A central question in Alzheimer's disease research is what role synaptic activity plays in the disease process. Synaptic activity has been shown to induce ␤-amyloid peptide release into the extracellular space, and extracellular ␤-amyloid has been shown to be toxic to synapses. We now provide evidence that the well established synaptotoxicity of extracellular ␤-amyloid requires ␥-secretase processing of amyloid precursor protein. Recent evidence supports an important role for intraneuronal ␤-amyloid in the pathogenesis of Alzheimer's disease. We show that synaptic activity reduces intraneuronal ␤-amyloid and protects against ␤-amyloid-related synaptic alterations. We demonstrate that synaptic activity promotes the transport of the amyloid precursor protein to synapses using live cell imaging, and that the protease neprilysin is involved in reduction of intraneuronal ␤-amyloid with synaptic activity.

Breast cancer specimens from 600 women were assayed for estrogen receptors (ER) using an immunocytochemical assay (JCA) employing the monoclonal antiestrophilin antibody H222 Sp 7. Results showed significant correlation with biochemical ER determinations as well as with tumor grade and menopausal status. In 449 cases, results of progesterone receptor assay by ICA using the monoclonal anti-PgR antibody KD 68, also correlated significantly with biochemical PgR measurements. The ERICA/PgRICA positivity was significantly more frequent in postmenopausal white women. Colloid carcinomas were most likely to be ERICA positive and PgRICA positive whereas medullary carcinomas were most often negative. In 47 patients with advanced mammary carcinoma, results of ERICA and PgRICA were more closely related to endocrine response than those of ER and PgR by dextran-coated charcoal assay (DCC). In 339 women with Stage I or Stage I1 breast cancer, ERICA was significantly associated with disease-free survival. Analysis by Cox's proportional hazard model, however, showed PgRICA to be the best predictor of survival and disease-free survival in 197 women at the same stages of disease. These data indicate that ICA is more predictive of prognosis than biochemical ER and PgR. The ease of ICA performance coupled with these results indicate that the method is an acceptable substitute for DCC in analyzing breast cancers for ER/PgR.

Matrine is an alkaloid extracted from traditional Chinese herbs including Sophora flavescentis, Sophora alopecuroides, Sophora root, etc. It has the dual advantages of traditional Chinese herbs and chemotherapy drugs. It exhibits distinct benefits in preventing and improving chronic diseases such as cardiovascular disease and tumors. The review introduced recent research progresses on extraction, synthesis and derivatization of Matrine. The summary focused on the latest research advances of Matrine on anti-atherosclerosis, anti-hypertension, anti-ischemia reperfusion injury, anti-arrhythmia, anti-diabetic cardiovascular complications, anti-tumor, anti-inflammatory, anti-bacterium, anti-virus, which would provide new core structures and new insights for new drug development in related fields.

Sleep deprivation (SD) leads to cognitive impairment due to neuroin ammation associated with impaired hippocampal neuronal plasticity and memory processes. Liver X receptors (LXRs), including LXRα and LXRβ isoforms, are crucial for synaptic plasticity as well as anti-in ammation. However, the potential roles of LXRs in the pathogenesis of cognitive impairment induced by SD remain unclear. We revealed that SD resulted in LXRβ reduction in hippocampus, which was associated with upregulated expression of high mobility group box1 (HMGB1)/toll-like receptor 4 (TLR4)/NF-κB p65, and knockdown of hippocampal LXRβ by shRNA (shLXRβ) led to cognitive impairment. GW3965, a dual agonist for both LXRα and LXRβ, ameliorated SD-induced cognitive impairment by inhibiting microglia activation, suppressing HMGB1/TLR4/NF-κB p65 pathway, and ultimately affecting the hippocampal expression of in ammatory cytokines in SD mice. LXRβ knockdown by shLXRβ, abrogated GW3965-mediated the inhibition of HMGB1/TLR4/NF-κB p65 pathway, therefore abolished the cognitive improvement.Moreover, inhibition of HMGB1 by glycyrrhizin (GLY) synergistic promoted GW3965-mediated antiin ammation in activated microglia after LPS/ATP stimulation and facilitated the cognitive improvement after GW administration by activating LXRβ. All the data suggested that GW3965 ameliorated impaired cognition in SD mice by suppressing HMGB1/TLR4/NF-κB p65 pathway followed LXRβ activation. This study correlates a de cit of LXRβ in cognitive dysfunction in SD associated with HMGB1 in ammatory pathway in hippocampus, and LXRs may serve as a potential therapeutic target for cognitive impairment with anti-in ammation.