDH1 and IDH2 mutations for clinical diagnosis based on the allele-specific (AS) coamplification with lower denaturing-polymerase chain reaction (COLD-PCR) and probe melting curve analysis (PMCA). The method includes 3 elements allowing for the sensitive detection of low-abundance mutations: (1) PCR amplification of the target fragments with AS primers; (2) COLD-PCR; and (3) PMCA for differentiating the different mutations after amplification. We conducted a blinded study with 45 paraffin-embedded gliomas specimens and 13 fresh specimens screened for IDH mutations using Sanger sequencing. Concordance between the results of our AS-COLD-PCR/PMCA assay and Sanger sequencing was 100%. Our assay appeared to be superior to direct sequencing with a much higher sensitivity of 0.4% mutations. In summary, our assay is a cost-effective, convenient, and sensitive method for detecting IDH mutations and could be applied in the clinical setting to assess small brain biopsies.

Portable detection of serum HER-2 in breast cancer by a pressure-based platform.

A high serum HER-2 extracellular domain (sHER-2 ECD) level has a reverse association with tumor behaviors. In this study, a portable platform for the disease biomarker sHER-2 ECD detection has been established using a pressure-based bioassay. The pressure bioassay consists of a monoclonal antibody immobilized on an eight-well strip, the analyte HER-2, and another monoclonal antibody labeled with the Pt nanoparticles (PtNPs), which have the catalytic ability to decompose H2O2 into H2O and O2(g). The increased pressure due to O2(g) generation is measured by a hand-held pressure meter. A total of 34 serum samples were collected to validate the performance of the pressure bioassay. The results showed that the pressure bioassay platform of HER-2 had a dynamic range from 2 to 50 ng/mL with a limit of detection (LOD) of 2 ng/mL, which was consistent with the ELISA result. In the real serum samples, there was a significant correlation between sHER-2 ECD level and several clinicopathological parameters, especially tissue HER-2 status. Furthermore, the sHER-2 ECD level was found to decrease after targeted therapy in a patient with tHER-2 positive. Overall, this bioassay can facilitate breast cancer diagnosis and prognosis in clinical scenarios and resource-limited areas.

Gas-generating reactions for point-of-care testing.

Gas generation-based measurement is an attractive alternative approach for POC (Point-of-care) testing, which relies on the amount of generated gas to detect the corresponding target concentrations. In gas generation-based POC testing, the integration of a target recognition component and a catalyzed gas-generating reaction initiated by the target introduction can lead to greatly amplified signals, which can be highly sensitive measured via distance readout or simple hand-held devices. More importantly, numerous gas-generating reactions are environment-friendly since their products such as oxygen and nitrogen are nontoxic and odourless, which makes gas generation-based POC testing safe and secure for inexperienced staff. Researchers have demonstrated that gas generation-based measurements enable the rapid and highly sensitive POC detection of a variety of analytes. In this review, we focus on the recent developments in gas generation-based POC testing systems. The common types of gas-generating reactions are first listed and the translation of gas signals to different signal readouts for POC testing are then summarized, including distance readouts and hand-held devices. Moreover, we introduce gas bubbles as actuators to power microfluidic devices. We finally provide the applications and future perspective of gas generation-based POC testing systems.

Integrating Target-Responsive Hydrogel with Pressuremeter Readout Enables Simple, Sensitive, User-Friendly, Quantitative Point-of-Care Testing.

Point-of-care testing (POCT) with the advantages of speed, simplicity, and low cost, as well as no need for instrumentation, is critical for the measurement of analytes in a variety of environments lacking access to laboratory infrastructure. In the present study, a hydrogel pressure-based assay for quantitative POCT was developed by integrating a target-responsive hydrogel with pressuremeter readout. The target-responsive hydrogels were constructed with DNA grafted linear polyacrylamide and the cross-linking DNA for selective target recognition. The hydrogel response to the target substance allows release of the preloaded Pt nanoparticles, which have good stability and excellent catalytic ability for decomposing H2O2 to O2. Then, the generated O2 in a sealed environment leads to significant pressure increase, which can be easily read out by a handheld pressuremeter. Using this target-responsive hydrogel pressure-based assay, portable and highly sensitive detection of cocaine, ochratoxin A, and lead ion were achieved with excellent accuracy and selectivity. With the advantages of portability, high sensitivity, and simple sample processing, the hydrogel pressure-based assay shows great potential for quantitative POCT of a broad range of targets in resource-limited settings.

A fully integrated distance readout ELISA-Chip for point-of-care testing with sample-in-answer-out capability.

