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Endoplasmic reticulum stress (ER stress) plays a crucial role in the process of Alzheimer's disease (AD). Activating transcription factor 6 (ATF6) is a crucial sensor of ER stress. In AD patients, the homeostasis of the endogenous signal H 2 S produced by cystathionine γ-lyase (CTH) is in disbalance. However, the role of ATF6 and CTH in AD is rarely reported. Herein, we found that ATF6 and CTH were reduced in AD patients and APP/PS1 mice by immunohistochemistry and western blots. In LN229 and U87 MG cells, knockdown of ATF6 attenuated CTH expression, whereas overexpression of ATF6 resulted in upregulation of CTH. Brain-specific ATF6 knockout mice expressed significantly down-regulated CTH in the hippocampus and cortex compared to wild-type mice. Mechanistically, ATF6 and CTH increased H 2 S generation and autophagy-related proteins. Further we observed that CTH promoted the sulfhydration of αSNAP. This is probably to be the specific mechanism by which AFT6 promotes autophagy. Through in vivo studies, we found that αSNAP sulfhydration expression was significantly lower in ATF6 knockout mice than in wild-type mice. Decreased ATF6 impaired spatial memory retention, while addition of CTH rescued memory loss. Together, we demonstrate that ATF6 positively regulates the expression of CTH, which is closely related to the rescue of AD. Targeting the ATF6/CTH signal pathway may provide a new strategy for the treatment of AD. • The important roles of ATF6 and CTH in AD are revealed. • ATF6 regulates the expression of CTH. • ATF6 and CTH promote the generation of H 2 S and then promote autophagy. • CTH supplementation rescues memory impairment in ATF6-deficient AD mice. [ABSTRACT FROM AUTHOR]

Neuraminidase, also known as sialidase, is ubiquitous in animals and microorganisms. It is predominantly distributed in the cell membrane, cytoplasmic vesicles, and lysosomes. Neuraminidase generally recognizes the sialic acid glycosidic bonds at the ends of glycoproteins or glycolipids and enzymatically removes sialic acid. There are four types of neuraminidases, named as Neu1, Neu2, Neu3, and Neu4. Among them, Neu1 is the most abundant in mammals. Recent studies have revealed the involvement of Neu1 in several diseases, including cardiovascular diseases, diabetes, cancers, and neurological disorders. In this review, we center the attention to the role of Neu1 in cardiovascular diseases, including atherosclerosis, ischemic myocardial injury, cerebrovascular disease, congenital heart disease, and pulmonary embolism. We also summarize inhibitors from Chinese herbal medicines (CHMs) in inhibiting virus neuraminidase or human Neu1. Many Chinese herbs and Chinese herb preparations, such as Lonicerae Japonicae Flos, Scutellariae Radix, Yupingfeng San, and Huanglian Jiedu Decoction, have neuraminidase inhibitory activity. We hope to highlight the emerging role of Neu1 in humans and potentially titillate interest for further studies in this area. [ABSTRACT FROM AUTHOR]

Jiyuan Oridonin A (JOA) is a naturally occurring ent -kaurane diterpenoid that exhibits significant potential in the field of anti-tumor drug development. However, its detailed anti-cancer mechanism of action has not been fully understood. In order to investigate its anticancer mode of action, two series of novel fluorescent derivatives of JOA conjugated with naphthalimide dyes were synthesized, and their antitumor activity against five selected cancer cell lines (MGC-803, SW1990, PC-3, TE-1 and HGC-27) was evaluated. Compared with JOA , the anti-tumor activity of the vast majority of compounds were improved. Among them, B12 exhibited promising anti-proliferative activity against HGC-27 cells with IC 50 value of 0.39 ± 0.09 μM. Fluorescence imaging studies demonstrated that probe B12 could enter HGC-27 cells in a dose-dependent and time-dependent manner and was mainly accumulated in mitochondria. Preliminary biological mechanism studies indicated that B12 was able to inhibit cell cloning and migration. Further studies suggested that B12 -induced apoptosis was related to the mitochondrial pathway. Overall, our results provide new approaches to explore the molecular mechanism of the natural product JOA , which would contribute to its further development as an antitumor agent. [Display omitted] • Two series of novel fluorescent derivatives of JOA were designed and evaluated for toxicity. • Compound B12 displayed the strongest inhibitory activity (IC 50 = 0.39 ± 0.09 μM) and selectivity against HGC-27 cells. • B12 could enter HGC-27 cells in a dose-dependent and time-dependent manner and was mainly accumulated in mitochondria. • Primary mechanism study indicated that B12 -induced apoptosis was related to the mitochondrial pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: Results of the published reports on the relationship between glutathione S-transferase P1 (GSTP1) gene polymorphism and the adenocarcinomas of lung cancer are still debated. OBJECTIVE: This meta-analysis was performed to evaluate the association between GSTP1 A/G gene polymorphism and the risk of adenocarcinomas of lung cancer. METHODS: The association investigations were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method.RESULTS: 16 reports were included into this meta-analysis for the association of GSTP1 A/G gene polymorphism and the risk of adenocarcinomas of lung cancer. The G allele and GG genotype were not associated with the susceptibility of risk of adenocarcinomas. Furthermore, in the sensitivity analysis, the results were similar with those from the non-sensitivity analysis. CONCLUSIONS: GSTP1 G allele or GG genotype is not a biomarker to be associated with the susceptibility of adenocarcinomas of lung cancer. [ABSTRACT FROM AUTHOR]

Abstract: There has been no an effective method to measure resistivity of mineral powder and other powder materials until now. According to the national standards GB/T1410-2006, the method to measure resistivity of mineral powder and other powder materials was studied by using the digital high resistance meter and a small measurement electrode which is adequate for the measurement of flat specimen whose diameter is 18mm. A formula to calculate resistivity of mineral powder by the testing data of its powder compacts was derived according to the compacts characteristics and the generalized effective medium equation (GEM). Then, taking micro-crystal muscovite for example, the experimental results proves that the measurement method is effective and feasible because the resistivity data of mineral powders are the same as that of their dense blocky samples. Further experimental results show that the volume resistivity and surface resistivity of mineral powder are not influenced by mineral particle size. And the upper and lower faces of powder compacts do not affect the volume resistivity of mineral powder, but affect the surface resistivity obviously. So, it is necessary to characterize the surface resistivity of mineral powder by the testing data of the upper face (punch face) of powder compacts. Moreover, the resistivity of mineral powder is greatly influenced by both the drying time and standing time in air. Therefore, in order to obtain correct result, the samples should be dried to constant weight before testing, isolated from air during cooling and measured immediately when exposed to air, and the testing time should be as short as possible. [Copyright &y& Elsevier]