Sharif Digital Repository

Introduction: The role of Hippo signaling pathway, which was identified by genetic studies as a key regulator for tissue growth and organ size, in promoting physiological cardiac hypertrophy has not been investigated. Methods: Fourteen male Wistar rats were randomly assigned to the exercise and control groups. The exercise group ran 1 hour per day, 5 days/week, at about 65%-75% VO2max on the motor-driven treadmill with 15ºslope, and the control group ran 15 min/d, 2 days/ week at 9 m/min (0ºinclination), throughout the eight-week experimental period. Forty-eight hours after the last session, hearts were dissected and left ventricles were weighed and stored for subsequent RT-PCR analysis.... 

Scar tissue size following myocardial infarction is an independent predictor of cardiovascular outcomes, yet little is known about factors regulating scar size. We demonstrate that collagen V, a minor constituent of heart scars, regulates the size of heart scars after ischemic injury. Depletion of collagen V led to a paradoxical increase in post-infarction scar size with worsening of heart function. A systems genetics approach across 100 in-bred strains of mice demonstrated that collagen V is a critical driver of postinjury heart function. We show that collagen V deficiency alters the mechanical properties of scar tissue, and altered reciprocal feedback between matrix and cells induces... 

Therapeutic fragmented antibodies show a poor pharmacokinetic profile that leads to frequent high-dose administration. In the current study, for the first time, a novel proline, alanine, serine (PAS) repeat sequence called PAS#208 was designed to extend the plasma half-life of a nanosized anti-vascular endothelial growth factor-A single-domain antibody. Polyacrylamide gel electrophoresis, circular dichroism, dynamic light scattering, and electrophoretic light scattering were used to assess the physicochemical properties of the newly designed PAS sequence. The effect of PAS#208 on the biologic activity of a single-domain antibody was studied using an in vitro proliferation assay. The... 

Introduction: This report describes the synthesis of 2-Amino-2-deoxy(S- benzoylthioacetyl)-D-glucose (S-Bz-TA-DG), radiolabeled with [ 99mTc(CO)3(OH2)3]+ complex with a procedure including deprotection of the benzoyl group, characterization by HPLC using a C18 reverse phase column and preliminary biodistribution study in normal mice. Methods: [99mTc(CO) 3(H2O)3]+ complex was used to label TA-DG with 99mTc. This complex was prepared using up to 46 mCi of Na99mTcO4 in 1mL saline. The radiochemical purity (>95%) was determined by TLC in normal saline solution as the mobile phase. Radio-HPLC analysis of [99mTc]-(TA-DG) at pH=9.5-10, revealed that labeling with 99mTc resulted in the formation of... 

Herein, the graphene oxide (GO)/cobalt ferrite nanoparticles were used to apply the heat treatment on the breast cancer cell line of MCF7. The synthesized nanoparticles were evaluated before in vitro and in vivo studies, using transmission electron microscopy (TEM), X-ray diffraction (XRD), vibrating sample magnetometer (VSM), X-ray photoelectron spectroscopy (XPS), thermal property and relaxivity measurement. The nanoparticles showed a diameter of 5 nm with the ferrimagnetic property. Also, the nanoparticles were well distributed on the GO nanosheets. The related peaks of cobalt ferrite nanoparticles were approved by using XRD and XPS assays. During the in vitro investigations, IC50 with... 

Passive finite element (FE) models of the spine are commonly used to simulate intact and various pre- and postoperative pathological conditions. Being devoid of muscles, these traditional models are driven by simplistic loading scenarios, e.g., a constant moment and compressive follower load (FL) that do not properly mimic the complex in vivo loading condition under muscle exertions. We aim to develop novel passive FE models that are driven by more realistic yet simple loading scenarios, i.e., in vivo vertebral rotations and pathological-condition dependent FLs (estimated based on detailed musculoskeletal finite element (MS-FE) models). In these novel force–displacement control FE models,... 

Background: Numerous studies have described the neuroprotective effect of lithium in spinal cord injury in addition to its ameliorative impact on pain sensation. In the present study, we aim to examine the efficacy of 85 mg/kg as well as 50 mg/kg dosage of the lithium chloride (LiCl) through oral consumption in spinal cord injured rats and their effect on gene expression of three candidate genes, corresponding to the hyper-sensitization. Methods: Adult Wistar (male) rats were divided into four experimental groups: control; oral administration of LiCl with 85 mg/kg and 50 mg/kg dosage; and 10 % sucrose receiver as the vehicle. BBB and heat plantar tests were performed weekly throughout four... 

