11 research outputs found
Secretory leukocyte protease inhibitor modulates FcεRI-dependent but not Mrgprb2-dependent mastocyte function in psoriasis
Differences in staining for neutrophil elastase and its controlling inhibitor SLPI reveal heterogeneity among neutrophils in psoriasis
Dreams - meaning and mechanisms of their formation
Tłumaczenie roli snów jest rozpatrywane na dwóch płaszczyznach. Pierwsza z nich, do której można zaliczyć klasyczne koncepcje roli marzeń sennych Freuda oraz Junga, opiera się na psychoanalizie. Freud uważał, że sny są formą zaspokajania pragnień oraz kompromisem pomiędzy świadomością, a nieświadomością. Jung natomiast przypisywał snom funkcję kompensacyjną, czyli zwrócenia uwagi świadomości na treści przez nią pominięte, a bardzo ważne z punktu widzenia rozwoju człowieka.Współczesne koncepcje roli marzeń sennych opierają się na badaniach struktur mózgu odpowiedzialnych za powstawania snów. Na ich podstawie powstała „Nowa poznawcza koncepcja marzeń sennych”. Według tej teorii, sny są efektem aktywności specyficznej sieci neuronalnej, a treść snu jest ściśle związana z osobistymi,. bieżącymi spawami osoby śniącej oraz jej troskami emocjonalnymi. Model AIM jest natomiast koncepcją traktującą sen jako specyficzny stan świadomości, determinowany przez trzy zależne od siebie procesy. Są nimi: modulacja aktywności korowej, regulacja udziału bodźców zewnętrznych oraz zmiany ilości wydzielanych neuroprzekaźników. Marzenia senne są fizjologiczną funkcją snu REM.Crick i Mitchison przypisują marzeniom sennym funkcję porządkowania informacji zgromadzonych podczas okresu czuwania. Szczególną rolę odgrywa tu faza snu REM, podczas której zachodzi proces „reverse learning”, czyli odwrotności uczenia się. W tym czasie dochodzi do analizy, selekcji oraz usuwania informacji zbędnych. Profesor A. Revonsuo wysunął natomiast hipotezę, traktującą marzenia senne jako produkt ewolucji, odpowiedzialny za rozwój i utrzymanie umiejętności unikania zagrożeń. Poprzez ciągłe odtwarzanie (powtarzanie) w czasie snu groźnych wydarzeń, organizm przyzwyczaja się do ich występowania i uczy się na nie reagować.Według kolejnej teorii, nazwanej teorią wybudzania, sen REM jest narzędziem pozwalającym na obudzenie się w odpowiednim momencie, po przespaniu wystarczającej ilości czasu. Marzenia senne mogą służyć jako wynagrodzenie śniącemu czegoś, czego nie przeżył oraz zwiększać jego doświadczenie życiowe.Istnieją także hipotezy sugerujące udział marzeń sennych w procesach uczenia się i zapamiętywania. Pierwsza z nich traktuje marzenia senne jako fragmenty tzw. „fałszywych” śladów pamięciowych, które w czasie snu ulegają eliminacji. Druga natomiast mówi, że w czasie snu REM zachodzi konsolidacja śladów pamięciowych, których konsekwencją są marzenia senne.An explanation the role of dreams, as the phenomenon of serving a particular purpose is considered at two levels. The first of this, includes Freud`s and Jung`s classical theories of the role of dreams, based primarily on psychoanalysis. The views of these two eminent psychiatrists are slightly different. Freud believed that dreams are a form of satisfaction of desire and they are closely related to conscious intellectual processes. When we are dreaming the unconscious comes to the fore, but only when conscious allows for it. Dreams are thus a compromise between consciousness and unconsciousness. Jung attributed to the compensatory function of dreams, that is, pay consciousness` attention to the contents omitted by it, but very important in terms of human development. Modern conceptions of the role of dreams are based on studies of the brain structures responsible for the formation of dreams. On the basis of such researches, scientists formulated “ A new neurocognitive theory of dreams”. According to this theory, dreams are the result of neural network activity localized in the forebrain. The output of this neural network for dreaming is guided by a continuity principle and repetition principle. It means that it is closely related to current personal concerns of dreaming person and his emotional preoccupations like misfortunes, negative emotions in contacts between people. The AIM model is a hypothesis, which treated dreams as a specific state of consciousness. This state is determined by three, independent processes: modulation of cortical activation, changes in amounts of neurotransmitter secretion and regulation of external inputs. Dreams are the physiological function of REM sleep.Crick and Mitchison attributed dreams organizing the information, collected during the wakefulness. Important role is played there by the REM sleep, because then occurs to the analysis, selection and removal of redundant information. Professor A. Revonsuo put forward the hypothesis, which treated dream as a product of evolution, responsible for development and maintenance of threat-avoidance skills. Through simulation, during the dreaming, threatening events over and over again, an organism is getting used to their occurrence and learns to respond.According to another theory, called The wake-up hypothesis, stage REM help us to wake up. Dream content can have reward properties, they can enhance the life experience.There are also hypothesis, suggesting participation of dreams in learning and memory. The first of these treats dreams as fragments of the so-called “false” memory traces, which are eliminated during the dreaming. The second one says that during REM sleep there is a consolidation of memory traces and dream is a result of this process
Condition and activity of mitochondria in porcine embryos developing in vitro with addition of hyaluronate.
