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1.
Psychother Psychosom ; : 1-7, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38934157

ABSTRACT

INTRODUCTION: The early and rapid identification of psychosomatic symptoms is crucial to prevent harmful outcomes in patients with human papillomavirus (HPV) infection in busy comprehensive clinics. This study aimed to explore the prevalence and rapid screening method of the Diagnostic Criteria for Psychosomatic Research-revised (DCPR) syndromes in patients with HPV infection. METHODS: A total of 504 participants underwent a clinical assessment that included DCPR, Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), the Social Support Rating Scale (SSRS), the Simplified Coping Style Questionnaire (SCSQ), fear of disease, sociodemographic and clinical characteristics. The prevalence of DCPR syndromes and DSM-5 diagnoses were compared between the HPV-positive and negative patients using χ2 tests. We explored the rapid screen indicator through multiple logistic regression analyses of the participants' psychosocial factors, sociodemographic and clinical characteristics. RESULTS: The incidence of DCPR syndromes in HPV-positive patients (56.6%) was significantly greater than that in HPV-negative patients (17.3%) and DSM-5 diagnoses (8.5%) in the HPV-positive group. Health anxiety, irritable mood, type A behavior, and demoralization were the most common psychosomatic syndromes in HPV-positive patients. As the degree of fear increased from 0 to 5 to 10, the risk of DCPR increased from 1.27 (95% CI: 0.21-7.63) to 3.24 (score range: 1-5, 95% CI: 1.01-10.39) to 9.91 (score range: 6-10, 95% CI: 3.21-30.62) in the HPV-positive group. CONCLUSION: The degree of fear, as an independent risk factor, could be used to quickly screen outpatients with a high risk of DCPR syndrome among women with HPV infection.

2.
China CDC Wkly ; 6(23): 553-557, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38933663

ABSTRACT

Introduction: Traditional methods for determining radiation dose in nuclear medicine include the Monte Carlo method, the discrete ordinate method, and the point kernel integration method. This study presents a new mathematical model for predicting the radiation dose rate in the vicinity of nuclear medicine patients. Methods: A new algorithm was created by combining the physical model of "cylinder superposition" of the human body with integral analysis to assess the radiation dose rate in the vicinity of nuclear medicine patients. Results: The model accurately predicted radiation dose rates within distances of 0.1-3.0 m, with a deviation of less than 11% compared to observed rates. The model demonstrated greater accuracy at shorter distances from the radiation source, with a deviation of only 1.55% from observed values at 0.1 m. Discussion: The model proposed in this study effectively represents the spatial and temporal distribution of the radiation field around nuclear medicine patients and demonstrates good agreement with actual measurements. This model has the potential to serve as a radiation dose rate alert system in hospital environments.

3.
Food Chem ; 456: 139935, 2024 Oct 30.
Article in English | MEDLINE | ID: mdl-38870805

ABSTRACT

This study investigated the effects of oil phases on the encapsulation rate, storage stability, and bioavailability of astaxanthin (ASTA) in Pickering emulsions (PEs). Results showed PEs of mixed oils (olive oil/edible tea oil) had excellent encapsulation efficiency (about 96.0%) and storage stability of ASTA. In vitro simulated gastrointestinal digestion results showed the mixed oil PE with a smaller interfacial area and higher monounsaturated fatty acid content may play a better role in improving ASTA retention and bioaccessibility. In vivo absorption results confirmed the mixed oil PE with an olive oil/edible tea oil of 7:3 was more favorable for ASTA absorption. Molecular dynamics simulation showed ASTA bound more strongly and stably to fatty acid molecules in the system of olive oil/edible tea oil of 7:3; and van der Waals force was the main binding force. NMR further proved there really were interactions between ASTA and four main fatty acids.


