Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 29
Filter
1.
Article in English | MEDLINE | ID: mdl-38922721

ABSTRACT

OBJECTIVE: Segmentation, the partitioning of patient imaging into multiple, labeled segments, has several potential clinical benefits but when performed manually is tedious and resource intensive. Automated deep learning (DL)-based segmentation methods can streamline the process. The objective of this study was to evaluate a label-efficient DL pipeline that requires only a small number of annotated scans for semantic segmentation of sinonasal structures in CT scans. STUDY DESIGN: Retrospective cohort study. SETTING: Academic institution. METHODS: Forty CT scans were used in this study including 16 scans in which the nasal septum (NS), inferior turbinate (IT), maxillary sinus (MS), and optic nerve (ON) were manually annotated using an open-source software. A label-efficient DL framework was used to train jointly on a few manually labeled scans and the remaining unlabeled scans. Quantitative analysis was then performed to obtain the number of annotated scans needed to achieve submillimeter average surface distances (ASDs). RESULTS: Our findings reveal that merely four labeled scans are necessary to achieve median submillimeter ASDs for large sinonasal structures-NS (0.96 mm), IT (0.74 mm), and MS (0.43 mm), whereas eight scans are required for smaller structures-ON (0.80 mm). CONCLUSION: We have evaluated a label-efficient pipeline for segmentation of sinonasal structures. Empirical results demonstrate that automated DL methods can achieve submillimeter accuracy using a small number of labeled CT scans. Our pipeline has the potential to improve pre-operative planning workflows, robotic- and image-guidance navigation systems, computer-assisted diagnosis, and the construction of statistical shape models to quantify population variations. LEVEL OF EVIDENCE: N/A.

2.
Food Chem X ; 22: 101351, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38623513

ABSTRACT

Katsuwonus pelamis is a tuna species mostly sold for canned fillets, its livers were lack of utilization. This study thus investigated an oil production method combining microwave (MW) pretreatment and subcritical dimethyl ether (SDME) in aim to reach improved efficiency and oil quality. The heating characteristics from different MW powers (400, 600, and 800 W) were evaluated, and SEM showed MW having hydrolysis effect on matrix lipoprotein, the fortified recovery rate was also found. Under the MW-SDME condition with 600 W power, 1:5 solid-to-liquid ratio, and 100 min, the recovery reached 93.21% in maximal (SDME ∼50%). To further improve quality, MW powers was noticed affecting lipid types, fatty acid composition, and oxidative stability of produced oils. 1286 lipid types (mostly glyceride and phospholipid-type) were identified, while higher MW lowered the emulsifying phospholipids prompting phase separation. Several oxidation indexes consistently increased with the rising MW power, GC-MS suggested 400 W for higher DHA.

3.
Article in English | MEDLINE | ID: mdl-38686594

ABSTRACT

OBJECTIVE: Obtaining automated, objective 3-dimensional (3D) models of the Eustachian tube (ET) and the internal carotid artery (ICA) from computed tomography (CT) scans could provide useful navigational and diagnostic information for ET pathologies and interventions. We aim to develop a deep learning (DL) pipeline to automatically segment the ET and ICA and use these segmentations to compute distances between these structures. STUDY DESIGN: Retrospective cohort. SETTING: Tertiary referral center. METHODS: From a database of 30 CT scans, 60 ET and ICA pairs were manually segmented and used to train an nnU-Net model, a DL segmentation framework. These segmentations were also used to develop a quantitative tool to capture the magnitude and location of the minimum distance point (MDP) between ET and ICA. Performance metrics for the nnU-Net automated segmentations were calculated via the average Hausdorff distance (AHD) and dice similarity coefficient (DSC). RESULTS: The AHD for the ET and ICA were 0.922 and 0.246 mm, respectively. Similarly, the DSC values for the ET and ICA were 0.578 and 0.884. The mean MDP from ET to ICA in the cartilaginous region was 2.6 mm (0.7-5.3 mm) and was located on average 1.9 mm caudal from the bony cartilaginous junction. CONCLUSION: This study describes the first end-to-end DL pipeline for automated ET and ICA segmentation and analyzes distances between these structures. In addition to helping to ensure the safe selection of patients for ET dilation, this method can facilitate large-scale studies exploring the relationship between ET pathologies and the 3D shape of the ET.

