The role of sex hormones and social determinants in assessment of facial attractiveness.

OBJECTIVES: The current study is focused on assessing the factors of attractiveness of opposite-sex individuals based on evaluating photographs of their faces. BACKGROUND: When assessing the attractiveness, factors of both, the assessed individual and the assessor play a role. The relationship of the preference for partners based on their physical appearance with the markers of prenatal testosterone is not fully understood. METHODS: Sex hormone levels were measured in saliva, while age, social status, income and occupation were recorded. A total of 30 women and 35 men were enrolled. RESULTS: The identified factors determining the attractiveness of menare their age and prenatal testosterone level (second-to-fourth digit ratio - 2D:4D). The attractiveness of men is more influenced by the factors of evaluating women, namely the rating assigned to the men positively correlates with age, 2D:4D, and salivary estradiol of the evaluating women. The attractiveness of women correlated negatively with age and positively with prenatal exposure to androgens (2D:4D).The women with lower estradiol were rated higher by men who themselves had low estradiol levels. The attractiveness did not correlate with current testosterone. CONCLUSION: This study contributes to the knowledge on the role of sex hormones in human sexuality and partner choice. Further studies should include genetic factors of testosterone metabolism. (Tab. 4, Ref. 23).

Extracellular DNA as a Prognostic and Therapeutic Target in Mouse Colitis under DNase I Treatment.

The aim of this study was to investigate the potential of extracellular DNA as a prognostic and/or therapeutic target in inflammatory bowel disease. Fifty male C57BL/6J mice were used in the experiment. Acute colitis was induced by intake of 2% dextran sulphate sodium (DSS) for seven days followed by three days of water intake. DNase I was injected intravenously on days 3 and 7. Plasmatic levels of extracellular DNA (ecDNA) were measured on days 6 and 10. Weight loss, stool consistency and liquid intake were monitored throughout the experiment. Colon length and weight, myeloperoxidase activity and tumour necrosis factor α (TNF-α) levels were measured at sacrifice. DSS-treated mice displayed severe colitis, as shown by disease activity parameters. Both groups with colitis (DNase treated and untreated) had significantly poorer weight loss, colon length and stool consistency compared with control groups on water. No differences between the DNasetreated and untreated DSS groups were recorded. Myeloperoxidase activity and levels of TNF-α in colonic tissue were notably greater in both groups with colitis compared to controls. In addition, both biochemical markers were improved in the DNasetreated group with colitis compared to the untreated group. Although the disease activity was proved by several independent parameters in both groups with colitis, levels of ecDNA did not show any difference between the groups throughout or at the end of experiment. The role of ecDNA in experimental colitis has not been confirmed. However, DNase I injection resulted in some improvement, and thus should be studied in more detail.

Extracellular DNA is Increased in Dextran Sulphate Sodium-Induced Colitis in Mice.

Ulcerative colitis and Crohn's disease constitute the two main forms of inflammatory bowel disease. Prevalence of these diseases increases. In the present day, inadequate and inefficient therapy causes complications and frequent relapse. Extracellular DNA (ecDNA) is the DNA that is outside of cells and may be responsible for activation of the inflammatory response. To determine whether colitis is associated with higher concentration of ecDNA we used male mice of the C57BL/6 strain. Colitis was induced by 2% dextran sulphate sodium (DSS). After 7 days, mice exhibited considerable weight loss compared to the control group. Also, there was a higher stool consistency score and the colon was significantly shorter in comparison to the control group. Higher concentration of ecDNA was found in the DSS group. Interestingly, deoxyribonuclease activity was lower in the colon of the DSS group compared with the negative control. These findings may point to ecDNA as a potential pathogenetic factor and marker of inflammation.

Putative Effects of Sex Hormones on Urinary Tract Infection.

