Hyaluronic acid-modified mesoporous silica nanoprobes for target identification of atherosclerosis.

Rupture of vulnerable plaque and secondary thrombosis caused by atherosclerosis are one of the main causes of acute cardiovascular and cerebrovascular events, and it is urgent to develop an in-situ, noninvasive, sensitive and targeted detection method at molecular level. We chose CD44, a specific receptor highly expressed on the surface of macrophages, as the target of the molecular probe, and modified the CD44 ligand HA onto the surface of Gd2O3@MSN, constructing the MRI imaging nanoprobe HA-Gd2O3@MSN for targeted recognition of atherosclerosis. The fundamental properties of HA-Gd2O3@MSN were initially investigated. The CCK-8, hemolysis, hematoxylin-eosin staining tests and blood biochemical assays confirmed that HA-Gd2O3@MSN possessed excellent biocompatibility. Laser confocal microscopy, cellular magnetic resonance imaging, flow cytometry and immunohistochemistry were used to verify that the nanoprobes had good targeting properties. The in vivo targeting performance of the nanoprobes was further validated by employing a rabbit atherosclerosis animal model. In summary, the synthesized HA-Gd2O3@MSN nanoprobes have excellent biocompatibility properties as well as good targeting properties. It could provide a new technical tool for early identification of atherosclerosis.

Functionalized europium-doped hollow mesoporous silica nanospheres as a cell imaging and drug delivery agents.

In an effort to enhance the antitumor efficacy of breast cancer treatment, the chemotherapeutic agent Paclitaxel (PTX) was encapsulated within hyaluronic acid (HA) modified hollow mesoporous silica (HMSNs). In vitro drug release assays showed that the resulting formulation, Eu-HMSNs-HA-PTX, exhibited enzyme-responsive drug release. In addition, cell cytotoxicity and hemolysis assays demonstrated the favorable biocompatibility of both Eu-HMSNs and Eu-HMSNs-HA. Notably, compared to Eu-HMSNs alone, Eu-HMSNs-HA showed enhanced accumulation within CD44-expressing cancer cells (MDA-MB-231). As anticipated, apoptosis experiments indicated that Eu-HMSNs-HA-PTX displayed significantly greater cytotoxicity toward MDA-MB-231 cells than non-targeted Eu-HMSNs-PTX and free PTX. In conclusion, Eu-HMSNs-HA-PTX demonstrated excellent anticancer effects and holds promise as a potent candidate for the efficient therapy of breast cancer.

Magnetic resonance/fluorescence dual-modality contrast agents targeting αvß6-overexpressing tumors based on A20FMDV2 peptide as a ligand.

Pancreatic ductal adenocarcinoma (PDAC) is a malignant digestive system tumor with a poor late-stage prognosis. This study aimed to identify new methods for the early detection of PDAC. The nanoprobe A20FMDV2-Gd-5-FAM was developed using A20FMDV2 (N1AVPNLRGDLQVLAQKVART20-NH2, A20FMDV2) as the ligand and characterized using dynamic light scattering, transmission electron microscopy, Fourier transform infrared analysis, and UV absorption spectroscopy. The binding of pancreatic cancer cells AsPC-1, MIA PaCa-2, and normal human pancreatic H6C7 cells (HPDE6-C7) to the probe was verified using laser confocal microscopy, and the biocompatibility of the probe was evaluated in vivo. In vivo magnetic resonance and fluorescence imaging were also performed on nude mice with subcutaneous pancreatic tumor xenografts to verify the bimodal imaging performance of the probe. The probe exhibited good stability and biocompatibility and an enhanced relaxation rate (25.46 ± 1.32 mM-1 s-1) than Gd-DTPA. Confocal laser scanning microscopy results revealed that the A20FMDV2-Gd-5-FAM probe could be successfully ingested and internalized, and infrared analysis results demonstrated that the probe was linked successfully. Finally, magnetic resonance T1WI imaging and intravital fluorescence imaging demonstrated the specific signal enhancement of the probe at the tumor site. In conclusion, the bimodal molecular probe A20FMDV2-Gd-5-FAM showed a stable magnetic resonance and fluorescence bimodal imaging performance and is a promising new approach for diagnosing early-stage cancers with a high integrin αvß6 expression.

Engineered Graphene Quantum Dots as a Magnetic Resonance Signal Amplifier for Biomedical Imaging.

