Molecular serological characteristics of ABO system A antigen

Background. One of the polymorphic antigens in the ABO system is antigen A, which includes many allelic variants with different expression. Immunological methods for determining the blood group of the ABO system have limitations in their use, including due to the presence of weekly expressed antigens in humans. For the correct determination of blood group according to the ABO system, genetic typing is becoming increasingly important. 89 alleles of the ABO*A gene are known. Knowledge of ABO*A gene polymorphisms and their prevalence contributes to the prevention of errors in determining the blood group of donors and recipients.Objective: to describe variants of ABO*A gene alleles in Russians and serological characteristics of the antigens encoded by them.Materials and methods. The blood of 14,000 people was examined. The blood group was determined using anti-A, anti- Aweak, anti-B, lectin (anti-A1) and gel cards. A molecular study of ABO*A gene polymorphisms was conducted in 151 people. Polymerase chain reaction with sequence-specific primers and direct Sanger sequencing were used.Results. 7 different ABO*A alleles were detected, including the ABO*A1.01 and ABO*A1.02 alleles. In 118 individuals with a weak A antigen, the ABO*A2.01 allele was the most frequent (87.29 %). Rare alleles ABO*A2.06 (5.93 %), ABO*AW.06 (4.23 %), ABO*A2.09 (0.85 %) and ABO*Ax (1.70 %) were found. Serological characteristics of A antigens variants depending on genotypes are described, variants A1, A2, A3 and very weak A were detected. Extraagglutinins α1 were absent in all persons with weakened A antigen.Conclusion. Small or mixed agglutination with Coliclones or red blood cell stratification in the gel suggest the presence of antigen A with weakened expression. Modern molecular methods make it possible to identify rare gene alleles and genotypes. Erythrocyte genomics helps to resolve the ambiguity of the serological results allows understanding the true mechanisms of particular phenotype formation and makes a contribution to ensuring the immunological safety of blood components transfusions.

Effects of microRNA-103 on the Proliferation and Apoptosis of Pancreatic Cancer Cells via Targeting Phosphatase and Tensin Homolog Deleted on Chromosome Ten (PTEN) and Activating Phosphoinositide 3-Kinase/A Serine/Threonine Kinase (PI3K/Akt) Signaling Pathway

Objective: To investigate whether micro ribonucleic acid (miR)-103 affects pancreatic cancer (PaCa) cells via PTEN-activated PI3K/Akt signaling pathway. Methods: Differences in miR-103 expression in 35 pairs of PaCa tissues and cell lines (SW1990 and PATU8988S) were detected by RT-qPCR. miR-103 inhibitor was transfected into PaCa PATU8988S cell followed by analysis of proliferation and apoptosis of PaCa cells by MTT assay and flow cytometry, respectively. Results: MiR-103 exhibited a significantly high expression in PaCa tissues and cell lines (p < 0.05). Besides, the exogenous inhibition of miR-103 expression in PATU8988S cells significantly inhibited cell proliferation and migration but increased apoptosis activity (p < 0.05). According to the prediction of TargetScan biological database, miR-103 could bind PTEN 3′ untranslated region (3′UTR) and miR-103 was confirmed to suppress PTEN expression in a targeted way (p<0.05). Furthermore, down-regulation of PTEN activated PI3K/Akt signaling to affect the proliferation and apoptosis of PaCa cells (p < 0.05 or p <0.01). Conclusion: MiR-103 displays a significantly increased expression in PaCa cells and targets PTEN to activate PI3K/Akt signaling pathway, thus promoting malignant phenotype formation.

Proposed O-GalNAc/Gal Glycosylation Pathways in Blood Group O and Non-O Blood Group Phenotypes During Plasmodium falciparum Infections. A Hypothesis Regarding how ABO(H) Blood Group Phenotype Formation Drives Evolution

The coevolution of species drives diversity in animals and plants and contributes to natural selection, whereas in host&ndash;parasite coevolution, a parasite may complete an incomplete evolutionary/developmental function by utilizing the host cell&rsquo;s machinery. Analysis of related older data suggests that Plasmodium falciparum (P. falciparum), the pathogen of malaria tropica, cannot survive outside its human host because it is unable to perform the evolutionarily first protein glycosylation of serologically A-like, O-GalNAc&alpha;1-Ser/Thr-R, Tn antigen (&ldquo;T nouvelle&rdquo;) formation, owing to its inability for synthesizing the amino sugar N-acetyl-d-galactosamine (GalNAc). Nevertheless, this parasite breaks the species barrier via hijacking the host's A-like/Tn formation through abundantly expressed serine residues and creating hybrid A-like/Tn structures, associated with the arising of the germline-encoded nonimmune polyreactive immunoglobulin M (IgM), exerting the highly anti-A/B/H-aggressive isoagglutinin avtivities. In the human, this nonimmune antibody molecule physiologically undergoes the ABO(H) blood group phenotype formation, occurring on the surfaces of red blood cells (RBC), epithelial and endothelia cells as well as on plasma proteins by identical glycosylation, performed by the ABO(H) allelic, specific glycotransferases in a single enzymatic step, reducing and/or removing anti-A/B/H-reactive IgM, or isoagglutinin activities. ABO(H) phenotype diversity, this way glycosidically linked to humoral immunity, becomes exposed to the evolution.