Urinary tract infections affect mostly females. The infection and possible consequent ascent of bacteria is enhanced by various risk factors. Sex hormones regulate gene transcription implicated in immune cell development and maturation, in regulation of immune responses and immune signalling pathways. Limited knowledge is available; however, recent findings underline the importance of understanding the interactions between sex hormones and urinary tract infection to diminish the occurrence of complications related to this infection. This review summarizes and discusses the current knowledge on the correlation and impact of sex hormones on urinary tract infections.

Beneficial effects of live and dead Salmonella-based vector strain on the course of colitis in mice.

Dysbiosis of intestinal microbiota and hyperactive immune responses seem to be crucial for the uncontrolled inflammation in inflammatory bowel diseases (IBD). Modulation of the microbiome and immune stimulation of the intestinal epithelium were suggested as therapeutic approaches. In this study, live attenuated and dead bacterial cells of Salmonella Typhimurium SL7207 - a widely used bacterial vector for gene therapy were administered in DSS-induced colitis in mice. C57BL/6 mice were divided into four groups. The first group received pure water (CTRL). The other three groups received 2% dextran sulphate sodium (DSS) to induce colitis. Two DSS groups were treated with live attenuated (DSS live) or inactivated (DSS dead) Salmonella by gastric gavage. Intake of 2% DSS caused weight loss in all DSS groups compared to control mice with some improvement in DSS live group on the last day of the experiment. Significantly longer colon and improved stool consistency were reported in DSS live group, but not DSS dead group, when compared with DSS. Significant enlargement of spleens was observed only in DSS and DSS dead groups compared to control. Significant differences in stool consistency, colon length and spleen enlargement were observed between DSS live and DSS dead groups with beneficial effects of live bacteria. Interestingly, significant decrease in myeloperoxidase activity was detected in both, DSS live and DSS dead groups compared to the DSS group. On the basis of these results, progression of colitis seems to be beneficially influenced not only by live attenuated but to some extent also by inactivated Salmonella Typhimurium SL7207. Our results provide evidence that Salmonella-based gene therapy vectors are able to positively alter gut homeostasis during DSS-induced colitis. SIGNIFICANCE AND IMPACT OF THE STUDY: Restoration of gut homeostasis has a great importance in IBD. Here, we tested the nonspecific effect of the strain Salmonella Typhimurium SL7207 on the course of colitis to find out whether the potential effect would be mediated by activity of live bacterial cells or by bacterial structures that are also present in dead bacteria. Live bacterial therapy of colitis showed a beneficial effect on clinical signs as well as on macroscopic and inflammatory markers of colitis. On the other hand, therapy with dead bacteria showed inconsistent effects, negative in most clinical outcomes, positive especially in myeloperoxidase activity. Our data indicate that the beneficial effect of bacterial gene therapy vectors carrying therapeutic genes might be, at least partially, caused by the bacterial vector instead of the therapeutic gene.

Effect of DSS on Bacterial Growth in Gastrointestinal Tract.

Inflammatory bowel disease is an idiopathic autoimmune disorder that is mainly divided into ulcerative colitis and Crohn's disease. Probiotics are known for their beneficial effect and used as a treatment option in different gastrointestinal problems. The aim of our study was to find suitable bacterial vectors for gene therapy of inflammatory bowel disease. Salmonella enterica serovar Typhimurium SL7207 and Escherichia coli Nissle 1917 were investigated as potential vectors. Our results show that the growth of Escherichia coli Nissle 1917 was inhibited in the majority of samples collected from dextran sodium sulphate-treated animals compared with control growth in phosphate-buffered saline. The growth of Salmonella enterica serovar Typhimurium SL7207 in all investigated samples was enhanced or unaffected in comparison with phosphate-buffered saline; however, it did not reach the growth rates of Escherichia coli Nissle 1917. Dextran sodium sulphate treatment had a stimulating effect on the growth of both strains in homogenates of distant small intestine and proximal colon samples. The gastrointestinal tract contents and tissue homogenates did not inhibit growth of Salmonella enterica serovar Typhimurium SL7207 in comparison with the negative control, and provided more suitable environment for growth compared to Escherichia coli Nissle 1917. We therefore conclude that Salmonella enterica serovar Typhimurium SL7207 is a more suitable candidate for a potential bacterial vector, even though it has no known probiotic properties.