4.
Int J Biol Macromol ; 266(Pt 2): 131425, 2024 May.
Article in English | MEDLINE | ID: mdl-38583830

ABSTRACT

Nano-MoS2 exhibit oxidoreductase-like activities, and has been shown to effectively eliminate excessive intracellular ROS and inhibit Aß aggregation, thus demonstrating promising potential for anti-Alzheimer's disease (anti-AD) intervention. However, the low water dispersibility and high toxicity of nano-MoS2 limits its further application. In this study, we developed a chondroitin sulphate (CS)-modified MoS2 nanoenzyme (CS@MoS2) by harnessing the excellent biocompatibility of CS and the exceptional activities of nano-MoS2 to explore its potential in anti-AD research. Promisingly, CS@MoS2 significantly inhibited Aß1-40 aggregation and prevented toxic injury in SH-SY5Y cells caused by Aß1-40. In addition, CS@MoS2 protected these cells from oxidative stress damage by regulating ROS production, as well as promoting the activities of SOD and GSH-Px. CS@MoS2 also modulated the intracellular Ca2+ imbalance and downregulated Tau hyperphosphorylation by activating GSK-3ß. CS@MoS2 suppressed p-NF-κB (p65) translocation to the nucleus by inhibiting MAPK phosphorylation, and modulated the expression of downstream anti- and proinflammatory cytokines. Owing to its multifunctional activities, CS@MoS2 effectively improved spatial learning, memory, and anxiety in D-gal/AlCl3-induced AD mice. Taken together, these results indicate that CS@MoS2 has significant potential for improving the therapeutic efficacy of the prevention and treatment of AD, while also presenting a novel framework for the application of nanoenzymes.


Subject(s)
Alzheimer Disease , Chondroitin Sulfates , Disulfides , Molybdenum , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Chondroitin Sulfates/chemistry , Chondroitin Sulfates/pharmacology , Animals , Mice , Humans , Molybdenum/chemistry , Molybdenum/pharmacology , Disulfides/chemistry , Disulfides/pharmacology , Amyloid beta-Peptides/metabolism , Reactive Oxygen Species/metabolism , Oxidative Stress/drug effects , Cell Line, Tumor , Neuroprotective Agents/pharmacology , Neuroprotective Agents/chemistry , Male , Disease Models, Animal
5.
Analyst ; 149(3): 599-613, 2024 Jan 29.
Article in English | MEDLINE | ID: mdl-38221846

ABSTRACT

Nucleic acids, including DNA and RNA, have been considered as powerful and functional biomaterials owing to their programmable structure, good biocompatibility, and ease of synthesis. However, traditional nucleic acid-based probes have always suffered from inherent limitations, including restricted cell internalization efficiency and structural instability. In recent years, DNA nanotechnology has shown great promise for the applications of bioimaging and drug delivery. The attractive superiorities of DNA nanostructures, such as precise geometries, spatial addressability, and improved biostability, have enabled them to be a novel category of nucleic acid delivery systems for biomedical applications. In this review, we introduce the development of DNA nanotechnology, and highlight recent advances of DNA nanostructure-based delivery systems for cellular imaging and therapeutic applications. Finally, we propose the challenges as well as opportunities for the future development of DNA nanotechnology in biomedical research.


Subject(s)
Nanostructures , Nucleic Acids , Nanotechnology/methods , DNA/genetics , DNA/chemistry , Nanostructures/chemistry , Drug Delivery Systems
6.
Eur J Med Chem ; 257: 115478, 2023 Sep 05.
Article in English | MEDLINE | ID: mdl-37269669

ABSTRACT

The BET (bromo and extra-terminal) family proteins are epigenetic readers and master transcription coactivators, which have attracted great interests as cancer therapeutic targets. However, there are few developed labeling toolkits that can be applied for the dynamic studies of BET family proteins in living cells and tissue slices. In order to label and study the distribution of the BET family proteins in tumor cells and tumor tissues, a novel series of environment-sensitive fluorescent probes (6a-6c) were designed and evaluated for their labeling properties. Interestingly, 6a is capable of identifying tumor tissue slices and making a distinction between the tumor and normal tissues. Moreover, it can localize to the nuclear bodies in tumor slices just like BRD3 antibody. In addition, it also played an anti-tumor role through the induction of apoptosis. All these features render 6a may compatible for immunofluorescent studies and future cancer diagnosis, and guide for the discovery of new anticancer drugs.