The application of magnetic resonance imaging (MRI) nano-contrast agents (nano-CAs) has increasingly attracted scholarly interest owing to their size, surface chemistry, and stability. Herein, a novel T1 nano-CA (Gd(DTPA)-GQDs) was successfully prepared through the functionalization of graphene quantum dots with poly(ethylene glycol) bis(amine) and their subsequent incorporation into Gd-DTPA. Remarkably, the resultant as-prepared nano-CA displayed an exceptionally high longitudinal proton relaxivity (r1) of 10.90 mM-1 s-1 (R2 = 0.998), which was significantly higher than that of commercial Gd-DTPA (4.18 mM-1 s-1, R2 = 0.996). The cytotoxicity studies indicated that the Gd(DTPA)-GQDs were not cytotoxic by themselves. The results of the hemolysis assay and the in vivo safety evaluation demonstrate the outstanding biocompatibility of Gd(DTPA)-GQDs. The in vivo MRI study provides evidence that Gd(DTPA)-GQDs exhibit exceptional performance as T1-CAs. This research constitutes a viable approach for the development of multiple potential nano-CAs with high-performance MR imaging capabilities.

cRGD-Conjugated GdIO Nanoclusters for the Theranostics of Pancreatic Cancer through the Combination of T1-T2 Dual-Modal MRI and DTX Delivery.

Clinically, magnetic resonance imaging (MRI) often uses contrast agents (CAs) to improve image contrast, but single-signal MRI CAs are often susceptible to calcification, hemorrhage, and magnetic sensitivity. Herein, iron acetylacetone and gadolinium acetylacetone were used as raw materials to synthesize a T1-T2 dual-mode imaging gadolinium-doped iron oxide (GdIO) nanocluster. Moreover, to endow the nanoclusters with targeting properties and achieve antitumor effects, the cyclic Arg-Gly-Asp (cRGD) peptide and docetaxel (DTX) were attached to the nanocluster surface, and the efficacy of the decorated nanoclusters against pancreatic cancer was evaluated. The final synthesized material cRGD-GdIO-DTX actively targeted αvß3 on the surface of Panc-1 pancreatic cancer cells. Compared with conventional passive targeting, the enrichment of cRGD-GdIO-DTX in tumor tissues improved, and the diagnostic accuracy was significantly enhanced. Moreover, the acidic tumor microenvironment triggered the release of DTX from cRGD-GdIO-DTX, thus achieving tumor treatment. The inhibition of the proliferation of SW1990 and Panc-1 pancreatic cancer cells by cRGD-GdIO-DTX was much stronger than that by the untargeted GdIO-DTX and free DTX in vitro. In addition, in a human pancreatic cancer xenograft model, cRGD-GdIO-DTX considerably slowed tumor development and demonstrated excellent magnetic resonance enhancement. Our results suggest that cRGD-GdIO-DTX has potential applications for the precise diagnosis and efficient treatment of pancreatic cancer.

pH-Responsive Drug Delivery and Imaging Study of Hybrid Mesoporous Silica Nanoparticles.

A system of pH-responsive and imaging nanocarriers was developed using mesoporous silica nanoparticles (MSNs), in which gadolinium (Gd) was doped through in situ doping (Gd2O3@MSN). Sodium alginate (SA) was attached to the surfaces of the amino groups of MSNs (NH2-Gd2O3@MSN) through the electrostatic adsorption between the amino groups and the carboxyl groups with the formation of hybrid SA-Gd2O3@MSN nanoparticles (NPs). The SA-coated NPs were spherical or near-spherical in shape with an average size of nearly 83.2 ± 8.7 nm. The in vitro drug release experiments of a model rhodamine B (RhB) cargo were performed at different pH values. The result confirmed the pH-responsiveness of the nanocarriers. The results of the cytotoxicity studies indicated that the SA-Gd2O3@MSN NPs were not cytotoxic by themselves. The results of the in vivo safety evaluation and the hemolysis assay confirmed that the system is highly biocompatible. It is noteworthy that the T1 contrast of the system was significantly enhanced by the Gd, as indicated by the result of the MR imaging. This study confirms that the synthesized hybrid nanosystem is promising for pH-responsive drug delivery and MR imaging for cancer diagnosis and treatment.

Upregulated circular RNA circ_0007534 indicates an unfavorable prognosis in pancreatic ductal adenocarcinoma and regulates cell proliferation, apoptosis, and invasion by sponging miR-625 and miR-892b.

