FTO-rs9939609 Polymorphism is a Predictor of Future Type 2 Diabetes: A Population-Based Prospective Study

Biochemical Genetics - The study aimed to evaluate the contribution of the FTO A/T polymorphism (rs9939609) to the prediction of the future type 2 diabetes (T2D). A population-based prospective...     

Comparative proteomics of colon cancer stem cells and differentiated tumor cells identifies BIRC6 as a potential therapeutic target

Patients with liver metastases from colon carcinoma show highly variable responses to chemotherapy and tumor recurrence is frequently observed. Therapy-resistant cancer stem cells have been implicated in drug resistance and tumor recurrence. However, the factors determining therapy resistance and tumor recurrence are poorly understood. The aim of this study was to gain insight into these mechanisms by comparing the proteomes of patient-derived cancer stem cell cultures and their differentiated isogenic offspring. We established colonosphere cultures derived from resection specimens of liver metastases in patients with colon cancer. These colonospheres, enriched for colon cancer stem cells, were used to establish isogenic cultures of stably differentiated nontumorigenic progeny. Proteomics based on one-dimensional gel electrophoresis coupled to nano liquid chromatography tandem MS was used to identify proteome differences between three of these paired cultures. The resulting data were analyzed using Ingenuity Pathway Software. Out of a total data set of 3048 identified proteins, 32 proteins were at least twofold up-regulated in the colon cancer stem cells when compared with the differentiated cells. Pathway analysis showed that "cell death " regulation is strikingly different between the two cell types. Interestingly, one of the top-up-regulated proteins was BIRC6, which belongs to the class of Inhibitor of Apoptosis Proteins. Knockdown of BIRC6 sensitized colon cancer stem cells against the chemotherapeutic drugs oxaliplatin and cisplatin. This study reveals that differentiation of colon cancer stem cells is accompanied by altered regulation of cell death pathways. We identified BIRC6 as an important mediator of cancer stem cell resistance against cisplatin and oxaliplatin. Targeting BIRC6, or other Inhibitors of Apoptosis Proteins, may help eradicating colon cancer stem cells.     

A retrospective analysis of the haemodynamic and metabolic effects of fluid resuscitation in Vietnamese adults with severe falciparum malaria

Background

Optimising the fluid resuscitation of patients with severe malaria is a simple and potentially cost-effective intervention. Current WHO guidelines recommend central venous pressure (CVP) guided, crystalloid based, resuscitation in adults.

Methods

Prospectively collected haemodynamic data from intervention trials in Vietnamese adults with severe malaria were analysed retrospectively to assess the responses to fluid resuscitation.

Results

43 patients were studied of whom 24 received a fluid load. The fluid load resulted in an increase in cardiac index (mean increase: 0.75 L/min/m² (95% Confidence interval (CI): 0.41 to 1.1)), but no significant change in acid-base status post resuscitation (mean increase base deficit 0.6 mmol/L (95% CI: −0.1 to 1.3). The CVP and PAoP (pulmonary artery occlusion pressure) were highly inter-correlated (r_s = 0.7, p<0.0001), but neither were correlated with acid-base status (arterial pH, serum bicarbonate, base deficit) or respiratory status (PaO₂/FiO₂ ratio). There was no correlation between the oxygen delivery (DO₂) and base deficit at the 63 time-points where they were assessed simultaneously (r_s = −0.09, p = 0.46).

Conclusions

In adults with severe falciparum malaria there was no observed improvement in patient outcomes or acid-base status with fluid loading. Neither CVP nor PAoP correlated with markers of end-organ perfusion or respiratory status, suggesting these measures are poor predictors of their fluid resuscitation needs.     

Two new flavones from Eupatorium coelestinum

Besides coumarin, nobiletin, lucidin dimethyl ether and 5,6,7,3′,4′-pentamethoxyflavone, two new highly oxygenated flavones were isolated from Eupatorium coelestinum. Their structures were determined by spectroscopic methods and alkaline degradations as 5,6,7,8,3′,4′,5′ -heptamethoxyflavone and 5,6,7,8,5′-pentamethoxy-3′,4′-methylenedioxyflavone.     

Kinetics of the early subcellular distribution of cadmium in rat hepatocytes

The kinetics of the early subcellular distribution of cadmium (Cd) was characterized in primary cultures of rat hepatocytes exposed to 10, 50 and 100 M Cd in a serum-free WME medium for 10, 30 or 60 min. Our results demonstrate a time- and concentration-dependent increase in Cd content with the highest metal concentration measured in the cytosol, whereas the lowest was observed in the mitochondria. With the exception of early localization in the plasma membrane, Cd concentrations in fractions were characterized by the following decreasing order of magnitude: cytosol > low density molecules nuclei > lysosomes mitochondria. We also found evidence for: (i) a two-step process for Cd distribution in the nuclei and mitochondria; and (ii) a time-dependent slow process of transfer from the plasma membrane to the cytosol. Saturation in Cd uptake was observed at 50 M in most cell fractions at 10 and 30 min, except for the plasma membrane. The lack of apparent saturation for Cd accumulation at 60 min was not related to an increase in metallothionein synthesis. Altogether, our data provide insights into the dynamics of transfer between intracellular compartments, and allow a better identification of the organelles that are the most subjected to Cd toxicity for early exposure conditions.Deceased March 25, 2004.     

Bullera hoabinhensis sp. nov., a new ballistoconidiogenous yeast isolated from a plant leaf collected in Vietnam

VY-68, a ballistoconidiogenous yeast strain, isolated from a plant leaf at Cuc Phuong National Park of Ninh Binh Province, Vietnam, was assigned to the genus Bullera based on morphological and chemotaxonomical characteristics. Based on the sequence analyses of 18S rDNA, D1/D2 region of 26S rDNA, and internal transcribed spacer regions (ITS), VY-68 was phylogenetically closely related to Bullera pseudoalba and Cryptococcus cellulolyticus. DNA-DNA reassociation experiments among VY-68, B. pseudoalba and C. cellulolyticus revealed that strain VY-68 is a distinct species, and the latter two are conspecific. Bullera hoabinhensis is proposed for VY-68.