Development of a novel liposomal nanoparticle formulation of cisplatin to breast cancer therapy

Cisplatin is one of the conventional drugs used in chemotherapy which has a potent antitumor function. However, due to the dangerous side effects, including the damage to DNA of the normal cells, its clinical use is limited. The aim of this study was to prepare and characterize nanoliposome containing cisplatin. We optimized liposome formulations through the modification of the proportion of SPC80 (soybeanphospholipids with 75% phosphatidylcholine) and cholesterol content. Then, novel PEGylated liposomal formulations containing SPC80: cholesterol: DSPE-mPEG (at ratios of 85:10:5) were designed and developed to serve as a therapy to achieve more improved pharmaceutical efficiency. Zeta Sizer showed that PEGylated nanoliposomes had a mean diameter of 119.7 ± 2.1 nm, a zeta potential of −26.03 ± 1.34 mV, and entrapment efficiency of 96.65 ± 3%. The optimum formulations represented sustained, thermo-sensitive release, and augmented cellular uptake. The cytotoxic effect of the liposomal drug was higher than the free medication drug that confirmed the efficiency of cellular uptake. This study suggests that nanoliposome-loaded cisplatin plays a vital role in improving drug efficacy and the reduction of dosage.     

Mesenchymal stem cell mediated effects on microglial phenotype in cuprizone-induced demyelination model

Microglial cells have an essential role in neurodegenerative disorders, such as multiple sclerosis. They are divided into two subgroups: M1 and M2 phenotypes. Mesenchymal stem cells (MSC), with neuroprotective and immunomodulating properties, could improve these diseases. We evaluate the immunomodulating effects of MSC on microglial phenotypes and the improvement of demyelination in a cuprizone (CPZ) model of multiple sclerosis (MS). For inducing the chronic demyelination model, C57BL6 mice were given a diet with 0.2% CPZ (w/w) for 12 weeks. In the MSC group, cells were transplanted into the right lateral ventricle of mice. The expression of targeted genes was assessed by real-time polymerase chain reaction. M1 and M2 microglial phenotypes were assessed by immunohistochemistry of inducible nitric oxide synthase (iNOS) and Arg-1, respectively. Remyelination was studied by luxal fast blue (LFB) staining and electron microscopy (EM). We found that MSC transplantation reduced the expression level of M1-specific messenger RNA (mRNA; iNOS and CD86) but increased the expression level of M2 specific genes (CD206, Arg-1, and CX3CR1) in comparison to the CPZ group. Moreover, cell therapy significantly decreased the M1 marker (iNOS⁺ cells), but M2 marker (Arg-1⁺ cells) significantly increased in comparison with the CPZ group. In addition, MSC treatment significantly increased the CX3CL1 expression level in comparison with the CPZ group and led to improvement in remyelination, which was confirmed by LFB and EM images. The results showed that MSC transplantation increases the M2 and decreases the M1 phenotype in MS. This change was accompanied by decrease in demyelination and axonal injury and indicated that MSCs have a positive effect on MS by modification of microglia cells.     

Optimization of Anti-CXCL10 Nanobody Expression Using Response Surface Methodology and Evaluation of its Anti-metastatic Effect on Breast Cancer cells

International Journal of Peptide Research and Therapeutics - Some chemokines and chemokine receptors play important roles in various types of autoimmune diseases, infectious diseases and cancer...     

New Engineered Fusion Peptide with Dual Functionality: Antibacterial and Strong Binding to Hydroxyapatite

International Journal of Peptide Research and Therapeutics - One of the main challenges in oral disease is prevention of bacterial infections considering antibiotic resistance as a result of...     