Nanoparticle encapsulation of HDACi with HA targeting in endometrial cancer models

Bespoke nanoparticle systems can enhance drug delivery, preventing systemic exposure by modifying release kinetics and increasing tumour penetration. Flexible nano vector systems have led to selective tumour targeting through surface modifications and the addition of target moieties over expressed in the cancer microenvironment. As such nanomedicines are enabling drug re-purposing and renewed applications in solid tumour cancers. Here we present the nanoscale encapsulation of Vorinostat within a F127 Pluronic polymer particle modified to incorporate a Hyaluronic Acid moiety, targeting increased CD44 expression in endometrial cancer cells. Encapsulation within a stable micellar structure stabilized SAHA activity, demonstrating increased cytotoxic efficacy in 2-D and 3-D cultures. In addition, nano delivery enhanced spheroid penetration, suppression in cell growth, P21 associated cell cycle arrest and overcome EMT associated phenotype formation observed in the free drug treated type II Hec50 cells. Together, this study clearly demonstrates that HDAC nanoparticle encapsulation and HA targeting may offer a solution to overcoming the toxicity and side effects issues observed in clinical trials. Given the demonstrated involvement of epigenetic processes in oncology, this study is an important demonstration of this class of anti-cancerous agents for the treatment of endometrial cancers.

Therapeutic resistance in depression from the genetics and pharmacogenetics point of view

Current trends in the concept of therapeutically resistant depression (TRD) tend to narrow its very heterogeneous group of patients. One of the most rapidly developing areas in the biological paradigm of TRD is genetic research aimed at finding biomarkers for predicting the therapeutic response. Obviously, the genetic risks of TR are not limited to combinations of genome genetic variants, but it also has phenotypic manifestations at all levels of phenotype formation. According to the fundamental possibility of achieving remission states, therapeutic resistance can be divided into relative and absolute. At present, it can be said that patients with relative and absolute resistance represent two biologically heterogeneous groups, the isolation of which requires the development of special laboratory approaches that will contribute to the development of a personalized approach to therapy.

Pre-eclampsia in a mother and programming of the child’s cardiovascular health

The authors present a review of the literature devoted to the problem of programming the formation of the cardiovascular system structure and function in children born from mothers with preeclampsia. These children are at high risk of developing cardiovascular diseases. Pre-eclampsia is caused by the endothelium dysfunction, deregulation of the immune and inflammatory factors during pregnancy. Experimental studies identify these factors as key epigenetic factors programming the condition of the cardiovascular system of the offspring. The modern concept of intrauterine programming, describing this phenomenon, focuses on three main areas of research: experimental models simulating the intrauterine environment with preeclampsia; research of the pathological phenotype formation under the influence of these factors; epigenetic studies of the influence of preeclampsia on the cardiovascular system functioning. The article discusses the perspectives of epigenetic programming prevention.

Primary Human Fibroblasts in Culture Switch to a Myofibroblast-Like Phenotype Independently of TGF Beta

Fibroblasts are the prevalent cell type and main source for extracellular matrix (ECM) in connective tissue. Depending on their origin, fibroblasts play a central role in non-pathological tissue remodeling and disease like fibrosis. This study examined the effect of established culture conditions of primary human fibroblasts, from different origins on the myofibroblast-like phenotype formation. We isolated primary human fibroblasts from aortic adventitia, lung, juvenile- and adult skin and investigated the expression levels of CD90, alpha smooth muscle actin (αSMA) and procollagen I under different concentrations of fetal calf serum (FCS) and ascorbic acid (AA) in culture media by immunoblot and immunofluorescence assays. Furthermore, we determined the viability using XTT and migration/wound healing in scratch assays. Collagen 1 secretion was quantified by specific ELISA. Primary human fibroblasts show in part a myofibroblast-like phenotype even without addition of FCS. Supplemented AA reduces migration of cultured fibroblasts with no or low concentrations of FCS. Furthermore, AA and higher concentrations of FCS in culture media lead to higher levels of collagen 1 secretion instead of procollagen I accumulation. This study provides evidence for a partial switch of primary human fibroblasts of different origin to a myofibroblast-like phenotype under common culture conditions.

Divergent Evolutional Mode and Purifying Selection of the KIT Gene in European and Asian Domestic Pig Breeds

The recent geographic expansion of wild boars and the even more recent development of numerous domestic pigs have spurred exploration on pig domestic origins. The porcine KIT gene has been showed to affect pleiotropic effects, blood parameters, and coat colour phenotypes, especially the white colour phenotype formation in European commercial breeds. Here, we described the use of SNPs to identify different selection patterns on the porcine KIT gene and the phylogenetic relationships of the inferred haplotypes. The phylogenetic tree revealed four clades in European and Asian wild and domestic pigs: two major clades with European and Asian origins and one minor clade with Iberian origins as well as the other minor clade in Asia, consistent with the major introgression of domestic Asian pigs in Europe around 18th -19th century. The domestication history of pigs, which occurred in the domestication centers (Europe and Asia), has also been demonstrated by mtDNA analysis. Furthermore, both Asian and European domestic pigs evolved under purifying selection. This study indicated that domestic pigs in Europe and Asia have different lineage origins but the porcine KIT gene was undergoing a purifying selection during their evolutional histories.