Insulin-like molecules in Momordica charantia seeds

Decorticated Momordica charantia seeds were extracted and processed by a method which was developed originally for the purification of insect and annelid insulins. Essentially, the method entailed HCl--ethanol extraction, neutralization with NH4OH, gel filtration on Sephadex G-50, ion exchange chromatography on CM Sepharose CL-6B and desalting on Sephadex G-10. Of the seven fractions collected, three fractions were obtained with antilipolytic and lipogenic activities in isolated adipocytes and one fraction with only lipogenic activity. The data indicate that molecules with insulin-like bioactivity are present in Momordica charantia seeds.     

Electrophysiological and functional effects of the KCNQ channel blocker XE991 on murine portal vein smooth muscle cells

The effect of the KCNQ channel blockers XE991, chromanol 293B and linopirdine, was studied on voltage-dependent K+ currents in smooth muscle cells dissociated freshly from mouse portal vein (mPV) and isometric tension recordings from whole mPV. Voltage clamp experiments showed XE991 inhibited an outward current in a concentration-dependent manner with an IC50 of 5.8 microM. Block was voltage independent. Chromanol 293B and linopirdine also blocked the voltage-dependent K+ current but were less potent than XE991. At least two components--a linear (I(linear)) and an outward relaxation (I(out))--contributed to the XE991-sensitive conductance. XE991-sensitive currents were sustained at all test potentials and XE991 inhibited the enhanced holding current at -60 mV produced by bathing cells in an external solution containing 36 mM KCl. Current clamp experiments in the perforated-patch configuration showed XE991 and linopirdine depolarised the resting membrane potential and augmented the evoked response in a concentration-dependent manner. In functional experiments the spontaneous contractile activity of the mPV was increased significantly by XE991 and linopirdine. The stimulatory effect of XE991 was not affected by the presence of 4-AP, glibenclamide nor paxilline. These data provide evidence for an important role for KCNQ channels in governing cellular excitability in mPV smooth muscle cells.     

香港的儿童严重急性呼吸综合征

世界卫生组织 (WHO)全球SARS病毒学协作实验室网络的协调专家KlausStohr博士认为 ,“这次攻克SARS取得的巨大成果向世界证明了全球科学家通力合作来解决一个问题的力量有多大”。他高度评价了在SARS病毒分离、新的诊断方法的研发方面所取得的快速进展。在他的评价中遗漏了一点 ,那就是由香港大学YuenKwok Yung和J .S .Peiris教授领导的研究小组所取得的显著成就。在 3月份香港公立医院发生SARS暴发流行后的 2个星期之内他们即确定了冠状病毒为SARS的病原体。另一个没有受到广泛关注的成果是在大批儿童患者中无一例死亡的事实。…     

Expectation and knowledge of pregnant women undergoing first and second trimester ultrasound examination in a Chinese population

OBJECTIVE: To evaluate expectation and knowledge on obstetric ultrasound examination in the first and second trimester in a Chinese population. METHOD: A cross-sectional survey was conducted in a university obstetric clinic in Hong Kong. Chinese pregnant women who underwent the first trimester early scan sessions, or the second trimester anomaly scan sessions were invited to complete a self-administered questionnaire, which contained items on their knowledge, expectation, and sociodemographic characteristics. RESULTS: In all 276 eligible pregnant women (117 in the first trimester and 159 in the second trimester) were recruited. Although 249 women (90.2%) claimed they understood the indication of the ultrasound examination, only 93 of them were correct (33.7%). The median perceived overall-detection rate for structural abnormalities was 66.5%. Living in Hong Kong for more than 7 years was significantly associated with higher knowledge level and expectation from ultrasound examination. Attaining tertiary education level was also significantly associated with higher knowledge level. Over 90% of the pregnant women studied wished to know the fetal gender from the anomaly scan examination. CONCLUSION: Knowledge of Chinese pregnant women on ultrasound was generally unsatisfactory. Understanding their limitation of knowledge and expectations helps to devise appropriate education in the local setting.     