Circular RNAs (circRNAs) have been regarded as critical regulators of human diseases and biological markers in some types of malignancies, including pancreatic ductal adenocarcinoma (PDAC). Recently, circ_0007534 has been identified as a novel cancer-related circRNA. Nevertheless, its clinical relevance, functional roles, and mechanism have not been studied in PDAC. In the current study, real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of circ_0007534 in 60-paired PDAC tissue samples and different cell lines. Loss-of-function and gain-of-function assays were performed to detect cell proliferation, apoptosis, and metastatic properties affected by circ_0007534. An animal study was also carried out. The luciferase reporter assay was performed to uncover the underlying mechanism of circ_0007534. As a result, circ_0007534 was overexpressed not only in PDAC tissues but also in a panel of PDAC cell lines, and this overexpression is closely associated with advanced tumor stage and positive lymph node invasion. In addition, circ_0007534 may be regarded as an independent prognostic factor for patients with PDAC. For the part of functional assays, circ_0007534 significantly increased cell proliferation, migratory, and invasive potential of PDAC cells. Circ_0007534 could inhibit cell apoptosis partly via a Bcl-2/caspase-3 pathway. The xenograft study further confirmed the cell growth promoting the role of circ_0007534. Mechanistically, miR-625 and miR-892b were sponged by circ_0007534. The oncogenic functions of circ_0007534 is partly dependent on its regulation of miR-625 and miR-892b. In conclusion, our study illuminates a novel circRNA that confers an oncogenic function in PDAC.

Circular RNA circ_0020123 promotes non-small cell lung cancer progression by acting as a ceRNA for miR-488-3p to regulate ADAM9 expression.

Circular RNAs (circRNAs) is a class of non-coding RNA with important functions in tumor development and progression. In the previous study, circ_0020123 was found to be an elevated circRNA in non-small cell lung cancer (NSCLC) tissues screened by high-throughput sequencing. In the current work, we uncovered the clinical significance, biological functions and mechanism of circ_0020123 in NSCLC. The expression profile of circ_0020123 was measured by RT-qPCR. Correlations between circ_0020123 expression and patients' clinical features were evaluated. Cell viability, apoptosis, migration and invasion were detected by cell counting kit-8 (CCK-8), flow cytometric and transwell assay, respectively. Bioinformatics database and luciferase reporter gene assays were utilized to identify the mechanisms of circ_0020123. The results revealed elevation of circ_0020123 in tissue specimens and cells than the nontumorous tissues and 16HBE, separately. The enhancement of circ_0020123 in tumor tissues correlated with positive lymph node metastasis, advanced TNM stages, and adverse prognosis for NSCLC patients. Functionally, silencing of circ_0020123 distinctly suppressed the growth, migration and invasion and inhibited the apoptosis of A549 cells. On the contrary, when circ_0020123 expression was ectopically expressed, the above effects were significantly strengthened in H1299 cell line. For the mechanism exploration, circ_0020123 could sponge miR-488-3p to release its inhibition on ADAM9 expression. Moreover, the functional role of circ_0020123 is partly dependent on its regulation of ADAM9 proved by rescue assays. Taken together, our findings provide the possibility that circ_0020123 may be a new target for NSCLC prognosis prediction and therapy.

Fe3O4-Cy5.5-trastuzumab magnetic nanoparticles for magnetic resonance/near-infrared imaging targeting HER2 in breast cancer.

