Medycyna estetyczna – humanistyczne dążenie czy „enhancement”?

The aim of the paper is to consider the issue of modern aesthetic medicine considered as a humanism or, on the contrary, as human enhancement. The aim of enhancement is to improve and expand human possibilities in order to change their nature eventually. I present arguments for and against the thesis that aesthetic medicine might be considered as a typical humanistic aspiration for perfection. I pay close attention to the purpose criterion of medical practice by analyzing its therapeutic and aesthetic tasks.The aim of the paper is to consider the issue of modern aesthetic medicine considered as a humanism or, on the contrary, as human enhancement. The aim of enhancement is to improve and expand human possibilities in order to change their nature eventually. I present arguments for and against the thesis that aesthetic medicine might be considered as a typical humanistic aspiration for perfection. I pay close attention to the purpose criterion of medical practice by analyzing its therapeutic and aesthetic tasks

Piękny czy dobry? Moralny wymiar upiększania ciała

The main purpose of the article is to point outsome relations between beauty and good in contemporary reality. The main question that arises here is as follows: is the relationship of beauty and moral good still relevant? The concept presented in the thesis refers to the ancient idea of kalokagathia. It stated that beauty is inseparable from moral good. As far as this ancient perspective is concerned, it can be treated as the background for contemporary considerations about the main issue of beauty and good. The article refers to the concept of aestheticization by Wolfgang Welsch. He defines aesthetics as the primary guiding value, where as experience and entertainment have become the guidelines for contemporary culture. Moreover, the thesis mentions the concept of the consumer society and new ethics of the relation to the body as it is described by Jean Budrillard. Then the narration of the article focuses on the following problem: in what sense can we talk nowadays about moral motivation for beauty treatments of body? One assumption leads to the case of looking after one’s body. Another point of view mentions the need of harmony which manifests itself in beautiful body. Eventually, the central question emerges whether contemporary practice of beautifying the body can be a part of the concept of the good life or not.The main purpose of the article is to point outsome relations between beauty and good in contemporary reality. The main question that arises here is as follows: is the relationship of beauty and moral good still relevant? The concept presented in the thesis refers to the ancient idea of kalokagathia. It stated that beauty is inseparable from moral good. As far as this ancient perspective is concerned, it can be treated as the background for contemporary considerations about the main issue of beauty and good. The article refers to the concept of aestheticization by Wolfgang Welsch. He defines aesthetics as the primary guiding value, where as experience and entertainment have become the guidelines for contemporary culture. Moreover, the thesis mentions the concept of the consumer society and new ethics of the relation to the body as it is described by Jean Budrillard. Then the narration of the article focuses on the following problem: in what sense can we talk nowadays about moral motivation for beauty treatments of body? One assumption leads to the case of looking after one’s body. Another point of view mentions the need of harmony which manifests itself in beautiful body. Eventually, the central question emerges whether contemporary practice of beautifying the body can be a part of the concept of the good life or not

In situ detection of DNA and mRNA of human cytomegalovirus to distinguish different forms of viral infection in leukocytes

In situ PCR and in situ reverse transcription PCR (RT-PCR) were applied to discriminate between latent and productive infection of human cytomegalovirus (HCMV) in leukocytes. We investigated 28 samples, in which viral pp65 antigen was detected only in the cytoplasm of leukocytes. Additionally we assayed 12 specimens lacking pp65 antigen. Using nested PCR (nPCR), viral DNA was detected in 27 samples. In six samples the results of nPCR were unreadable due to the presence of polymerase inhibitors. By application of in situ PCR, we were able to confirm the presence of viral DNA in the nucleus and/or cytoplasm. Productive infection was recognized in 20 samples in which transcripts for late viral genes were detected. Among the 20 samples negative by in situ RT-PCR, we recognized phagocytosis of viral particles in eight and the latent form of HCMV infection in five

Effect of pulmonary surfactant on innate immune responses in influenza virus infected human airway epithelial cells

Overwhelming inflammatory responses leading to neutrophil invasion are hypothesised to be the main cause of mortality in influenza virus induced acute respiratory distress syndrome (ARDS). Previously, pulmonary surfactant has been shown to modulate inflammatory responses to bacterial agents. The aim of the present study was to investigate the effect of pulmonary surfactant on innate immune responses in an in vitro model of influenza virus infected human airway epithelial cells. Human lung type II alveolar epithelial cells A549 and BEAS-2B human bronchial epithelial cells were infected with influenza A virus H1N1 strains A/Swine/1976/31, A/WSN/33 and A/PR/8/34. Poly I:C, Escherichia coli Ol 11 :B4 LPS and measles virus strain Edmonston were used as cytokine stimulation controls. The effect of pulmonary surfactant was compared to that of dexamethasone. This in vitro study showed that physiological concentrations (up to 500 ug/ml) of clinically approved SP-A and SP-D depleted surfactant preparations (i) were non-toxic in BEAS-2B cells, (ii) had no effect on influenza virus infectivity, and (iii) reduced influenza virus induced cytokine production comparable to dexamethasone. Porcine Curosurf* significantly inhibited IL-8 and RANTES production in A/WSN/33 infected cells, by 30 and 35% respectively (p<0.05). Bovine Survanta* had a less pronounced effect. In luciferase reporter assays pulmonary surfactant, in contrast to dexamethasone, non-specifically inhibited both TLR3/RIG-I mediated NF-kappaB promoter activation and IFN-beta promoter activation. Our results indicate that SP-A and SP-D depleted surfactant preparations attenuate pro-inflammatory responses in influenza A virus infected human airway epithelial cells, but inhibitory effects on IFN-beta promoter activity were also observed. This suggests that pulmonary surfactant may be of clinical benefit in reducing pro-inflammatory responses in virus induced ARDS, however, a weakening of IFN-beta mediated anti-viral responses can not be excluded

Inflammation mobilizes copper metabolism to promote colon tumorigenesis via an IL-17-STEAP4-XIAP axis.

