ABSTRACT
Retinal pericyte migration occurs in the early stage of diabetic retinopathy (DR), which is one of the important causes of pericyte loss. Autophagy has been found to play essential roles in the regulation of many types of cell migration. In this study, we explored the relationship between autophagy and retinal pericyte migration. In diabetic rats, the retinas became thinner, and the level of autophagy in each cell layer increased. In the primary culture of bovine retinal pericytes, we found that advanced glycation end products (AGEs) increased the migratory cell ability without influencing cell viability, which also increased the phosphorylation of focal adhesion kinase (FAK) and the expression of matrix metalloproteinase (MMP)-2 and decreased the expression of vinculin. AGEs-induced retinal pericyte autophagy and the inhibition of autophagy with chloroquine significantly inhibited cell migration, reversed AGEs-induced FAK phosphorylation, and changed vinculin and MMP-2 protein expression. These results provide a new insight into the migration mechanism of retinal pericytes. The early control of autophagy has a potential effect on regulating pericyte migration, which may contribute to keeping the integrity of retinal vessels in DR.
ABSTRACT
Intracerebral haemorrhage (ICH) can be a catastrophic event; even if the initial stages of the pathology were well-managed, a number of patients experience varied residual neurological deficits following the insult. Ferroptosis is a recently identified type of cell demise which is tightly linked to the neurological impairment associated with ICH. In the current work, the prophylactic impact of scalp acupuncture (SA) therapy on autologous blood injection murine models of ICH was investigated in order to establish whether SA could mitigate the secondary damage arising following ICH by moderating ferroptosis. The pathophysiological mechanisms associated with this process were also explored. Ludmila Belayev tests were utilised for the characterisation of neurological damage. Haematoxylin-eosin staining was employed in order to determine the cerebral impact of the induced ICH. Malondialdehyde (MDA) and iron titres in peri-haemorrhagic cerebral tissues were appraised using purchased assay kits. Transmission electron microscopy delineated mitochondrial appearances within nerve cell bodies from the area of haemorrhage. Western blotting techniques were utilised to assay the degree of protein expression of NeuN, sequestosome 1 (p62), nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1). The frequencies of Nrf2, GPX4 and FTH1 positive cells, respectively, were documented with immunohistochemical staining. The results demonstrated that therapy with SA after ICH mitigated MDA and iron sequestration, diminished the appearance of contracted mitochondria with increased outer mitochondrial membrane diameter within the nerve cell bodies, and suppressed neuronal ferroptosis. The pathways responsible for these effects may encompass amplified p62, Nrf2, GPX4 and FTH1 expression, together with decreased Keap1 expression. Application of SA reduced identified neurobehavioural abnormalities after ICH; no disparities were observed between the consequences of SA therapy and deferoxamine delivery. It can be surmised that intervention with SA enhanced recovery after ICH by triggering the antioxidant pathway, p62/Keap1/Nrf2, and causing FTH1 and GPX4 upregulation, factors that participate in diminishing excess iron and thus in mitigating lipid peroxidation insults arising from ferroptosis following ICH.
Subject(s)
Acupuncture Therapy , Ferroptosis , Animals , Cerebral Hemorrhage/metabolism , Cerebral Hemorrhage/therapy , Humans , Kelch-Like ECH-Associated Protein 1/metabolism , Mice , NF-E2-Related Factor 2/metabolism , Rats , Scalp/metabolism , Signal TransductionABSTRACT
OBJECTIVE: To explore the effects of nutritional liquid supplement designed for diabetes mellitus on postprandial glucose state and pregnancy outcomes in patients with gestational diabetes mellitus (GDM). METHODS: A total of 69 cases of pregnant GDM women at Department of Obstetrics & Gynecology, First Affiliated Hospital, Chongqing Medical University from October 2011 to January 2012 were randomized into the intervention and control groups. But only 31 cases in intervention group finished the study versus 29 cases in control group. The inter-group differences were analyzed for general clinical profiles before intervention, 2-hour postprandial blood glucose levels and pregnancy outcomes, etc. The General Linear Model Repeated Measures process was used to analyze the variance of 2-hour postprandial blood glucose data. And the Mauchy's test of sphericity was employed to determine the correlation. RESULTS: (1) No significant difference in general clinical profiles before intervention between intervention and control groups (P > 0.05). (2) The mean values of 2-hour postprandial blood glucose were as follows: intervention group (mmol/L) : 6.2 ± 0.7(1w), 5.9 ± 0.5(2w), 5.7 ± 0.5(3w), 5.8 ± 0.6 (4w), 5.7 ± 0.5(5w), 5.7 ± 0.4(6w), 5.9 ± 0.3(7w), 6.0 ± 0.4(8w), 6.0 ± 0.5(9w); control group: 6.7 ± 0.3 (1w), 6.2 ± 0.4(2w), 6.2 ± 0.5(3w), 6.2 ± 0.4(4w), 6.1 ± 0.4(5w), 6.0 ± 0.3 (6w), 5.8 ± 0.4 (7w), 6.1 ± 0.4 (8w), 6.1 ± 0.4(9w). The results of Mauchy's test of sphericity indicated that the blood glucose level of the intervention group was significantly lower than that of the control group (P < 0.01). (3) The incidence of premature rupture of membranes and polyhydramnios, rate of neonatal pneumonia, weight of newborn and pregnancy women and level of glycosylated hemoglobin in intervention group were significantly lower than those in control group (P < 0.05). CONCLUSION: Compared with common diet, after using nutritional supplement, the postprandial blood glucose level is significantly reduced and the pregnancy outcomes also improved in GDM patients.