Dysregulated microRNAs in prostate cancer: In silico prediction and in vitro validation.

Objectives: MicroRNAs, which are micro-coordinators of gene expression, have been recently investigated as a potential treatment for cancer. The study used computational techniques to identify microRNAs that could target a set of genes simultaneously. Due to their multi-target-directed nature, microRNAs have the potential to impact multiple key pathways and their pathogenic cross-talk. Materials and Methods: We identified microRNAs that target a prostate cancer-associated gene set using integrated bioinformatics analyses and experimental validation. The candidate gene set included genes targeted by clinically approved prostate cancer medications. We used STRING, GO, and KEGG web tools to confirm gene-gene interactions and their clinical significance. Then, we employed integrated predicted and validated bioinformatics approaches to retrieve hsa-miR-124-3p, 16-5p, and 27a-3p as the top three relevant microRNAs. KEGG and DIANA-miRPath showed the related pathways for the candidate genes and microRNAs. Results: The Real-time PCR results showed that miR-16-5p simultaneously down-regulated all genes significantly except for PIK3CA/CB in LNCaP; miR-27a-3p simultaneously down-regulated all genes significantly, excluding MET in LNCaP and PIK3CA in PC-3; and miR-124-3p could not down-regulate significantly PIK3CB, MET, and FGFR4 in LNCaP and FGFR4 in PC-3. Finally, we used a cell cycle assay to show significant G0/G1 arrest by transfecting miR-124-3p in LNCaP and miR-16-5p in both cell lines. Conclusion: Our findings suggest that this novel approach may have therapeutic benefits and these predicted microRNAs could effectively target the candidate genes.

Synthesis and evaluation of gene delivery vectors based on PEI-modified metal-organic framework (MOF) nanoparticles.

Objectives: Zirconium-based metal-organic frameworks (MOFs) nanostructures, due to their capability of easy surface modification, are considered interesting structures for delivery. In the present study, the surfaces of UIO-66 and NH2-UIO-66 MOFs were modified by polyethyleneimine (PEI) 10000 Da, and their efficiency for plasmid delivery was evaluated. Materials and Methods: Two different approaches, were employed to prepare surface-modified nanoparticles. The physicochemical characteristics of the resulting nanoparticles, as well as their transfection efficiency and cytotoxicity, were investigated on the A549 cell line. Results: The sizes of DNA/nanocarriers for PEI-modified UIO-66 (PEI-UIO-66) were between 212-291 nm and 267-321 nm for PEI 6-bromohexanoic acid linked UIO-66 (PEI-HEX-UIO-66). The zeta potential of all was positive with the ranges of +16 to +20 mV and +23 to +26 mV for PEI-UIO-66 and PEI-HEX-UIO-66, respectively. Cellular assay results showed that the PEI linking method had a higher rate of gene transfection efficiency with minimal cytotoxicity than the wet impregnation method. The difference between transfection of modified nanoparticles compared to the PEI 10 kDa was not significant but the PEI-HEX-UIO-66 showed less cytotoxicity. Conclusion: The present study suggested that the post-synthetic modification of MOFs with PEI 10000 Da through EDC/NHS+6-bromohexanoic acid reaction can be considered as an effective approach for modifying MOFs' structure in order to obtain nanoparticles with better biological function in the gene delivery process.

Design and characterization of adipose-derived mesenchymal stem cell loaded alginate/pullulan/hyaluronic acid hydrogel scaffold for wound healing applications.

Recently, significant attention has been focused on the progression of skin equivalents to facilitate faster wound healing and thereby skin restoration. The main aim of this study was the design and characterization of a novel polysaccharide-based hydrogel scaffold by using alginate, pullulan, and hyaluronic acid polymers to provide an appropriate microenvironment to deliver Adipose-derived mesenchymal Stem Cells (ASC) in order to promote wound healing in an animal model. Characterization of synthesized hydrogel was done by using a field emission scanning electron microscope (FE-SEM), Fourier Transform-Infrared spectroscopy (FT-IR), and Differential Scanning Calorimetry (DSC). Also, contact angle analysis, the swelling and mechanical tests were performed. As a result of in vitro studies, cells can be attached, alive, and migrate through the prepared hydrogel scaffold. Finally, the therapeutic effect of the cell-seeded hydrogels was tested in the full-thickness animal wound model. Based on obtained results, the hydrogel-ASC treatment improved the healing process and accelerated wound closure.