This study developed a probe Fe3O4-Cy5.5-trastuzumab with fluorescence and magnetic resonance imaging functions that can target breast cancer with high HER2 expression, aiming to provide a new theoretical method for the diagnosis of early breast cancer. Fe3O4-Cy5.5-trastuzumab nanoparticles were combined with Fe3O4for T2imaging and Cy5.5 for near-infrared imaging, and coupled with trastuzumab for HER2 targeting. We characterized the nanoparticles used transmission electron microscopy, hydration particle size, Zeta potential, UV and Fourier transform infrared spectroscopy, and examined its magnetism, fluorescence, and relaxation rate related properties. CCK-8 and blood biochemistry analysis evaluated the biosafety and stability of the nanoparticles, and validated the targeting ability of Fe3O4-Cy5.5 trastuzumab nanoparticles throughin vitroandin vivocell and animal experiments. Characterization results showed the successful synthesis of Fe3O4-Cy5.5-trastuzumab nanoparticles with a diameter of 93.72 ± 6.34 nm. The nanoparticles showed a T2relaxation rate 42.29 mM-1s-1, magnetic saturation strength of 27.58 emg g-1. Laser confocal and flow cytometry uptake assay showed that the nanoparticles could effectively target HER2 expressed by breast cancer cells. As indicated byin vitroandin vivostudies, Fe3O4-Cy5.5-trastuzumab were specifically taken up and effectively aggregated to tumour regions with prominent NIRF/MR imaging properties. CCK-8, blood biochemical analysis and histological results suggested Fe3O4-Cy5.5-trastuzumab that exhibited low toxicity to major organs and goodin vivobiocompatibility. The prepared Fe3O4-Cy5.5-trastuzumab exhibited excellent targeting, NIRF/MR imaging performance. It is expected to serve as a safe and effective diagnostic method that lays a theoretical basis for the effective diagnosis of early breast cancer. This study successfully prepared a kind of nanoparticles with near-infrared fluorescence imaging and T2imaging properties, which is expected to serve as a new theory and strategy for early detection of breast cancer.

pH-responsive albumin-mimetic synthetic nanoprobes for magnetic resonance/fluorescence imaging of thyroid cancer.

The combination of magnetic resonance and fluorescence imaging in dual-modality imaging not only resolves the limitations of conventional single molecular imaging techniques in terms of specificity, sensitivity, and resolution but also expands the possibilities of molecular imaging techniques in diagnostics and therapeutic monitoring. Herein, a novel pH-responsive magnetic resonance/near-infrared fluorescence (MR/NIRF) nanoprobe (MnO2@BSA-Cy5.5) was successfully prepared by biomineralizing manganese dioxide (MnO2) with bovine serum albumin (BSA) while coupling fluorescent dye Cy5.5 for precise tumor detection and visualization. The synthesized MnO2@BSA-Cy5.5 nanoprobes were spherical particles of approximately 22.62 ± 3.31 nm in size, and their relaxation rates and T1 imaging signals were activated-enhanced in an acidic environment. Cytotoxicity assay and hematoxylin and eosin staining demonstrated that MnO2@BSA-Cy5.5 had low cytotoxicity and good biocompatibility. More importantly, active targeting via solid tumor albumin-binding protein receptor and enhanced permeability and retention effect, the probe can be specifically aggregated to the tumor site of the 8305C tumor model and exhibit excellent MR/NIRF imaging properties. Our results show that MnO2@BSA-Cy5.5 has high resolution and sensitivity in tumor imaging and is expected to be applied as an MR/NIRF contrast agent for accurate diagnosis of thyroid cancer.

A Novel pH-Responsive Iron Oxide Core-Shell Magnetic Mesoporous Silica Nanoparticle (M-MSN) System Encapsulating Doxorubicin (DOX) and Glucose Oxidase (Gox) for Pancreatic Cancer Treatment.

Introduction: This study developed a pancreatic cancer targeted drug delivery system that responds to changes in acidity. The system was based on iron oxide core-shell magnetic mesoporous silica nanoparticles (M-MSNs) to treat pancreatic cancer through combined chemotherapy and starvation therapy. Methods: Glucose oxidase (Gox) was coupled to the cancer cell surface to reduce glucose availability for cancer cells, exacerbating the heterogeneity of the tumor microenvironment. Reduced pH accelerated the depolymerization of pH-sensitive polydopamine (PDA), thereby controlling the spatial distribution of Gox and release of doxorubicin (DOX) within tumor cells. Results: Characterization results showed the successful synthesis of DG@M-MSN-PDA-PEG-FA (DG@NPs) with a diameter of 66.02 ± 3.6 nm. In vitro data indicated DG@NPs were highly effective and stable with good cellular uptake shown by confocal laser scanning microscopy (CLSM). DG@NPs exhibited high cytotoxicity and induced apoptosis. Additionally, in vivo experiments confirmed DG@NPs effectively inhibited tumor growth in nude mice with good biosafety. The combination of starvation therapy and chemotherapy facilitated drug release, suggesting DG@NPs as a novel drug delivery system for pancreatic cancer treatment. Conclusion: This study successfully constructed a doxorubicin release system responsive to acidity changes for targeted delivery in pancreatic cancer, providing a new strategy for combination therapy.

