RESUMEN
Despite years of research, miscarriage, particularly when recurrent, continues to pose a medical challenge. An embryo chromosomal error is responsible for 50-60% of recurrent cases; however, up to 30-50% remains an enigma. Successful pregnancy involves different maternal physiologic changes and certain complex interactions between the fetus and the mother by cytokines, angiogenic mediators and hormones. To date, research lines have focused on genetic and epigenetic polymorphisms related mainly to immune response and inflammatory mediators, and have yielded a significant relationship between recurrent miscarriage and immune mechanisms. Thus, unknown causes of miscarriage could be due to an immune imbalance induced by T-helper Th1/Th2/Th17 cytokines and regulatory T cells. Furthermore, these genes and mediators have long been suspected of being blood markers for the clinical diagnosis and management of miscarriage; however, more evidence is required for them to be included in medical practice and obstetric guidelines.
Asunto(s)
Aborto Habitual/genética , Aberraciones Cromosómicas , Trastornos de los Cromosomas/genética , Polimorfismo Genético , Femenino , Feto , Humanos , EmbarazoRESUMEN
Hepatocyte invasion by malaria parasites is mediated by specific molecular interactions. Several lines of evidence suggest the importance of the surface plasmodial circumsporozoite (CS) protein in the sporozoite invasion of hepatocytes. Identification of the sequences involved in binding to hepatocytes is an important step towards understanding the structural basis for the sporozoite-hepatocyte interaction. In this study, binding assays between Plasmodium falciparum CS peptides and HepG2 cells were performed. Fifteen overlapping residue 20 mer long peptides, spanning the entire CS sequence, were tested in HepG2 cell binding assays. Five High Binding Activity Peptides (HBAPs) to HepG2 cells were identified: 4593, (NANPNANPNANP); 4383, (NSRSLGENDDGNNEDNEKLR); 4388, (GNGQGHNMPNDPNRNVDENA); 4389, (HNMPNDPNRNVDENANANSA) and 4390, (DPNRNVDENANANSAVKNNN). The HBAP HepG2 interaction is independent of charge and amino-acid composition, but sequence dependent. Four HBAPs (4383, 4388, 4389 and 4390) are bound with similar affinity to a 50 kDa molecule. These HBAPs define three Hepatocyte Binding Sequences (HBSs): HBS-1, located between residues 68 and 87 (HBAP 4383); HBS-11, the repeat NANP region (HBAP 4593), for which anti repeat antibodies are able to specifically inhibit sporozoite invasion of hepatocytes have been reported; and HBS-111, between residues 286 and 315 (HBAPs 4388, 4388 and 4390), respectively. Interestingly, HBS 111 carries two earlier-reported B-epitopes (underlined) in peptides 4388, 4389 and 4390 (GNGQGHNMPNDPNRNVD ENANANSAVKNN) in its sequence. The HBSs reported here show lesser interspecie-variability than the entire protein in species invading the same kind of hepatic cells. This data supports these HBSs' important role in CS-protein function; they could be used as ligand by the sporozoite to invade hepatic cells.