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A Biophysical View on the Function and Activity of Endotoxins
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
Ulrich Seydel, Andre Wiese, Andra B. Schromm, Klaus Brandenburg
In further studies, measurements of the aggregate structure were extended to other lipid A samples, i.e., enterobacterial LPS and lipid A in different salt forms as well as monophosphoryl lipid A and lipid A from nonenterobacterial sources like those of Rhodobacter capsulatus, Rhodopseudomonas viridis, Rhodocyclusgelatinosus, Rhodospirillum fulvum, Campylobacter jejuni, and Chromobacterium violaceum (145,172,173). The measurements were carried out exclusively under near physiological conditions with the purpose of directly correlating the results to data from biological test systems. It was found that the kind of counterions present (endotoxins in different salt forms) significantly influenced the aggregate structure of LPS and that different nonenterobacterial lipid A samples showed a variety of aggregate structures ranging from HII (lipid A from R. gelatinosus) over mixed cubic/lamellar (monophosphoryl lipid A from S. minnesota and lipid A from C. jejuni) to pure lamellar structures (lipid A from C. violaceum, R. capsulatus, R. viridis, and R. fulvum) (145,172,173). It was later shown that these different structural preferences are important for the expression of biological activity (see below).
Excitotoxicity and Nitric Oxide
Published in Richard A. Jonas, Jane W. Newburger, Joseph J. Volpe, John W. Kirklin, Brain Injury and Pediatric Cardiac Surgery, 2019
I do not want to give the false impression that there are free nitrosonium ions. Under most physiological conditions, there are not. However, consider the structure of the NO group within one of these molecules, sodium nitroprusside, nitroglycerin or S-nitrosocysteine, or the more general cases of any protein that has an NO attached to a cysteine (RSNO). All of these are similar or identical to NO+, as can be seen by counting the electrons associated with the NO group. Therefore, they tend to donate NO+.
The Concept of Health
Published in Dien Ho, A Philosopher Goes to the Doctor, 2019
Cooper’s analysis represents a prime example of a normativist definition of health. The defining characteristic of normativism is that some social or personal value must play an indispensable role in explicating health and disease. What makes a particular physiological condition a disease accordingly is that the condition must negatively impact the patient’s ability to acquire things that are valuable. In other words, there is no objective biological way to determine if a given physiological condition is a disease. All diseases are diseases only relative to a set of values of the patient or the community. The same physiological condition might be a disease in one context and a non-disease in another. The difference lies in how the condition affects the person’s values. In a literate society, for instance, dyslexia might be a disorder because we value literacy. The same condition in a non-literate community obviously wouldn’t even surface and therefore would not be considered a disease.
L-Kynurenine participates in cancer immune evasion by downregulating hypoxic signaling in T lymphocytes
Published in OncoImmunology, 2023
Stephanie Schlichtner, Inna M. Yasinska, Elena Klenova, Maryam Abooali, Gurprit S. Lall, Steffen M. Berger, Sabrina Ruggiero, Dietmar Cholewa, Milan Milošević, Bernhard F. Gibbs, Elizaveta Fasler-Kan, Vadim V. Sumbayev
However, recent evidence has demonstrated that certain small molecular weight compounds can also effectively suppress T cell function and thus support the evasion of anti-cancer immunity7,8. Recently, concerns have been raised regarding the role of L-kynurenine (LKU) and its metabolites in suppressing cytotoxic lymphoid cell function during cancer progression. LKU is an amino acid that is formed during L-tryptophan (L-Trp) catabolism. LKU and its metabolites are formed via the kynurenine pathway (KP)7,8. KP accounts for approximately 95% of dietary L-tryptophan degradation. Under normal physiological conditions ca. 90% of LKU is generated by the hepatic KP9,10. In the case of immune activation, the extrahepatic KP plays a more active role. The KP is rate-limited by its first enzyme, Trp 2,3-dioxygenase (TDO), mainly in the liver, and indoleamine 2,3-dioxygenases 1 and 2 (IDO1 and IDO2) elsewhere. IDO1 has been reported to display higher activity than IDO29–11. The entire KP is presented in Supplementary figure S1.9–12
Examining the correlation between salivary cytokine concentrations and CRP in people experiencing social-cognitive stress
Published in Neurological Research, 2023
Eric Chun Pu Chu, Anastasiya Spaska, Dimitar Monov, Mikhail Kasatkin, Natalia Stroiteleva
Along with measuring cytokine levels in the systemic circulation, it is vital to estimate cytokine concentrations in other biological fluids, such as urine and saliva. The latter is a valuable non-invasive tool for assessing the physiological condition of the body. Compared with the blood collection process, the collection of saliva is more convenient, easier, and painless process. The method of collecting saliva reduces the risk of infection among medical personnel. The concentrations of certain substances in saliva reflect their concentrations in blood [22]. Most pro- and anti-inflammatory cytokines, including IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, TNFα, and IFNγ, can be found not only in peripheral blood, but also in saliva [23]. However, no studies have been conducted to compare salivary levels of IL-1β and IL-6 between TTH/migraine patients and age-matched controls.
Recent developments in Phos-tag electrophoresis for the analysis of phosphoproteins in proteomics
Published in Expert Review of Proteomics, 2022
Additionally, this study revealed an important possibility. Shotgun and database analyses have found that the human 26S proteasome has more than 450 phosphorylation sites [86]. Since there are about 30 types of proteasome subunits in total, there may be about 15 phosphorylation sites in one subunit on average. Suppose the phosphorylation states of all or any of these sites change considerably in relation to protein function. In that case, many subunits (proteoforms) with different phosphorylated states could be detected via Phos-tag electrophoresis. However, when examined using Phos-tag diagonal electrophoresis, Okawara et al. [23] found that the number of major CBB-stained subunits with varying phosphorylation states was unexpectedly small. A possibility exists that the phosphorylation state may be changed significantly due to differences in stress, illness, and physiological conditions. However, there are likely relatively few types of significant subunits. In humans, it is said that there are over 290,000 protein phosphorylation sites [64]. From this number, it seems that the number of proteins with different phosphorylation states is astronomic. Nonetheless, in reality, the phosphorylation state is relatively controlled, and the proteoforms might not be so many. Therefore, Phos-tag diagonal electrophoresis may play an important role in quickly analyzing the differences in the phosphorylation states of proteins.