scholarly journals Sepsis and ARDS: The Dark Side of Histones

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Zhiheng Xu ◽  
Yongbo Huang ◽  
Pu Mao ◽  
Jianrong Zhang ◽  
Yimin Li

Despite advances in management over the last several decades, sepsis and acute respiratory distress syndrome (ARDS) still remain major clinical challenges and the leading causes of death for patients in intensive care units (ICUs) due to insufficient understanding of the pathophysiological mechanisms of these diseases. However, recent studies have shown that histones, also known as chromatin-basic structure proteins, could be released into the extracellular space during severe stress and physical challenges to the body (e.g., sepsis and ARDS). Due to their cytotoxic and proinflammatory effects, extracellular histones can lead to excessive and overwhelming cell damage and death, thus contributing to the pathogenesis of both sepsis and ARDS. In addition, antihistone-based treatments (e.g., neutralizing antibodies, activated protein C, and heparin) have shown protective effects and have significantly improved the outcomes of mice suffering from sepsis and ARDS. Here, we review researches related to the pathological role of histone in context of sepsis and ARDS and evaluate the potential value of histones as biomarkers and therapeutic targets of these diseases.

Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 222 ◽  
Author(s):  
Izabela Maurício Rezende ◽  
Leonardo Soares Pereira ◽  
Jordana Rodrigues Barbosa Fradico ◽  
Marcelo Antônio Pascoal Xavier ◽  
Pedro Augusto Alves ◽  
...  

One patient presented hyporexia, asthenia, adynamia, and jaundice two months after acute yellow fever (YF) onset; plus laboratory tests indicating hepatic cytolysis and a rebound of alanine and aspartate transaminases, and total and direct bilirubin levels. Laboratory tests discarded autoimmune hepatitis, inflammatory or metabolic liver disease, and new infections caused by hepatotropic agents. Anti-YFV IgM, IgG and neutralizing antibodies were detected in different times, but no viremia. A liver biopsy was collected three months after YF onset and tested positive for YFV antigens and wild-type YFV-RNA (364 RNA-copies/gram/liver). Transaminases and bilirubin levels remained elevated for five months, and the arresting of symptoms persisted for six months after the acute YF onset. Several serum chemokines, cytokines, and growth factors were measured. A similar immune response profile was observed in the earlier phases of the disease, followed by more pronounced changes in the later stages, when transaminases levels returned to normal. The results indicated viral persistence in the liver and continual liver cell damage three months after YF onset and reinforced the need for extended follow-ups of YF patients. Further studies to investigate the role of possible viral persistence and the immune response causing relapsing hepatitis following YF are also necessary.


2019 ◽  
Vol 2019 ◽  
pp. 1-24 ◽  
Author(s):  
Zhihua Ren ◽  
Changhao Chen ◽  
Yu Fan ◽  
Chaoxi Chen ◽  
Hongyi He ◽  
...  

Deoxynivalenol (DON) is a common contaminant of grain worldwide and is often detected in the human diet and animal feed. Selenium is an essential trace element in animals. It has many biological functions. The role of selenium in the body is mainly orchestrated by selenoprotein. Glutathione peroxidase (GPx) also exists widely in the body and has attracted much attention due to its high antioxidant capacity. In order to explore the effect of the GPx1 gene on toxicity of DON, in this study, we overexpressed or knockdown GPx1 in porcine splenic lymphocytes, then added different concentrations of DON (0.1025, 0.205, 0.41, and 0.82 μg/mL) and sodium selenite (2 μmol/L) to the culture system. Using various techniques, we detected antioxidant function, free radical content, cell apoptosis, and methylation-related gene expression to explore the effect of GPx1 expression on DON-induced cell damage. We also explored whether selenium can antagonize the toxicity of DON in these two cell models and revealed the protective effect of sodium selenite on DON-induced cell damage in GPx1-overexpressing or knockdown splenic lymphocytes. Finally, our findings revealed the following: (1) GPx1 can regulate the antioxidant capacity, apoptosis rate, and expression of DNA methylation-related genes in pig splenic lymphocytes. (2) Na2SeO3 (2 μmol/L) can regulate the antioxidant capacity, apoptosis rate, and expression of DNA methylation-related genes in pig splenic lymphocytes, and this effect is more significant in GPx1-overexpressing cells than in GPx1-knockdown cells. (3) DON can cause oxidative damage, apoptosis, and methylation injury in GPx1-overexpressing or knockdown pig splenic lymphocytes in a concentration-dependent manner. (4) Na2SeO3 (2 μmol/L) can antagonize the toxic effect of DON on GPx1-overexpressing or knockdown pig splenic lymphocytes. Our findings may have important implications for food/feed safety, human health, and environmental protection.