Subject(s)
Nuclear Proteins , Transcription Factors , Nuclear Proteins/metabolism , Transcription Factors/metabolism , Cell Line, Tumor , Apoptosis , Cell Cycle Proteins/metabolism
7.
Int J Biol Macromol ; 230: 123125, 2023 Mar 01.
Article in English | MEDLINE | ID: mdl-36603725

ABSTRACT

The purpose of this study was to construct a transmembrane peptide-chondroitin sulphate­gold nanoparticle (TAT-CS@Au) delivery system and investigate its activity as an anti-Alzheimer's disease (AD) drug. We successfully prepared TAT-CS@Au nanoparticles, investigated their anti-AD effects, and explored the possible mechanisms in in vitro models. TAT-CS@Au exhibited excellent cellular uptake and transport capacity, effectively inhibited the accumulation of Aß1-40, and significantly reduced Aß1-40-induced apoptosis in SH-SY5Y cells. Furthermore, TAT-CS@Au significantly reduced oxidative stress damage and cholinergic injury induced by Aß1-40 by regulating intracellular concentrations of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and acetylcholine (ACh). Western blotting results demonstrated that TAT-CS@Au inhibited aberrant tau phosphorylation (Ser199, Thr205, Ser404, and Ser396) through GSK3ß inactivation. TAT-CS@Au decreased the levels of inflammatory factors, specifically TNF-α, IL-6, and IL-1ß, by inhibiting NF-κB nuclear translocation by activating MAPK signalling pathways. Overall, these results indicate that TAT-CS@Au exhibits excellent transmembrane ability, inhibits Aß1-40 accumulation, antagonises oxidative stress, reduces aberrant tau phosphorylation, and suppresses the expression of inflammatory factors. TAT-CS@Au may be a multi-target anti-AD drug with good cell permeability, providing new insights into the design and research of anti-AD therapeutics.


Subject(s)
Alzheimer Disease , Metal Nanoparticles , Neuroblastoma , Humans , Gold/pharmacology , Chondroitin Sulfates/pharmacology , Pharmaceutical Preparations , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Peptide Fragments/pharmacology , Peptide Fragments/metabolism , Oxidative Stress
8.
Altern Ther Health Med ; 29(2): 224-229, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36480681

ABSTRACT

Context: Helicobacter pylori (H. pylori) infection has become a global public-health problem, and people living in low-resource settings may be more likely to be infected because of unhealthy life habits, poor sanitary conditions, and overuse of antibiotics without a prescription. Objectives: The study intended to assess the susceptibility of H. pylori to nine antibiotics commonly prescribed for eradication of H. pylori infections among minority people in Yunnan province, China, to provide updated recommendations for H. pylori eradication therapy among adults. Design: The research team designed a cross-sectional observational study. Setting: The study took place in the First Affiliated Hospital of Kunming Medical University, Yunnan Province. Participants: Participants were 276 people in the Mosuo or Pumi minority population who had lived on the shores of Lugu Lake in Ninglang county, Yunnan province in China for generations. Outcome Measures: After completing a questionnaire, all participants underwent 13C-urea breath test, and those with a positive result participated in an antimicrobial-susceptibility test. For each H. pylori isolate, the research team tested the minimum inhibitory concentrations (MICs) of nine commonly used antibiotics: amoxicillin, azithromycin, levofloxacin, clarithromycin, metronidazole, tetracycline, rifampicin, gentamicin, and moxifloxacin. Results: The research team confirmed that 276 participants were resistant to at least one antibiotic. The resistances rates for moxifloxacin, metronidazole, and levofloxacin were the highest, while that for amoxicillin was the lowest, and no isolates were resistant to gentamicin. Double resistance (33.20%) had the highest proportion of all multiple-resistance patterns. Moreover, the metronidazole resistance rate was higher in females than in males and in nonsmokers than in smokers, and rifampicin resistance was higher in nondrinkers than in drinkers, suggesting that smoking and drinking might be protective against metronidazole and rifampicin resistance. Conclusions: Most of the Mosuo and Pumi people in Yunnan were resistant to antibiotics. Moxifloxacin, metronidazole, and levofloxacin should no longer be the main medicines for H. pylori, whereas amoxicillin and gentamicin should be recommended to be the first-line clinical therapy for H. pylori eradication regimens.


