Effect of Human HSP90 on Secondary and Tertiary Structures of Core Protein of Hepatitis C Virus and HbsAg of Hepatitis B Virus

The secondary structure of recombinant proteins can change through complex formation with other proteins. Here, we have determined the spatial structure of two proteins, including core protein of hepatitis C virus and HbsAg of hepatitis B virus, without the effect of human HSP90 as well as with the effect of this recombinant chaperone. As a result, the increase in intensity from 297.5 to 346.64 was accompanied by different folding and being non-polar protein in complex with the chaperone. HbsAg protein, combined with HSP90, showed a reduction in the maximum peak wavelength from 385 to 369.07 nm. The property of protein of being non-polar and hydrophobic, as well as having an increase in intensity from 200 to 219, indicates the protein folding. The shift from 342 to 337 nm along with blue shift indicates hydrophobic properties and the removal of protein from the water environment

Evaluation of the Coagulant Effect of the Zanjani and Latifi Viper Venom Endemic in Iran

The venom of the viper is very important in pharmaceutical usage, such as in the process of coagulation during medical care. This study aims to evaluate the coagulant factor of Latifi and Zanjani viper venom. In the current study, after electrophoresis of proteins found in viper venom, all of the thick and strong bands of proteins were isolated and prepared for examination of coagulation characteristics, like pro-thrombin time (PTT) and active partial thromboplastic time (APTT), followed by further study by mass spectroscopy. In this way, 11 bands of proteins were recognized in sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). After PT and APTT tests, one common band in 26 KDa could lead to coagulation of blood plasma in less than one second. Mass spectroscopy identified this band as serine protease isoform4. The results confirmed the coagulation effect of a 26 KDa protein fraction of venom from Latifi and Zanjani vipers

Apoptotic Effects of the B Subunit of Bacterial Cytolethal Distending Toxin on the A549 Lung Cancer Cell Line

Cytolethal distending toxin (CDT) is a secreted tripartite genotoxin produced by many pathogenic gram-negative bacteria. It is composed of three subunits, CdtA, CdtB and CdtC, and CdtB-associated deoxyribonuclease (DNase) activity is essential for the CDT toxicity. In the present study, to design a novel potentially antitumor drug against lung cancer, the possible mechanisms of cdtB anticancer properties were explored in the A549 human lung adenocarcinoma cell line. A recombinant plasmid pcDNA3.1/cdtB was constructed expressing CdtB of human periodontal bacterium Aggregatibacter actinomycetemcomitans and investigated for toxic properties in A549 cells and possible mechanisms. It was observed that plasmid pcDNA3.1/cdtB caused loss of cell viability, morphologic changes and induction of apoptosis. Furthermore, measurement of caspase activity indicated involvement of an intrinsic pathway of cell apoptosis. Consequently, the recombinant plasmid pcDNA3.1/cdtB may have potential as a new class of therapeutic agent for gene therapy of lung cancer

The Role of Immune System in Thalassemia Major: A Narrative Review

Abstract Context: Thalassemia is a genetic disorder of hemoglobin production. Patients with thalassemia major (TM) require regular blood transfusions to keep a compatible hemoglobin level for oxygenating organs. These patients suffer from different complications such as infections, autoimmunity and alloimmunization due to transfusion. Such complications link the immune system to TM pathogenesis. In the present study, we have reviewed the latest data available on interactions of TM pathophysiologic determinants and immune system components. Evidence Acquisition: A comprehensive search was performed on PubMed, Scopous, and Web of Knowledge databases using keywords thalassemia, immune system, autoimmune, alloimmune, adaptive immunity, innate immunity, complications, and immunesenescnce. Results: It seems that persistent antigenic stimulation and oxidative stress from excessive iron are the 2 main pathophysiologic factors of TM impacting the immune system. Regarding innate immunity, functional activity of neutrophils, and natural killer cells (NKCs) is decreased in TM. On the other hand, higher levels of TNF-α and IL-1β, IL-6, IL-8, and C-reactive protein proinflammatory cytokines have been observed in the serum of patients. TM patients have demonstrated higher ratios of regulatory B lymphocytes (CD19+, CD38+, CD24+), helper T cells, suppressor T cells, and T regulatory (CD4+/CD25+/Foxp3+) lymphocytes. TM patients have shown significant higher levels of IgA immunoglobin respective to normal counterparts that may predispose them to diabetes and coeliac disease. Immune cells, however, rendered lower than optimal activity in TM patients, which may be due to nutritional insuf- ficiencies. Potential relationships have been suggested between immune system and various thalassemia compilations including heart infraction, hypertension, atherosclerosis, diabetes, thyroid dysfunction, and osteoporosis. Conclusions: Immune genetic determinants may be involved in modulating the clinical picture of TM. TM patients generally represents with higher immune cell counts, likely as a result of persistent antigenic challenge from blood transfusions. However, these patients face compromised immune cell functions. The role of immunologic interactions in pathogenesis of TM needs to be further divulged in future studies