Selective Cellular Uptake and Cytotoxicity of Curcumin-encapsulated SPC and HSPC Liposome Nanoparticles on Human Bladder Cancer Cells.

BACKGROUND: Curcumin is a main bioactive constituent of turmeric (Curcuma longa L.) with pleiotropic health beneficial effects. However, poor bioavailability is the major barrier to the efficient pharmacological effects of curcumin in humans. AIMS: The present study aimed to develop liposome formulations based on soybean phosphatidylcholine (SPC) and hydrogenated SPC (HSPC) to enhance the bioavailability of curcumin in bladder cancer cells. METHODS: Curcumin was encapsulated in HSPC and SPC liposome nanoparticles using the solvent evaporation method. Physical properties, encapsulation efficiency (%), stability, and in vitro drug release of the prepared liposome formulations have been evaluated. The cellular uptake and cytotoxicity of curcumin-encapsulated nanoliposomes on bladder carcinoma HTB9 cell line and normal fibroblast L929 cell line were studied. DNA fragmentation, apoptosis, and genotoxicity assessments have been carried out to determine the molecular mechanisms underlying the cytotoxic effects of liposomal curcumin formulations on bladder cancer cells. RESULTS: The results indicated that curcumin could be efficiently encapsulated in the HSPC and SPC liposome formulations. The liposomal curcumin formulations have shown shelf-life stability for 14 weeks at 4°C. The accelerated stability testing showed that curcumin encapsulated in nanoliposomes was significantly (p < 0.001) more stable than free curcumin at various pH degrees ranging from alkaline to acidic pH. The in vitro drug release study showed curcumin to be sustainably released from the liposome nanoparticles. Of note, SPC and HSPC nanoliposome formulations significantly increased the cellular uptake and cytotoxicity of curcumin on bladder cancer HTB9 cells. Mechanistically, liposomal curcumin was found to exert a selective inhibitory effect on the viability of cancer cells by inducing apoptosis and DNA damage. CONCLUSION: In conclusion, SPC and HSPC liposome nanoparticles can significantly increase the stability and bioavailability of curcumin, which are important for improving its pharmacological effect.

A new molecularly imprinted polymer electrochemical sensor based on CuCo2 O4 /N-doped CNTs/P-doped GO nanocomposite for detection of 25-hydroxyvitamin D3 in serum samples.

25-Hydroxyvitamin D3 as a main circulating metabolite of vitamin D is usually measured in serum to evaluate the vitamin D status of humans. So, developing an accessible, fast response, sensitive, and selective detection method for 25-hydroxyvitamin D3 is highly important. In this study, we designed a sensitive and selective electrochemical sensor based on the modification of glassy carbon electrode by nanocomposite of CuCo2 O4 /nitrogen-doped carbon nanotubes and phosphorus-doped graphene oxide. Then 25-hydroxyvitamin D3 -imprinted polypyrrole was coated on the electrode surface through electropolymerization. Moreover, ferricyanide was used as a mediator for the creation of a readable signal, which was considerably decreased after rebinding of 25-hydroxyvitamin D3 on the electrode. The proposed sensor successfully detected 25-hydroxyvitamin D3 in the range of 0.002-10 µM, with a detection limit of 0.38 nM, which was highly lower than deficiency concentration (20 ng/ml; 49.92 nM). Finally, the proposed sensor was checked for detection of 25-hydroxyvitamin D3 in serum samples with recovery in the range of 80%-106.42%. The results demonstrated the applicability of the designed sensor for the detection of 25-hydroxyvitamin D3 in biological samples.

Development of Lateral Flow Assays for Rapid Detection of Troponin I: A Review.