Subject(s)
Helicobacter Infections , Helicobacter pylori , Adult , Male , Female , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Metronidazole/pharmacology , Metronidazole/therapeutic use , Levofloxacin/pharmacology , Levofloxacin/therapeutic use , Moxifloxacin/therapeutic use , Rifampin/therapeutic use , Cross-Sectional Studies , East Asian People , Drug Resistance, Bacterial , Drug Resistance, Multiple, Bacterial , China/epidemiology , Helicobacter Infections/drug therapy , Helicobacter Infections/epidemiology , Amoxicillin/pharmacology , Amoxicillin/therapeutic use , Gentamicins
9.
Oxid Med Cell Longev ; 2022: 9466166, 2022.
Article in English | MEDLINE | ID: mdl-36411758

ABSTRACT

Previous studies have demonstrated that both CS and LiCl possess anti-Alzheimer's disease (AD) activities. We prepared chondroitin sulfate-Li (CS-Li) and investigated its effect on AD and explored the possible mechanisms both in vitro and in vivo. We found that CS-Li could inhibit amyloid ß (Aß) aggregation and protect SH-SY5Y cells from Aß 1-42-induced cytotoxicity in vitro. In D-gal and AlCl3-induced AD mouse model, CS-Li improves the spatial learning and memory abilities of AD mice, reverses the nuclear pyknosis and cell edema, and increases the survival rate of neurons in hippocampus of mice. Moreover, CS-Li significantly increased the levels of GSH-Px, Na+/K+-ATPase, and ChAT and decreased the levels of MDA and AchE in AD mice. Western blot results demonstrated that CS-Li could decrease the hyperphosphorylation of tau (Ser396/Ser404) by regulating the expression of p-GSK-3ß (Ser9) and PP2A and inhibit the expression of proinflammatory factors through inhibiting NF-κB nuclear translocation by activating the MAPK signaling pathways. In a word, CS-Li can delay AD development through multitarget processes, including Aß aggregation inhibition, oxidative stress damage, tau hyperphosphorylation, and inflammatory response, thereby improves learning and memory abilities.


Subject(s)
Amyloid beta-Peptides , Neuroblastoma , Animals , Humans , Mice , Amyloid beta-Peptides/toxicity , Amyloid beta-Peptides/metabolism , Chondroitin Sulfates , Glycogen Synthase Kinase 3 beta , Lithium , Alzheimer Disease/drug therapy , Aluminum Compounds/toxicity
10.
Int J Biol Macromol ; 182: 512-523, 2021 Jul 01.
Article in English | MEDLINE | ID: mdl-33848546

ABSTRACT

Wound dressing composed of polyelectrolyte complexes (PECs), based on chitosan/alginate/hyaluronic acid (CS/ALG/HYA) crosslinked by genipin, was prepared by freeze-dried molding. Genipin as excellent natural biological crosslinker was chose for high biocompatibility and improving mechanical properties of materials. The CS/ALG/HYA sponges (CAHSs) were characterized by FTIR, XRD, DSC and SEM. Porosity, swelling behavior and mechanical properties and in vitro degradation of CAHSs were investigated. The cytotoxicity assay was carried out on HUVEC cells in vitro and the result proves the good biocompatibility of CAHSs. Hemolysis tests indicated that the prepared CAHSs were non-hemolytic material (hemolysis ratio < 5%, no cytotoxicity). PT and aPPT coagulation tests demonstrated that CAHS2 and CAHS3 could both activate the extrinsic and intrinsic coagulation pathway and thus accelerated blood coagulation. Further, in a rat full-thickness wounds model, the CAHS2 sponge significantly facilitates wound closure compared to other groups. CAHSs exhibited adjustable physical, mechanical and biological properties. Thus, the chitosan-based polyelectrolyte composite sponges exhibit great potential as promising wound dressings.


Subject(s)
Alginates/chemistry , Biological Dressings/adverse effects , Chitosan/analogs & derivatives , Hyaluronic Acid/chemistry , Iridoids/chemistry , Polyelectrolytes/chemistry , Animals , Cross-Linking Reagents/chemistry , Female , Human Umbilical Vein Endothelial Cells/drug effects , Humans , Nanocomposites/chemistry , Rabbits , Rats , Rats, Wistar
11.
Eur J Med Chem ; 201: 112446, 2020 Sep 01.
Article in English | MEDLINE | ID: mdl-32563811

ABSTRACT

B-cell lymphoma-2 (Bcl-2) proteins family is an essential checkpoint in apoptosis. Extensive evidences suggested that overexpression of anti-apoptotic Bcl-2 proteins can be observed in multiple cancer cell lines and primary tumor biopsy samples, which is an important reason for tumor cells to evade apoptosis and further acquire drug resistance for chemotherapy. Hence, down-regulation of anti-apoptotic Bcl-2 proteins is effective for the treatment of cancers. In view that Bcl-2 inhibitors and some other anti-tumor agents, such as HDAC inhibitors and Mdm2 inhibitors, exert synergy effects in tumor cells, it is pointed out that dual-targeting therapies based on these targets are regarded as rational strategies to enhance the effectiveness of single target agents for cancer treatment. This review briefly introduces the apoptosis, the structure of Bcl-2 family proteins, and focuses on the current status and recent advances of Bcl-2 inhibitors and the corresponding SARs of them. Moreover, we discuss the synergisms between Bcl-2 and other anti-tumor targets, and summarize the current dual-target agents.


