Sense-antisense gene-pairs in breast cancer and associated pathological pathways

More than 30% of human protein-coding genes form hereditary complex genome architectures composed of sense-antisense (SA) gene pairs (SAGPs) transcribing their RNAs from both strands of a given locus. Such architectures represent important novel components of genome complexity contributing to gene expression deregulation in cancer cells. Therefore, the architectures might be involved in cancer pathways and, in turn, be used for novel drug targets discovery. However, the global roles of SAGPs in cancer pathways has not been studied. Here we investigated SAGPs associated with breast cancer (BC)-related pathways using systems biology, prognostic survival and experimental methods. Gene expression analysis identified 73 BC-relevant SAGPs that are highly correlated in BC. Survival modelling and metadata analysis of the 1161 BC patients allowed us to develop a novel patient prognostic grouping method selecting the 12 survival-significant SAGPs. The qRT-PCR-validated 12-SAGP prognostic signature reproducibly stratified BC patients into low- and high-risk prognostic subgroups. The 1381 SAGP-defined differentially expressed genes common across three studied cohorts were identified. The functional enrichment analysis of these genes revealed the GABPA gene network, including BC-relevant SAGPs, specific gene sets involved in cell cycle, spliceosomal and proteasomal pathways. The co-regulatory function of GABPA in BC cells was supported using siRNA knockdown studies. Thus, we demonstrated SAGPs as the synergistically functional genome architectures interconnected with cancer-related pathways and associated with BC patient clinical outcomes. Taken together, SAGPs represent an important component of genome complexity which can be used to identify novel aspects of coordinated pathological gene networks in cancers.     

Use of biologically active food additive cardiohels in the treatment of patients with ischemic heart disease

Biologically active food additive (Inrich production) cardiohels was added to the diet of ischemic heart disease patients with hypertension and chronic heart failure stage IIB receiving basic medication with hypotensive, coronarolytic drugs and cardiac glycosides. As shown by control 24-h blood pressure and ECG monitoring, echocardiography, cardiohels has a mild hypotensive effect, improves coronary circulation and microcirculation, myocardial contractility. Mechanism of these positive effects are discussed. Cardiohels is recommended for patients with ischemic heart disease as it allows to reduce the dose of hypotensive and coronarolytic drugs by 35% and cardiac glycosides by 25%, thus lowering the risk of relevand side effects.     

The length‐dependent activation of contraction is equally impaired in impuberal male and female rats in monocrotaline‐induced right ventricular failure

The length‐dependent activation of contraction is attenuated in the failing myocardium of adult male rats. This pathological change is not seen in adult female rats, possibly because of a protective effect of sex hormones. The present study evaluated length‐dependent changes in isometric twitch, Ca²⁺ transient (CaT) and action potential (AP) in the right ventricular myocardium of impuberal healthy male and female rats (control) and in rats treated with a single injection of 50 mg/kg monocrotaline (MCT). Compared with sex‐matched control rats, MCT‐treated male and female rats exhibited increased right ventricular weight (134% and 142% of control, respectively), decreased left ventricular weight (72% and 79%), twitch attenuation (48.8 ± 2.7% and 57.5 ± 1.2%) and prolongation (125 ± 3% and 127 ± 2%), CaT attenuation (37.8 ± 0.4% and 39.1 ± 1.1%) and prolongation (114 ± 1% and 116 ± 1%) and AP prolongation at 90% repolarization (195 ± 2% and 203 ± 1%). The MCT‐treated male rats exhibited a 50% lower integral magnitude and an approximately 25% larger time‐to‐peak ‘bump’ compared with control male rats. These parameters in MCT‐treated female rats tended to show similar changes to those seen in the control female rats, with no significant difference between the two groups. In all groups, integral magnitude and time‐to‐peak ‘bump’ increased with length. In conclusion, the length‐dependent activation of contraction was equally blunted in the failing right ventricular myocardium of impuberal male and female rats. This was related to changes in CaT and AP, which were similar between male and female rats. Therefore, puberty is necessary for manifestation of the protective effects of sex hormones on this remodelling.     

Effect of plant phenolic compounds on biofilm formation by Pseudomonas aeruginosa

In the natural environment, bacteria predominantly exist in matrix‐enclosed multicellular communities associated with various surfaces, referred to as biofilms. Bacteria in biofilms are extremely resistant to antibacterial agents thus causing serious problems for antimicrobial therapy. In this study, we showed that different plant phenolic compounds, at concentrations that did not or weakly suppressed bacterial growth, increased the capacity of Pseudomonas aeruginosa PAO1 to form biofilms. Biofilm formation of P. aeruginosa PAO1 was enhanced 3‐ to 7‐fold under the action of vanillin and epicatechin, and 2‐ to 2.5‐fold in the presence of 4‐hydroxybenzoic, gallic, cinnamic, sinapic, ferulic, and chlorogenic acids. At higher concentrations, these compounds displayed an inhibiting effect. Similar experiments carried out for comparison with Agrobacterium tumefaciens C58 showed the same pattern. Vanillin, 4‐hydroxybenzoic, and gallic acids at concentrations within the range of 40 to 400 μg/mL increased the production of N–3‐oxo‐dodecanoyl‐homoserine lactone in P. aeruginosa PAO1 which suggests a possible relationship between stimulation of biofilm formation and Las Quorum Sensing system of this bacterium. Using biosensors to detect N‐acyl‐homoserine lactones (AHL), we demonstrated that the plant phenolics studied did not mimic AHLs.     

Kinematics of Chiropteran Shoulder Girdle in Flight

New data on the mechanisms of movements of the shoulder girdle and humerus of bats are described; potential mobility is compared to the movements actually used in flight. The study was performed on the basis of morphological and functional analysis of anatomical specimens of 15 species, high speed and high definition filming of two species and X‐ray survey of Rousettus aegyptiacus flight. Our observations indicate that any excursions of the shoulder girdle in bats have relatively small input in the wing amplitude. Shoulder girdle movements resemble kinematics of a crank mechanism: clavicle plays the role of crank, and scapula—the role of connecting rod. Previously described osseous “locking mechanisms” in shoulder joint of advanced bats do not affect the movements, actually used in flight. The wing beats in bats are performed predominantly by movements of humerus relative to shoulder girdle, although these movements occupy the caudal‐most sector of available shoulder mobility. Anat Rec, 296:382–394, 2013. © 2013 Wiley Periodicals, Inc.     

Synthesis,Antimicrobial Activity,and Behavioral Response Effects of N-Substituted 4-Aryl-2-Hydroxy-4-Oxobut-2-Enoic Acid Hydrazides and Their Metal Complexes

Pharmaceutical Chemistry Journal - N-Substituted 4-aryl-2-hydroxy-4-oxobut-2-enoic acid hydrazides and their complexes with Ni(II), Mn(II), Co(II), Cu(II), and Zn(II) were prepared. Their...     

Cell tracking technologies for acute ischemic brain injury

Stem cell therapy has showed considerable potential in the treatment of stroke over the last decade. In order that these therapies may be optimized, the relative benefits of growth factor release, immunomodulation, and direct tissue replacement by therapeutic stem cells are widely under investigation. Fundamental to the progress of this research are effective imaging techniques that enable cell tracking in vivo. Direct analysis of the benefit of cell therapy includes the study of cell migration, localization, division and/or differentiation, and survival. This review explores the various imaging tools currently used in clinics and laboratories, addressing image resolution, long-term cell monitoring, imaging agents/isotopes, as well as safety and costs associated with each technique. Finally, burgeoning tracking techniques are discussed, with emphasis on multimodal imaging.