Troponin I as a particular and major biomarker of cardiac failure is released to blood demonstrating hurt of myocardial cells. Unfortunately, troponin I detection in the first hours of acute myocardial infarction usually faces with most negligence. Therefore, developments of point of care devices such as lateral flow strips are highly required for timely diagnosis and prognosis. Lateral flow assays are low-cost paper-based detection platforms relying on specific diagnostic agents such as aptamers and antibodies for a rapid, selective, quantitative and semi-quantitative detection of the analyte in a complex mixture. Moreover, lateral flow assay devices are portable, and their simplicity of use eliminates the need for experts or any complicated equipment to operate and interpret the test results. Additionally, by coupling the lateral flow assay technology with nanotechnology, for labeling and signal amplification, many breakthroughs in the field of diagnostics have been achieved. The present study reviews the use of lateral flow assays in early stage, quantitative, and sensitive detection of cardiac troponin I and mainly focuses on the structure of each type of developed lateral flow assays. Finally, this review summarized the improvements, detection time, and limit of detection of each study as well as the advantages and disadvantages.

An overview of polyallylamine applications in gene delivery.

A chief objective of gene transportation studies is to manipulate clinically accepted carriers that can be utilized to combat incurable diseases. Despite various strategies, efficiency and application of these vectors have been hindered, owing to different obstacles. Polyallylamine (PAA) is a synthetic water-soluble, weak base cationic polymer with different properties that could be administrated as an ideal candidate for biomedical applications such as gene delivery, drug delivery, or even tissue engineering. However, some intrinsic properties of this polymer limit its application. The two associated problems with the use of PAA in gene delivery are low transfection efficiency (because of low buffering capacity) and cytotoxic effects attributed to intense cationic character. Most of the strategies for structural modification of the PAA structure have focused on introducing hydrophobic groups to the polymeric backbone that target both cytotoxicity and transfection. In this perspective, we concentrate on PAA as a gene delivery vehicle and the existing approaches for modification of this cationic polymer to give insight to researchers for exploitation of PAA as an efficient carrier in biomedical applications.

Synthesis and characterization of polyethyleneimine-terminated poly(ß-amino esters) conjugated with pullulan for gene delivery.

Cationic polymers endowed with a flexible system for condensing DNA, are regarded as effective materials for gene delivery. The synthesis of poly(ß-amino esters) (pBAEs) based on 1,4-butanediol diacrylate-ethanolamine monomer (1.2:1 molar ratio) and 1,4-butanediol diacrylate-ethylene diamine (1:2 molar ratio) was carried out and modification with 1800 Da polyethyleneimine (PEI) at different weight ratios (3 and 1) as well as conjugation with pullulan in various weight ratios of (0.0625, 0.125, 0.25, and 1) was performed. Gel-retardation assay demonstrated that the synthesized polymers were able to condense DNA at low carrier/plasmid (C/P) ratios. The polyplexes with ratio 3 of PEI (pß1/PEI3) were restricted in all C/P ratios and the polyplexes of pß1/PEI3/pull0.125 were condensed at C/P ratios higher than 0.5. The particle size at C/P was approximately about 200 nm with a positive surface charge. The presence of the pullulan in the structure of the synthesized pBAEs could be effective in reducing toxicity of the base polymer. Highest metabolic activity was dedicated to C/P2 of pß2/PEI3/pull0.125 with 80.6% viability. Furthermore, the most efficient gene reporter delivery was seen at C/P ratio of 6 in pß2/PEI3/pull0.125 nanoparticles. Therefore, pullulan grafting could enhance the cellular response of cells in terms of cytotoxicity and transfection efficiency.

Preparation and Characterization of Platelet Lysate (Pl)-Loaded Electrospun Nanofibers for Epidermal Wound Healing.