Relationship between γ‐interferon gene polymorphisms and susceptibility to brucellosis infection

Interferon‐gamma (IFN‐γ) is a pro‐inflammatory cytokine that plays a pivotal role in the defense mechanism against Brucella infection. It was hypothesized that the IFN‐γ in (+874 A/T in intron 1) TT and +5644 T/A, TT genotypes, which are reportedly associated with high IFN production, are associated with susceptibility to brucellosis in Iranian subjects. Genotyping of these IFN‐γ variants by an allele‐specific polymerase chain reaction method was performed in 281 subjects, comprising 153 patients with active brucellosis and 128 healthy controls. It was found that the +874 minor allele (A) and homozygote genotype (AA) were significantly more frequently present in brucellosis patients than in controls (OR = 2.588; 95% CI, 1.313–5.104; P = 0.006 for the AA genotype; OR = 1.575; 95% CI, 1.124–2.216; P = 0.010 for the A allele). However, the allelic and genotypic distribution of the IFN‐γ polymorphism at position UTR5644 A>T did not differ significantly between patients and controls (P > 0.05). The distribution of haplotypes in this study suggests that the T/A haplotype (+874/UTR5644), which was present more frequently in controls than in patients, may protect subjects against Brucella infection. It is suggested that IFN‐γ +874 AA genotype and A allele are risk factors for developing brucellosis infection in Iranian subjects.     

Gene expression analysis supports tumor threshold over 2.0 cm for T-category breast cancer

Tumor size, as indicated by the T-category, is known as a strong prognostic indicator for breast cancer. It is common practice to distinguish the T1 and T2 groups at a tumor size of 2.0 cm. We investigated the 2.0-cm rule from a new point of view. Here, we try to find the optimal threshold based on the differences between the gene expression profiles of the T1 and T2 groups (as defined by the threshold). We developed a numerical algorithm to measure the overall differential gene expression between patients with smaller tumors and those with larger tumors among multiple expression datasets from different studies. We confirmed the performance of the proposed algorithm by a simulation study and then applied it to three different studies conducted at two Norwegian hospitals. We found that the maximum difference in gene expression is obtained at a threshold of 2.2–2.4 cm, and we confirmed that the optimum threshold was over 2.0 cm, as indicated by a validation study using five publicly available expression datasets. Furthermore, we observed a significant differentiation between the two threshold groups in terms of time to local recurrence for the Norwegian datasets. In addition, we performed an associated network and canonical pathway analyses for the genes differentially expressed between tumors below and above the given thresholds, 2.0 and 2.4 cm, using the Norwegian datasets. The associated network function illustrated a cellular assembly of the genes for the 2.0-cm threshold: an energy production for the 2.4-cm threshold and an enrichment in lipid metabolism based on the genes in the intersection for the 2.0- and 2.4-cm thresholds.     

Apelin-13 Protects PC12 Cells Against Methamphetamine-Induced Oxidative Stress,Autophagy and Apoptosis

Methamphetamine (METH) is a potent psychomotor stimulant that has a high potential for abuse in humans. In addition, it is neurotoxic, especially in dopaminergic neurons. Long-lasting exposure to METH causes psychosis and increases the risk of Parkinson’s disease. Apelin-13 is a novel endogenous ligand which studies have shown that may have a neuroprotective effect. Therefore, we hypothesized that Apelin-13 might adequately prevent METH-induced neurotoxicity via the inhibition of apoptotic, autophagy, and ROS responses. In this study, PC12 cells were exposed to both METH (0.5, 1, 2, 3, 4, 6 mmol/L) and Apelin-13 (0.5, 1.0, 2.0, 4.0, 8.0 μmol/L) in vitro for 24 h to measure determined dose, and then downstream pathways were measured to investigate apoptosis, autophagy, and ROS responses. The results have indicated that Apelin-13 decreased the apoptotic response post-METH exposure in PC12 cells by increasing cell viability, reducing apoptotic rates. In addition, the study has revealed Apelin-13 decreased gene expression of Beclin-1 by Real-Time PCR and LC3-II by western blotting in METH-induced PC12 cells, which demonstrated autophagy is reduced. In addition, this study has shown that Apelin-13 reduces intracellular ROS of METH-induced PC12 cells. These results support Apelin-13 to be investigated as a potential drug for treatment of neurodegenerative diseases. It is suggested that Apelin-13 is beneficial in reducing oxidative stress, which may also play an important role in the regulation of METH-triggered apoptotic response. Hence, these data indicate that Apelin-13 could potentially alleviate METH-induced neurotoxicity via the reduction of oxidative damages, apoptotic, and autophagy cell death.