Background: Acetylation has a vital role in the pathogenesis of end-stage renal disease (ESRD). Lysine 2-hydroxyisobutyrylation (Khib) is a novel type of acetylation. In this study, we aimed to reveal the key features of Khib in peripheral blood monocytes (PBMCs) of patients with ESRD. Method: We combined TMT labeling with LC-MS/MS analysis to compare Khib modification of PBMCs between 20 ESRD patients and 20 healthy controls. The pan 2-hydroxyisobutyrylation antibody-based affinity enrichment method was used to reveal the features of Khib, and the bioinformatics analysis was conducted to analyze the pathology of these Khib-modified proteins. Result: Compared to healthy controls, we identified 440 upregulated proteins and 552 downregulated proteins in PBMCs of ESRD, among which 579 Khib sites on 324 upregulated proteins and 287 Khib sites on 188 downregulated proteins were identified. The site abundance, distribution, and function of the Khib protein were further analyzed. The bioinformatics analysis revealed that the Rho/ROCK signaling pathway was highly enriched in ESRD, suggesting that it might contribute to renal fibrosis in ESRD patients. Conclusion: In this study, we found that Khib-modified proteins correlated with the occurrence and progression of ESRD.
It is proved that the C_0-semigroup generated by the operator (?) is analytic in the evolu-tion equation (dy)/(dt)=(?)y,y(0)=y_0 corresponding to the slender flying vehicle system withthe structural damp (the elastic beam with two free ends).
To investigate mechanism of the antibody-mediated cardiac cytotoxicity and clinical significance in dilated cardiomyopathy (DCM), and study the effects of the antibodies against the myocardial mitochondrial ADP / ATP carrier from sera of patients with dilated cardiomyopathy on the guinea pig ventricular myocytes.This study included 18 patients with DCM (12 men and 6 women), with mean age of 43 years. Control group included 18 health donors, (9 men and 9 women), with mean age of 32 years. The antibodies against the ADP / ATP carrier and cell membrane 52 000 peptide were examined by immunoblotting. The antibody-mediated cardiac cytotoxicity was studied with the cytotoxic test and whole cell patch-clamp technique.The antibodies against myocardial mitochondrial ADP / ATP carrier and cell membrane 52 000 peptide were positive in 18 patients with DCM, while negative in controls. The antibodies induced cytotoxic damage with time-dependent and enhanced Ca-current in cardiac myocytes. The increasing amplitude of peak Ca(2+)-current was 100 pA-840 pA (n = 8) in different dilution of the antibodies. The effect of the antibodies might be inhibited by verapamil, and were null in controls (n = 4).The above findings suggest that an increase in the antibody-mediated Ca(2+)-current of cardiac myocytes is related to the cytotoxic damage in dilated cardiomyopathy.
Population theories in China before the revolution are reviewed. The author considers whether there was a population problem, whether a surplus population did exist, and to what extent population pressures existed.
To explore the effects of progesterone (PROG) on learning and memory and P2X7 receptor expression in the hippocampus after global cerebral ischemia/reperfusion (I/R) injury in rats.Forty-eight male SD rats were randomly divided into four groups (n = 12) that were normal group, sham-operated group, I/R group and I/R+ PROG group. The global cerebral I/R injury models were established by improved Pulsinelli's four vessel occlusion, the learning and memory were evaluated by Y-maze, the expression of P2X7 receptor protein in the hippocampus were detected by the immunofluorescence, the activity of superoxide dismutase (SOD) in the hippocampus were detected with hydroxylamine oxidation method, the content of malondialdehyde (MDA) in the hippocampus were detected with pen-thiobarbituric acid method.There was no significant difference of the learning and memory and positive expression cells of P2X7 receptor protein and the activity of SOD and the content of MDA in the hippocampus between normal group and sham-operated group. Compared with sham-operated group, the learning and memory of I/R group were significantly decreased (P < 0.01), Compared with I/R group, the learning and memory of I/R + PROG group were significantly increased (P < 0.05). Compared with sham-operated group, the positive expression cells of P2X7 receptor protein in the hippocampus of I/R group was significantly increased (P < 0.01), Compared with I/R group, the positive expression cells of P2X7 receptor protein in the hippocampus of I/R + PROG group was significantly decreased (P < 0.01). Compared with sham-operated group, the activity of SOD in the hippocampus of of I/R group was significantly decreased (P < 0.01), and the content of MDA in the hippocampus of I/R group was significantly increased (P < 0.01). Compared with I/R group, the activity of SOD in the hippocampus of I/R+ PROG group was significantly increased (P < 0.05), and the content of MDA in the hippocampus of I/R + PROG group was significantly decreased (P < 0.01).PROG could improve the learning and memory ability following global cerebral ischemia/reperfusion injury in rats, the protective mechanism might be associated with down-regulating the expression of P2X7 receptor protein and attenuating oxygen-derived free radicals in the hippocampus.
To explore the role of TLR4 in myocardial ischemia reperfusion injury (MI/RI) by observing the dynamic TLR4 expression changes at mRNA and protein levels early after myocardial ischemia reperfusion.Male SD rats were randomly divided into Sham and IR group and the rats were killed according to different reperfusion time (0, 0.5, 1, 2, 4 and 8 hours). Myocardial changes under light microscope and transmission electronic microscope were observed. TLR4 expressions at protein and mRNA levels were detected by immunohistochemistry and realtime RT-PCR respectively. Myocardial TNF-alpha was determined by ELISA.(1) Myocardial injury was observed in IR but not in Sham group and histopathological and ultrastructural changes in IR group remained unchanged up to 8 hours after reperfusion. (2) Positive TLR4 protein staining was visualized in both Sham and IR groups and significantly increased and peaked at 1 hour of reperfusion in IR group. (3) Compared to Sham group, TLR4 mRNA level was upregulated in myocardium in IR group and peaked at 1 hour of reperfusion. (4) Concentration of TNF-alpha in IR group was significantly higher than that of Sham group at corresponding time points (all P < 0.05), and myocardial TLR4 mRNA level correlated positively with myocardial TNF-alpha (r = 0.728, P < 0.01).Expression of TLR4 in myocardium during early after myocardial ischemia reperfusion was upregulated and actived TLR4 might play an important role in MI/RI through promoting myocardial TNF-alpha excretion.
The harmonious society breeds mental health,which,in turn,makes the harmonious society.Attention to peo-ple's mental health is of vital significance to the individual development and the realization of a harmonious society.The gov-ernment should perfect the social mechanism and establish the psychological dredging mechanism by multi-channels.It should also reinforce the mental health education,thus eliminating resentful emotions and creating a harmonious relation.Only by do-ing so,can the public mental health be realized and a harmonious society be established.
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