In vivo reprogramming in inflammatory bowel disease.

The direct reprogramming of somatic cells has immense implications in various areas of medicine. Although remarkable progress has been made in developing novel reprogramming methods, the efficiency and fidelity of reprogramming still need to be improved. Inflammatory bowel disease (IBD) involves chronic inflammatory diseases of the gastrointestinal tract with a complex etiology caused by various genetic, immunological and environmental factors. Recently, the role of stem cells has been proposed in pathogenesis and therapy of IBD. However, the efficiency and the safety of the stem cell treatments depend on the origin of the stem cell and the administration method. We hypothesize that the reprogramming of the intestinal cells into a pluripotent state is of huge importance for IBD therapy and prevention. The vectors carrying reprogramming genes encoding pluripotency factors can be transferred to the damaged tissue, in this case the intestine, by means of invasive bacterial vectors able to colonize colon mucosa. Reconstruction of tissues in vivo might avoid problems encountered in tissue rebuilding in vitro because of lack of appropriate scaffolds and microenvironments. Herein we present a review of recent literature and a perspective of in vivo reprogramming in IBD using bacterial vectors and analyze the rationale for such approach.

Recombinant probiotic therapy in experimental colitis in mice.

Recently, high interest has been attracted to the research of inflammatory bowel diseases (IBD). Recombinant probiotic bacteria may represent an interesting way to influence the course of IBD. Their benefits include cheap and simple production and easy manipulation of the genetic material. Several gene therapy and probiotic approaches already showed promising results in the past. The aim of this study was to test the probiotic potential of IL-10-expressing Escherichia coli Nissle 1917 in a mouse model of IBD and to compare it with control bacterial strains. The dextran sulphate sodium (DSS) model of colitis was examined for this purpose. Animals received control probiotic bacteria or modified probiotics (expressing IL-10) via gastric gavage. Body weight, stool consistency, food and water consumption were monitored. At the end of the experiment, the parameters of inflammation, oxidative stress and carbonyl stress were analysed in the samples and statistical analysis was performed. We prepared an anti-inflammatory probiotic Escherichia coli strain that we designated Nissle 1917/pMEC-IL10 and proved its anti-inflammatory properties, which are similar to those of the control probiotic strains Nissle 1917 and Lactococcus lactis/pMEC-IL10 in vivo. The probiotic therapy was successful according to several parameters, including colon length, and oxidative and carbonyl stress. Bacterially produced IL-10 was detected in the plasma. The potential of bacterial anti-inflammatory therapy of IBD using modified probiotics was outlined. The results opened a way for upcoming studies using modified probiotics for therapy of systemic diseases.

Targeting angiogenesis for cancer (gene) therapy.

Suppression of development of new blood vessels in solid tumors provides a clear therapeutic benefit both in experimental animals and human patients. Molecules targeting multiple pathways with VEGF pathway being one of the best described are currently under consideration to reach use in clinical settings. Even though some success has been observed using traditional protein-based inhibitors, alternative strategies and new approaches to inhibit excessive tumor angiogenesis are being developed and tested. Gene therapy represents a powerful tool for therapeutic intervention to angiogenesis. Delivery of genes encoding endogenous angiogenesis inhibitors and decoy receptors for proangiogenic factors may bear an advantage over classic non-gene therapy in terms of specific targeting, cost-effectiveness and safety. Modern approaches focused on gene targeting such as RNA interference and microRNA will show the future direction in the field of angiogenesis inhibition for cancer treatment (Ref. 68).

Gene therapy for cancer: bacteria-mediated anti-angiogenesis therapy.

