Magnetic drug targeting through a realistic model of human tracheobronchial airways using computational fluid and particle dynamics

Biomechanics and Modeling in Mechanobiology - Magnetic drug targeting (MDT) is a local drug delivery system which aims to concentrate a pharmacological agent at its site of action in order to...     

Enhanced Protective Efficacy of Nonpathogenic Recombinant Leishmania tarentolae Expressing Cysteine Proteinases Combined with a Sand Fly Salivary Antigen

Background

Novel vaccination approaches are needed to prevent leishmaniasis. Live attenuated vaccines are the gold standard for protection against intracellular pathogens such as Leishmania and there have been new developments in this field. The nonpathogenic to humans lizard protozoan parasite, Leishmania (L) tarentolae, has been used effectively as a vaccine platform against visceral leishmaniasis in experimental animal models. Correspondingly, pre-exposure to sand fly saliva or immunization with a salivary protein has been shown to protect mice against cutaneous leishmaniasis.

Methodology/Principal Findings

Here, we tested the efficacy of a novel combination of established protective parasite antigens expressed by L. tarentolae together with a sand fly salivary antigen as a vaccine strategy against L. major infection. The immunogenicity and protective efficacy of different DNA/Live and Live/Live prime-boost vaccination modalities with live recombinant L. tarentolae stably expressing cysteine proteinases (type I and II, CPA/CPB) and PpSP15, an immunogenic salivary protein from Phlebotomus papatasi, a natural vector of L. major, were tested both in susceptible BALB/c and resistant C57BL/6 mice. Both humoral and cellular immune responses were assessed before challenge and at 3 and 10 weeks after Leishmania infection. In both strains of mice, the strongest protective effect was observed when priming with PpSP15 DNA and boosting with PpSP15 DNA and live recombinant L. tarentolae stably expressing cysteine proteinase genes.

Conclusion/Significance

The present study is the first to use a combination of recombinant L. tarentolae with a sand fly salivary antigen (PpSP15) and represents a novel promising vaccination approach against leishmaniasis.     

Oxidative Stress Parameters,Trace Elements,and Lipid Profile in Iranian Patients with Gaucher Disease

Biological Trace Element Research - Gaucher disease (GD) is most frequent disorder of glycolipid storage. The glucosylceramide accumulation might lead to oxidative stress and changes in lipid...     

Up-regulation of KISS1 as a novel target of Let-7i in melanoma serves as a potential suppressor of migration and proliferation in vitro

Melanoma is a kind of skin cancer that is begun by the alteration of melanocytes. miRNAs are small non-coding RNA molecules that regulate a variety of biological processes. KISS1, the metastasis-suppressor gene, encodes kisspeptins which inhibits migration and proliferation of cancers. This study was aimed to determine the role of Let-7i and KISS1 in melanoma cell migration and proliferation. At first, the expression of Let-7i and KISS1 was determined in patients with melanoma. In the in vitro part of the study, Let-7i mimics were transfected and the impact of its restoration on target gene expression, proliferation, migration and apoptosis of SK-MEL-3 melanoma cell line was assessed by real-time PCR and Western blotting, MTT assay, wound-healing assay and flow cytometry, respectively. Besides, KISS1 inhibitor siRNA alone and along with Let-7i was transfected to determine their probable correlation. The results revealed that either Let-7i or KISS1 were down-regulated in patients with melanoma. The results obtained from the in vitro part of the study revealed that restoration of Let-7i reduced the expression of metastasis- and proliferation-related target genes. Moreover, it was revealed that up-regulation of Let-7i attenuated migration and proliferation capability of SK-MEL-3 cells. Besides, it was demonstrated that Let-7i restoration induced apoptosis in melanoma cells. More importantly, the KISS1 inhibitor caused a prominent cell migration and proliferation, attenuated by Let-7i re-expression. To sum up, the present study revealed the impressive role of Let-7i restoration along with its correlation with KISS1 on melanoma carcinogenicity which may be applicable in future in vivo studies.     

A study on differences between radiation-induced micronuclei and apoptosis of lymphocytes in breast cancer patients after radiotherapy

Cancer patients' responses to radiotherapy vary in severity. It has been suggested that it may be due to differences in intrinsic cellular radiosensitivity. Prediction of tissue reactions to radiotherapy would permit tailoring of dosage to each patient. Towards this goal the micronucleus and apoptosis tests have been proposed as methods for measurement of chromosomal damage in peripheral blood lymphocytes. In this study, gamma-ray sensitivity of cultured lymphocytes of 26 breast cancer patients with early or late reactions was investigated. After irradiation with 4 Gy gamma radiation in G0, the frequency of micronuclei for patients with early reactions was significantly higher (P < 0.05) than for patients with late reactions. In the contrary the frequency of apoptosis for patients with early reactions was significantly lower (P < 0.05) than in the other group. It could be suggested that such a reduced amount of micronuclei in the late effects group is due to the presence of some residual DNA damages which are not completely repaired and lesions show increasing severity when the patients' cells are irradiated again. These induced damages, probably are high enough to stimulate other endpoints like apoptosis instead of micronuclei.     

