SS31, a Small Molecule Antioxidant Peptide, Attenuates ß-Amyloid Elevation, Mitochondrial/Synaptic Deterioration and Cognitive Deficit in SAMP8 Mice.

Mitochondrial dysfunction, oxidative stress and ß -amyloid (Aß) formation are thought to cause neuronal and synaptic degeneration underlying cognitive decline in Alzheimer's disease (AD). The senescence-accelerated mouse-prone 8 (SAMP8) mice have been used as an animal model for mechanistic and translational research for AD. In the present study we characterized mitochondrial and synaptic alterations in SAMP8 mice relative to SAMR1control mice and explored a protective effect of the small molecule peptide SS31, a cell membrane penetrant antioxidant, on mitochondrial and synaptic protein integrity as well as cognitive performance. Electron microscopic analysis revealed mitochondrial/synaptic deterioration in 10 months-old SAMP8 relative to SAMR1 mice, with the changes in the former rescued following 8 weeks treatment with SS31 (5 mg/kg/day, i.p.). Elevation of Aß42, mitochondrial fission protein (DLP1, Fis1) and matrix protein cyclophilin D (CypD), and reductions of mitochondrial fusion protein (Mfn2) and synaptic (i.e., synaptophysin, postsynaptic density protein 95 and growth associated protein 43) proteins, were detected in hippocampal lysates in SAMP8 mice relative to SAMR1. The above altered protein expressions in the SAMP8 mouse brain were restored with the SS31 treatment. Moreover, the SS31 treatment rescued learning and memory deficits detected in 10 month-old SAMP8 mice. Together, the findings suggest that this mitochondria-targeting antioxidant peptide may be of potential utility for AD therapy, with its pharmacological efficacy involves lowering of central Aß levels and protection of mitochondrial homeostasis and synaptic integrity, which may help slow down cognitive decline.

Effective components of Chinese herbs reduce central nervous system function decline induced by iron overload.

Abnormally increased levels of iron in the brain trigger cascade amplification in Alzheimer's disease patients, resulting in neuronal death. This study investigated whether components extracted from the Chinese herbs epimedium herb, milkvetch root and kudzuvine root could relieve the abnormal expression of iron metabolism-related protein in Alzheimer's disease patients. An APPswe /PS1ΔE9 double transgenic mouse model of Alzheimer's disease was used. The intragastric administration of compounds from epimedium herb, milkvetch root and kudzuvine root improved pathological alterations such as neuronal edema, increased the number of neurons, downregulated divalent metal transporter 1 expression, upregulated ferroportin 1 expression, and inhibited iron overload in the cerebral cortex of mice with Alzheimer's disease. These compounds reduced iron overload-induced impairment of the central nervous system, indicating a new strategy for developing novel drugs for the treatment of Alzheimer's disease.

Preliminary investigation on the dynamic change in epidermal stem cells under mechanical stress in vivo / 中华烧伤杂志

<p><b>OBJECTIVE</b>To observe the distribution of epidermal stem cell (ESC) after soft tissue expansion, and to explore dynamic change in ESC under mechanical stress and kinetic mechanism of skin expansion.</p><p><b>METHODS</b>Skin samples were collected from patients after expansion of the scalp. They were divided into three groups: A group (scalp harvested 3 cm away from the center of dilator), B group (scalp tissues at the edge of dilator), and control group (scalp without dilatation). The tissue structures were observed with optical microscope with HE staining. The distribution and differentiation characteristics of cell keratin 19 (CK19) positive cells were observed with inverted phase contrast microscope after immunohistochemistry staining.</p><p><b>RESULTS</b>HE staining showed that the epidermis was thickened and distributed densely with uneven, rugged and increased layers in A, B groups. With immunohistochemistry staining, CK19 positive cells appeared in multilayers in basal membrane, a few of them were in cluster or dispersed , with" hollowing" structure formation. These phenomena were not seen in control group.</p><p><b>CONCLUSION</b>ESC can proliferate with abnormal distribution and "hollowing" structure formation after mechanical dilatation, which may be related to dynamic changes in basal layer cells.</p>

Study on the relationship between the human leucocyte antigen-DR expression on CD14+ monocytes and sepsis / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the changes in the expression of HLA-DR on CD14+ monocytes of burn patients with delayed resuscitation, and to analyze the relationship between it and sepsis.</p><p><b>METHODS</b>Twenty-five patients with total burn surface area over 30% TBSA and delayed resuscitation were enrolled in the study, among which 7 were complicated by sepsis during hospitalization. Peripheral blood was collected on 1, 3, 7, 14 and 28 post-burn days (PBD), and the blood of the patients with sepsis were also collected on the 1 and 2 days after the occurrence of sepsis. Twenty healthy volunteers were enrolled as controls. Expression rate of HLA-DR on CD14+ monocytes was determined by flow cytometry. The level of TNF-alpha and IL-10 were measured by ELISA.</p><p><b>RESULTS</b>Expression rate of HLA-DR antigen on CD14+ monocytes in burn patients without sepsis on 1, 3, 7, 14, 28 PBD were (15 +/- 6)%, (7 +/- 5)%, (26 +/- 17)%, (28 +/- 16)% and (47 +/- 16)%, respectively, which were obviously lower than that of healthy people [(92 +/- 10)%, P < 0.01], and it was also markedly lower on 1 and 2 days after the occurrence of sepsis than that of controls and those of patients without sepsis on 1, 7, 14, 28 PBD (P < 0.01). The positive rate and concentration of TNF-alpha in patients with sepsis were obviously higher than that of healthy people and patients without sepsis (P < 0.05 or P < 0.01). There was a negative correlation between the expression rate of HLA-DR on CD14+ monocytes and IL-10 levels, and it showed significant difference on 1, 7, and 28 PBD (r = -0.9963, -0.7459, -0.8474, respectively, P < 0.01).</p><p><b>CONCLUSION</b>Immune function is suppressed and proinflammatory mediators are excessively released in severely burn patients after delayed resuscitation, especially when complicated with sepsis. Expression of HLA-DR on CD14+ monocytes may be an useful parameter for monitoring the immune function of burn patients.</p>