Antitumor activity of amides of dihydrobetulonic acid in vitro and in vivo

Amides containing homopiperidine and piperazine cycles were synthesized from dihydrobetulonic acid obtained by the oxidation of dihydrobetulin. All substances were shown to have a high antitumor activity (CCID₅₀ = 3.5–36.2 μM) in vitro in lymphoid (CEM-13, U-937) and monocytic (MT-4) human cell lines. Amides containing the methyl- and ethylpiperazine residues do not influence the viability of Lung Lewis Carcinoma cells in culture and do not have a significant effect on its transplants in C57BL/6 mice. However, these amides efficiently inhibit the development of metastases in lungs of these mice. The antimetastatic activity of the studied amides increases with changing the methyl by ethyl aliphatic residue in the piperazine cycle.     

Plant virus infection development as affected by heavy metal stress

The work was focused on the investigation of possible dependencies between the development of viral infection in plants and the presence of high heavy metal concentrations in soil. Field experiments have been conducted in order to study the development of systemic tobacco mosaic virus (TMV) infection in Lycopersicon esculentum L. cv. Miliana plants under effect of separate salts of heavy metals Cu, Zn and Pb deposited in soil. As it is shown, simultaneous effect of viral infection and heavy metals in tenfold maximum permissible concentration leads to decrease of total chlorophyll content in experiment plants mainly due to the degradation of chlorophyll a. The reduction of chlorophyll concentration under the combined influence of both stress factors was more serious comparing to the separate effect of every single factor. Plants' treatment with toxic concentrations of lead and zinc leaded to slight delay in the development of systemic TMV infection together with more than twofold increase of virus content in plants that may be an evidence of synergism between these heavy metal's and virus' effects. Contrary, copper although decreased total chlorophyll content but showed protective properties and significantly reduced amount of virus in plants.     

Delivery and processing of exogenous double-stranded DNA in mouse CD34 + hematopoietic progenitor cells and their cell cycle changes upon combined treatment with cyclophosphamide and double-stranded DNA

We previously reported that fragments of exogenous double-stranded DNA can be internalized by mouse bone marrow cells without any transfection. Our present analysis shows that only 2% of bone marrow cells take up the fragments of extracellular exogenous DNA. Of these, ~ 45% of the cells correspond to CD34 + hematopoietic stem cells. Taking into account that CD34 + stem cells constituted 2.5% of the total cell population in the bone marrow samples analyzed, these data indicate that as much as 40% of CD34 + cells readily internalize fragments of extracellular exogenous DNA. This suggests that internalization of fragmented dsDNA is a general feature of poorly differentiated cells, in particular CD34 + bone marrow cells.     

Extramedullary hematopoiesis in a case of benign mixed mammary tumor in a female dog: cytological and histopathological assessment

Backgroud  

Extramedullary hematopoiesis (EMH) is defined as the presence of hematopoietic stem cells such as erythroid and myeloid lineage plus megakaryocytes in extramedullary sites like liver, spleen and lymph nodes and is usually associated with either bone marrow or hematological disorders. Mammary EMH is a rare condition either in human and veterinary medicine and can be associated with benign mixed mammary tumors, similarly to that described in this case.     

Excessive folate synthesis limits lifespan in the C. elegans: E. coli aging model

Background

Repeated adaptive radiations are evident when phenotypic divergence occurs within lineages, but this divergence into different forms is convergent when compared across lineages. Classic examples of such repeated adaptive divergence occur in island (for example, Caribbean Anolis lizards) and lake systems (for example, African cichlids). Host-parasite systems in many respects are analogous to island systems, where host species represent isolated islands for parasites whose life cycle is highly tied to that of their hosts. Thus, host-parasite systems might exhibit interesting cases of repeated adaptive divergence as seen in island and lake systems. The feather lice of birds spend their entire life cycle on the body of the host and occupy distinct microhabitats on the host: head, wing, body and generalist. These microhabitat specialists show pronounced morphological differences corresponding to how they escape from host preening. We tested whether these different microhabitat specialists were a case of repeated adaptive divergence by constructing both morphological and molecular phylogenies for a diversity of avian feather lice, including many examples of head, wing, body and generalist forms.

Results

Morphological and molecular based phylogenies were highly incongruent, which could be explained by rampant convergence in morphology related to microhabitat specialization on the host. In many cases lice from different microhabitat specializations, but from the same group of birds, were sister taxa.

Conclusions

This pattern indicates a process of repeated adaptive divergence of these parasites within host group, but convergence when comparing parasites across host groups. These results suggest that host-parasite systems might be another case in which repeated adaptive radiations could be relatively common, but potentially overlooked, because morphological convergence can obscure evolutionary relationships.     

Macrophage enhancement of the immunogenicity of a suboptimal dosage of antigen-antibody complex]

Dawley mice were immunized with rabbit gamma globulin combined with allotypical antibodies, introduced alone or after preliminary incubation with syngeneic macrophages. Enhanced immune response was observed in the rats immunized both with low (0.11 mg) and high (1.1 mg) doses of the antigen with macrophages. A conclusion was made that this enhanced response had no connection with the elimination of the excess antigen by the macrophages.     

Inhibition of metastasis development by daily administration of ultralow doses of RNase A and DNase I

Recent data on the involvement of miRNA and circulating tumor-derived DNA in regulation of tumorigenesis showed a great prospect for these molecules as a novel class of therapeutic targets and gave a new start for the study of enzymes cleaving nucleic acids as potential antitumor and antimetastatic agents. In the present paper using two murine tumor models with pulmonary or liver metastases we studied the antimetastatic potential of RNase A and DNase I and performed a search for possible molecular targets of the enzymes. Herein, we show for the first time that daily administration of ultralow doses of RNase A (0.5-50 μg/kg) and DNase I (0.02-2.3 mg/kg) inhibits the development of metastasis to 60-90% and RNase A exerts 30% retardation of tumor growth. Remarkably, the increase in RNase A dose from 50 μg/kg to 10 mg/kg leads to a disappearance of antitumor and antimetastatic effects. Simultaneous treatment of tumor-bearing animals with RNase A and DNase I leads to an additive effect and results in almost total absence of metastases. The use of RNase A as an adjuvant in conjunction with conventional cytostatic cyclophosphamide results in a reliable enhancement of antitumor and antimetastatic effect of the therapy compared with the use of these agents individually. The search for possible molecular mechanism of antimetastatic effect of nucleases showed that daily administration of the enzymes reduced the pathologically increased level of extracellular nucleic acids and increased nuclease activity of the blood plasma of tumor-bearing mice back to the level of healthy animals. Thus, we unequivocally show that the proposed protocol of treatment of tumor-bearing animals with RNase A and DNase I has a general systemic and immunomodulatory effect, leads to a drastic suppression of metastasis development, and in perspective may become an effective component of intensive complex therapy of cancer.