Cholesterol-conjugated PEGylated PAMAM as an efficient nanocarrier for plasmid encoding interleukin-12 immunogene delivery toward colon cancer cells

IL-12 is a pleiotropic cytokine, which shows an ideal applicant for tumor immunotherapy, because of its features of creating an interconnection between innate (NK cells) and adaptive (cytotoxic T lymphocyte) immunity. IL-12 gene therapy is a useful technique to deliver an immune-modulatory gene directly into tumor site thereby limiting the adverse effects of systemic administration of IL-12 proteins. One of the most largely investigated non-viral gene carriers is polyamidoamine (PAMAM). In the current research, 5 and 3% of PAMAM primary amines were substituted to transmit the plasmid encoding IL-12 gene to cells by cholesteryl chloroformate and alkyl-PEG, respectively. The features of modified PAMAMs containing size and surface charge density, cytotoxicity, and transfection efficiency were investigated in colon cancer cells. in vitro experiment showed that this modified carrier with average size of about 160 nm and zeta potential of 30 mV was able to increase the level of IL-12 production up to two folds as compared to that of the unmodified PAMAM. Improvement of the polymer hydrophobic balance along with of the modulation of the surface positive charge could provide an efficient and safe non-viral IL-12 gene for colon cancer immunogene therapy.     

Synthesis of a novel nanocomposite containing chitosan as a three-dimensional printed wound dressing technique: Emphasis on gene expression

In this study, a highly porous three-dimensional (3D)-printed wound healing core/shell scaffold fabricated using poly-lactic acid (PLA). The core of scaffold was composed of hyaluronic acid (HA), copper carbon dots (Cu-CDs), rosmarinic acid, and chitosan hydrogel. Cu-CDs were synthesized using ammonium hydrogen citrate under hydrothermal conditions. Formulation containing 1 mg ml⁻¹concentration of Cu-CDs showed an excellent antibacterial activity against gram bacteria. At 0.25 mg ml⁻¹ of Cu-CDs concentration, scaffold had a good biocompatibility as confirmed by cytotoxicity assay on L929 fibroblast stem cells. in vivo wound healing experiments on groups of rats revealed that after 15 days of treatment, the optimal formulation of composite scaffold significantly improves the wound healing process compared to the PLA scaffold. This finding was confirmed by histological analysis and the relative expression of PDGF, TGF-β, and MMP-1 genes. The biocompatible antibacterial CU-CDS/PLA/HA/chitosan/rosmarinic acid nanocomposite is a promising wound healing scaffold which highly accelerates the process of skin regeneration.     

Modulation of Glucose Transporter Protein by Dietary Flavonoids in Type 2 Diabetes Mellitus

Diabetes mellitus (DM) is a metabolic diseases characterized by hyperglycemia due to insufficient or inefficient insulin secretory response. This chronic disease is a global problem and there is a need for greater emphasis on therapeutic strategies in the health system. Phytochemicals such as flavonoids have recently attracted attention as source materials for the development of new antidiabetic drugs or alternative therapy for the management of diabetes and its related complications. The antidiabetic potential of flavonoids are mainly through their modulatory effects on glucose transporter by enhancing GLUT-2 expression in pancreatic β cells and increasing expression and promoting translocation of GLUT-4 via PI3K/AKT, CAP/Cb1/TC10 and AMPK pathways. This review highlights the recent findings on beneficial effects of flavonoids in the management of diabetes with particular emphasis on the investigations that explore the role of these compounds in modulating glucose transporter proteins at cellular and molecular level.     