Subject(s)
Biological Availability , Emulsions , Molecular Dynamics Simulation , Olive Oil , Xanthophylls , Xanthophylls/chemistry , Xanthophylls/metabolism , Emulsions/chemistry , Olive Oil/chemistry , Animals , Male , Digestion , Humans , Drug Stability
4.
Mol Pharm ; 21(8): 3992-4003, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-38941565

ABSTRACT

Lymphocyte activation gene 3 (LAG-3) has attracted much attention as a potentially valuable immune checkpoint. Individual identification of LAG-3 expression at screening and during treatment could improve the successful implementation of anti-LAG-3 therapies. HuL13 is a human IgG1 monoclonal antibody that binds to the LAG-3 receptor in T cells. Here, we used [89Zr]Zr-labeled HuL13 to delineate LAG-3+ T-cell infiltration into tumors via positron emission tomography (PET) imaging. A549/LAG-3 cells, which stably express LAG-3, were generated by infection with lentivirus. The uptake of [89Zr]Zr-DFO-HuL13 in A549/LAG-3 cells was greater than that in the negative control (A549/NC) cells at each time point. The equilibrium dissociation constant (Kd) of [89Zr]Zr-DFO-HuL13 for the LAG-3 receptor was 8.22 nM. PET imaging revealed significant uptake in the tumor areas of A549/LAG-3 tumor-bearing mice from 24 h after injection (SUVmax = 2.43 ± 0.06 at 24 h). As a proof of concept, PET imaging of the [89Zr]Zr-DFO-HuL13 tracer was further investigated in an MC38 tumor-bearing humanized LAG-3 mouse model. PET imaging revealed that the [89Zr]Zr-DFO-HuL13 tracer specifically targets human LAG-3 expressed on tumor-infiltrating lymphocytes (TILs). In addition to the tumors, the spleen was also noticeably visible. Tumor uptake of the [89Zr]Zr-DFO-HuL13 tracer was lower than its uptake in the spleen, but high uptake in the spleen could be reduced by coinjection of unlabeled antibodies. Coinjection of unlabeled antibodies increases tracer activity in the blood pool, thereby improving tumor uptake. Dosimetry evaluation of the healthy mouse models revealed that the highest absorbed radiation dose was in the spleen, followed by the liver and heart wall. In summary, these studies demonstrate the feasibility of using the [89Zr]Zr-DFO-HuL13 tracer for the detection of LAG-3 expression on TILs. Further clinical evaluation of the [89Zr]Zr-DFO-HuL13 tracer may be of significant help in the stratification and management of patients suitable for anti-LAG-3 therapy.


Subject(s)
Lymphocyte Activation Gene 3 Protein , Lymphocytes, Tumor-Infiltrating , Positron-Emission Tomography , Zirconium , Animals , Humans , Mice , Zirconium/chemistry , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Positron-Emission Tomography/methods , Cell Line, Tumor , Antigens, CD/metabolism , Antigens, CD/immunology , Radioisotopes/chemistry , Antibodies, Monoclonal/chemistry , Female , Tissue Distribution
5.
Nutrients ; 16(9)2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38732526

ABSTRACT

Distillers' grains are rich in protein and constitute a high-quality source of various bioactive peptides. The purpose of this study is to identify novel bioactive peptides with α-glucosidase inhibitory, antioxidant, and insulin resistance-ameliorating effects from distiller's grains protein hydrolysate. Three novel peptides (YPLPR, AFEPLR, and NDPF) showed good potential bioactivities, and the YPLPR peptide had the strongest bioactivities, whose IC50 values towards α-glucosidase inhibition, radical scavenging rates of 2,2'-azino-bis (3-ethylbenzothiazoline-6- sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) were about 5.31 mmol/L, 6.05 mmol/L, and 7.94 mmol/L, respectively. The glucose consumption of HepG2 cells treated with YPLPR increased significantly under insulin resistance condition. Moreover, the YPLPR peptide also had a good scavenging effect on intracellular reactive oxygen species (ROS) induced by H2O2 (the relative contents: 102.35% vs. 100%). Molecular docking results showed that these peptides could stably combine with α-glucosidase, ABTS, and DPPH free radicals, as well as related targets of the insulin signaling pathway through hydrogen bonding and van der Waals forces. This research presents a potentially valuable natural resource for reducing oxidative stress damage and regulating blood glucose in diabetes, thereby increasing the usage of distillers' grains peptides and boosting their economic worth.