Conodont biostratigraphy of the Upper Devonian-Lower Carboniferous Shahmirzad section, central Alborz, Iran

The conodont fauna from the Devonian-Carboniferous Shahmirzad section, located in the Central Alborz Mountains (North Iran), have been studied mainly for biostratigraphic purposes. Some levels were barren of conodonts, whereas others yielded a not very abundant, but quite differentiated fauna. No conodonts have been found from the mainly terrigenous and shaly Geirud Formation, whereas representative of genera Bispathodus, Clydagnathus, Gnathodus, Hindeodus, Mehlina, Polygnathus, Protognathodus, Pseudopolygnathus and Siphonodella have been collected from the mainly calcareous overlaying Mobarak Formation. The fauna allowed to discriminate five biointervals, from the sulcata Zone to a “Lower typicus - anchoralis-latus interval” in the central part of the section, while the lower and upper parts cannot be zoned on the basis of conodonts. This paper is the first report on lowermost Carboniferous conodonts from the Mobarak Formation in central Alborz.     

Effects of Buprenorphine on Balance of Oxidant/Antioxidant System in the Different Ages of Male Rat Liver

Our knowledge about a link between buprenorphine and hepatotoxicity is controversial. This study evaluated the effects of buprenorphine on the liver of young, adult, and aged rats. For this reason, young, adult, and aged rats received intraperitoneally 0.25, 0.5, and 1 mg/kg buprenorphine for 30 days. The present results revealed that the normal aging was associated with a significant decrease in the activities of antioxidant enzymes, and an increase in the liver lipid peroxidation, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities in the aged rats. This study also demonstrated that buprenorphine led to a significant increase in the serum activities of ALT, AST, and LDH as well as liver lipid peroxidation content with a decrease in the antioxidant enzymes in the liver of buprenorphine‐treated aged rat versus the aged matched control animals. In conclusion, the present results demonstrate that buprenorphine deteriorated oxidative damage in the aged livers.     

Short-term carbon input increases microbial nitrogen demand,but not microbial nitrogen mining,in a set of boreal forest soils

Rising carbon dioxide (CO₂) concentrations and temperatures are expected to stimulate plant productivity and ecosystem C sequestration, but these effects require a concurrent increase in N availability for plants. Plants might indirectly promote N availability as they release organic C into the soil (e.g., by root exudation) that can increase microbial soil organic matter (SOM) decomposition (“priming effect”), and possibly the enzymatic breakdown of N-rich polymers, such as proteins, into bio-available units (“N mining”). We tested the adjustment of protein depolymerization to changing soil C and N availability in a laboratory experiment. We added easily available C or N sources to six boreal forest soils, and determined soil organic C mineralization, gross protein depolymerization and gross ammonification rates (using ¹⁵N pool dilution assays), and potential extracellular enzyme activities after 1 week of incubation. Added C sources were ¹³C-labelled to distinguish substrate from soil derived C mineralization. Observed effects reflect short-term adaptations of non-symbiotic soil microorganisms to increased C or N availability. Although C input promoted microbial growth and N demand, we did not find indicators of increased N mobilization from SOM polymers, given that none of the soils showed a significant increase in protein depolymerization, and only one soil showed a significant increase in N-targeting enzymes. Instead, our findings suggest that microorganisms immobilized the already available N more efficiently, as indicated by decreased ammonification and inorganic N concentrations. Likewise, although N input stimulated ammonification, we found no significant effect on protein depolymerization. Although our findings do not rule out in general that higher plant-soil C allocation can promote microbial N mining, they suggest that such an effect can be counteracted, at least in the short term, by increased microbial N immobilization, further aggravating plant N limitation.     

Effect of BMP4 preceded by retinoic acid and co‐culturing ovarian somatic cells on differentiation of mouse embryonic stem cells into oocyte‐like cells

Bone morphogenetic protein 4 (BMP4) and retinoic acid (RA) signaling are the key regulators for germ cell and meiosis induction, respectively. Gonadal tissue also provides an appropriate microenvironment for oocyte differentiation in vivo. The current study aimed to determine whether mimicking in vivo niche is more efficient for oocyte differentiation from embryonic stem (ES) cells. Here, differentiation of mouse ES cells toward oocyte‐like cells using embryoid body (EB) and monolayer protocols was induced in the presence (+BMP4) or absence (‐BMP4) of BMP4. On day 5, each group was co‐cultured with ovarian somatic cells in the presence or absence of RA (+RA or –RA) for an additional 14 days. Our results showed a significant increase in expression of meiotic markers in the +BMP4 condition in EB differentiation protocol. Further differentiation with ovarian somatic cells led to a subpopulation of oocyte‐like cell formation. Compared to the controls, the +RA condition resulted in a significant elevation of the meiotic gene expression in contrast to Oct4 that significantly decreased in both protocols. In the cells pre‐treated with BMP4 and then exposed to RA in the monolayer differentiation protocol, the gene expression levels of germ cell, Mvh, and maturation markers, Cx37, Zp2, and Gdf9, were also upregulated significantly. Therefore, it can be concluded that +BMP4 and +RA along with ovarian somatic cell co‐culture improved the rate of in vitro oocyte differentiation.