W niniejszej pracy badano wpływ suplementacji pożywki hodowlanej kwasem hialuronowym (HA) o stężeniu 1 mg/ml na aktywność mitochondrialną przedimplantacyjnych zarodków świni znajdujących się w stadium 2-4 blastomerów, 8-16 blastomerów, moruli oraz blastocysty. Sprawdzano również i porównywano wpływ dodatku HA o stężeniu 0,25 mg/ml, 0,5 mg/ml i 1 mg/ml na zarodki w stadium blastocysty. Oba eksperymenty wykazały obniżenie potencjału wewnętrznej błony mitochondrialnej w stosunku do kontroli. Prawdopodobnie jest to mechanizm ochronny, powodujący obniżenie produkcji wolnych rodników tlenowych (ROS), zapewniający lepszą przeżywalność i bardziej optymalny rozwój zarodków. Suplementacja HA może wpłynąć na jakość i wydajność hodowli zarodków świni.In present study we investigated an influence of medium supplementation by hyaluronic acid (HA) with 1 mg/ml concentration on mitochondrial activity in preimplantation porcine embryos. We collected embryos in four development stages: 2-4 blastomeres, 8-16 blastomeres, morula and blastocyst. An influence of HA supplementation with concentrations: 0,25 mg/ml, 0,5 mg/ml and 1 mg/ml on embryos in blastocyst stage was also investigated. Both experiments showed a reduction of inner mitochondrial membrane potential compared to control group. It may be a protective mechanism, which reduce radical oxygen species (ROS) production. It can provide embryos survival and development. HA supplementation may affect quality and efficiency of porcine embryos culturing
Secretory leukocyte protease inhibitor is present in circulating and tissue-recruited human eosinophils and regulates their migratory function
Eosinophils and secretory leukocyte protease inhibitor (SLPI) are both associated with Th2 immune responses and allergic diseases, but whether the fact that they are both implicated in these conditions is pathophysiologically related remains unknown. Here we demonstrate that human eosinophils derived from normal individuals are one of the major sources of SLPI among circulating leukocytes. SLPI was found to be stored in the crystalline core of eosinophil granules, and its dislocation/rearrangement in the crystalline core likely resulted in changes in immunostaining for SLPI in these cells. High levels of SLPI were also detected in blood eosinophils from patients with allergy-associated diseases marked by eosinophilia. These include individuals with eosinophilic granulomatosis with polyangiitis (EGPA) and atopic dermatitis (AD), who were also found to have elevated SLPI levels in their plasma. In addition to the circulating eosinophils, diseased skin of AD patients also contained SLPI-positive eosinophils. Exogenous, recombinant SLPI increased numbers of migratory eosinophils and supported their chemotactic response to CCL11, one of the key chemokines that regulate eosinophil migratory cues. Together, these findings suggest a role for SLPI in controlling Th2 pathophysiologic processes via its impact on and/or from eosinophils
Redox Active Antimicrobial Peptides in Controlling Growth of Microorganisms at Body Barriers
Epithelia in the skin, gut and other environmentally exposed organs display a variety of mechanisms to control microbial communities and limit potential pathogenic microbial invasion. Naturally occurring antimicrobial proteins/peptides and their synthetic derivatives (here collectively referred to as AMPs) reinforce the antimicrobial barrier function of epithelial cells. Understanding how these AMPs are functionally regulated may be important for new therapeutic approaches to combat microbial infections. Some AMPs are subject to redox-dependent regulation. This review aims to: (i) explore cysteine-based redox active AMPs in skin and intestine; (ii) discuss casual links between various redox environments of these barrier tissues and the ability of AMPs to control cutaneous and intestinal microbes; (iii) highlight how bacteria, through intrinsic mechanisms, can influence the bactericidal potential of redox-sensitive AMPs
