Complement activation leads to membrane attack complex formation, which can lyse not only pathogens but also host cells. Histones can be released from the lysed or damaged cells and serve as a major type of damage-associated molecular pattern, but their effects on the complement system are not clear. In this study, we pulled down two major proteins from human serum using histone-conjugated beads: one was C-reactive protein and the other was C4, as identified by mass spectrometry. In surface plasmon resonance analysis, histone H3 and H4 showed stronger binding to C4 than other histones, with KD around 1 nM. The interaction did not affect C4 cleavage to C4a and C4b. Because histones bind to C4b, a component of C3 and C5 convertases, their activities were significantly inhibited in the presence of histones. Although it is not clear whether the inhibition was achieved through blocking C3 and C5 convertase assembly or just through reducing their activity, the outcome was that both classical and mannose-binding lectin pathways were dramatically inhibited. Using a high concentration of C4 protein, histone-suppressed complement activity could not be fully restored, indicating C4 is not the only target of histones in those pathways. In contrast, the alternative pathway was almost spared, but the overall complement activity activated by zymosan was inhibited by histones. Therefore, we believe that histones inhibiting complement activation is a natural feedback mechanism to prevent the excessive injury of host cells.
The Back-Propagation (BP) is the best known and widely used learning algorithm in training multiple neural network. A vast variety of improvements to BP algorithm have been proposed since ninety’s. in this paper, the effects of changing the number of hidden neurons and activation equation are investigated. According to the simulation results, the convergence speed have been improved and become much faster by the previous two modifications on the BP algorithm.
zine level in serum was mesured from patients suffering ftom cancer and healthy indiciduals hindred from each individuals were classified into three according to thier age the groups were
A theoretical and protection study was conducted of the corrosion behavior of carbon steel surface with different concentrations of the derivative (Quinolin-2-one), namly (1-Amino-4,7-dimethyl-6-nitro-1H-quinolin-2-one (ADNQ2O)). Theoretically, Density Functional Theory (DFT) of B3LYP/ 6-311++G (2d, 2p) level was used to calculate the optimized geometry, physical properties and chemical inhibition parameters, with the local reactivity to predict both the reactive centers and to locate the possible sites of nucleophilic and electrophilic attacks, in vacuum, and in two solvents (DMSO and H2O), all at the equilibrium geometry. Experimentally, the inhibition efficiencies (%IE) in the saline solution (of 3.5%) NaCl were st
... Show MoreColorectal cancer (CRC), the second most fatal cancer and the 3rd most common cancer is expected to cause 0.9 million deaths globally in 2025. Carcinoembryonic antigen (CEA) is currently used in the follow-up of patients with colorectal cancer, and in this study, we are trying to find a better marker than CEA in following up on patients' health and knowing the effectiveness of the treatment used and as a diagnostic marker for colorectal cancer. To determine the significance of Cancer antigen 72-4 (CA72-4) as a prognosis predictor in patients with colorectal cancer, compare its prognostic validity to the CEA biomarker. this case-control study includes (150) participants, 100 patients (59 males and 41 females), and 50 healthy controls
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