Copper levels are known to be elevated in inflamed and malignant tissues. But the mechanism underlying this selective enrichment has been elusive. In this study, we report a axis by which inflammatory cytokines, such as IL-17, drive cellular copper uptake via the induction of a metalloreductase, STEAP4. IL-17-induced elevated intracellular copper level leads to the activation of an E3-ligase, XIAP, which potentiates IL-17-induced NFκB activation and suppresses the caspase 3 activity. Importantly, this IL-17-induced STEAP4-dependent cellular copper uptake is critical for colon tumor formation in a murine model of colitis-associated tumorigenesis and STEAP4 expression correlates with IL-17 level and XIAP activation in human colon cancer. In summary, this study reveals a IL-17-STEAP4-XIAP axis through which the inflammatory response induces copper uptake, promoting colon tumorigenesis

IKKα negatively regulates ASC-dependent inflammasome activation.

The inflammasomes are multiprotein complexes that activate caspase-1 in response to infections and stress, resulting in the secretion of pro-inflammatory cytokines. Here we report that IκB kinase α (IKKα) is a critical negative regulator of apoptosis-associated specklike protein containing a C-terminal caspase-activation-andrecruitment (CARD) domain (ASC)-dependent inflammasomes. IKKα controls the inflammasome at the level of the adaptor ASC, which interacts with IKKα in the nucleus of resting macrophages in an IKKα kinase-dependent manner. Loss of IKKα kinase activity results in inflammasome hyperactivation. Mechanistically, the downstream nuclear effector IKK-related kinase (IKKi) facilitates translocation of ASC from the nucleus to the perinuclear area during inflammasome activation. ASC remains under the control of IKKα in the perinuclear area following translocation of the ASC/IKKα complex. Signal 2 of NLRP3 activation leads to inhibition of IKKα kinase activity through the recruitment of PP2A, allowing ASC to participate in NLRP3 inflammasome assembly. Taken together, these findings reveal a IKKi-IKKα-ASC axis that serves as a common regulatory mechanism for ASC-dependent inflammasomes

In silico and structural analyses demonstrate that intrinsic protein motions guide T cell receptor complementarity determining region loop flexibility

T-cell immunity is controlled by T cell receptor (TCR) binding to peptide major histocompatibility complexes (pMHCs). The nature of the interaction between these two proteins has been the subject of many investigations because of its central role in immunity against pathogens, cancer, in autoimmunity, and during organ transplant rejection. Crystal structures comparing unbound and pMHC-bound TCRs have revealed flexibility at the interaction interface, particularly from the perspective of the TCR. However, crystal structures represent only a snapshot of protein conformation that could be influenced through biologically irrelevant crystal lattice contacts and other factors. Here, we solved the structures of three unbound TCRs from multiple crystals. Superposition of identical TCR structures from different crystals revealed some conformation differences of up to 5 Å in individual complementarity determining region (CDR) loops that are similar to those that have previously been attributed to antigen engagement. We then used a combination of rigidity analysis and simulations of protein motion to reveal the theoretical potential of TCR CDR loop flexibility in unbound state. These simulations of protein motion support the notion that crystal structures may only offer an artifactual indication of TCR flexibility, influenced by crystallization conditions and crystal packing that is inconsistent with the theoretical potential of intrinsic TCR motions

A molecular switch abrogates glycoprotein 100 (gp100) T-cell Receptor (TCR) targeting of a human melanoma antigen

Human CD8+ cytotoxic T lymphocytes can mediate tumor regression in melanoma through the specific recognition of HLA-restricted peptides. Because of the relatively weak affinity of most anti-cancer T-cell receptors (TCRs), there is growing emphasis on immunizing melanoma patients with altered peptide ligands in order to induce strong anti-tumor immunity capable of breaking tolerance toward these self-antigens. However, previous studies have shown that these immunogenic designer peptides are not always effective. The melanocyte differentiation protein, glycoprotein 100 (gp100), encodes a naturally processed epitope that is an attractive target for melanoma immunotherapies, in particular peptide-based vaccines. Previous studies have shown that substitutions at peptide residue Glu3 have a broad negative impact on polyclonal T-cell responses. Here, we describe the first atomic structure of a natural cognate TCR in complex with this gp100 epitope and highlight the relatively high affinity of the interaction. Alanine scan mutagenesis performed across the gp100280–288 peptide showed that Glu3 was critically important for TCR binding. Unexpectedly, structural analysis demonstrated that the Glu3 → Ala substitution resulted in a molecular switch that was transmitted to adjacent residues, abrogating TCR binding and T-cell recognition. These findings help to clarify the mechanism of T-cell recognition of gp100 during melanoma responses and could direct the development of altered peptides for vaccination