Time filter

Source Type

Nouri M.,Womens Reproductive Health Research Center | Aghadavod E.,Kashan University of Medical Sciences | Khani S.,Research Center for Pharmaceutical Nanotechnology | Jamilian M.,Arak University of Medical Sciences | And 4 more authors.
Clinical Endocrinology | Year: 2016

Background: Anti-Müllerian hormone (AMH) is one of the most reliable markers of ovarian reserve. There is evidence which suggests that BMI may be associated with gene expression of AMH, AMH type II receptor (AMHR-II) and androgen receptor (AR) in human granulosa cells (GC) in women with and without polycystic ovary syndrome (PCOS). Objective: To investigate the association between BMI and gene expression of AMH, AMHR-II and AR in human GC in women with and without PCOS. Design, Patients and Measurements: In a cross-sectional study, hormonal profiles were measured among 38 patients with PCOS and 38 subjects without PCOS aged 18–40. AMH, AMHR-II and AR mRNA levels were quantified in cumulus GC. Pearson correlation and multiple linear regressions were used to assess the relationships. Results: Quantitative RT-PCR demonstrated that AMH and AMHR-II expression were negatively correlated with BMI (r = −0·39, P < 0·001 for AMH and r = −0·49, P < 0·001 for AMHR-II), whereas AR expression was positively correlated with BMI (r = 0·46, P < 0·001). Conclusions: There is a negative association between AMH, AMHR-II expression and BMI, and a positive association between AR expression and BMI in the GC of PCOS and non-PCOS women. © 2016 John Wiley & Sons Ltd


Nourazarian A.R.,University of Sfax | Najar A.G.,Kerman Medical University | Farajnia S.,Drug Applied Research Center and Biotechnology Research Center | Khosroushahi A.Y.,Research Center for Pharmaceutical Nanotechnology | And 4 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2012

Colon cancer continues to be one of the most common cancers, and the importance and necessity of new therapies needs to be stressed. The most important proto-oncogen factors for colon cancer appear to be epidermal growth factor receptor, EGFR, and c-Src with high expression and activity leading to tumor growth and ultimately to colon cancer progression. Application of c-Src and EGFR antisense agents simultaneously should theoretically therefore have major benefit. In the present study, anti-EGFR and c-Src specific antisense oligodeoxynucleotides were combined in a formulation using PAMAM dendrimers as a carrier. Nano drug entry into cells was confirmed by flow cytometry and fluorescence microscopy imaging and real time PCR showed gene expression of c-Src and EGFR, as well as downstream STAT5 and MAPK-1 with the tumor suppressor gene P53 to all be downregulated. EGFR and c-Src protein expression was also reduced when assessed by western blotting techniques. The effect of the antisense oligonucleotide on HT29 cell proliferation was determined by MTT assay, reduction beijng observed after 48 hours. In summary, nano-drug, anti-EGFR and c-Src specific antisense oligodeoxynucleotides were effectively transferred into HT-29 cells and inhibited gene expression in target cells. Based on the results of this study it appears that the use of antisense EGFR and c-Src simultaneously might have a significant effect on colon cancer growth by down regulation of EGFR and its downstream genes.


Babaei S.,Biotechnology Research Center | Ghanbarzadeh S.,Zanjan University of Medical Sciences | Adib Z.M.,Students Research Committee | Davaran S.,Research Center for Pharmaceutical Nanotechnology | Hamishehkar H.,Tabriz University of Medical Sciences
Pharmazie | Year: 2016