Subject(s)
Antioxidants , Glycoside Hydrolase Inhibitors , Insulin Resistance , Molecular Docking Simulation , Peptides , Glycoside Hydrolase Inhibitors/pharmacology , Hep G2 Cells , Humans , Antioxidants/pharmacology , Peptides/pharmacology , Peptides/chemistry , Edible Grain , alpha-Glucosidases/metabolism , Protein Hydrolysates/pharmacology , Reactive Oxygen Species/metabolism , Hypoglycemic Agents/pharmacology , Computer Simulation , Insulin , Sulfonic Acids , Biphenyl Compounds , Picrates , Benzothiazoles
6.
Foods ; 13(2)2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38254595

ABSTRACT

This study aimed to explore the potential of umami peptides for lowering blood glucose. Molecular docking results showed that the peptides LADW and EEAEGT bound to the active amino acid residues of α-glucosidase via hydrogen bonds and Van der Waals forces, a finding supported by an independent gradient model (IGM). Molecular dynamics (MD) simulations demonstrated that the peptides LADW and EEAEGT can decelerate the outward expansion of α-glucosidase and reduce amino acid fluctuations at the active site. In vitro findings indicated that the peptides LADW and EEAEGT showed potent inhibitory activity against α-glucosidase, with IC50 values of 4.40 ± 0.04 and 6.46 ± 0.22 mM, respectively. Furthermore, MD simulation and morphological observation results also revealed that LADW and EEAEGT alter starch structure and form weak interactions with starch through intermolecular hydrogen bonding, leading to the inhibition of starch hydrolysis. Peptides inhibit the ability of starch to produce reducing sugars after simulated gastrointestinal digestion, providing additional evidence of the inhibition of starch hydrolysis by the added peptides. Taken together, these findings suggest that consuming the umami peptides LADW and EEAEGT may alleviate postprandial blood glucose elevations via inhibiting α-glucosidase and starch hydrolysis.

7.
J Chromatogr A ; 1705: 464181, 2023 Aug 30.
Article in English | MEDLINE | ID: mdl-37442071

ABSTRACT

The hollow MCM-48 polyethyleneimine carboxyphenylboronic acid molecularly imprinted polymers (H-MPC@MIPs) were synthesized to efficiently and selectively separate and enrich the ovalbumin (OVA) in egg white samples. Polyethyleneimine contained enough active amino groups to increase the amount of boric acid molecules modified to silica nanoparticles. Meanwhile, the materials were etched to enhance the adsorption effect. The H-MPC@MIPs exhibited a rapid adsorption equilibrium rate (within 30 min) and outstanding adsorption capacity for OVA (1334.1 mg g-1). It possessed a good reusability after 5 cycles. In addition, both the high density and the imprinting action of boric acid were essential for enhancing the identification and binding of OVA. The OVA in egg white samples was successfully selectively enriched using this method.


Subject(s)
Molecular Imprinting , Nanoparticles , Ovalbumin , Polymers/chemistry , Polyethyleneimine , Nanoparticles/chemistry , Adsorption
8.
Mol Pharm ; 20(7): 3672-3682, 2023 07 03.
Article in English | MEDLINE | ID: mdl-37212215

ABSTRACT

Real-time monitoring of the biological behavior of extracellular vesicles (EVs) in vivo is limited, which hinders its application in biomedicine and clinical translation. A noninvasive imaging strategy could provide us with useful information on EVs' distribution, accumulation and homing in vivo, and pharmacokinetics. In this study, the long half-life radionuclide iodine-124 (124I) was used to directly label umbilical cord mesenchymal stem cell-derived EVs. The resulting probe, namely, 124I-MSC-EVs, was manufactured and ready to use within 1 min. 124I-labeled MSC-EVs had high radiochemical purity (RCP, >99.4%) and stable in 5% human serum album (HSA) with RCP > 95% for 96 h. We demonstrated efficient intracellular internalization of 124I-MSC-EVs in two prostate cancer cell lines (22RV1 and DU145 cell). The uptake rates of 124I-MSC-EVs in human prostate cancer cell lines 22RV1 and DU145 cells were 10.35 ± 0.78 and 2.56 ± 0.21 (AD%) at 4 h. The promising cellular data has prompted us to investigate the biodistribution and in vivo tracking capability of this isotope-based labeling technique in tumor bearing animals. Using positron emission tomography (PET) technology, we showed that the signal from intravenously injected 124I-MSC-EVs mainly accumulated in the heart, liver, spleen, lung, and kidney in healthy kun ming (KM) mice, and the biodistribution study was similar to the imaging results. In the 22RV1 xenograft model, 124I-MSC-EVs accumulated significantly in the tumor after administration, and with the optimal image acquired at 48 h postinjection, the maximum of standard uptake value (SUVmax) of the tumor was 3-fold higher than that of DU145. Taken together, the probe has a high application prospect in immuno-PET imaging of EVs. Our technique provides a powerful and convenient tool for understanding the biological behavior and pharmacokinetic characteristics of EVs in vivo and facilitates the acquirement of comprehensive and objective data for future clinical studies of EVs.