Subject(s)
Antineoplastic Agents/pharmacology , Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors , Amino Acid Sequence , Animals , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Line, Tumor , G-Quadruplexes , Histone Deacetylase Inhibitors/chemistry , Histone Deacetylase Inhibitors/pharmacology , Humans , Molecular Structure , Proto-Oncogene Proteins c-mdm2/antagonists & inhibitors , Proto-Oncogene Proteins c-myc/antagonists & inhibitors , Proto-Oncogene Proteins c-myc/genetics , Structure-Activity Relationship
12.
J Med Chem ; 63(17): 8977-9002, 2020 09 10.
Article in English | MEDLINE | ID: mdl-32320239

ABSTRACT

Histone deacetylases (HDACs) play an important role in regulating target gene expression. They have been highlighted as a novel category of anticancer targets, and their inhibition can induce apoptosis, differentiation, and growth arrest in cancer cells. In view of the fact that HDAC inhibitors and other antitumor agents, such as BET inhibitors, topoisomerase inhibitors, and RTK pathway inhibitors, exert a synergistic effect on cellular processes in cancer cells, the combined inhibition of two targets is regarded as a rational strategy to improve the effectiveness of these single-target drugs for cancer treatment. In this review, we discuss the theoretical basis for designing HDAC-involved dual-target drugs and provide insight into the structure-activity relationships of these dual-target agents.


Subject(s)
Antineoplastic Agents/chemistry , Histone Deacetylase Inhibitors/chemistry , Histone Deacetylases/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , DNA Damage/drug effects , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylase Inhibitors/therapeutic use , Histone Deacetylases/chemistry , Humans , Neoplasms/drug therapy , Protein Kinases/chemistry , Protein Kinases/metabolism , Protein Kinases/pharmacology , Proteins/antagonists & inhibitors , Proteins/metabolism , Structure-Activity Relationship , Topoisomerase Inhibitors/chemistry , Topoisomerase Inhibitors/pharmacology , Topoisomerase Inhibitors/therapeutic use
13.
Int J Biol Macromol ; 154: 233-245, 2020 Jul 01.
Article in English | MEDLINE | ID: mdl-32171837

ABSTRACT

In this study, the effect of chondroitin sulphate nano-selenium (CS@Se) on Alzheimer's disease (AD) in mice was investigated. CS@Se alleviated anxiety and improved the spatial learning and memory impairment in AD mice. CS@Se significantly reduced cell oedema and pyknosis, protected the mitochondria, and improved abnormal changes in the ultrastructure of hippocampal neuron synapses of AD mice. Moreover, CS@Se significantly increased the levels of superoxide dismutase(SOD), glutathione peroxidase (GSH-Px), Na+/K+-ATPase assay (Na+/K+-ATPase) and acetyltransferase (ChAT), and decreased the levels of malondialdehyde (MDA) and acetylcholinesterase (ChAE) in AD mice. Western blot results showed that CS@Se can attenuate excessive phosphorylation of tau (Ser396/Ser404) by regulating the expression of glycogen synthase kinase-3 beta (GSK-3ß). In addition, CS@Se can activate the extracellular signal-regulated kinase 1/2 (ERK 1/2) and p38 mitogen-activated protein kinase (p38 MAPK) signalling pathways to inhibit nuclear transcription factor kappa B (NF-κB) nuclear translocation, thereby regulating the expression of pro-inflammatory cytokines. In summary, CS@Se can reduce oxidative stress damage, inhibit excessive tau phosphorylation, reduce inflammation to delay AD development, and increase the learning and memory capacities of AD mice.


Subject(s)
Alzheimer Disease/drug therapy , Chondroitin Sulfates/therapeutic use , Hippocampus/drug effects , Neurons/drug effects , Selenium/therapeutic use , Animals , Hippocampus/pathology , Male , Memory/drug effects , Mice , Mice, Inbred C57BL , Nanoparticles/chemistry , Neurons/pathology , Oxidative Stress/drug effects , Spatial Learning/drug effects
14.
Biomed Res Int ; 2020: 1693602, 2020.
Article in English | MEDLINE | ID: mdl-32104676

ABSTRACT

Salbutamol (SBAL), a kind of short-acting beta 2-adrenergic agonist, has been mainly used to treat bronchial asthma and other allergic airway diseases clinically. In this study, the interaction mechanism between salbutamol and human serum albumin was researched by the multispectral method and molecular docking. The fluorescence intensity of HSA could be regularly enhanced with the increase of SBAL concentration. Both the results of the multispectral method and molecular docking showed that SBAL could bind HSA with van der Waals force and hydrogen bonds. The binding mechanism was further analysed by UV-Vis and synchronous fluorescence spectra. The contents of the secondary structure of free HSA and SBAL-HSA complex were evaluated using CD spectra.