Several bacterial species have inherent ability to colonize solid tumors in vivo. However, their natural anti-tumor activity can be enhanced by genetic engineering that enables these bacteria express or transfer therapeutic molecules into target cells. In this review, we summarize latest research on cancer therapy using genetically modified bacteria with particular emphasis on blocking tumor angiogenesis. Despite recent progress, only a few recent studies on bacterial tumor therapy have focused on anti-angiogenesis. Bacteria-mediated anti-angiogenesis therapy for cancer, however, is an attractive approach given that solid tumors are often characterized by increased vascularization. Here, we discuss four different approaches for using modified bacteria as anti-cancer therapeutics--bactofection, DNA vaccination, alternative gene therapy and transkingdom RNA interference--with a specific focus on angiogenesis suppression. Critical areas and future directions for this field are also outlined.

Genetic screening of patients with hypertrophic cardiomyopathy--a new diagnostic strategy for risk stratification?

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant inherited disease of the heart muscle and its main characteristic is unexplained hypertrophy of the left and/or the right ventricle. HCM is the most common genetically determined cardiovascular disease and is prevalent in approximately in 1 of 500 of the population. The most serious complication of HCM is sudden cardiac death (SCD) which can be the first manifestation of the disease. However, there are other forms of benign prognosis which do not jeopardize patient's health or life. The clinical symptoms of HCM are partly dependent on mutations in affected sarcomere genes. Different mutations in the same gene can present as malign with a high risk of SCD, while other mutations can be benign. The clinical symptomatology can also be influenced by other factors such as the presence of polymorphisms in other genes. Nowadays the aim of intensive clinical research is to access the contribution of molecular genetic methods in HCM diagnostics as well as in risk stratification of SCD. It is expected that genetic analyses will have an important consequence in the screening the relatives of HCM patients and also in the prenatal diagnostics and genetic counseling (Tab. 2, Fig. 1, Ref. 45). Full Text (Free, PDF) www.bmj.sk.

Bacteria in gene therapy: bactofection versus alternative gene therapy.

Recent advances in gene therapy can be attributed to improvements of gene delivery vectors. New viral and nonviral transport vehicles that considerably increase the efficiency of transfection have been prepared. However, these vectors still have many disadvantages that are difficult to overcome, thus, a new approach is needed. The approach of bacterial delivery could in the future be important for gene therapy applications. In this article we try to summarize the most important modifications that are used for the preparation of applied strains, difficulties that are related with bacterial gene delivery and the current use of bactofection in animal experiments and clinical trials. Important differences to the alternative gene therapy (AGT) are discussed. AGT resembles bacteria-mediated protein delivery, as the therapeutical proteins are produced not by host cells but by the bacteria in situ and the expression can be regulated exogenously. Although the procedure of bacterial gene delivery is far from being definitely solved, bactofection remains a promising technique for transfection in human gene therapy.

Ubiquitin--the kiss of death goes Nobel. Will you be quitting?

The Nobel prize in chemistry 2004 was given to Aaron Ciechanover, Avram Hershko and Irwin Rose for their discovery of the ubiquitin mediated proteolysis. Years of research have shown that the ubiquitin pathway plays a crucial role in the cellular metabolism and its regulation. These scientists together with Alexander Varshavsky have identified the most important elements of this pathway as well as their interactions. The ubiquitin pathway degrades intracellular proteins with an ubiquitin chain being the tag that marks proteins assigned for degradation. This process is mediated by ubiquitin-activating enzyme (El), ubiquitin-conjugating enzymes (E2) and ubiquitin-protein ligases (E3). Mono-ubiquitination and deubiquitination play a classic regulatory role in numerous processes including cell-cycle, transcription, translation, DNA repair, stress response etc. This article tries to summarize current knowledge on the molecular basis of the ubiqutin pathway. (Fig. 1, Ref. 52.)