Subject(s)
Extracellular Vesicles , Iodine , Prostatic Neoplasms , Male , Humans , Animals , Mice , Iodine/metabolism , Tissue Distribution , Isotope Labeling , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/metabolism , Extracellular Vesicles/metabolism
9.
Anal Methods ; 15(7): 925-936, 2023 02 16.
Article in English | MEDLINE | ID: mdl-36688606

ABSTRACT

In this study, 3-carboxyphenylboronic acid (CP)-functionalized amino-modified Fe3O4 (Fe3O4@NH2-CP, FNC) magnetic molecularly imprinted polymers (FNC@MIPs) were synthesized and applied for the quick identification and selective separation of luteolin (LTL). The structure and morphology were characterized in detail by Fourier transform-infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), dynamic light scattering (DLS), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and vibrating specimen magnetometry (VSM) methods. The FNC@MIPs had a homogeneous shape, excellent magnetic characteristics, quick binding kinetics, a high adsorption capacity, acceptable selectivity, and stable reusability. The solid-phase extraction parameters and preparation conditions were both optimized. Under optimized conditions, the maximal adsorption capacity was 14.26 mg g-1 and the imprinting factor was 3.62. Furthermore, the experimental kinetics data were best fitted with the pseudo-first-order model (R2 = 0.9877), and the Langmuir model could describe the adsorption process (R2 = 0.9979), suggesting a monolayer covering. The practical application of the sorbent for LTL detection in Lonicera japonica Thunb samples showed recoveries in the range of 84.5-108.7%. Therefore, the strategy offers a fresh avenue for the extraction and purification of LTL.


Subject(s)
Molecular Imprinting , Molecularly Imprinted Polymers , Molecular Imprinting/methods , Luteolin , Polymers/chemistry , Spectroscopy, Fourier Transform Infrared , Magnetic Phenomena
10.
Gen Psychiatr ; 35(5): e100856, 2022.
Article in English | MEDLINE | ID: mdl-36447756

ABSTRACT

The biomedical model, which limits itself to finding the attributions of organic disease, is challenged by gastrointestinal (GI) symptoms. Simultaneously, physicians' attribution of GI symptoms to underlying psychological issues is not readily accepted by patients and can negatively affect the clinical rapport between doctor and patient. In reality, psychosocial aspects are involved in many functional disorders and organic diseases, not just in mental disorders. Time is overdue for gastroenterologists to recognise the inadequacy and limitations of conventional gastroenterology and consider the role of psychological, social and biological variables throughout the entire clinical course of the illness, as is shown in George Engel's model. This review discusses the following: (1) the current challenges of using the conventional clinical model for both functional and organic GI illness, (2) the inadequacy and limitations of explaining GI symptoms simply as psychological disorders, (3) the exploration of the symptom-centred, stepped reattribution clinical model, (4) the clarification of psychosomatic medical concepts for use in gastroenterology, and (5) the significance of a systematic and interdisciplinary framework for a comprehensive psychosomatic model in gastroenterology.