Skin defects are among the most prevalent and serious problems worldwide; it is necessary to provide appropriate coverage in order to reduce possible mortality risk and accelerate wound healing. In this study, we have designed a series of extracellular matrix (ECM)-mimicking nanofibrous scaffolds composed of both natural (gelatin (GEL) and chitosan (CS)) and synthetic (poly(ε-caprolactone) (PCL) and poly (vinyl alcohol) (PVA)) polymers. The 3D constructs (PCL/GEL-PVA/CS) were reinforced with 5% (w/w) of platelet lysate (PL) for promoting cells viability and mobility. The physicochemical characterizations of nanofibers confirmed suitable hydrophilicity, controlled degradability, and water uptake of 250.31 ± 62.74%, and 222.425 ± 86.37% for the PCL/GEL-PVA/CS and PCL/GEL-PVA/CS + PL nanofibers, respectively. The scanning electron microscopy (SEM) images exhibited the mean diameter of the fabricated fibers (PCL/GEL-PVA/CS) in the range of 454 ± 257 nm. The blended samples (PCL/GEL-PVA/CS) were also confirmed to have higher ultimate tensile stress (UTS) (3.71 ± 0.32 MPa). From a biological point of view, the fabricated scaffolds showed appropriate blood compatibility and great potential to avoid bacterial invasion. Altogether, the tailored fabrication of PCL/GEL-PVA/CS nanofibers may be considered a suitable construct for epidermal wound healing.

Application of a transition metal oxide/carbon-based nanocomposite for designing a molecularly imprinted poly (l-cysteine) electrochemical sensor for curcumin.

In this study an electrochemical sensor was fabricated for detection of curcumin, as a functional herbal food, using molecularly imprinted polymer and highly conductive transition metal oxide/carbon-based nanocomposite. In this way, CuCo2O4/nitrogen-doped carbon nanotubes/phosphorus-doped graphene oxide nanocomposite was dropped on the electrode. This nanocomposite synergically possesses conductivity features of copper and phosphorus-doping sites, specific surface area of carbon nanotubes, and carbons Fermi level of graphene oxide. In the following, l-Cystein electropolymerized on the electrode in presence of curcumin. The sensor was produced by removing curcumin from poly (L- cystein) matrix. The sensor was successfully used for detection of curcumin in the ranges of 0.1-1 µmol L-1 and 1-30 µmol L-1, with acceptable detection limit (30 nmol L-1). Finally, the proposed method was used for detection of curcumin in serum samples with recoveries of 80-110.87%. The results demonstrated that aforementioned method can be used for detection of curcumin in biological samples.

Characterization and Evaluation of Cell-Penetrating Activity of Brevinin-2R: An Amphibian Skin Antimicrobial Peptide.

Natural peptides have been the source of some important tools to address challenges in protein therapy of diseases. Bypassing cell plasma membrane has been a bottleneck in the intracellular delivery of biomolecules. Among others, cell-penetrating peptides (CPPs) provide an efficient strategy for intracellular delivery of various cargos. Brevinin-2R peptide is an antimicrobial peptide isolated from the skin secretions of marsh frog, Rana ridibunda with semi-selective anticancer properties. Here, we investigated cell-penetrating properties of Brevinin-2R peptide and its ability to deliver functional protein cargos. Bioinformatics studies showed that Brevinin-2R is a cationic peptide with a net charge of + 5 with an alpha-helix structure and a heptameric ring at the carboxylic terminal due to disulfide bond between C19 and C25 amino acids and a hinge region at A10. To evaluate the ability of this peptide as a CPP, ß-galactosidase protein and GFP were transfected into HeLa cells. The entry pathway of the peptide/protein complex into the cell was investigated by inhibiting endocytic pathways at 4 °C. It was observed that Brevinin-2R can efficiently transfer ß-galactosidase and GFP with 21% and 90% efficacy, respectively. Brevinin-2R opts for endocytosis pathways to enter cells. The cytotoxicity of this peptide against HeLa cells was studied using MTT assay. The results showed that at the concentration of 131.5 µg/ml of Brevinin-2R peptide, the proliferation of 50% of HeLa cells was inhibited. The results of this study suggest that Brevinin-2R peptide can act as a CPP of natural origin and low cytotoxicity.

