PurposeImage-guided prostate biopsies are routinely acquired in the diagnosis and treatment monitoring of prostate cancer, yielding useful tissue for identifying metabolic biomarkers and therapeutic targets. We developed an optimized biopsy tissue culture protocol in combination with [1,6-C-13(2)]glucose labeling and quantitative high-resolution NMR to measure glycolysis and tricarboxcylic acid (TCA) cycle activity in freshly acquired living human prostate biopsies. MethodsWe acquired 34 MRI-ultrasound fusion-guided prostate biopsies in vials on ice from 22 previously untreated patients. Within 15 min, biopsies were transferred to rotary tissue culture in 37 degrees C prostate medium containing [1,6-C-13(2)]glucose. Following 24 h of culture, tissue lactate and glutamate pool sizes and fractional enrichments were quantified using quantitative H-1 high resolution magic angle spinning Carr-Purcell-Meiboom-Gill (CPMG) spectroscopy at 1 degrees C with and without C-13 decoupling. Lactate effluxed from the biopsy tissue was quantified in the culture medium using quantitative solution-state high-resolution NMR. ResultsLactate concentration in low-grade cancer (1.15 0.78 nmol/mg) and benign (0.74 +/- 0.15 nmol/mg) biopsies agreed with prior published measurements of snap-frozen biopsies. There was substantial fractional enrichment of [3-C-13]lactate (approximate to 70%) and [4-C-13]glutamate (approximate to 24%) in both low-grade cancer and benign biopsies. Although a significant difference in tissue [3-C-13]lactate fractional enrichment was not observed, lactate efflux was significantly higher (P < 0.05) in low-grade cancer biopsies (0.55 +/- 0.14 nmol/min/mg) versus benign biopsies (0.31 +/- 0.04 nmol/min/mg). ConclusionA protocol was developed for quantification of lactate production-efflux and TCA cycle activity in single living human prostate biopsies, allowing metabolic labeling on a wide spectrum of human tissues (e.g., metastatic, post-non-surgical therapy) from patients not receiving surgery.
To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1016/j.cub.2017.11.002 Culture, broadly defined as a set of behaviours acquired by social learning, underlies much of what makes our species different from other animals. In recent years, however, evidence of such cultural behaviour has accumulated from the observation of other species including primates, birds, and cetaceans. The latter, living in an environment most alien from ours, can provide crucial insights into how cultural traits and genes may have co-evolved in our ancestors, meaning that learned behaviour changed genetically determined phenotypes including brain size and menopause. Michael Gross reports.
The concept of tumor stem cells (TSCs) provides a new paradigm for understanding tumor biology, although it remains unclear whether TSCs will prove to be a more robust model than traditional cancer cell lines. We demonstrate marked phenotypic and genotypic differences between primary human tumor-derived TSCs and their matched glioma cell lines. Unlike the matched, traditionally grown tumor cell lines, TSCs derived directly from primary glioblastomas harbor extensive similarities to normal neural stem cells and recapitulate the genotype, gene expression patterns, and in vivo biology of human glioblastomas. These findings suggest that TSCs may be a more reliable model than many commonly utilized cancer cell lines for understanding the biology of primary human tumors.
Microplastics are present throughout the marine environment and ingestion of these plastic particles (<1 mm) has been demonstrated in a laboratory setting for a wide array of marine organisms. Here, we investigate the presence of microplastics in two species of commercially grown bivalves: and . Microplastics were recovered from the soft tissues of both species. At time of human consumption, contains on average 0.36 ± 0.07 particles g (wet weight), while a plastic load of 0.47 ± 0.16 particles g ww was detected in . As a result, the annual dietary exposure for European shellfish consumers can amount to 11,000 microplastics per year. The presence of marine microplastics in seafood could pose a threat to food safety, however, due to the complexity of estimating microplastic toxicity, estimations of the potential risks for human health posed by microplastics in food stuffs is not (yet) possible. Microplastics were detected in two commercially grown bivalve species ( and ), enabling us to estimate a preliminary human dietary exposure.
(AC), a highly valued polypore mushroom native only to Taiwan, has been traditionally used as a medicine for the treatment of food and drug intoxication, diarrhea, abdominal pain, hypertension, skin itching, and cancer. In this study, both of solid-state-cultured AC (S-AC) and wood-cultured AC (W-AC) were evaluated the anti-inflammatory effects on hyperoxia-induced lung injury in NF-κB-luciferase transgenic mice. The homozygous transgenic mice (NF-κB-luciferase ) were randomly assigned to four groups for treatment ( = 6) including Normoxia/DMSO group, Hyperoxia/DMSO group, Hyperoxia/S-AC group, and Hyperoxia/W-AC group. After 72 h of hyperoxia, we examined the bioluminescence images, reactive oxygen species (ROS), the mRNA and protein expression levels of inflammation factors, and histopathological analyses of the lung tissues. Hyperoxia-induced lung injury significantly increased the generation of ROS, the mRNA levels of , , and , and the protein expression levels of IKKα/β, iNOS and IL-6. Pulmonary edema and alveolar infiltration of neutrophils was also observed in the hyperoxia-induced lung tissue. However, treatment with either S-AC or W-AC obviously decreased hyperoxia-induced generation of ROS and the expression of IL-6, TNF-α, IL-1β, IL-8, IKKα/β and iNOS compared to hyperoxia treatment alone. Lung histopathology also showed that treatment with either S-AC or W-AC significantly reduced neutrophil infiltration and lung edema compared to treatment with hyperoxia treated alone. To find out their major compounds, eburicoic acid and dehydroeburicoic acid were both isolated and identified from S-AC and W-AC by using HPLC, MS, and NMR spectrometry. These results demonstrated that methanolic extracts both of S-AC and W-AC have excellent anti-inflammatory activities and thus have great potential as a source for natural health products.
Islet amyloid polypeptide (IAPP, amylin) is the major protein component of the islet amyloid deposits associated with type 2 diabetes. The polypeptide lacks a well-defined structure in its monomeric state but readily assembles to form amyloid. Amyloid fibrils formed from TAPP, intermediates generated in the assembly of IAPP amyloid, or both are toxic to beta-cells, suggesting that islet amyloid formation may contribute to the pathology of type 2 diabetes. There are relatively few reported inhibitors of amyloid formation by IAPP. Here we show that the tea-derived flavanol, (-)-epigallocatechin 3-gallate [(2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-1-benzopyran-3-yl 3,4,5-trihydroxybenzoate] (EGCG), is an effective inhibitor of in vitro IAPP amyloid formation and disaggregates preformed amyloid fibrils derived from IAPP. The compound is thus one of a very small set of molecules which have been shown to disaggregate TAPP amyloid fibrils. Fluorescence-detected thioflavin-T binding assays and transmission electron microscopy confirm that the compound inhibits unseeded amyloid fibril formation as well as disaggregates IAPP amyloid. Seeding studies show that the complex formed by IAPP and EGCG does not seed amyloid formation by LAPP. In this regard, the behavior of IAPP is similar to the reported interactions of A beta and alpha-synuclein with EGCG. Alamar blue assays and light microscopy indicate that the compound protects cultured rat INS-1 cells against IAPP-induced toxicity. Thus, EGCG offers an interesting lead structure for further development of inhibitors of IAPP amyloid formation and compounds that disaggregate IAPP amyloid.