2020 ◽  
Vol 7 (3, jul.-dez.) ◽  
pp. 323-354
Author(s):  
Martín Mercado-Vásquez

El presente artículo de investigación estudia la relación entre experiencias corporales e identidad personal, a partir de la pregunta sobre si aquellas son fundamento de esta. En la primera parte del artículo se justifica el tema abordado, mediante la revisión del planteamiento del problema de la identidad personal de J. Locke; por lo que se estudia el rol del cuerpo en la idea de hombre y en la identidad personal. Después, se analiza la noción de identidad personal tomando en cuenta las experiencias de dolor y placer. En la segunda parte, se aborda la antropología neo-fenomenológica de Hermann Schmitz, a partir de la tesis de “sin propio-cuerpo no hay persona” y de su descripción del dolor como fundamento propio-corporal de la identidad personal. A continuación, se expone la dinámica entre actitud propio-corporal y equilibrio personal como estructura básica de la situación personal. Finalmente, se ofrece una breve conclusión (3). Palabras clave: Identidad personal, cuerpo, propio-cuerpo, dinámica propio-corporal, situación personal.   Abstract The following research article examines the relationship between felt-bodily experiences and personal identity, and whether the former can be considered the basis for the latter. The first part of the article deals with the relationship of these two concepts within Locke's view of personal identity in order to justify the question. Therefore, the role of the body in the conception of man and in personal identity is revised. Then the idea of personal identity in relation to pain experience is questioned. The second part deals with the neo-phenomenological anthropology of Hermann Schmitz, which is based on the thesis: “without felt-body no person”. Next, the dynamics between attitude and composure as the basic structure of the personal situation identity is revealed, which can be assumed as an answer to the question of personal identity. Finally, a brief conclusion is given. Key words: Personal identity, body, felt-body, felt-body dynamics, personal situation.   Resumo O presente artigo estuda a relação entre experiências corporais e identidade pessoal, tomando como base a indagação se aquelas são fundamentos desta. Na primeira parte do artigo, justifica-se o problema mediante a revisão da abordagem de J. Locke para o problema da identidade pessoal; razão pela qual o papel do corpo na ideia do homem e na identidade pessoal é estudado. Na sequência, estuda-se a noção de identidade pessoal, levando-se em consideração as experiências de dor e de prazer. Na segunda parte, aborda-se a antropologia neo-fenomenológica de Hermann Schmitz, com base na tese de "sem o seu próprio-corpo, não existe pessoa" e sua descrição da dor como fundamento próprio-corporal da identidade pessoal. Em seguida, a dinâmica entre atitude próprio-corporal e equilíbrio pessoal é exposta como estrutura básica da situação pessoal. Por fim, é oferecida uma breve conclusão. Palavras-chave: Identidade pessoal, corpo, próprio-corpo, dinâmica do próprio-corpo, situação pessoal.


2015 ◽  
Vol 34 (11) ◽  
pp. 1043-1052 ◽  
Author(s):  
SK Lee ◽  
KH Oh ◽  
AY Chung ◽  
HC Park ◽  
SH Lee ◽  
...  

Background and objectives: The aim of this study was to evaluate the protective effects of quercetin on cisplatin-induced hair cell damage in transgenic zebrafish embryos. Materials and methods: Five days postfertilization zebrafish embryos were exposed to 1 mM cisplatin and quercetin at 10, 50, 100, or 200 μM for 4 h. Hair cells within neuromasts of the supraorbital, otic, and occipital lateral lines were analyzed by fluorescent microscopy ( n = 10). Survival of hair cells was calculated as the average number of hair cells in the control group that were not exposed to cisplatin. Ultrastructural changes were evaluated using scanning electron microscopy. Results: Hair cell damage in neuromasts was decreased by co-treatment of quercetin and cisplatin (quercetin 100 μM: 8.6 ± 1.1 cells; 1 mM cisplatin only: 5.0 ± 0.5 cells; n = 10, p < 0.05); apoptosis of hair cells examined by special stain was also decreased by quercetin. The ultrastructure of hair cells within neuromasts was preserved in zebrafish by the combination of quercetin (100 μM) and cisplatin (1 mM). Conclusion: In conclusion, quercetin showed protective effects against cisplatin-induced toxicity in a zebrafish model. The results of this study suggest the possibility of a protective role of quercetin against cisplatin-induced apoptotic cell death in zebrafish.