Ellagic acid as a potent anticancer drug: A comprehensive review on in vitro, in vivo, in silico, and drug delivery studies.

Ellagic acid as a polyphenol or micronutrient, which can be naturally found in different vegetables and fruits, has gained considerable attention for cancer therapy due to considerable biological activities and different molecular targets. Ellagic acid with low hydrolysis and lipophilic and hydrophobic nature is not able to be absorbed in circulation. So, accumulation inside the intestinal epithelial cells or metabolization to other urolithins leads to the limitation of direct evaluation of EA effects in clinical studies. This review focuses on the studies which supported anticancer activity of pure or fruit-extracted ellagic acid through in vitro, in vivo, in silico, and drug delivery methods. The results demonstrate ellagic acid modulates the expression of various genes incorporated in the cancer-related process of apoptosis and proliferation, inflammation related-gens, and oxidative-related genes. Moreover, the ellagic acid formulation in carriers composed of lipid, silica, chitosan, iron- bovine serum albumin nanoparticles obviously enhanced the stable release and confident delivery with minimum loss. Also, in silico analysis proved that ellagic acid was able to be placed at a position of cocrystal ADP, in the deep cavity of the protein target, and tightly interact with binding pocket residues leading to suppression of substrate availability of protein and its activation inhibition.

Biosensors based on aptamer-conjugated gold nanoparticles: A review.

Simply synthetized gold nanoparticles have been highly used in medicine and biotechnology as a result of their biocompatibility, conductivity, and being easily functionalized with biomolecules such as aptamer. Aptamer-conjugated gold nanoparticle structures synergically possess characteristics of both aptamer and gold nanoparticles including high binding affinity, high biocompatibility, enhanced target selectivity, and long circulatory half-life. Aptamer-conjugated gold nanoparticles have extensively gained considerable attention for designing of biosensing systems due to their interesting optical and electrochemical features. Moreover, biosensors based on aptamer-gold nanoparticles are easy to use, with fast response, and inexpensive which make them ideal in individualized medicine, disease markers detection, food safety, and so forth. Moreover, due to high selectivity and biocompatibility of aptamer-gold nanoparticles, these biosensing platforms are ideal tools for targeted drug delivery systems. The application of this nanostructure as diagnostic and therapeutic tool has been developed for detection of cancer in the early stage by detecting cancer biomarkers, pathogens, proteins, toxins, antibiotics, adenosine triphosphate, and other small molecules. This review obviously demonstrates that this nanostructure effectively is applicable in the field of biomedicine and possesses potential of commercialization aims.

A Critical Systematic Review of Developing Aptasensors for Diagnosis and Detection of Diabetes Biomarkers.

Diabetes mellitus is known as an epidemic problem of public health in worldwide. According to the reports of International Diabetes Federation, the global number of diabetic adults has been growing annually. Unfortunately, millions of diabetes cases may remain undiagnosed every year. Unfortunately, the glucose level of blood can be fluctuated by lifestyle. So, development of reliable, simple and fast response diagnostic methods is urgently required. Aptamer-based sensors have been recently developed as a sensitive and fast method for the diagnosis and detection of diabetes. We systematically checked the scientific literature including studies related to aptasensors as a diagnostic tool for diabetes. Many electronic databases such as Google Scholar, Scopus, PubMed and Science Direct were searched up to 2020. The present study obviously demonstrates important and unavoidable role of aptasensors as a potential technique for the diagnosis of diabetes. Different aptasenosrs such as optical, mass-related, microfluidic, and electrochemical aptasenors were successfully designed for diagnosis of diabetic biomarkers in desired range which is necessary for diagnosis or pre-diagnosis of diabetes. Although the introduced aptasensors were interestingly useful for detection of biomarkers in biological samples, but some defects may limit the incorporation of aptasensors, especially optical, mass-related, and microfluidic types, and lateral flow strips with point-of-care test (POCT) method which is necessary for self-controlling the diabetes. The results obviously demonstrate that electrochemical aptasensors, specially label-free types, due to the unbelievable sensitivity and easy to fabrication can be a promising methods for designing the POCT chips to diagnosis the diabetic biomarkers.

