Zeaxanthin Attenuates the Vicious Circle Between Endoplasmic Reticulum Stress and Tau Phosphorylation: Involvement of GSK-3ß Activation.

BACKGROUND: Alzheimer's disease (AD) characterized by neurofibrillary tangles caused by hyperphosphorylated tau is the most common cause of dementia. Zeaxanthin (Zea), derived from fruits and vegetables, may reduce the risk of AD. Endoplasmic reticulum stress (ERS) might cause memory impairment in AD. OBJECTIVE: Here, we studied protective role of Zea on the relationship among ERS, activity of glycogen synthase kinase 3ß (GSK-3ß, tau phosphorylated kinase), and p-Tau (Ser 396 and Thr 231). METHODS: The results were obtained in non-RA and RA group by using different treatment, such as 9-cis-retinoic acid (RA), TM (ERS inducer), Zea, 4-PBA (ERS inhibitor), and SB216763 (GSK-3ß inhibitor). The methods included flow cytometry and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] for the detections of cell cycle and cell viability and western blot as a third measure of proteins in relation to ERS and tau phosphorylation. We have collected and analyzed all the data that suggested application of drugs for the treatment in non-RA and RA group. RESULTS: Zea displays its protection on TM-induced cell injury, upregulation of GRP78 expression, and change of GSK-3ß activity and tau phosphorylation when 4-PBA and SB216763 interfere with the process. CONCLUSION: These studies indicated that Zea is in vicious circle in ERS, GSK-3ß, and tau phosphorylation, and further reflect its potential value in AD.

Independent and Correlated Role of Apolipoprotein E ɛ4 Genotype and Herpes Simplex Virus Type 1 in Alzheimer's Disease.

The ɛ4 allele of the Apolipoprotein E (APOE) gene in individuals infected by Herpes simplex virus type 1 (HSV-1) has been demonstrated to be a risk factor in Alzheimer's disease (AD). APOE-ɛ4 reduces the levels of neuronal cholesterol, interferes with the transportation of cholesterol, impairs repair of synapses, decreases the clearance of neurotoxic peptide amyloid-ß (Aß), and promotes the deposition of amyloid plaque, and eventually may cause development of AD. HSV-1 enters host cells and can infect the olfactory system, trigeminal ganglia, entorhinal cortex, and hippocampus, and may cause AD-like pathological changes. The lifecycle of HSV-1 goes through a long latent phase. HSV-1 induces neurotropic cytokine expression with pro-inflammatory action and inhibits antiviral cytokine production in AD. It should be noted that interferons display antiviral activity in HSV-1-infected AD patients. Reactivated HSV-1 is associated with infectious burden in cognitive decline and AD. Finally, HSV-1 DNA has been confirmed as present in human brains and is associated with APOEɛ4 in AD. HSV-1 and APOEɛ4 increase the risk of AD and relate to abnormal autophagy, higher concentrations of HSV-1 DNA in AD, and formation of Aß plaques and neurofibrillary tangles.

Flavonoids isolated from Sinopodophylli Fructus and their bioactivities against human breast cancer cells.

Four prenylated flavonoids compounds 1-4, named sinopodophyllines A-D, and a flavonoid glycoside (compound 13), sinopodophylliside A, together with 19 known compounds (compounds 5-12 and 14-24) were isolated from the fruits of Sinopodophyllum hexandrum. The structures of new compounds were elucidated by extensive spectroscopic analysis, including HRESIMS, 1D and 2D NMR. Compounds 1-6, 9-11, and 14-17 were tested for their cytotoxicity against human breast-cancer T47D, MCF-7 and MDA-MB-231 cells in vitro, and compounds 2, 5, 6, 10 and 11 showed significant cytotoxicity (IC50 values < 10 µmol·L-1) against T47D cells.

Modulation of AßPP and GSK3ß by Endoplasmic Reticulum Stress and Involvement in Alzheimer's Disease.

Alzheimer's disease (AD) is a dementia disease with neuronal loss and synaptic impairment. This impairment is caused, at least partly, by the generation of two main AD hallmarks, namely the hyperphosphorylated tau protein comprising neurofibrillary tangles and senile plaques containing amyloid-ß (Aß) peptides. The amyloid-ß protein precursor (AßPP) and glycogen synthase kinase-3ß (GSK3ß) are two main proteins associated with AD and are closely correlated with these hallmarks. Recently, both of the proteins were reported to be modulated by endoplasmic reticulum stress (ERS) and are involved in the pathogenesis of AD. The mechanism of ERS plus the modulation of AßPP processing and GSK3ß activity by ERS in AD are summarized and explored in this review.

[The efficacy and safety of autologous cryopreserved platelet transfusion in management of thrombocytopenia after chemotherapy in hematological malignancy].

OBJECTIVE: To investigate the efficacy and safety of autologous cryopreserved platelet transfusion in the management of thrombocytopenia after chemotherapy in hematological malignancy. METHODS: A total of 40 patients diagnosed as hematological malignancy with complete remission were equally assigned into study group and control group. During chemotherapy interval in the study group, when platelet counts exceeded 120 × 10(9)/L, autologous platelets were collected with CS3000 Cell Separator and cryopreserved at -80°C with 5% dimethylsulfoxide. When platelet counts dropped below 15 × 10(9)/L after chemotherapy, autologous platelets were thawed with 40°C water bath and transfused back to each patient. In the control group, when platelet counts dropped below 15 × 10(9)/L after chemotherapy, allogeneic fresh platelets were transfused. Median loss during the freeze-thaw-wash procedure in study group was observed, and the 1 h, 24 h corrected count increments (CCI) were calculated in the both groups. The hemostatic effects and adverse reactions were also observed. RESULTS: In the control group, 1hCCI and 24h CCI were (19.3 ± 6.1) × 10(9)/L and (12.2 ± 7.0) × 10(9)/L, respectively, with the effective rate of 80% and the transfusion reaction rate of 45%. Totally 20 collection and transfusions were finished in the study group. A total of (3.4 - 8.5) × 10(11) platelet were obtained in each collection. Platelet recovery after freezing and thawing was (73.51 ± 9.03)% (62% - 83%). 1hCCI was (17.4 ± 7.6) × 10(9)/L, 24h CCI was (10.5 ± 5.8) × 10(9)/L and the effective rate was 85%. There was no significant different between the two groups (P > 0.05). The transfusion reaction rate was 15%, which was significantly lower than that of the control group (P < 0.05). Meanwhile, adverse reactions were occurred less in the study group. CONCLUSION: This study demonstrates that autologous cryopreserved platelet transfusions can be safely administered for supporting thrombocytopenia in hematological malignancy patients undergoing chemotherapy.