Flavonoids isolated from the flowers of Pulsatilla flavescens and their anti-piroplasm activity

Journal of Natural Medicines - Pulsatilla species are known as “Yargui”, and their flowers are traditionally used in Mongolia as a tonic and for the treatment of inflammatory diseases....     

Interleukin 10 and TNFalpha synergistically enhance the expression of the G protein-coupled formylpeptide receptor 2 in microglia

Microglia are important participants in inflammatory responses in the central nervous system. We previously observed that tumor necrosis factor alpha (TNFalpha) induces the expression of the formylpeptide receptor mFPR2 on microglial cells. This chemoattractant receptor mediates microglial cell chemotaxis in response to a variety of peptides, including amyloid beta peptide (Abeta(42)), a major pathogenic factor in Alzheimer's disease (AD). In search for agents that regulate microglial activation, we unexpectedly found that IL-10 enhanced the expression of mFPR2 on TNFalpha-activated microglia. This was associated with a markedly increased microglial chemotaxis to Abeta(42) and its endocytosis via mFPR2. Mechanistic studies revealed that the synergistic effect of IL-10 on TNFalpha-induction of mFPR2 in microglia was dependent on activation of p38 MAPK. Our results suggest that IL-10 may affect the pathogenic process of AD by up-regulating mFPR2 and thus favoring the recognition and internalization of Abeta(42) by activated microglial cells.     

防风在临床中的应用体会

目的：探讨中药防风在临床中的应用范围.方法：将防风与其他中药配伍使用,在经典方剂的基础上加减化裁,给药方式包括外敷及内服两种途径.结果：中药防风具有良好的解表祛风,止痉止泻作用,在临床应用治疗风邪所致的面瘫、眼疾及肝郁脾虚之泄泻有良好的效果.结论：明确药性药效,灵活运用配伍,以不变之法则应万变之病证,是中医药学的灵魂所在.在研究手段日益发达,研究方式日趋细化的今天,评判各类药物疗法的标准始终不变,就是药品的疗效.中医药从系统、整体的角度出发,全方位、多靶点的作用于人体,能够取得明确的临床疗效,这为中医药现代化、国际化的发展奠定了重要的基础.     

Non-contact determination of parasympathetic activation induced by a full stomach using microwave radar

In order to evaluate parasympathetic activation which causes driving errors, without placing any burden on the monitored individuals, we conducted a non-contact parasympathetic activation monitoring through the back of a chair using a compact 24-GHz microwave-radar. We measured the high-frequency (HF, 0.15–0.4 Hz) power spectrum of heart rate variability (HRV) which reflects parasympathetic activation, induced by a full stomach. All participants had a large all-you-can-eat meal with beverages for lunch within 20 min. Before and after the large meals for durations of 10 min, the non-contact measurement was conducted for seven healthy male volunteers (mean age: 23 ± 1-year-old). In both non-contact (microwave radar) and contact (ECG as a reference) measurement, HF shows similar variations before and after large meal. Large meal significantly (p < 0.05) increased non-contact-derived HF from 1,026 ± 510 to 1,893 ± 613 ms² (922 ± 628 to 1,861 ± 940 ms², p < 0.05). This technique allows parasympathetic activation monitoring for safety precautions.     

Cell type-specific, topoisomerase II-dependent inhibition of hypoxia-inducible factor-1alpha protein accumulation by NSC 644221.

PURPOSE: The discovery and development of small-molecule inhibitors of hypoxia-inducible factor-1 (HIF-1) is an attractive, yet challenging, strategy for the development of new cancer therapeutic agents. Here, we report on a novel tricyclic carboxamide inhibitor of HIF-1alpha, NSC 644221. EXPERIMENTAL DESIGN: We investigated the mechanism by which the novel compound NSC 644221 inhibited HIF-1alpha. RESULTS: NSC 644221 inhibited HIF-1-dependent, but not constitutive, luciferase expression in U251-HRE and U251-pGL3 cells, respectively, as well as hypoxic induction of vascular endothelial growth factor mRNA expression in U251 cells. HIF-1alpha, but not HIF-1beta, protein expression was inhibited by NSC 644221 in a time- and dose-dependent fashion. Interestingly, NSC 644221 was unable to inhibit HIF-1alpha protein accumulation in the presence of the proteasome inhibitors MG132 or PS341, yet it did not directly affect the degradation of HIF-1alpha as shown by experiments done in the presence of cyclohexamide or pulse-chase labeling using [35S]methionine. In contrast, NSC 644221 decreased the rate of HIF-1alpha translation relative to untreated controls. Silencing of topoisomerase (topo) IIalpha, but not topo I, by specific small interfering RNA completely blocked the ability of NSC 644221 to inhibit HIF-1alpha. The data presented show that topo II is required for the inhibition of HIF-1alpha by NSC 644221. Furthermore, although NSC 644221 induced p21 expression, gammaH2A.X, and G2-M arrest in the majority of cell lines tested, it only inhibited HIF-1alpha in a distinct subset of cells, raising the possibility of pathway-specific "resistance" to HIF-1 inhibition in cancer cells. CONCLUSIONS: NSC 644221 is a novel HIF-1 inhibitor with potential for use as both an analytic tool and a therapeutic agent. Our data provide a strong rationale for pursuing the preclinical development of NSC 644221 as a HIF-1 inhibitor.