Lipid based nanoparticles have become a major research object in topical drug delivery to enable drugs to pass the stratum corneum and reach the desired skin layer. The present investigation deals with the encapsulation of lidoacine into nanostructured lipid carriers (NLCs) and nanoethosomes for improving its dermal delivery and consequently local anesthetic efficacy. Concurrently these two topical delivery systems were compared. Lidocaine-loaded NLCs and nanoethosomes were characterized by various techniques and used for an in vitro skin penetration study using excised rat skin and Franz diffusion cells. The nanoparticles were tracked in the skin by following the Rhodamine-labled nanocarriers under fluorescent microscopy. Optimized lidocaine-loaded NLCs (size 96 nm, zeta potential -13.7 mV, encapsulation efficiency (EE) % 69.86% and loading capacity (LC) % 10.47%) and nanoethosomes (size 105.4 nm, zeta potential -33.6 mV, EE 40.14% and LC 8.02%) were chosen for a skin drug delivery study. Higher skin drug deposition of NLCs and nanoethosomal formulations compared to lidocaine hydroalcoholic solution represented a better localization of the drug in the skin. NLC formulation showed the lowest entered drug in the receptor phase of Franz diffusion cell in comparison with nanoethosomes and hydroalcoholic solution confirming the highest skin accumulation of drug. Both colloidal systems showed superiority over the drug solution for dermal delivery of lidocaine, however, NLC exhibited more promising characteristics than nanoethosomes regarding drug loading and skin targeted delivery.


PubMed | Kashan University of Medical Sciences, Arak University of Medical Sciences, Womens Reproductive Health Research Center, Tehran University of Medical Sciences and 2 more.
Type: Journal Article | Journal: Clinical endocrinology | Year: 2016

Anti-Mllerian hormone (AMH) is one of the most reliable markers of ovarian reserve. There is evidence which suggests that BMI may be associated with gene expression of AMH, AMH type II receptor (AMHR-II) and androgen receptor (AR) in human granulosa cells (GC) in women with and without polycystic ovary syndrome (PCOS).To investigate the association between BMI and gene expression of AMH, AMHR-II and AR in human GC in women with and without PCOS.In a cross-sectional study, hormonal profiles were measured among 38 patients with PCOS and 38 subjects without PCOS aged 18-40. AMH, AMHR-II and AR mRNA levels were quantified in cumulus GC. Pearson correlation and multiple linear regressions were used to assess the relationships.Quantitative RT-PCR demonstrated that AMH and AMHR-II expression were negatively correlated with BMI (r=-039, P<0001 for AMH and r=-049, P<0001 for AMHR-II), whereas AR expression was positively correlated with BMI (r=046, P<0001).There is a negative association between AMH, AMHR-II expression and BMI, and a positive association between AR expression and BMI in the GC of PCOS and non-PCOS women.


Barar J.,Research Center for Pharmaceutical Nanotechnology | Barar J.,Tabriz University of Medical Sciences | Kafil V.,Research Center for Pharmaceutical Nanotechnology | Kafil V.,Tabriz University of Medical Sciences | And 11 more authors.
Journal of Nanobiotechnology | Year: 2015

Background: Targeted delivery of anticancer chemotherapeutics such as mitoxantrone (MTX) can significantly intensify their cytotoxic effects selectively in solid tumors such as breast cancer. In the current study, folic acid (FA)-armed and MTX-conjugated magnetic nanoparticles (MNPs) were engineered for targeted eradication of folate receptor (FR)-positive cancerous cells. Polyethylene glycol (PEG), FA and MTX were covalently conjugated onto the MNPs to engineer the PEGylated FA-MTX-MNPs. The internalization studies were performed using fluorescein isothiocyanate (FITC)-labeled FA-decorated MNPs (FA-FITC-MNPs) in both FR-positive MCF-7 cells and FR-negative A549 cells by means of fluorescence microscopy and flow cytometry. The cellular and molecular impacts of FA-MTX-MNPs were examined using trypan blue cell viability and FITC-labeled annexin V apoptosis assays and 4',6-diamidino-2-phenylindole (DAPI) staining, DNA ladder and quantitative polymerase chain reaction (qPCR) assays. Results: The FR-positive MCF-7 cells showed significant internalization of the FA-FITC-MNPs, but not the FR-negative A549 cells. The FR-positive cells treated with the PEGylated FA-MTX-MNPs exhibited the IC50 values of 3 μg/mL and 1.7 μg/mL, 24 h and 48 h post-treatment, respectively. DAPI staining and DNA ladder assays revealed significant condensation of nucleus and fragmentation of genomic DNA in the FR-positive MCF-7 cells treated with the PEGylated FA-MTX-MNPs as compared to the FR-negative A549 cells. The FITC-labeled annexin V assay confirmed emergence of late apoptosis (>80%) in the FR-positive MCF-7 cells treated with the PEGylated FA-MTX-MNPs, but not in the FR-negative A549 cells. The qPCR analysis confirmed profound cytotoxic impacts via alterations of apoptosis-related genes induced by MTX-FA-MNPs in MCF-7 cells, but not in the A549 cells. Conclusion: Our findings evince that the engineered PEGylated FA-MTX-MNPs can be specifically taken up by the FR-positive malignant cells and effectively demolish them through up-regulation of Bcl-2-associated X protein (Bax) and Caspase 9 and down-regulation of AKt. Hence, the engineered nanosystem is proposed for simultaneous targeted imaging and therapy of various cancers overexpressing FRs. © Barar et al.; licensee BioMed Central.