Targeting the ERAD pathway via inhibition of signal peptide peptidase for antiparasitic therapeutic design

Early secretory and endoplasmic reticulum (ER)-localized proteins that are terminally misfolded or misassembled are degraded by a ubiquitin- and proteasome-mediated process known as ER-associated degradation (ERAD). Protozoan pathogens, including the causative agents of malaria, toxoplasmosis, trypanosomiasis, and leishmaniasis, contain a minimal ERAD network relative to higher eukaryotic cells, and, because of this, we observe that the malaria parasite Plasmodium falciparum is highly sensitive to the inhibition of components of this protein quality control system. Inhibitors that specifically target a putative protease component of ERAD, signal peptide peptidase (SPP), have high selectivity and potency for P. falciparum. By using a variety of methodologies, we validate that SPP inhibitors target P. falciparum SPP in parasites, disrupt the protein’s ability to facilitate degradation of unstable proteins, and inhibit its proteolytic activity. These compounds also show low nanomolar activity against liver-stage malaria parasites and are also equipotent against a panel of pathogenic protozoan parasites. Collectively, these data suggest ER quality control as a vulnerability of protozoan parasites, and that SPP inhibition may represent a suitable transmission blocking antimalarial strategy and potential pan-protozoan drug target.     

RKIP regulates CCL5 expression to inhibit breast cancer invasion and metastasis by controlling macrophage infiltration

Accumulating evidence suggests that presence of macrophages in the tumor microenvironment add to the invasive and tumor-promoting hallmarks of cancer cells by secreting angiogenic and growth factors. RKIP is a known metastasis suppressor and interferes with several steps of metastasis. However, the mechanistic underpinnings of its function as a broad metastasis suppressor remain poorly understood. Here, we establish a novel pathway for RKIP regulation of metastasis inhibition through the negative regulation of RANTES/CCL5 thereby limiting tumor macrophage infiltration and inhibition of angiogenesis. Using a combination of loss- and gain-of-function approaches, we show that RKIP hinders breast cancer cell invasion by inhibiting expression of the CC chemokine CCL5 in vitro. We also show that the expression levels of RKIP and CCL5 are inversely correlated among clinical human breast cancer samples. Using a mouse allograft breast cancer transplantation model, we highlight that ectopic expression of RKIP significantly decreases tumor vasculature, macrophage infiltration and lung metastases. Mechanistically, we demonstrate that the inhibition of the CCL5 expression is the cause of the observed effects resulting from RKIP expression. Taken together, our results underscore the significance of RKIP as important negative regulator of tumor microenvironment.     

Risk and protective factors for wellbeing in older veterans in New Zealand

Objectives: To compare indicators relating to aging and health among veterans and non-veterans, and identify factors associated with subjective wellbeing (SWB) of older New Zealand veterans.

Methods: Self-reported data were obtained from participants in a longitudinal cohort study of New Zealand older adults. Responses from 352 veterans and 1500 non-veterans (age range of 55–86 and gender matched) were selected as a comparison group on indicators related to health and aging. The association of these indicators with veterans’ SWB were assessed using hierarchical regression.

Results: Apart from being older, smoking more, and having more chronic conditions, veterans did not differ from non-veterans on indicators of health and wellbeing. Mental health, physical health, purpose in life, housing satisfaction, and capabilities (choice and freedom) accounted for a significant amount of variance in veterans’ SWB.

Conclusion: Our results suggest that older veterans do not differ greatly on indices of health and aging from their non-veteran peers. Results support previous findings that lower mental and physical health is associated with lower SWB for veterans. Building upon prior findings, the current results demonstrate that interventions focusing on enhancing a sense of purpose in life, supporting one's capability to achieve, and strengthening social and physical environment through social connectedness, may serve as protective factors for SWB in veterans.