Recent advances on biocompatible and biodegradable nanoparticles as gene carriers

Introduction: Gene therapy mainly depends on the use of appropriate delivery vehicles with no induction of immune responses and toxicity. The limitations of viral gene carriers such as induction of immunogenicity, random integration in the genome of the host, limitations in the size, has led to a movement toward non-viral systems with much safer properties. Biodegradable and biocompatible polymeric nanocarriers due to several unique properties such as excellent biocompatibility, prolonged gene circulation time, prevented gene degradation, passive targeting by using the enhanced permeability and retention (EPR) effect, and possibility of modulating polymers structure to obtain desirable therapeutic efficacy, are among the most promising systems for gene delivery. However, biodegradable gene delivery systems have some limitations such as inadequate stability and slow release of therapeutics which have to be overcome. Thus, a variety of advanced functional biodegradable delivery systems with more efficient gene delivery activity has recently been introduced. Areas covered: This review summarizes different aspects of biodegradable and biocompatible nano carriers including formulation, mechanism of intracellular uptake, various potential applications of biodegradable nanoparticles and finally recent studies on the therapeutic efficacy of these nanoparticles in sustained delivery of genes

Assessment of expression of interferon γ (IFN-G) gene and its antisense (IFNG-AS1) in breast cancer

Background The role of long non-coding RNAs has been extensively appreciated in the contexts of cancer. Interferon γ-antisense RNA1 (IFNG-AS1) is an lncRNA located near to IFN-γ-encoding (IFNG) gene and regulates expression of IFNG in Th1 cells. Methods In the present study, we evaluated expression of IFNG and IFNG-AS1 in 108 breast samples including tumoral tissues and their adjacent non-cancerous tissues (ANCTs) using real-time PCR. IFNG-AS1 was significantly upregulated in tumoral tissues compared with ANCTs (expression ratio = 2.23, P = 0.03). Results Although the expression of IFNG was higher in tumoral tissues compared with ANCTs (relative expression = 1.89), it did not reach the level of significance (P = 0.07). IFNG expression was significantly higher in HER2-negative tumoral tissues compared with HER2-positive ones (P = 0.01) and in grade 1 samples compared with grade 2 ones (P = 0.03). No other significant difference was found in expressions of genes between other groups. Conclusion Significant strong correlations were detected between expression of IFNG and IFNG-AS1 in both tumoral tissues and ANCTs. The present study provides evidences for participation of IFNG and IFNG-AS1 in the pathogenesis of breast cancer and warrants future studies to elaborate the underlying mechanism

Modulation of the Immune Response to DNA Vaccine Encoding Gene of 8-kDa Subunit of Echinococcus granulosus Antigen B Using Murine Interleukin-12 Plasmid in BALB/c Mice

Abstract Background: The current study was designed to evaluate immune responses induced by DNA vaccines encoding 8-kDa subunit of antigen B (HydI) of Echinococcus granulosus and murine interleukin 12 (IL-12) as genetic adjuvants in BALB/c mice. Methods: Expression plasmid pcDNA3.1 containing HydI (pcHyd1) as vaccine along with the murine interleukin 12 (pcMIL12) as adjuvant were used. Thirty-five mice in the five experimental groups received PBS, empty pcDNA3.1, pcHydІ, pcMIL-12, and pcHydІ+ pcMIL-12 in days zero, 14th and 28th. Two weeks after the last immunization, evaluation of the immune response was performed by evaluating the proliferation of splenic lymphocytes, IFN-γ and IL-4, determination of IgG isotyping titer. Results: Mice that received the pcHydI+pcMIL12 exhibited higher levels of lymphocyte proliferation compared to mice that received the pcHydI alone (P<0.001), and produced significantly more IFN-γ in comparison to other groups (P< 0.001). In addition, they produced significantly less IL-4 than mice receiving the PBS and the empty plasmid (P<0.023). The IgG2a levels were clearly higher in pcHydI+pcMIL12 group in comparison with the groups of pcHydI alone, empty plasmid, and PBS. In contrast, IgG1 was elevated in the group of pcHydI. Conclusion: Co-delivery of IL-12 with DNA encoding 8-kDa subunit of antigen B was effective significantly in inducing the immune response in mice