11.
Toxicol Res (Camb) ; 10(4): 875-884, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34484679

ABSTRACT

Cervical cancer (CC) is a type of pelvic malignant tumor that severely threatens women's health. Current evidence suggests that IER5, as a potential radiosensitizer, promotes irradiation-induced apoptosis in CC tissues in patients undergoing chemoradiotherapy. IER5 has been shown to be involved in the G2/M-phase transition. In the present study, we used Cdc25B as the breakthrough point to explore the underlying mechanism of IER5 in the cell cycle regulation of radiation-damaged HeLa cells. IER5 was evidently upregulated after irradiation, but Cdc25B was significantly downregulated. In monoclonal IER5-silenced HeLa cells, irradiation-induced downregulation of Cdc25B was attenuated. The effect of irradiation on Cdc25B promoter activity was determined by dual-luciferase reporter assays. The response elements on the Cdc25B promoter related to irradiation were predicted by JASPAR. These conserved sequences were mutated individually or in combination by splicing-by-overlap extension PCR, and their function was confirmed by dual-luciferase reporter assays. The enrichment efficiency of transcription factors after irradiation was determined by chromatin immunoprecipitation (ChIP) assay. Both Sp1/Sp3 and NF-YB binding sites were involved in irradiation-mediated regulation of Cdc25B. IER5 was involved in irradiation-mediated regulation of Cdc25B through the NF-YB binding site. Furthermore, ChIP assays showed that IER5 bound to the Cdc25B promoter, and the binding of IER5 to the Cdc25B promoter region in irradiation-induced HeLa cells induced the release of the coactivator p300 through interaction with NF-YB. Taken together, these findings indicate that IER5 is the transcriptional repressor that accelerates the downregulation of Cdc25B expression after irradiation.

12.
J Immunother Cancer ; 9(7)2021 07.
Article in English | MEDLINE | ID: mdl-34301815

ABSTRACT

BACKGROUND: Death receptor 5 (DR5) is a promising therapeutic target for cancer therapy. However, many clinical trials of DR5 agonists failed to show significant therapeutic efficacy in patients with cancer. The study aimed to investigate the feasibility of using 89Zr-CTB006 positron emission tomography (PET) for noninvasive imaging of DR5 expression in preclinical models and patients with gastrointestinal (GI) cancers. METHODS: Balb/c, Sp2/0 xenograft and patient-derived tumor xenograft were employed for micro-PET/CT imaging in vivo. In the clinical study, patients with GI cancers planning to undergo surgical operation were enrolled and underwent 18F-FDG and 89Zr-CTB006 PET/CT. The tumor tissues were obtained through surgical operation and DR5 expression levels were confirmed by RNAscope. RESULTS: Preclinical studies showed that 89Zr-CTB006 PET could specifically detect DR5 expression levels in vivo. Twenty-one patients, including nine gastric cancers and 12 colorectal cancers, were enrolled. The biodistribution showed high uptake in the liver and spleen and low uptake in the brain, lung and muscle with an acceptable whole-body dosimetry of 0.349 mSv/MBq. Strikingly, the adrenal glands maintained stable high uptake over the entire examination in all patients. The tumor lesions showed different levels of uptake of 89Zr-CTB006 with a mean maximum standardized uptake value (SUVmax) of 6.63±3.29 (range 1.8-13.8). Tumor tissue was obtained from 18 patients, and 89Zr-CTB006 uptake in patients with RNAscope scores of 3-4 was significantly higher than that in patients with scores of 0-2. An SUVmax of 9.3 at 48 hours and 6.3 at 72 hours could be used to discriminate the DR5 expression status of tumors both with a sensitivity and specificity of 100% and 92.9%, respectively. CONCLUSIONS: 89Zr-CTB006 PET/CT is capable of detecting DR5 expression in cancer patients and is a promising approach to screen patients with DR5 overexpression.


Subject(s)
Gastrointestinal Neoplasms/diagnostic imaging , Gastrointestinal Neoplasms/genetics , Positron Emission Tomography Computed Tomography/methods , Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism , Cell Line, Tumor , Female , Humans
13.
Clin Nucl Med ; 46(5): 382-388, 2021 May 01.
Article in English | MEDLINE | ID: mdl-33512952