Aptamer-mediated hollow MnO2 for targeting the delivery of sorafenib.

Sorafenib (SRF) presents undesirable effects in clinical treatment, due to the lack of targeting, poor water solubility, and obvious side effects. In this study, we constructed a novel nanodrug carrier system for accurate and efficient delivery of SRF, improving its therapeutic effects and achieving tumor-specific imaging. The hollow mesoporous MnO2 (H-MnO2) nanoparticles equipped with target substance aptamers (APT) on the surface were used to load SRF for the first time. The resulting H-MnO2-SRF-APT could specifically bound to glypican-3 (GPC3) receptors on the surface of hepatocellular carcinoma (HCC), rapidly undergoing subsequent degradation under decreased pH conditions in the tumor microenvironment (TME) and releasing the loaded SRF. In this process, Mn2+ ions were used for T1-weighted magnetic resonance imaging simultaneously. The in vitro cell experiments indicated that H-MnO2-SRF-APT showed much more effects on the inhibition in the proliferation of Huh7 and HepG2 HCC cells than that of the non-targeted H-MnO2-SRF and free SRF. Besides, the in vivo results further confirmed that H-MnO2-SRF-APT could effectively inhibit the growth of xenograft tumors Huh7 in the naked mouse with good biosafety. In conclusion, H-MnO2-SRF-APT could significantly enhance the therapeutic effect of SRF and is expected to be a new way of diagnosis and treatment of HCC.

Redox/pH-responsive hollow manganese dioxide nanoparticles for thyroid cancer treatment.

The nano drug delivery system MnO2/CDDP@PDA-Cy5.5 was synthesized in this study to increase the efficacy of Cisplatin (CDDP) on thyroid cancer and alleviate the damage to normal tissue, with the aim of enhancing the anti-cancer efficacy, increasing the drug load, optimizing the control of drug release, and alleviating the systemic toxicity arising from drug off-target. On that basis, high efficacy and low toxicity win-win can be obtained. In this study, hollow manganese dioxide nanoparticles (MnO2 NPs) were prepared based on the template method. CDDP was loaded into the hollow cavity and then modified with polydopamine (PDA) and Cy5.5, with the aim of obtaining the nano-drug loading system MnO2/CDDP@PDA-Cy5.5 NPs. The NPs precisely delivered drugs by intelligently responding to the tumor microenvironment (TME). As indicated by the release curves, the NPs release CDDP rapidly by inducing the decomposition of PDA and MnO2 under acidic or redox conditions, and Magnetic resonance imaging (MRI) contrast agent Mn2+ was generated. The results of the in vivo MRI studies suggested that T1 contrast at the tumor site was notably enhanced under the Enhanced permeability and retention (EPR) effect. After the intravenous administration, the effective tumor accumulation exhibited by the NPs was confirmed by magnetic resonance imaging as a function of time. Compared with free CDDP, the in vivo therapeutic effect was remarkably increased. As indicated by the above-described results, MnO2/CDDP@PDA-Cy5.5 NPs is a drug delivery system exhibiting diagnostic and therapeutic functions.

Gadolinium-Coated Mesoporous Silica Nanoparticle for Magnetic Resonance Imaging.

Magnetic resonance molecular imaging can provide anatomic, functional and molecular information. However, because of the intrinsically low sensitivity of magnetic resonance imaging (MRI), high-performance MRI contrast agents are required to generate powerful image information for image diagnosis. Herein, we describe a novel T 1 contrast agent with magnetic-imaging properties facilitated by the gadolinium oxide (Gd2O3) doping of mesoporous silica nanoparticles (MSN). The size, morphology, composition, MRI relaxivity (r 1 ), surface area and pore size of these nanoparticles were evaluated following their conjugation with Gd2O3 to produce Gd2O3@MSN. This unique structure led to a significant enhancement in T 1 contrast with longitudinal relaxivity (r 1 ) as high as 51.85 ± 1.38 mM-1s-1. Gd2O3@MSN has a larger T 1 relaxivity than commercial gadolinium diethylene triamine pentaacetate (Gd-DTPA), likely due to the geometrical confinement effect of silica nanoparticles. These results suggest that we could successfully prepare a novel high-performance T 1 contrast agent, which may be a potential candidate for in-vivo MRI.

Construction of novel coumarin-carbazole-based fluorescent probe for tracking of endogenous and exogenous H2S in vivo with yellow-emission and large Stokes shift.