Enzyme-linked immunosorbent assay (ELISA) is a popular laboratory technique for detection of disease-specific protein biomarkers with high specificity and sensitivity. However, ELISA requires labor-intensive and time-consuming procedures with skilled operators and spectroscopic instrumentation. Simplification of the procedures and miniaturization of the devices are crucial for ELISA-based point-of-care (POC) testing in resource-limited settings. Here, we present a fully integrated, instrument-free, low-cost and portable POC platform which integrates the process of ELISA and the distance readout into a single microfluidic chip. Based on manipulation using a permanent magnet, the process is initiated by moving magnetic beads with capture antibody through different aqueous phases containing ELISA reagents to form bead/antibody/antigen/antibody sandwich structure, and finally converts the molecular recognition signal into a highly sensitive distance readout for visual quantitative bioanalysis. Without additional equipment and complicated operations, our integrated ELISA-Chip with distance readout allows ultrasensitive quantitation of disease biomarkers within 2h. The ELISA-Chip method also showed high specificity, good precision and great accuracy. Furthermore, the ELISA-Chip system is highly applicable as a sandwich-based platform for the detection of a variety of protein biomarkers. With the advantages of visual analysis, easy operation, high sensitivity, and low cost, the integrated sample-in-answer-out ELISA-Chip with distance readout shows great potential for quantitative POCT in resource-limited settings.

Metabolomic analysis reveals altered metabolic pathways in a rat model of gastric carcinogenesis.

Gastric cancer (GC) is one of the most malignant tumors with a poor prognosis. Alterations in metabolic pathways are inextricably linked to GC progression. However, the underlying molecular mechanisms remain elusive. We performed NMR-based metabolomic analysis of sera derived from a rat model of gastric carcinogenesis, revealed significantly altered metabolic pathways correlated with the progression of gastric carcinogenesis. Rats were histologically classified into four pathological groups (gastritis, GS; low-grade gastric dysplasia, LGD; high-grade gastric dysplasia, HGD; GC) and the normal control group (CON). The metabolic profiles of the five groups were clearly distinguished from each other. Furthermore, significant inter-metabolite correlations were extracted and used to reconstruct perturbed metabolic networks associated with the four pathological stages compared with the normal stage. Then, significantly altered metabolic pathways were identified by pathway analysis. Our results showed that oxidative stress-related metabolic pathways, choline phosphorylation and fatty acid degradation were continually disturbed during gastric carcinogenesis. Moreover, amino acid metabolism was perturbed dramatically in gastric dysplasia and GC. The GC stage showed more changed metabolite levels and more altered metabolic pathways. Two activated pathways (glycolysis; glycine, serine and threonine metabolism) substantially contributed to the metabolic alterations in GC. These results lay the basis for addressing the molecular mechanisms underlying gastric carcinogenesis and extend our understanding of GC progression.

A pressure-based bioassay for the rapid, portable and quantitative detection of C-reactive protein.

A portable method for the rapid detection of the disease biomarker C-reactive protein (CRP) with a hand-held pressuremeter was developed. The method allows an ultrasensitive quantitation of CRP within the entire clinical range. The pressure-based method could facilitate CRP measurements in point-of-care testing (POCT) scenarios, such as clinical offices, emergency departments, and community service centers.

Enzyme-Encapsulated Liposome-Linked Immunosorbent Assay Enabling Sensitive Personal Glucose Meter Readout for Portable Detection of Disease Biomarkers.

There is considerable demand for sensitive, selective, and portable detection of disease-associated proteins, particularly in clinical practice and diagnostic applications. Portable devices are highly desired for detection of disease biomarkers in daily life due to the advantages of being simple, rapid, user-friendly, and low-cost. Herein we report an enzyme-encapsulated liposome-linked immunosorbent assay for sensitive detection of proteins using personal glucose meters (PGM) for portable quantitative readout. Liposomes encapsulating a large amount of amyloglucosidase or invertase are surface-coated with recognition elements such as aptamers or antibodies for target recognition. By translating molecular recognition signal into a large amount of glucose with the encapsulated enzyme, disease biomarkers such as thrombin or C-reactive protein (CRP) can be quantitatively detected by a PGM with a high detection limit of 1.8 or 0.30 nM, respectively. With the advantages of portability, ease of use, and low-cost, the method reported here has potential for portable and quantitative detection of various targets for different POC testing scenarios, such as rapid diagnosis in clinic offices, health monitoring at the bedside, and chemical/biochemical safety control in the field.

GCN5 Potentiates Glioma Proliferation and Invasion via STAT3 and AKT Signaling Pathways.

The general control of nucleotide synthesis 5 (GCN5), which is one kind of lysine acetyltransferases, regulates a number of cellular processes, such as cell proliferation, differentiation, cell cycle and DNA damage repair. However, its biological role in human glioma development remains elusive. In the present study, we firstly reported that GCN5 was frequently overexpressed in human glioma tissues and GCN5 was positively correlated with proliferation of cell nuclear antigen PCNA and matrix metallopeptidase MMP9. Meanwhile, down-regulation of GCN5 by siRNA interfering inhibited glioma cell proliferation and invasion. In addition, GCN5 knockdown reduced expression of p-STAT3, p-AKT, PCNA and MMP9 and increased the expression of p21 in glioma cells. In conclusion, GCN5 exhibited critical roles in glioma development by regulating cell proliferation and invasion, which suggested that GCN5 might be a potential molecular target for glioma treatment.