ABSTRACT

PURPOSE: Although anti-programmed cell death molecule-1 (PD-1)/PD-1 ligand therapy has achieved remarkable success in oncology field, the low response rate and lack of accurate prognostic biomarker identifying benefiting patients remain unresolved challenges. This study developed a PD-1 targeting radiotracer 124I-labeled toripalimab (124I-JS001) for clinical PET imaging and evaluated its biodistribution, safety, and dosimetry in human. METHODS: Patients with melanoma or urologic cancer confirmed by pathology were enrolled. 124I-JS001 PET/CT and PET/MR were performed with or without coinjection of 5 mg unlabeled JS001, and 18F-FDG PET was undertaken within 1 week. RESULTS: Eight melanoma and 3 urologic cancer patients were enrolled. No adverse events were noticed during the whole examination after the injection of 124I-JS001 and an acceptable dosimetry of 0.236 mSv/MBq was found. 124I-JS001 PET/CT showed high uptake in spleen and liver and slight uptake in bone marrow and lung. All primary and metastatic tumor lesions in 11 patients demonstrated different levels of uptake of 124I-JS001 with SUVmax ranging from 0.2 to 4.7. With coinjection of unlabeled JS001, the uptake in spleen was reduced significantly (P < 0.05), whereas tumor uptake and tumor background ratio increased significantly (P < 0.05). Four patients undertook regional 124I-JS001 PET/MR. All tumor lesions were detected effectively with abnormal MR signal on PET/MR, whereas PET/MR detected liver lesions more sensitively than PET/CT. CONCLUSIONS: The first-in-human study demonstrated 124I-JS001 was a safe tracer for PET with acceptable dosimetry, and the PET/CT results showed a favorable biodistribution. PET/MR could detect liver lesions more sensitively than PET/CT.


Subject(s)
Antibodies, Monoclonal, Humanized , Gene Expression Regulation, Neoplastic , Iodine Radioisotopes , Melanoma/diagnostic imaging , Positron Emission Tomography Computed Tomography , Programmed Cell Death 1 Receptor/metabolism , Urologic Neoplasms/diagnostic imaging , Adult , Antibodies, Monoclonal, Humanized/pharmacokinetics , Female , Fluorodeoxyglucose F18 , Humans , Isotope Labeling , Male , Melanoma/metabolism , Middle Aged , Pilot Projects , Radiometry , Tissue Distribution , Translational Research, Biomedical , Urologic Neoplasms/metabolism
14.
J Labelled Comp Radiopharm ; 64(1): 47-56, 2021 01.
Article in English | MEDLINE | ID: mdl-33067822

ABSTRACT

The next-generation positron zirconium-89 (89 Zr, T1/2 = 3.27 days) is a novel nuclide for immunological positron emission tomography because of its favorite longer half-life. The aim of this work is to develop optimized methods for routine production and purification of 89 Zr through Monte Carlo (MC) simulation and laboratory experiments. 89 Y(p,n)89 Zr reaction was used for 89 Zr production. Optimized thicknesses of Al degrader (0.11 cm) and 89 Y foil (0.064 cm) were simulated through MC method. 89 Zr (15.0-40.7 mCi) with an average production rate of 0.92 ± 0.12 mCi/µA·h was produced after 1- to 2-h bombardment at the proton beam energy of 20 MeV and current of 20 µA. High radio-purity 89 Zr (6.14-26.8 mCi) obtained eluted from hydroxamate resin using 1-mol/L oxalic acid solution, with the concentration of 2.7 × 104 mCi/L. The gamma spectrum showed that the characteristic peak of 89 Zr was 511 and 909 keV, and no impurities were found. [89 Zr]Zr-DFO-trastuzumab was successfully labeled and performed good radiochemical purity (>95%) and stability that showed potential application in tumor molecular imaging.


Subject(s)
Monte Carlo Method , Radioisotopes , Zirconium , Electrons
15.
Toxicol Res (Camb) ; 9(2): 107-116, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32440342

ABSTRACT

Radiation resistance is the most common challenge for improving radiotherapy. The mechanisms underlying the development of radioresistance remain poorly understood. This study aims to explore the role of LINC00460 in ionizing radiation-induced radioresistance as well as the mechanisms by which LINC00460 is regulated by radiation exposure. The expression of LINC00460 was measured. Cell proliferation and colony formation were measured in HCT116 cells after treatment by radiation. The development of epithelial-mesenchymal transition (EMT) was determined with or without knockdown LINC00460 expression using western blot analysis. Transcription activity was determined using a series of LINC00460-promoter luciferase reporter gene vectors. LINC00460 expression was significantly higher in HCT116 cells, relative to other cell types, with LINC00460 expression significantly affecting HCT116 cell proliferation. Suppression of LINC00460 inhibits EMT development in HCT116 cells via regulation of ZEB1 expression. Furthermore, LINC00460 expression was induced by irradiation via the activation of c-jun transcription factor-binding element located on the LINC00460 promoter. LINC00460 was shown to play a crucial role in EMT-associated progression of colorectal cancer, indicating that LINC00460 may be an indicator or new potential therapeutic target for colorectal cancer radiosensitization.