Simvastatin, a well-known antihyperlipidemic drug, has antibacterial activity against a broad range of bacteria, especially Staphylococcus aureus. In present study, a nanoemulsion gel-based formulation containing Simvastatin was developed for infected wound therapy. Therefore, different formulations of Simvastatin nanoemulsion were prepared. Based on droplet size, polydispersity index and zeta potential, the best nanoemulsion formulation containing Simvastatin was selected for development of nanoemulsion gel formulation of drug using carbomer 934 as gelling agent. Thermodynamic stability of Simvastatin nanoemulsion was assessed at different conditions. The in vitro antibacterial activity... 

Cervical cancer is the second-most-common cause of malignancies in women worldwide, and the oncogenic activity of the human papilloma virus types (HPV) E7 protein has a crucial role in anogenital tumors. In this study, we have designed a therapeutic vaccine based on chitosan nanodelivery systems to deliver HPV-16 E7 DNA vaccine, considered as a tumor specific antigen for immunotherapy of HPV-associated cervical cancer. We have developed a Nano-chitosan (NCS) as a carrier system for intramuscular administration using a recombinant DNA vaccine expressing HPV-16 E7 (NCS-DNA E7 vaccine). NCS were characterized in vitro for their gene transfection ability. Results: The transfection of CS-pEGFP... 

Context: Elevated expression of the folate receptor (FR) occurs in many human malignancies. Thus, folate targeting is widely utilized in drug delivery purposes specially using nano-radioactive agents. Aims: In this work, we report production and biological evaluation of gallium-67 labeled superparamagnetic iron oxide nanoparticles, embedded by folic acid (67 Ga-SPION-folate) complex especially in tumor-bearing mice for tumor imaging studies. Settings and Design: The structure of SPION-folate was confirmed by X-ray diffraction (XRD), transmission electron microscopy (TEM) and foureir transform infrared spectroscopy (FT-IR) analyses. The radiolabeled SPION-folate formation was confirmed by... 

Background: Recent clinical studies of treating traumatic brain injury (TBI) with autologous adult stem cells led us to compare effect of intravenous injection of bone marrow mesenchymal stem cells (BMSC) and bone marrow hematopoietic stem cell mobilization, induced by granulocyte colony stimulating factor (G-CSF), in rats with a cortical compact device. Methods: Forty adult male Wistar rats were injured with controlled cortical impact device and divided randomly into four groups. The treatment groups were injected with 2 × 106 intravenous bone marrow stromal stem cell (n = 10) and also with subcutaneous G-CSF (n = 10) and sham-operation group (n = 10) received PBS and "bromodeoxyuridine... 

The oxidation-reduction (redox)–responsive micelle system is based on a diselenide-containing triblock copolymer, poly(ε-caprolactone)-bis(diselenide-methoxy poly(ethylene glycol)/poly(ethylene glycol)-folate) [PCL-(SeSe-mPEG/PEG-FA)2]. This has helped in the development of tumor-targeted delivery for hydrophobic anticancer drugs. The diselenide bond, as a redox-sensitive linkage, was designed in such a manner that it is located at the hydrophilic–hydrophobic hinge to allow complete collapse of the micelle and thus efficient drug release in redox environments. The amphiphilic block copolymers self-assembled into micelles at concentrations higher than the critical micelle concentration (CMC)... 

Herein, a hybrid hydrogel/microsphere system is introduced for accelerated wound healing by sustained release of basic fibroblast growth factor (bFGF). The hydrogel is composed of a mixture of PVA, gelatin and chitosan. The double-emulsion-solvent-evaporation method was utilized to obtain microspheres composed of PCL, as the organic phase, and PVA, as the aqueous phase. Subsequently, various in-vitro and in-vivo assays were performed to characterize the system. BSA was used to optimize the release mechanism, and encapsulation efficiency in microspheres, where a combination of 3% (w/v) PCL and 1% (w/v) PVA was found to be the optimum microsphere sample. Incorporation of microspheres within... 