Secretory leukocyte protease inhibitor regulates nerve reflex-mediated skin barrier function in psoriasis
BACKGROUND: Secretory leukocyte protease inhibitor (SLPI), a ~12 kDa protein is an important regulator of innate and adaptive immunity and a component of tissue regenerative programmes. SLPI expression is markedly elevated in chronically inflamed skin, including that of individuals suffering from psoriasis. However, the role of SLPI in these diseases remains elusive. OBJECTIVES: The poor understanding of the early stages of the development of psoriasis is a major obstacle to successful intervention in the skin pathology. We hypothesized that SLPI and peripheral nerves that might be activated early in the progression of the disease likely form a functional relationship to maintain skin barrier homeostasis and respond to a variety of threats. METHODS: We used skin biopsies of healthy donors and individuals with psoriasis to show expression pattern of SLPI. A role of SLPI in psoriasis was mechanistically assessed using SLPI‐deficient mice and an imiquimod (IMQ)‐induced experimental model of psoriasis. RESULTS: We show that mice lacking SLPI had exaggerated skin alterations that extended beyond the treatment site in an imiquimod‐induced psoriasis. The spatiotemporally distinct skin responses in SLPI‐deficient mice, compared to their wild‐type littermates, resulted from a compromised skin barrier function that manifested itself in heightened transepidermal water loss through the larger skin area surrounding the IMQ‐challenged skin. The increased pathogenic skin changes in the absence of SLPI were reversible through pharmacological treatment that blocks a nerve‐reflex arc. CONCLUSIONS: Together, these data indicate that SLPI plays a protective role in psoriasis through preventing skin dryness, inherent in the pathogenesis of psoriasis and that this SLPI action depends on neuronal input operating in a reflex manner. These findings reveal a previously unrecognized mechanism that maintains cutaneous homeostasis, which involves a crosstalk between the nervous system and a protein anatomically poised to fortify the epidermal permeability barrier
Molecular mechanisms of ZC3H12C/Reg-3 biological activity and its involvement in Psoriasis pathology
The members of the ZC3H12/MCPIP/Regnase family of RNases have emerged as important regulators of inflammation. In contrast to Regnase-1, -2 and -4, a thorough characterization of Regnase-3 (Reg-3) has not yet been explored. Here we demonstrate that Reg-3 differs from other family members in terms of NYN/PIN domain features, cellular localization pattern and substrate specificity. Together with Reg-1, the most comprehensively characterized family member, Reg-3 shared IL-6, IER-3 and Reg-1 mRNAs, but not IL-1 beta mRNA, as substrates. In addition, Reg-3 was found to be the only family member which regulates transcript levels of TNF, a cytokine implicated in chronic inflammatory diseases including psoriasis. Previous meta-analysis of genome-wide association studies revealed Reg-3 to be among new psoriasis susceptibility loci. Here we demonstrate that Reg-3 transcript levels are increased in psoriasis patient skin tissue and in an experimental model of psoriasis, supporting the immunomodulatory role of Reg-3 in psoriasis, possibly through degradation of mRNA for TNF and other factors such as Reg-1. On the other hand, Reg-1 was found to destabilize Reg-3 transcripts, suggesting reciprocal regulation between Reg-3 and Reg-1 in the skin. We found that either Reg-1 or Reg-3 were expressed in human keratinocytes in vitro. However, in contrast to robustly upregulated Reg-1 mRNA levels, Reg-3 expression was not affected in the epidermis of psoriasis patients. Taken together, these data suggest that epidermal levels of Reg-3 are negatively regulated by Reg-1 in psoriasis, and that Reg-1 and Reg-3 are both involved in psoriasis pathophysiology through controlling, at least in part different transcripts