Recent medical studies have confirmed that endogenous H2S serves as the third gas-messenger besides nitric oxide (NO) and carbon monoxide (CO), which is produced by enzyme-catalyzed metabolism of cysteine and takes part in multiple physiological processes. The abnormal levels induced by H2S overproduction in mammals can destroy tissues and organ systems, which lead to certain serious diseases, such as neurodegenerative diseases, cardiovascular diseases, and various cancers. In this work, we developed a novel coumarin-carbazole fluorescent probe COZ-DNB with yellow emission and a large Stokes shift for H2S detection. In probe COZ-DNB, the newly dye COZ-OH as a luminophore and the 2,4-dinitrophenyl ether moiety was chosen as a trigger group for H2S. Probe COZ-DNB itself displayed nearly non-fluorescent. However, COZ-DNB gave the remarkable fluorescence with an 83-fold enhancement in the yellow region after interaction with H2S. The sensing mechanism of COZ-DNB toward H2S was checked by means of UHPLC, HRMS and DFT/TD-DFT calculations. What's more, probe COZ-DNB also exhibited fast response (2.0 min), high sensitivity (65.0 nM), a large Stokes shift (161.0 nm), high stability and excellent selectivity. Furthermore, COZ-DNB was applied for imaging of exogenous and endogenous H2S in living HeLa cells and zebrafish with satisfactory performances. We anticipate COZ-DNB would be served as a potential tool for investigating the biological functions of H2S in pathological processes.

A fast-responsive fluorescent probe based on a styrylcoumarin dye for visualizing hydrogen sulfide in living MCF-7 cells and zebrafish.

As a vital antioxidant molecule, H2S can make an important contribution to regulating blood vessels and inhibiting apoptosis when present at an appropriate concentration. Higher levels of H2S can interfere with the physiological responses of the respiratory system and central nervous system carried out by mammalian cells. This is associated with many illnesses, such as diabetes, mental decline, cardiovascular diseases, and cancer. Therefore, the accurate measurement of H2S in organisms and the environment is of great significance for in-depth studies of the pathogenesis of related diseases. In this contribution, a new coumarin-carbazole-based fluorescent probe, COZ-DNBS, showing a rapid response and large Stokes shift was rationally devised and applied to effectively sense H2S in vivo and in vitro. Upon using the probe COZ-DNBS, the established fluorescent platform could detect H2S with excellent selectivity, showing 62-fold fluorescence enhancement, a fast-response time (<1 min), high sensitivity (38.6 nM), a large Stokes shift (173 nm), and bright-yellow emission. Importantly, the probe COZ-DNBS works well for monitoring levels of H2S in realistic samples, living MCF-7 cells, and zebrafish, showing that COZ-DNBS is a promising signaling tool for H2S detection in biosystems.

Upregulation of circ-ASPH contributes to glioma cell proliferation and aggressiveness by targeting the miR-599/AR/SOCS2-AS1 signaling pathway.

Glioma (GM) is the most common type of malignant brain tumor with a high recurrence rate. Circular RNAs (circRNAs) play a key role in mediating tumorigenesis. However, the functions and mechanisms of circRNAs in GM are still not fully understood. A circRNA microarray was performed to identify differentially expressed circRNAs in GM and non-cancerous specimens. Reverse transcription-quantitative PCR was used to detect circ-aspartyl/asparaginyl ß-hydroxylase (ASPH) expression in GM tissues and cells. The clinical importance of circ-ASPH was investigated using Kaplan-Meier analysis. The functions of circ-ASPH were investigated in LN229 and U87MG cells. Bioinformatics, RNA immunoprecipitation, RNA pull-down and luciferase reporter assays were used to explore the mechanisms of circ-ASPH in GM. circ-ASPH levels were upregulated in GM specimens and cells. The prognostic role of circ-ASPH was identified in patients with GM. Loss/gain of function assays demonstrated that circ-ASPH increased cell proliferation, migration and invasion in GM cells. Mechanistically, circ-ASPH counteracted microRNA (miR)-599-mediated androgen receptor (AR) suppression by acting as a sponge for miR-599. Rescue assays indicated that circ-ASPH facilitated cell progression by regulating AR expression. Moreover, AR activated long non-coding RNA suppressor of cytokine signaling 2-antisense RNA 1 (SOCS2-AS1) expression in GM cells. Taken together, circ-ASPH/miR-599/AR/SOCS2-AS1 signaling may be a promising biomarker/therapeutic target for GM.