Biosensors, microfluidics systems and lateral flow assays for circulating microRNA detection: A review.

MicroRNAs (miRNAs) are short RNA sequences found in eukaryotic cells and they are involved in several diseases pathogenesis including different types of cancers, metabolic and cardiovascular disorders. Thus, miRNAs circulating in serum, plasma, and other body fluids are employed as biomarkers for diagnostic and prognostic purposes and in assessment of drug response. Thus, various methods have been developed for detection of miRNAs including northern blotting, reverse transcriptase polymerase chain reaction (RT-PCR), next-generation sequencing, microarray, and isothermal amplification that are recognized as traditional methods. Considering the importance of early diagnosis and treatment of miRNAs-related diseases, development of simple, one-step, sensitive methods is of great interest. Nowadays developing technologies including lateral flow assay, biosensors (optical and electrochemical) and microfluidic systems which are simple fast responding, user-friendly, and are enabled with visible detection have gained considerable attention. This review briefly discusses miRNAs detection' methods, with a particular focus on lateral flow assay, biosensors, and microfluidic systems as novel and practical procedures.

Potential SARS-CoV-2 vaccines: Concept, progress, and challenges.

Since September 2020, the world has had more than 28 million cases of coronavirus disease 2019 (COVID-19). Many countries are facing a second wave of the COVID-19 outbreak. A pressing need is evident for the development of a potent vaccine to control the SARS-CoV-2. Institutions and companies in many countries have announced their vaccine research programs and progress against the COVID-19. While most vaccines go through the designation and preparation stages, some of them are under evaluation for efficacy among animal models and clinical trials, and three approved vaccine candidates have been introduced for limited exploitation in Russia and China. An effective vaccine must induce a protective response of both cell-mediated and humoral immunity and should meet the safety and efficacy criteria. Although the emergence of new technologies has accelerated the development of vaccines, there are several challenges on the way, such as limited knowledge about the pathophysiology of the virus, inducing humoral or cellular immunity, immune enhancement with animal coronavirus vaccines, and lack of an appropriate animal model. In this review, we firstly discuss the immune responses against SARS-CoV-2 disease, subsequently, give an overview of several vaccine platforms for SARS-CoV-2 under clinical trials and challenges in vaccine development against this virus.

Genetic modification of cystic fibrosis with ΔF508 mutation of CFTR gene using the CRISPR system in peripheral blood mononuclear cells.

OBJECTIVES: Cystic fibrosis (CF) is an inherited autosomal recessive disease that is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The present study aimed to investigate the genetic modification of CF with ΔF508 mutation of the CFTR gene using CRISPR in peripheral blood mononuclear cells (PBMCs). MATERIALS AND METHODS: Two single guide RNAs were designed to target sequences in the CFTR gene. The transfection efficiency of PBMC cells was examined through evaluation of green fluorescent protein (GFP) expression using fluorescent microscopy. Moreover, a sgRNA-Cas9 plasmid was tested to target the CFTR gene. The ΔF508 gene modification was evaluated and confirmed by PCR and Sanger sequencing methods. RESULTS: Our results indicate the feasibility of site-specific gene targeting with the CRISPR/Cas9 system. 33% of the samples were corrected using CRISPR in mutant locus and confirmed by sequence blast at NCBI databases and primers outside the arm locus. CRISPR/Cas9 approach represents an efficient tool to repair the ΔF508 mutation of the CFTR gene in PBMC Cells. CONCLUSION: Therefore, the CRISPR system can be highly efficient and specific and provides a powerful approach for genetic engineering of cells and model animals. Generally, the proposed method opens new insights into the treatment of human diseases.

Preparation of Chitosan Nanoparticles as a Capable Carrier for Antigen Delivery and Antibody Production.