17.
Article in English | MEDLINE | ID: mdl-31057655

ABSTRACT

The pairing of Sophora flavescens and Fructus Ligustri lucidi is taken from Shi Jinmo Medicine. The idea behind this pairing was inspired by the similarity in pharmacological effects of the two herbal drugs, both of which are known to be effective in the treatment and protection against liver fibrosis. To quantitatively study the extent of the interaction between these drugs and the effect of pairing on the treatment of liver fibrosis, an animal model of liver fibrosis mice was established by intraperitoneal injection of low-dose carbon tetrachloride. The drugs were then administered individually, or in predefined compatibility ratio pairs, by gavage, and the effects on indexes of liver fibrosis were observed. The multisynthetic index method was adopted using Matlab software in order to construct a three-dimensional response surface map of the integration effect and conduct interaction analysis of Sophora flavescens and Fructus Ligustri lucidi. The quadratic surface fitting pattern was designed by quadratic regression to determine the optimal range of each drug. The obtained results show that when the compatibility ratio of Sophora flavescens-Fructus Ligustri lucidi drug pairs is less than or equal to 1:1, their therapeutic effect is enhanced by synergy (interaction value ranging between -0.2 and -1). Overall, the synergy of the high-dose drug pairs is stronger than that of the low-dose drug pairs. The optimal dose ranges are 6~12 g and 8~17 g for Sophora flavescens and Fructus Ligustri lucidi, respectively.

18.
IEEE Trans Neural Netw Learn Syst ; 26(3): 551-64, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25720010

ABSTRACT

This paper studies the generalization performance of radial basis function (RBF) networks using local Rademacher complexities. We propose a general result on controlling local Rademacher complexities with the L1 -metric capacity. We then apply this result to estimate the RBF networks' complexities, based on which a novel estimation error bound is obtained. An effective approximation error bound is also derived by carefully investigating the Hölder continuity of the lp loss function's derivative. Furthermore, it is demonstrated that the RBF network minimizing an appropriately constructed structural risk admits a significantly better learning rate when compared with the existing results. An empirical study is also performed to justify the application of our structural risk in model selection.

19.
Neural Comput ; 26(4): 739-60, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24479777

ABSTRACT

Estimating the Rademacher chaos complexity of order two is important for understanding the performance of multikernel learning (MKL) machines. In this letter, we develop a novel entropy integral for Rademacher chaos complexities. As compared to the previous bounds, our result is much improved in that it introduces an adjustable parameter ε to prohibit the divergence of the involved integral. With the use of the iteration technique in Steinwart and Scovel (2007), we also apply our Rademacher chaos complexity bound to the MKL problems and improve existing learning rates.


Subject(s)
Artificial Intelligence , Learning/physiology , Nonlinear Dynamics , Pattern Recognition, Automated , Algorithms , Humans
20.
Neural Netw ; 49: 59-73, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24140985

ABSTRACT

In this paper, the problem of learning the functional dependency between input and output variables from scattered data using fractional polynomial models (FPM) is investigated. The estimation error bounds are obtained by calculating the pseudo-dimension of FPM, which is shown to be equal to that of sparse polynomial models (SPM). A linear decay of the approximation error is obtained for a class of target functions which are dense in the space of continuous functions. We derive a structural risk analogous to the Schwartz Criterion and demonstrate theoretically that the model minimizing this structural risk can achieve a favorable balance between estimation and approximation errors. An empirical model selection comparison is also performed to justify the usage of this structural risk in selecting the optimal complexity index from the data. We show that the construction of FPM can be efficiently addressed by the variable projection method. Furthermore, our empirical study implies that FPM could attain better generalization performance when compared with SPM and cubic splines.


Subject(s)
Algorithms , Artificial Intelligence , Generalization, Psychological , Computer Simulation , Least-Squares Analysis , Models, Neurological , Models, Statistical
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