Tabasinezhad M.,Tabriz University of Medical Sciences | Tabasinezhad M.,Research Center for Pharmaceutical Nanotechnology | Samadi N.,Tabriz University of Medical Sciences | Samadi N.,Research Center for Pharmaceutical Nanotechnology | And 9 more authors.
Journal of Cancer Research and Therapeutics | Year: 2013

Sphingosine-1 phosphate (S1P) is a bioactive lipid that mediates diverse cellular responses. Signaling of S1P is carried out by a family of G-protein coupled receptors (GPCRs), which show differential expression patterns depending on tissue and cell types. Activation of S1P receptors induces signaling pathway, which can subsequently lead to physiological process. Intercellular S1P concentration is regulated and determined by several enzymes including S1P lyase, S1P kinase and S1P phosphatase. Numerous studies showed the role of S1P in malignant behavior of cancer cells including breast, lung, colon, and leukemia cell lines. In the past decade, extensive research activities have focused on elucidating S1P signaling pathway, its receptors, enzymes involved in S1P metabolism, and its performance in cancer biology. In this review, we will explain the function of S1P in tumor progression that demonstrated in past research articles and we will express its importance as a target for designing futuristic anticancer drug.


Rameshrad M.,Student Research Committee | Maleki-Dizaji N.,Tabriz University of Medical Sciences | Vaez H.,Tabriz University of Medical Sciences | Soraya H.,Urmia University of Medical Sciences | And 2 more authors.
Iranian Journal of Immunology | Year: 2015

Background: Myocardial dysfunction is one of the major complications in patients with sepsis where there is a relationship between the blood level of cytokines and the onset of myocardial depression. In many cases of sepsis, the presence of Lipopolysaccharide (LPS) has been established. LPS Binding Protein (LBP) bound endotoxin is recognized by CD14/toll-like receptor-4 (TLR4) complexes in innate immune cells which stimulates TNF-α release. Objectives: To investigate whether isolated rat heart is capable of producing TNF-α locally through TLR4 activation by LPS. Methods: Using langendorff method, LPS in 120 mL of the modified Krebs-Henseleit buffer solution (KHBS) at final concentration of 1 µg/mL was perfused at recycling mode. The effect of LPS on cardiac function was evaluated. To assess the TLR4 activity and TNF-α release, western blotting, real time-PCR, and ELISA were used. Results: Compared with control, coronary perfusion pressure (CPP) as well as left ventricular developed pressure (LVDP), maximum and minimum rates of the left ventricular developed pressure (dP/dtmax; dP/dtmin; p<0.001) were depressed to a maximum level after 180 minutes recycling with LPS. This myocardial depression was associated with a significant increase in TLR4 expression (p<0.01), MyD88 activity (p<0.01) and TNF-α (p<0.05) concentration in the heart tissue. Conclusion: The results of this study show that heart is capable of producing TNF-α through TLR4 and MyD88 activation independent of classic immune system and suggest a local immune response. © 2015, Shiraz University of Medical Sciences. All rights reserved.