Background: Chitosan (CS) nanoparticles have attracted considerable attention as a non-viral and cationic carrier for delivery of therapeutic proteins and antigens and offer non-invasive routes of administration such as oral, nasal and ocular routes, and also show adjuvant characteristics for vaccines. Objectives: Preparation and formulation of CS nanoparticles as a capable carrier with immunoadjuvant properties to enhance the bioavailability of antigen and produce antibody with high affinity. Materials and Methods: CS nanoparticles were produced by ionic gelation process of sodium tripolyphosphate (TPP) with CS. Particle size and morphology of nanoparticles were determined using Dynamic Light Scattering (DLS) and Scanning Electron Microscopy (SEM) and also direct observation under light microscope. The influence of the initial BSA concentration and CS concentration on loading efficiency and release behavior was evaluated. The ε-toxin (derived from Clostridium perfringens type D) was loaded on CS nanoparticles and the complex was injected hypodermically into the rabbits for once. The anti ε-toxin antibody level in blood serum was evaluated using Dot Blot and ELISA methods. Results: The CS nanoparticles in different groups have a particle diameter (Z-average) in approximate ranges of 200-400, 300-600, 450-800 nm and a positive Zeta potential (32.4 - 48.6 mv). Optimum loading efficiency was achieved for CS at a concentration of 0.5 mg.mL-1 and TPP of 1.0 mg.mL-1. The results showed that the toxin-CS complex produces antitoxin at levels more than twice as high the control. Conclusion: The CS nanoparticles can be used as a good biodegradable carrier for protein and antigen delivery.

Cerium oxide nanoparticles: A promising tool for the treatment of fibrosarcoma in-vivo.

In this study, we used cerium oxide nanoparticles and evaluated their anti-cancer effects in a mouse model of fibrosarcoma. For evaluation of anti-cancer effects of nanoceria, tumor volume measurement, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay, quantitative real-time PCR (qPCR) for Bax and Bcl2 genes, a panel of liver and kidney function tests and hematoxylin-eosin staining were done. Nanoceria dominantly accumulated in the tumor and it could significantly decrease tumor growth and volume in tumor-bearing mice that received nanoceria for four weeks. Cerium oxide nanoparticle showed potential anti-cancer properties against fibrosarcoma.

The effects of nanomicelle of curcumin on the matrix metalloproteinase (MMP-2, 9) activity and expression in patients with coronary artery disease (CAD): A randomized controlled clinical trial.

BACKGROUND: Coronary artery disease (CAD) is the most common type of cardiovascular disease. Increasing the expression and activity of matrix metalloproteinases (MMPs) facilitates vascular remodeling and cardiovascular complications. Curcumin (the active ingredient of turmeric) is a potent natural anti-inflammatory agent, with cardiovascular protective effects. The present study was a clinical trial for investigating the effects of curcumin on activity and gene expression of MMP-2 and MMP-9 in patients with CAD. METHODS: In this study, 70 patients with CAD (with 40%-50% stenosis) were randomly divided into two groups of curcumin (80 mg nanomicelle per day) and placebo. The intervention lasted 3 months. The activity levels of MMP-2 and MMP-9 in serum samples of patients were measured using gelatin zymography assay before and after the intervention. MMP-2 and MMP-9 gene expression in peripheral blood mononuclear cells (PBMCs) was also analyzed using real-time polymerase chain reaction (PCR). Statistical significance was set at P < 0.0500. RESULTS: After 3 months of medication, the expression of MMP-9 produced by PBMCs significantly decreased in the curcumin group (0.811 ± 0.25) in comparison with the placebo group (2.23 ± 0.94) (P < 0.0001). Furthermore, the zymographic analysis showed that the administration of curcumin significantly inhibited the activity levels of MMP-2 (12469.7 ± 5308.64 pixels) and MMP-9 (14007.2 ± 5371.67 pixels) in comparison with that in patients receiving placebo (MMP-2: 17613.8 ± 5250.68 pixels; MMP-9: 20010.1 ± 3259.37 pixels) (P < 0.0500). CONCLUSION: Our results show that curcumin can significantly reduce the expression and activity of MMP-2 and MMP-9. Because of the anti-inflammatory effects of curcumin, this compound can be considered as a new strategy for the prevention of cardiovascular events.