2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Wei-Lian Phan ◽  
Yu-Tzu Huang ◽  
Ming-Chieh Ma

The present results demonstrated that high glucose (G), salt (S), and cholesterol C (either alone or in combination), as mimicking extracellular changes in metabolic syndrome, damage cardiomyocyte-like H9c2 cells and reduce their viability in a time-dependent manner. However, the effects were greatest when cells were exposed to all three agents (GSC). The mRNA of glycoprotein (gp) 130 and WSX-1, both components of the interleukin (IL)-27 receptor, were present in H9c2 cells. Although mRNA expression was not affected by exogenous treatment with IL-27, the expression of gp130 mRNA (but not that of WSX-1 mRNA) was attenuated by GSC. Treatment of IL-27 to H9c2 cells increased activation of signal transducer and activator of transcription 3 (STAT3) and protected cells from GSC-induced cytochrome c release and cell damage. The protective effects of IL-27 were abrogated by the STAT3 inhibitor, stattic. The results of the present study clearly demonstrate that the STAT3 pathway triggered by anti-inflammatory IL-27 plays a role in protecting cardiomyocytes against GSC-mediated damage.


Author(s):  
Bharat Kwatra

The present review is based mainly on papers published between 2000 and 2011 and gives information about the properties of the carotenoid lycopene in chemical and biological systems and its possible role in preventing cardiovascular diseases (CVD). The main aim of this report is to highlight its role as an antioxidant, also reported are bioactive properties that may influence the development of foam cells and protection against endothelial cell damage. The paper will also examine recent observations that lycopene may improve blood flow and reduce inflammatory responses. Lycopene possesses antioxidant properties in vitro, and some epidemiological studies have reported protective effects against the progression of CVD. The oxidation of human low density lipoproteins (LDL) is a fundamental mechanism in the initiation of atherosclerosis. A beneficial role of lycopene as antioxidant in the prevention of CVD is suggested but the data are still controversial. Lycopene is believed to be the most potent carotenoid antioxidant in vitro. Tissue culture experiments and animal studies support potential cardioprotective effects for lycopene and other carotenoids in the blood. Most studies showed beneficial effects of lycopene to individuals who are antioxidant-deficient like elderly patients, or humans exposed to higher levels of oxidative stress like smokers, diabetics, hemodialysis patients and acute myocardial infarction patients. By defining the right population and combining antioxidant potentials of lycopene with vitamins and other bioactive plant compounds, the beneficial role of lycopene in CVD can be clarified in future studies. Keywords: Atherosclerosis, isomerization, in vitro, in vivo, LDL oxidatin


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Xide Chen ◽  
Yuanli Yan ◽  
Zhiyan Weng ◽  
Chao Chen ◽  
Miaoru Lv ◽  
...  

Metabolic inflammatory damage, characterized by Toll-like receptor 4 (TLR4) signaling activation, is a major mechanism underlying lipotoxicity-induced β-cell damage. The present study is aimed at determining whether G protein-coupled receptor 4 (GPR40) agonist can improve β-cell lipotoxicity-induced damage by inhibiting the TLR4-NF-κB pathway. Lipotoxicity, inflammation-damaged β-cells, obese SD, and TLR4KO rat models were used in the study. In vitro, TAK-875 inhibited the lipotoxicity- and LPS-induced β-cell apoptosis in a concentration-dependent manner, improved the insulin secretion, and inhibited the expression of TLR4 and NF-κB subunit P65. Besides, silencing of TLR4 expression enhanced the protective effects of TAK-875, while TLR4 overexpression attenuated this protective effect. Activation of TLR4 or NF-κB attenuated the antagonism of TAK-875 on PA-induced damage. Moreover, the above process of TAK-875 was partially independent of GPR40 expression. TAK-875 reduced the body weight and inflammatory factors, rebalanced the number and distribution of α or β-cells, inhibited the apoptosis of islet cells, and inhibited the expression of TLR4 and NF-κB subunit P65 in obese rats. Further knockout of the rat TLR4 gene delayed the damage induced by the high-fat diet and synergy with the action of TAK-875. These data suggest that GPR40 agonists antagonized the lipotoxicity β-cell damage by inhibiting the TLR4-NF-κB pathway.


Author(s):  
Dr.N.M. Khirale

The Preamble to the constitution has a noble vision which is reflected in the body of constitution in two parts. Chapter on fundamental rights and directive principles both are constitutional goals. The foundation of welfare state and democratic setup is a basic feature which directs state machinery to respect the way, access to exercise of right to life of millions in India. The Supreme nature of the constitution, Republic and Democratic form of Government. Secular in itself and partially adoption of theory of Separation of powers with Federal character are the basic elements of the constitution which can easily be understand by anybody by simply reading the contents of the preamble. The Constitution-makers with legitimate voice finalized the competency parliament to make amendments in rights to cater the present needs of nation and also to find remedial measures for the problems of socio-economic progress and development of the country. KEYWORDS: Preamble, Basic structure, Amending powers, limited power theory.


2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.


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