Background: Accurate tracking of the heart surface motion is a major requirement for robot assisted beating heart surgery. Method: The feasibility of a stereo infrared tracking system for measuring the free beating heart motion was investigated by experiments on a heart motion simulator, as well as model surgery on a dog. Results: Simulator experiments revealed a high tracking accuracy (81 μm root mean square error) when the capturing times were synchronized and the tracker pointed at the target from a 100 cm distance. The animal experiment revealed the applicability of the infrared tracker with passive markers in practical heart surgery conditions. Conclusion: With the current technology,... 

The magnetic composite hydrogel was fabricated by the graft copolymerization of itaconic acid (IA) onto starch and Alginic acid in the presence graphene sheets (Gr) and Fe3O4 nanoparticles (Fe3O4@Gr-IA/St-Alg) for Guaifenesin (GFN) delivery and wound healing. The Fe3O4@Gr-IA/St-Alg biomaterial is a hydrogel network endowed the material with magnetic property. In addition, GFN not only achieved effectively bound to the magnetic hydrogel, but also released in a controlled manner. The using external magnetic field has significantly positive influence on the drug release rate. To close, these hydrogel drug carriers offer a favorable platform for magnetically targeted drug delivery as well as a... 

This study presents a bilayer structure as a skin scaffold comprised of an electrospun sheet layer made of polycaprolactone and polyvinil alcohol and a porous hydrogel layer made of chitosan and gelatin. The hydrogel layer was fabricated by employing the freeze-gelation technique. The bilayer structure was achieved by pouring the hydrogel solution on the electrospun sheet at the bottom of a mold followed by the freeze-gelation technique to obtain a porous structure in the hydrogel. The hydrogel and hydrogel-electrospun samples were characterized by scanning electron microscopy, swelling, tensile strength, in vitro and in vivo analyses. From a mechanical strength standpoint, the combination... 

Background: Newcastle disease virus (NDV) has shown noticeable oncolytic properties, especially against cervical cancer. However, in order to improve the spread rate and oncotoxicity of the virus, employment of other therapeutic reagents would be helpful. It has been shown that some viral fusogenic membrane glycoproteins (FMGs) could facilitate viral propagation and increase the infection rate of tumor cells by oncolytic viruses. Additionally, immune checkpoint blockade has widely been investigated for its anti-tumor effects against several types of cancers. Here, we investigated for the first time whether the incorporation of influenza hemagglutinin-2 (HA2) FMG could improve the oncolytic... 

Human infertility is a multifactorial disease that affects 8%–12% of reproductive-aged couples worldwide. However, the genetic causes of human infertility are still poorly understood. Synaptonemal complex (SC) is a conserved tripartite structure that holds homologous chromosomes together and plays an indispensable role in the meiotic progression. Here, we identified three homozygous mutations in the SC coding gene C14orf39/SIX6OS1 in infertile individuals from different ethnic populations by whole-exome sequencing (WES). These mutations include a frameshift mutation (c.204_205del [p.His68Glnfs∗2]) from a consanguineous Pakistani family with two males suffering from non-obstructive... 

Mechanical ventilation (MV) can result in long-term brain impairments that are resistant to treatment. The mechanisms underlying MV-induced brain function impairment remain unclear. Since nasal airflow modulates brain activity, here we evaluated whether reinstating airflow during MV could influence the memory performance of rats after recovery. Rats were allocated into two study groups: one group received rhythmic air-puff into the nasal cavity during MV and a control group that underwent ventilation without air-puff. During MV, air-puffs induced time-locked event potentials in OB, mPFC and vHPC and significantly increased the oscillatory activity at the air-puff frequency. Furthermore, in... 

Although simvastatin (SIM) has been proven to be a powerful agent against myocardial ischemia/reperfusion (MI/R) injury, poor water solubility, short half-life, and low bioavailability have made it futile while using conventional drug delivery system. Hence, this study aims to investigate therapeutic efficacy of SIM-loaded nano-niosomes on MI/R injury. Surface active agent film hydration method was used to synthesize nano-niosomes. The physicochemical properties of nano-niosomes were characterized using dynamic light scattering (DLS) and transmission electron microscopy (TEM). Moreover, niosomes were characterized in entrapment efficiency (EE) and releasing pattern. Male Wistar rats were...