The role of liposome charge on immune response generated in BALB/c mice immunized with recombinant major surface glycoprotein of Leishmania (rgp63)

Liposomes as a lipid-based system have been shown to be an effective adjuvant formulation. In this study, the role of liposome charge in induction of a Th1 type of immune response and protection against leishmaniasis in BALB/c mice was studied. Liposomes containing rgp63 were prepared by Dehydration-Rehydration Vesicle (DRV) method. Neutral liposomes consisted of dipalmitoylphosphatidylcholine and cholesterol. Positively and negatively charged liposomes were prepared by adding dimethyldioctadecylammonium bromide (DDAB) or dicetyl phosphate (DCP) to the neutral liposome formulation, respectively. Female BALB/c mice were immunized subcutaneously with negatively, positively charged or neutral liposomes encapsulated with rgp63, rgp63 in soluble form or PBS, three times in 3 week intervals. The extent of protection and type of immune response generated were studied in different groups of mice. The group of mice immunized with rgp63 encapsulated in neutral liposomes showed a significantly (P < 0.01) smaller footpad swelling upon challenge with Leishmania major compared with positively or negatively charged liposomes. The mice immunized with neutral liposomes also showed a significantly (P < 0.01) the lowest splenic parasite burden, the highest IgG2a/IgG1 ratio and IFN-γ production and the lowest IL-4 level compared to the other groups. The results indicated that a Th1 type of immune response was induced in mice immunized with neutral liposomes more efficiently than positively charged liposomes and conversely negatively charged liposomes induced a Th2 type of immune response.     

Biotransformation of glycerol to 3-hydroxypropionaldehyde: Improved production by in situ complexation with bisulfite in a fed-batch mode and separation on anion exchanger

3-Hydroxypropionaldehyde (3HPA) is an important C3 chemical that can be produced from renewable glycerol by resting whole cells of Lactobacillus reuteri. However the process efficiency is limited due to substrate inhibition, product-mediated loss of enzyme activity and cell viability, and also formation of by-products. Complex formation of 3HPA with sodium bisulfite and subsequent binding to Amberlite IRA-400 was investigated as a means of in situ product recovery and for overcoming inhibition. The adsorption capacity and -isotherm of the resin were evaluated using the Langmuir model. The resin exhibited maximum capacity of 2.92 mmol complex/g when equilibrated with 45 mL solution containing an equilibrium mixture of 2.74 mmol 3HPA-bisulfite complex and 2.01 mmol free 3HPA. The dynamic binding capacity based on the breakthrough curve of 3HPA and its complex on passing a solution with 2.49 mmol complex and 1.65 mmol free 3HPA was 2.01 mmol/g resin. The bound 3HPA was desorbed from the resin using 0.20 M NaCl with a high purity as a mixture of complexed- and free 3HPA at a ratio of 0.77 mol/mol. Fed-batch biotransformation of glycerol (818.85 mmol) with in situ 3HPA complexation and separation on the bisulfite-functionalized resin resulted in an improved process with consumption of 481.36 mmol glycerol yielding 325.54 mmol 3HPA at a rate of 17.13 mmol/h and a yield of 68 mol%. Also, the cell activity was maintained for at least 28 h.     

The role of bla(OXA-like carbapenemase) and their insertion sequences (ISS) in the induction of resistance against carbapenem antibiotics among Acinetobacter baumannii isolates in Tehran hospitals

This study aimed to evaluate the occurrence and dissemination of bla(OXA-like) carbapenemase genes and their insertion sequences among Acinetobacter baumannii isolates, taken from different hospitals in Tehran city and also their roles in the induction of resistance to carbapenem drugs. A total number of 100 non duplicate Acinetobacter baumannii with different origins, were isolated from patients with proved nosocomial infections at eight university hospital in Tehran city. Antimicrobial susceptibility of these strains was done by E-test against 7 antimicrobial agents according to CLSI guideline. PCR of bla(OXA-51-like), bla(OXA-23-like), bla(OXA-24-like), bla(OXA-58-like), IS(ABA-1), IS(1133) was carried out by specialized primers and then these strains were typed by REP-fingerprinting. Colistin, imipenem and meropenem were the most sensitive antibiotics against Acinetobacter baumannii isolates with 96%, 51% and 51% sensitivity respectively. All the isolates had a bla(OXA-51-like) intrinsic to these species. The rates of bla(OXA-23), 23 and 58-like were 38%, 32% and 1% respectively. Coexistence of bla(OXA-51/23/24-like) was observed among 16% of these isolates. All bla(OXA-23-like) carbapenemase genes had only one IS(ABA1). REP fingerprinting showed 5 genotypes among carbapenem resistant isolates, 16 of them being genotype A. This study emphasized on the major role of bla(OXA-like) carbapenemase, particularly bla(OXA-23-like) carbapenemase and their IS(ABA1), in the dissemination of carbapenem resistant Acinetobacter baumannii. This study confirmed a presumptive role of IS element neighboring the carbapenemase gene in the elevation of resistance to carbapenem drug among Acinetobacter baumannii isolates for the first time in Iran.     

Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis

Identification of the factors critical to the tumor-initiating cell (TIC) state may open new avenues in cancer therapy. Here we show that the metabolic enzyme glycine decarboxylase (GLDC) is critical for TICs in non-small cell lung cancer (NSCLC). TICs from primary NSCLC tumors express high levels of the oncogenic stem cell factor LIN28B and GLDC, which are both required for TIC growth and tumorigenesis. Overexpression of GLDC and other glycine/serine enzymes, but not catalytically inactive GLDC, promotes cellular transformation and tumorigenesis. We found that GLDC induces dramatic changes in glycolysis and glycine/serine metabolism, leading to changes in pyrimidine metabolism to regulate cancer cell proliferation. In the clinic, aberrant activation of GLDC correlates with poorer survival in lung cancer patients, and aberrant GLDC expression is observed in multiple cancer types. This link between glycine metabolism and tumorigenesis may provide novel targets for advancing anticancer therapy.     

Application of antimicrobial peptides in agriculture and food industry

Antimicrobial peptides have captured the attention of researchers in recent years because of their efficiency in fighting against pathogens. These peptides are found in nature and have been isolated from a wide range of organisms. Furthermore, analogs or synthetic derivatives have successfully been developed on the basis of natural peptide patterns. Long use of pesticides and antibiotics has led to development of resistance among pathogens and other pests as well as increase of environmental and health risks. Antimicrobial peptides are under consideration as new substitutes for conventional pesticides and antibiotics. Many plants and animals have been manipulated with antimicrobial peptide-encoding genes and several pesticides and drugs have been produced based on these peptides. Such strategies and products may still have a long way to go before being confirmed by regulatory bodies and others need to surmount technical problems before being accepted as applicable ones. In spite of these facts, several cases of successful use of antimicrobial peptides in agriculture and food industry indicate a promising future for extensive application of these peptides. In this review, we consider the developing field of antimicrobial peptide applications in various agricultural activities.     

Angiotensin-converting enzyme genotype and late respiratory complications of mustard gas exposure

Background

Exposure to mustard gas frequently results in long-term respiratory complications. However the factors which drive the development and progression of these complications remain unclear. The Renin Angiotensin System (RAS) has been implicated in lung inflammatory and fibrotic responses. Genetic variation within the gene coding for the Angiotensin Converting Enzyme (ACE), specifically the Insertion/Deletion polymorphism (I/D), is associated with variable levels of ACE and with the severity of several acute and chronic respiratory diseases. We hypothesized that the ACE genotype might influence the severity of late respiratory complications of mustard gas exposure.

Methods

208 Kurdish patients who had suffered high exposure to mustard gas, as defined by cutaneous lesions at initial assessment, in Sardasht, Iran on June 29 1987, underwent clinical examination, spirometric evaluation and ACE Insertion/Deletion genotyping in September 2005.

Results

ACE genotype was determined in 207 subjects. As a continuous variable, FEV₁ % predicted tended to be higher in association with the D allele 68.03 ± 20.5%, 69.4 ± 21.4% and 74.8 ± 20.1% for II, ID and DD genotypes respectively. Median FEV₁ % predicted was 73 and this was taken as a cut off between groups defined as having better or worse lung function. The ACE DD genotype was overrepresented in the better spirometry group (Chi² 4.9 p = 0.03). Increasing age at the time of exposure was associated with reduced FEV₁ %predicted (p = 0.001), whereas gender was not (p = 0.43).

Conclusion

The ACE D allele is associated with higher FEV₁ % predicted when assessed 18 years after high exposure to mustard gas.     

Neuroprotective Effect of Apigenin on Depressive-Like Behavior: Mechanistic Approach

Apigenin, as a natural flavonoid present in several plants is characterized with potential anticancer, antioxidant, and anti-inflammatory properties. Recent studies proposed that apigenin affects depression disorder through unknown mechanistic pathways. The effects of apigenin’s anti-depressive properties on streptozocin-mediated depression have been investigated through the evaluation of behavioral tests, oxidative stress, cellular energy homeostasis and inflammatory responses. The results demonstrated anti-depressive properties of apigenin in behavioral test including forced swimming and splash tests and oxidative stress biomarkers such as reduced glutathione, lipid peroxidation, total antioxidant power and coenzyme Q₁₀ levels. Apigenin, also, demonstrated its regulatory potency in cellular energy homeostasis and immune system gene expression through inhibiting Nlrp3 and Tlr4 overexpression. Furthermore, failure in energy production as the key factor in various psychiatric disorders was reversed by apigenin modulating effect on AMPK gene expression. Overall, 20 mg/kg of apigenin was recognized as the dose suitable for minimizing the undesirable adverse effects in the STZ-mediated depression model proposed in this study. Our data suggested that apigenin could be able to adjust behavioral dysfunction, biochemical biomarkers and recovered cellular antioxidant level in depressed animals. The surprising results were achieved by raise in COQ₁₀ level, which could regulate the overexpression of the AMPK gene in stressful conditions. The regulatory effect of apigenin in inflammatory signaling pathways such as Nlrp3, and Tlr4 gene expression was studied at the surface part of the hippocampus.