Subject(s)
Adrenergic beta-2 Receptor Agonists/chemistry , Albuterol/chemistry , Molecular Docking Simulation , Serum Albumin, Human/chemistry , Adrenergic beta-2 Receptor Agonists/therapeutic use , Albuterol/therapeutic use , Asthma/drug therapy , Humans , Receptors, Adrenergic, beta-2/chemistry , Receptors, Adrenergic, beta-2/drug effects
15.
Int J Biol Macromol ; 142: 265-276, 2020 Jan 01.
Article in English | MEDLINE | ID: mdl-31593732

ABSTRACT

The purpose of this study was to ascertain the effect of selenium-chondroitin sulfate nanoparticles (CS@Se) on multi-target-directed therapy for the treatment of Alzheimer's disease (AD). CS@Se nanoparticles were successfully synthesized, and their therapeutic effects were studied in in vitro AD models. CS@Se effectively inhibited amyloid-ß (Aß) aggregation and protected SH-SY5Y cells from Aß1-42-induced cytotoxicity. Moreover, CS@Se significantly decreased okadaic acid-induced actin cytoskeleton instability in SH-SY5Y cells. In addition, CS@Se decreased the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and increased the levels of glutathione peroxidase (GSH-Px). The Western blot results indicated that CS@Se attenuated the hyperphosphorylation of tau (Ser396/Ser404) by regulating the expression of GSK-3ß. In summary, this study demonstrated that CS@Se could inhibit the aggregation of Aß, reduce damage to the cytoskeleton, mitigate oxidative stress and attenuate the hyperphosphorylation of tau protein. CS@Se might be a potent multi-functional agent for the treatment of AD and thus warrants further research and evaluation.


Subject(s)
Chondroitin Sulfates , Drug Discovery , Metal Nanoparticles , Selenium , Alzheimer Disease , Amyloid/antagonists & inhibitors , Amyloid/chemistry , Amyloid/ultrastructure , Amyloid beta-Peptides/chemistry , Amyloid beta-Peptides/metabolism , Cell Line, Tumor , Cell Survival/drug effects , Chemical Phenomena , Chondroitin Sulfates/chemistry , Glutathione/metabolism , Humans , Metal Nanoparticles/chemistry , Metal Nanoparticles/ultrastructure , Molecular Targeted Therapy , Oxidation-Reduction/drug effects , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , Selenium/chemistry , Spectrum Analysis
16.
Carbohydr Polym ; 213: 17-26, 2019 Jun 01.
Article in English | MEDLINE | ID: mdl-30879657

ABSTRACT

The purpose of this study was to ascertain the effect of chondroitin sulphate-modified doxorubicin (Dox) nanoparticles on enhancing the tumour-targeting effect and tumour growth inhibition effect of doxorubicin both in vitro and in vivo. The chondroitin sulphate-doxorubicin conjugate and its poly(lactic-co-glycolic acid) (PLGA) nanoparticles (CS-Dox-PLGA) were successfully synthesised, and then characterized by Fourier-transform infrared spectroscopy (FTIR), proton magnetic resonance (1HNMR), thermogravimetric analysis/differential scanning calorimetry (TGA/DSC), transmission electron microscope (TEM), zeta potential and laser light scattering. Taking advantage of the enhanced permeability and CD44-mediated endocytosis, CS-Dox-PLGA showed excellent capacity for penetrating the peripheral tumour barrier and into the nucleus of tumour cells. The CS-Dox-PLGA cellular uptake was improved and exhibited a significantly higher level of cytotoxicity in U251 cells. After intravenous administration, the CS-Dox-PLGA showed good pharmacokinetic properties and excellent U251-induced tumour inhibition with low cardiac toxicity. Therefore, CS-Dox-PLGA with low cardiac toxicity and good anti-tumour ability might be a better choice for Dox in clinical practice.