Direct growth of ternary copper nickel cobalt oxide nanowires as binder-free electrode on carbon cloth for nonenzymatic glucose sensing

A new binder free electrode based on ternary copper nickel cobalt oxide nanowires grown on the carbon cloth (CuNiCoO4 NWs@ carbon cloth) was prepared and characterized by field emission scanning electron microscopy (FE-SEM), x-ray diffraction (XRD), Energy-dispersive X-ray spectroscopy (EDX), and cyclic voltammetry (CV). The prepared electrocatalyst was directly used for electrochemical sensing of glucose without using enzyme. The effect of different parameters such as potential scan rate, switching potential, and glucose concentration on the electrochemical oxidation of glucose was investigated. The results showed that such an electrode presents excellent catalytic activity toward the oxidation of glucose in aqueous alkaline solution. Under optimum conditions, the potential application of the electrode was evaluated by applying it to the analytical determination of glucose concentration. The results revealed that the electrocatalytic current increased linearly with the glucose concentration in the range from 0.02 to 1.4 mM with a low detection limit of 6.5 μM and good sensitivity of as high as 1782 μA mM−1 cm−2 . Selectivity investigations demonstrate that the CuNiCoO4 NWs@CC electrode could be used for selective detection of glucose in the presence of interfering species. Real sample analysis shows reasonable RSD values implying negligible matrix effect in determination of glucose in human serum samples

PTEN-induced putative kinase 1 (PINK1) down-regulation in breast cancer samples in association with mitotic rate

PINK1 codes for a serine/threonine-protein kinase located in the mitochondria. This protein contributes in the pathophysiology of both neurodegenerative diseases and cancer. Its transcription has been shown to be regulated by a natural occurring antisense (AS) RNA named PINK1-AS. We examined expression levels of PINK1 and PINK1-AS in 54 breast cancer specimens versus their nearby non-cancerous tissues. We found significant down-regulation of PINK1 in tumoral tissues compared with nearby tissues (P = .003). Yet, expression of PINK1-AS was not remarkably different between tumoral tissues and nearby tissues. Relative expression of PINK1 was associated with mitotic rate (P = .03). We also found trends toward over-expression of PINK1 in younger patient compared with older patients (P = .09) and in grade 2 tumors compared with grade 3 ones (P = .08). The current study delivers further evidences for contribution of PINK1 in the pathophysiology of breast cancer and highlights the context-dependent properties the encoded protein

Naltrexone; as an efficient adjuvant in induction of Th1 immunity and protection against Fasciola hepatica infection

Toxic effects of available therapeutics are major drawbacks for conventional management approaches in parasitic infections. Vaccines have provided a promising opportunity to obviate such unwanted complications. In present study, we examined immune augmenting capacities of an emerging adjuvant, Naltrexone, against Fasciola hepatica infection in BALB/c mice. Seventy BALB/c mice were divided into five experimental groups (14 mice per group) including 1- control (received PBS), 2- vaccine (immunized with F. hepatica E/S antigens), 3- Alum-vaccine (immunized with Alum adjuvant and E/S antigens), 4- NLT-vaccine (immunized with NLT adjuvant and E/S antigens), and 5- Alum-NLT-vaccine (immunized with mixed Alum-NLT adjuvant and E/S antigens). Lymphocyte stimulation index was assessed by MTT assay. Production of IFN-γ, IL-4, IgG2a and IgG1 was assessed by ELISA method. Results showed that NLT, either alone or in combination with alum, can induce immune response toward production of IFN-γ and IgG2a as representatives of Th1 immune response. Also, using this adjuvant in immunization experiment was associated with significantly high proliferative response of splenocytes/lymphocytes. Utilization of mixed Alum-NLT adjuvant revealed the highest protection rate (73.8%) in challenge test of mice infected with F. hepatica. These findings suggest the potential role of NLT as an effective adjuvant in induction of protective cellular and Th1 immune responses against fasciolosis. © 2018 Elsevier Inc