Deep Learning Technology in Pathological Image Analysis of Breast Tissue.

To explore the application value of the multilevel pyramid convolutional neural network (MPCNN) model based on convolutional neural network (CNN) in breast histopathology image analysis, in this study, based on CNN algorithm and softmax classifier (SMC), a sparse autoencoder (SAE) is introduced to optimize it. The sliding window method is used to identify cells, and the CNN + SMC pathological image cell detection method is established. Furthermore, the local region active contour (LRAC) is introduced to optimize it and the LRAC fine segmentation model driven by local Gaussian distribution is established. On this basis, the sparse automatic encoder is further introduced to optimize it and the MPCNN model is established. The proposed algorithm is evaluated on the pathological image data set. The results showed that the Acc value, F value, and Re value of pathological cell detection of CNN + SMC algorithm were significantly higher than those of the other two algorithms (P < 0.05). The Dice, OL, Sen, and Spe values of pathological image regional segmentation of CNN algorithm were significantly higher than those of the other two algorithms, and the difference was statistically significant (P < 0.05). The accuracy, recall, and F-measure of the optimized CNN algorithm for detecting breast histopathological images were 85.25%, 89.27%, and 80.09%, respectively. In the two databases with segmentation standards, the segmentation accuracy of MPCNN is 55%, 73.1%, 78.8%, and 82.1%. In the deep convolution network model, the training time of the MPCNN algorithm is about 80 min. It shows that when the feature dimension is low, the feature map extracted by MPCNN is more effective than the traditional feature extraction method.

Exploring the optimal dose of low ionizing radiation to enhance immune function: a rabbit model.

Primary liver cancer is one of the most common malignant tumors in China. Currently, immunotherapy for liver cancer is a research hotspot. Experimental studies and epidemiological investigations have confirmed the antineoplastic activity of low ionizing radiation. The aim of this study was to explore the optimal dose of low ionizing radiation to enhance immune function. Twenty-five New Zealand rabbits were randomly divided into five groups (n = 5 each): experimental group 1 (25 mGy), experimental group 2 (50 mGy), experimental group 3 (75 mGy), experimental group 4 (100 mGy), and the control group (0 mGy). VX-2 tumor tissue was injected into rabbits using a high-frequency B-ultrasound probe (3.5 MHz). Rabbits were irradiated, and on day 4 after irradiation, blood was collected from each rabbit. Blood chemistry, interleukin (IL)-4, interferon (IFN)-γ, immunoglobulin (Ig)G, and IgM levels were assessed. On day 15 after irradiation, macrophage phagocytic function was assessed. The rabbits were sacrificed, and the spleen was removed and weighed to calculate its spleen index. Each parameter was highest in the experimental group 3 (75 mGy). Thus, we suspect the optimal low ionizing radiation dose to improve immune function may be 75 mGy.

Circular RNA circ­CCT3 promotes hepatocellular carcinoma progression by regulating the miR­1287­5p/TEAD1/PTCH1/LOX axis.

Hepatocellular carcinoma (HCC) is characterized by a poor prognosis because of its insensitivity to radiation and chemotherapy. Recently, circular RNAs (circRNAs) have been found to serve important roles in hepatocellular carcinogenesis. circ­CCT3, a novel circRNA, was screened from the differential tissue expression results of a circRNA microarray. Relative expression levels of circ­CCT3 in specimens and cell lines were evaluated by reverse transcription­quantitative PCR and the relationship between circ­CCT3 and prognosis was analyzed by Kaplan­Meier curves. The oncogenic role of circ­CCT3 was confirmed in HCC cells through a cell counting kit­8 (CCK­8) assay, a colony formation assay, acridine orange/ethidium bromide double fluorescence staining, flow cytometry, a wound­healing assay and a Transwell assay. Bioinformatics prediction and luciferase reporter assays validated that circ­CCT3 facilitated HCC progression through the miR­1287­5p/TEA domain transcription factor 1 (TEAD1) axis. TEAD1 could then directly activate patched 1 and lysyl oxidase transcription, as analyzed by chromatin immunoprecipitation and luciferase reporter assays. The present study identified a novel circRNA, circ­CCT3, which may be used as a potential therapeutic target for HCC.