Subject(s)
Antineoplastic Agents/pharmacology , Chondroitin Sulfates/pharmacology , Doxorubicin/pharmacology , Glioma/drug therapy , Hyaluronan Receptors/antagonists & inhibitors , Nanoparticles/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Chondroitin Sulfates/chemistry , Doxorubicin/chemistry , Drug Screening Assays, Antitumor , Endocytosis/drug effects , Glioma/metabolism , Glioma/pathology , Humans , Hyaluronan Receptors/metabolism , Mice , Mice, Inbred Strains , Molecular Structure , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/metabolism , Neoplasms, Experimental/pathology , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Tumor Cells, Cultured
17.
Biomed Pharmacother ; 107: 1523-1529, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30257370

ABSTRACT

6-Gingerol, the major component of gingerols extracted from Zingiber officinale, has been shown to exhibit anti-inflammatory and antioxidant bioactivities. Since neuroinflammation plays an important role in neurodegenerative diseases, such as Alzheimer's disease (AD), and astrocytes have been considered important in the process of neurodegeneration, it was of interest to know whether 6-gingerol reduced astrocytes activation or even attenuated cognitive impairment. Here we examined the neuroprotective effects of 6-gingerol in lipopolysaccharide (LPS)-induced disorder models both in vitro and in vivo. C6 astroglioma cells treated with LPS were found to release excessive pro-inflammatory cytokines, including TNF-α and IL-6, and also increase intercellular ROS, NO, and iNOS (i.e. NOS2). All these were blocked by 6-gingerol in a concentration-dependent manner. The spatial learning and memory of rats challenged with LPS (10 µg, i.c.v.) in the absence or presence of 6-gingerol were evaluated using the Morris water-maze (MWM) test. 6-Gingerol attenuated LPS-induced imapirement of MWM learning and memory in a dose-dependent manner. Besides, 6-gingerol inhibited LPS-induced increases in levels of GFAP and TNF-α in the rat brain. The results suggest that 6-gingerol suppresses astrocyte overactivation, through which it contributes to improvement of cognitive ability.


Subject(s)
Astrocytes/drug effects , Catechols/pharmacology , Cognitive Dysfunction/drug therapy , Fatty Alcohols/pharmacology , Neuroprotective Agents/pharmacology , Animals , Astrocytes/pathology , Catechols/administration & dosage , Cognitive Dysfunction/physiopathology , Cytokines/metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , Fatty Alcohols/administration & dosage , Glial Fibrillary Acidic Protein/metabolism , Inflammation/drug therapy , Inflammation/pathology , Inflammation Mediators/metabolism , Lipopolysaccharides/toxicity , Male , Maze Learning/drug effects , Memory/drug effects , Memory Disorders/drug therapy , Memory Disorders/physiopathology , Neurodegenerative Diseases/drug therapy , Neurodegenerative Diseases/physiopathology , Neuroprotective Agents/administration & dosage , Rats , Rats, Sprague-Dawley
18.
Oncol Lett ; 12(5): 3695-3700, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27900056

ABSTRACT

Understanding the role and mechanism of signaling pathways including Notch and Wnt in colorectal carcinogenesis is critical to the development of novel therapeutics. In the present study, we analyzed the cell proliferation, migration, G2/M percentage and the expression of molecules of signaling pathways in HCT-116 cells through the inhibition of Wnt and Notch pathways, and also investigated the effect of inhibitors of Wnt and Notch pathways on tumor growth in a transplantation tumor model. We observed that rDDK-1 (an inhibitor of the Wnt signaling pathway) and LY374973 (an inhibitor of the Notch signaling pathway) synergistically inhibited the proliferation, migration and G2/M percentage of HCT-116 cell lines, and could further synergistically inhibit the tumor volume and weight in the transplantation tumor model. In the cell line and the transplantation tumor model, rDDK-1 and LY374973 further synergistically inhibited the expression level of all detected Wnt and Notch pathway genes. Our results may pave the way for using inhibitors of Wnt and Notch signaling pathways together to treat colorectal cancer.