PubMed | Research Center for Pharmaceutical Nanotechnology
Type: Journal Article | Journal: Pharmaceutical development and technology | Year: 2015

The purpose of the present investigation was to prepare a plasma stable, pH-sensitive niosomal formulation to enhance Sirolimus efficacy and selectivity.pH-sensitive niosomal formulations bearing PEG-Poly (monomethyl itaconate)-CholC6 (PEG-PMMI-CholC6) copolymers and cholesteryl hemisuccinate (CHEMS) were prepared by a modified ethanol injection method and characterized with regard to pH-responsiveness and stability in human serum. The ability of pH-sensitive niosomes to enhance the Sirolimus cytotoxicity was evaluated in vitro using human erythromyeloblastoid leukemia cell line (K562) and compared with cytotoxicity effect on human umbilical vein endothelial cells (HUVEC).This study showed that both formulations can be rendered pH-sensitive property and were found to rapidly release their contents under mildly acidic conditions. However, the CHEMS-based niosomes lost their pH-sensitivity after incubation in plasma, whereas, PEG-PMMI-CholC6 niosomes preserved their ability to respond to pH change. Sirolimus encapsulated in pH-sensitive niosomes exhibited a higher cytotoxicity than the control conventional formulation on K562 cell line. On the other hand, both pH-sensitive niosomes showed lower antiproliferative effect on HUVEC cells.Plasma stable, pH-sensitive PEG-PMMI-CholC6-based niosomes can improve the in vitro efficiency and also reduce the side effects of Sirolimus.


PubMed | University of Lausanne and Research Center for Pharmaceutical Nanotechnology
Type: | Journal: Journal of nanobiotechnology | Year: 2015

Targeted delivery of anticancer chemotherapeutics such as mitoxantrone (MTX) can significantly intensify their cytotoxic effects selectively in solid tumors such as breast cancer. In the current study, folic acid (FA)-armed and MTX-conjugated magnetic nanoparticles (MNPs) were engineered for targeted eradication of folate receptor (FR)-positive cancerous cells. Polyethylene glycol (PEG), FA and MTX were covalently conjugated onto the MNPs to engineer the PEGylated FA-MTX-MNPs. The internalization studies were performed using fluorescein isothiocyanate (FITC)-labeled FA-decorated MNPs (FA-FITC-MNPs) in both FR-positive MCF-7 cells and FR-negative A549 cells by means of fluorescence microscopy and flow cytometry. The cellular and molecular impacts of FA-MTX-MNPs were examined using trypan blue cell viability and FITC-labeled annexin V apoptosis assays and 4,6-diamidino-2-phenylindole (DAPI) staining, DNA ladder and quantitative polymerase chain reaction (qPCR) assays.The FR-positive MCF-7 cells showed significant internalization of the FA-FITC-MNPs, but not the FR-negative A549 cells. The FR-positive cells treated with the PEGylated FA-MTX-MNPs exhibited the IC50 values of 3 g/mL and 1.7 g/mL, 24 h and 48 h post-treatment, respectively. DAPI staining and DNA ladder assays revealed significant condensation of nucleus and fragmentation of genomic DNA in the FR-positive MCF-7 cells treated with the PEGylated FA-MTX-MNPs as compared to the FR-negative A549 cells. The FITC-labeled annexin V assay confirmed emergence of late apoptosis (>80%) in the FR-positive MCF-7 cells treated with the PEGylated FA-MTX-MNPs, but not in the FR-negative A549 cells. The qPCR analysis confirmed profound cytotoxic impacts via alterations of apoptosis-related genes induced by MTX-FA-MNPs in MCF-7 cells, but not in the A549 cells.Our findings evince that the engineered PEGylated FA-MTX-MNPs can be specifically taken up by the FR-positive malignant cells and effectively demolish them through up-regulation of Bcl-2-associated X protein (Bax) and Caspase 9 and down-regulation of AKt. Hence, the engineered nanosystem is proposed for simultaneous targeted imaging and therapy of various cancers overexpressing FRs.

Loading Research Center for Pharmaceutical Nanotechnology collaborators
Loading Research Center for Pharmaceutical Nanotechnology collaborators