Thrombophilia is a genetic predisposition to hypercoagulable states caused by acquired haemostasis conditions; pregnancy causes the haemostatic system to become hypercoagulable, which grows throughout the pregnancy and peaks around delivery. Genetic testing for thrombophilic gene mutations is evaluated using different methodologies of real-time polymerase chain reaction and DNA microarrays of specific genes. Adapting the general care of the pregnant woman to the particularities caused by thrombophilia is an important component, so screening is preferred to assess the degree of genetic damage that manifests itself as a risk of thrombosis. The major goal of this narrative review was to quantitatively evaluate the literature data on the specific care of pregnant women with thrombophilia that are at risk of developing unplanned miscarriages.

Myocardial infarction (MI) is one of the most frequent cardiac emergencies, with significant potential for mortality. One of the major challenges of the post-MI healing response is that replacement fibrosis could lead to left ventricular remodeling (LVR) and heart failure (HF). This process involves canonical and non-canonical transforming growth factor-beta (TGF-β) signaling pathways translating into an intricate activation of cardiac fibroblasts and disproportionate collagen synthesis. Accumulating evidence has indicated that microRNAs (miRNAs) significantly contribute to the modulation of these signaling pathways. This review summarizes the recent updates regarding the molecular mechanisms underlying the role of the over 30 miRNAs involved in post-MI LVR. In addition, we compare the contradictory roles of several multifunctional miRNAs and highlight their potential use in pressure overload and ischemia-induced fibrosis. Finally, we discuss their attractive role as prognostic biomarkers for HF, highlighting the most relevant human trials involving these miRNAs.

Estrogen receptor alpha polymorphisms: correlation with clinicopathological parameters in breast cancer

The present clinical trial analyzed the safety of gene therapy using plasmidial constructs expressing vascular endothelial and hepatocyte growth factors in patients with critical limb ischemia. The study included 43 patients: 29 in the treatment group and 14 allocated to the placebo group. The primary end points were the rate of major amputations and the clinical safety of the method. Secondary end points were improvement of pain at rest, walking ability and the ankle/brachial pressure index. The overall major amputation rate was 31.04% in the treatment group and 71.42% in the placebo group (p=0.029). Pain at rest was improved in 65% of patients in the gene therapy group and in 7% in the placebo group (p=0.0006). There were no significant adverse effects in the treatment group. Conclusion: Gene therapy with vascular endothelial and hepatocyte growth factors is therapeutically safe and reduces the rate of major amputations and relieves pain at rest in patients with critical limb ischemia.

MiRNAs are a class of potential gene regulators of critical importance in Inflammatory Bowel Disease (IBD). This review aims to present the connection between gut microbiota, probiotics administration and microRNA (miRNA) expression in IBD. It also brings into question cross-kingdom RNAi (RNA interference). Not only that gut host cells garden the intestinal microbiome via miRNA, but also strong evidence supports the idea that different species of bacteria have an impact on the intestinal immune response by modulating miRNA expression. Cross-kingdom RNAi refers to RNA silencing signals that travel between two unrelated, interacting organisms. RNAs communication between prokaryotes and eukaryotes (bacteria and nematodes) via RNAs transfer has been proved. Some authors also support the idea that non-coding RNAs are being transferred by bacterial pathogens to the host cells as part of the intracellular infection process. Further studies are required in order to clarify whether the mechanism by which bacteria modulate miRNA expression concerns RNAs transfer. These findings may lead to a different approach to IBD therapy in the future. Abbreviations: AChE: Acetylcholinesterase; AIEC: Adherent-invasive E coli; ATF: Activating transcription factor; Bcl-2: B-cell lymphoma 2; BMDC: Bone marrow-derived dendritic cells; C elegans: Caenorhabditis elegans; CCL: Chemokine C-C motif ligand; CD: Crohn’s disease; CDC42: Cell division control protein 42 homolog; CXCL: Chemokine (C-X-C motif) ligand; DC: Dendritic cells; E Coli: Escherichia coli; EcN: E coli Nissle; EPEC: Entheropathogenic E coli; FOXO3: Forkhead box protein O3; GF: Germ-free; IBD: Inflammatory bowel disease; IECs: Intestinal epithelial cells; IGLC: Immunoglobulin Lambda Constant Region; IkB: Inhibitor of NF-Kb; IL: Interleukin; IRGM: Immunity-related GTPase family M protein; L del: Lactobacillus delbrueckii; LGG: Lactobacillus rhamnosus GG; MAPK: Mitogen-activated protein kinases; miRNA: MicroRNA; mRNA: Messenger RNA; MyD88: Myeloid differentiation primary response gene 88; NF-kB: Nuclear factor kappa B; NOD2: Nucleotide-binding oligomerization domain-containing protein 2; PAR: Partitioning defective protein; RhoB: Ras Homolog Family Member B; RISC: RNA induced silencing complex; RNAi: RNA interference; SHH: Sonic hedgehog (gene); SPF: Specific-pathogen-free; SRNA: Small RNA; STAT3: Signal transducer and activator of transcription 3; TGF: Transforming growth factor; Th17: T helper 17 cells; TJ: Tight junction; TLR: Toll like receptor; TNF: Tumor necrosis factor; UC: Ulcerative colitis; Xcv: Xanthomonas campestris pv. Vesicatoria; ZO-2: Zonula occludens-2.