19.
Biochim Biophys Acta ; 1860(11 Pt A): 2589-2597, 2016 11.
Article in English | MEDLINE | ID: mdl-27491336

ABSTRACT

METHODS: 8-week-age male ApoE(-/-) mice were fed with the atherogenic diet together with or without tested compounds (rosuvastatin calcium, α-LNA-LMWCS, LMWCS and α-LNA) for 16 weeks. When the animals were killed, blood plasma was isolated to test the level of TC, LDL-C, TNF-α, IL-6 and CRP by biochemistry analysis and ELISA method. The whole aorta and aortic root sections were also collected to study atherogenesis level and reveal the possible mechanism by histological examination, real-time PCR and Western blot analysis. RESULTS: The level of TC, LDL-C, TNF-α, IL-6 and CRP in plasma in H-LNA-LMWCS group were significantly lower than those of the control group (rosuvastatin calcium). Plaques in H-LNA-LMWCS group showed higher content of smooth muscle cells, lower content of lipid and macrophages, and lower mRNA levels of TNF-α, IL-6, CRP, MCP-1, VCAM-1 and ICAM-1 than those in the control group. In addition, α-LNA-LMWCS could reduce the nuclear translocation of NF-κB, inhibit expressions of p-ERK1/2, p-p38, MCP-1, VCAM-1 and ICAM-1 in mice aorta. CONCLUSION: α-LNA-LMWCS exhibited anti-atherosclerosis effect through regulating the lipid metabolism and diminishing the synthesis of pro-inflammatory cytokines. The possible mechanism may be that α-LNA-LMWCS could influence MAPK/ NF-κB related signal pathway. GENERAL SIGNIFICANCE: The results may provide significant suggestions for the application of α-LNA-LMWCS in anti-atherosclerosis.


Subject(s)
Apolipoproteins E/genetics , Atherosclerosis/drug therapy , Chondroitin Sulfates/therapeutic use , Animals , Aorta/drug effects , Aorta/metabolism , Aorta/pathology , Atherosclerosis/genetics , Chemokine CCL2/metabolism , Chondroitin Sulfates/administration & dosage , Chondroitin Sulfates/pharmacology , Cytokines/metabolism , Intercellular Adhesion Molecule-1/metabolism , Linolenic Acids/chemistry , MAP Kinase Signaling System , Male , Mice , NF-kappa B/metabolism , Vascular Cell Adhesion Molecule-1/metabolism
20.
PLoS One ; 9(2): e88822, 2014.
Article in English | MEDLINE | ID: mdl-24533153

ABSTRACT

BACKGROUND AND AIMS: The morbidity of ulcerative colitis (UC) is increasing in China every year. In addition, there is a lack of accurate diagnostic indices with which to evaluate the activity of the disease. The aim of this study was to identify UC-associated proteins as biomarkers for the diagnosis, and objective assessment of disease activity. METHODS: Differential expression of serum proteins from UC patients compared to normal controls was analyzed by two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS). The expression of heat shock factor 2(HSF2)in colonic mucosa in Crohn's disease, Behcet's disease, ulcerative colitis, intestinal tuberculosis, infective enteritis, intestinal lymphoma, and normal controls was investigated by immunohistochemistry (IHC). The expression of the HSF2 in colonic mucosa of UC subjects with varying severity of disease was measured by real time-PCR and Western Blots. The expression of HSF2 was inhibited by HSF2 small interfering RNA (siRNA) transfection in Caco-2 cells. The concentrations of HSF2, IL-1ß, and TNF-α in serum and IL-1ß, and TNF-α in the supernatants of transfected Caco-2 cells were determined by ELISA. RESULTS: HSF2 was differentially expressed in UC patients compared to normal controls. HSF2 expression was significantly higher in the intestinal mucosa of UC patients compared to other six groups. The results of immunohistochemistry, real time-PCR, Western Blots, and ELISA showed that the expression of HSF2 increased in parallel with the severity of UC. The serum concentration of HSF2 also positively correlated with levels of IL-1ß and TNF-α. After down-regulation expression of HSF2 in Caco-2 cells by RNA interference, the productions of IL-1ß and TNF-α stimulated by lipopolysaccharide (LPS) increased dramatically. CONCLUSIONS: HSF2 appears to be a potential novel molecular marker for UC activity, and may provide a basis for studies on the pathogenesis and novel therapeutic targets for UC.


Subject(s)
Colitis, Ulcerative/blood , Colitis, Ulcerative/genetics , Gene Expression Profiling , Heat-Shock Proteins/blood , Heat-Shock Proteins/genetics , Transcription Factors/blood , Transcription Factors/genetics , Adult , Behcet Syndrome/metabolism , Biomarkers/blood , Biomarkers/metabolism , Case-Control Studies , Colon/metabolism , Crohn Disease/metabolism , Enteritis/metabolism , Female , Humans , Interleukin-1beta/metabolism , Intestinal Mucosa/metabolism , Lymphoma/metabolism , Male , Middle Aged , Transcription, Genetic , Tuberculosis/metabolism , Tumor Necrosis Factor-alpha/metabolism , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL
...