A Review of the Role of ERp57 in Cancerous and Non-Cancerous Cell Physiology and its Potential as a Therapeutic Target

The protein ERp57 is a stress-responsive protein, mainly exists in the endoplasmic reticulum (ER), and a small amount in the cell membrane, cytoplasm, nucleus and mitochondria, which is involved in the signal transduction from the cell surface, the regulation process that occurs in the nucleus, and the formation of polymer protein complexes involved in DNA repair. Various degrees of ERp57 dysregulation has been observed in many types of non-communicable diseases especially in cancers. Previous studies showed that the expression of ERp57 could play a key role in occurrence and development of cancers such as breast cancer, gastric cancer, ovarian cancer, etc.; in addition, it has been suggested to play a pivotal role in disease progression of non-cancerous diseases such as neurodegeneration, liver disease, kidney disease, intestinal irritability syndrome and airway hypersensitivity. Thus, abnormal expression of ERp57 could be used as promising biomarker for cancer diagnosis and prognosis based on the previous studies. In this regard, current study was aimed to review the literature, which have been elucidate the role of ERp57 protein expression in both non-cancer and cancer disease. Overall, most studies have shown that inhibiting/knocking out of ERp57 could inhibit the cell proliferation and also induce apoptosis in both human cancerous and non-cancerous cells. Also, it has been suggested that the overexpression of ERp57 could intensify the cancer development. Therefore, it could be hypothesized that targeting of ERp57 might be a potential treatment in cancerous and non-cancerous diseases.     

Resveratrol attenuates chronic social isolation stress-induced affective disorders: Involvement of NF-κB/NLRP3 axis

Social isolation stress (SIS) is associated with affective disorders (i.e., anxiety and depression) in adults. In a preclinical study, we aimed to investigate the effects of resveratrol (RV) on the mood swings of rats exposed to SIS. Animals were randomized into six different groups, including control: healthy animals received normal saline (NS) as a vehicle; SIS + NS: SIS animals received NS; SIS + FL: SIS animals received fluoxetine (10 mg/kg/i.p.); SIS + RV20, SIS + RV40, and SIS + RV80: SIS animals received RV (20, 40, and 80 mg/kg/i.p). SIS was induced for 4 weeks, then animals were treated with NS, FL, and RV for 4 weeks. Rats were evaluated by the behavioral tests, including the elevated plus-maze, tail suspension test, the open field test, and forced-swimming test, for mood alterations and nuclear factor kappa B (NF-κB) levels, along with NLRP3, apoptosis-associated speck-like (ASC), and proCaspase-1 were determined in the hippocampus. Behavioral tests confirmed that exposing the animals to SIS caused anxiety and depression. The highest concentrations of NLRP3, proCaspase-1, ASC, and NF-κB, were confirmed in the SIS + NS group. Compared to FL, RV showed antidepressant potential according to the behavioral tests. In particular, the administration of RV (20, 40, and 80 mg/kg) revered the NF-κB/NLRP3 axis cascade in rats exposed to chronic SIS. Our findings revealed that RV attenuated anxiety and depression of SIS-exposed rats via regulation of NF-κB/NLRP3 signaling pathways. RV can be used as a potential anxiolytic agent and antidepressant.     

Bitter apricot ethanolic extract induces apoptosis through increasing expression of Bax/Bcl-2 ratio and caspase-3 in PANC-1 pancreatic cancer cells

Molecular Biology Reports - Pancreatic cancer is the fourth common cause of cancer death. Surgery and chemotherapy are the common treatment strategies for pancreatic cancer patients; however, the...     

A Novel Molecular Design for a Hybrid Phage-DNA Construct Against DKK1

Nucleic acid immunization has recently exhibited a great promise for immunotherapy of various diseases. However, it is now clear that powerful strategies are imminently needed to improve their efficiency. In this regard, whole bacteriophage particles have been described as efficient DNA vaccine delivery vehicles, capable of circumventing the limitations of naked DNA immunization. Moreover, phage particles could be engineered to display specific peptides on their surfaces. Given these inherent characteristics of phages, we have designed a novel hybrid phage-DNA immunization vector using both M13 and pAAV plasmid elements. Following the construction and in vitro confirmation of the designed vectors, they were used for comparative mice immunization, carrying the same DNA sequence. The results indicated the efficacy of the designed hybrid phage particles, to elicit higher humoral immunity, in comparison to conventional DNA-immunization vectors (pCI). In light of these findings, it could be concluded that using adeno-associated virus (AAV) expression cassette along with displaying TAT peptide on the surface of the phage particle could be deemed as an appealing strategy to enhance the DNA-immunization and vaccination efficacy.