Recent Metabolomics Analysis in Tumor Metabolism Reprogramming

Metabolic reprogramming has been suggested as a hallmark of cancer progression. Metabolomic analysis of various metabolic profiles represents a powerful and technically feasible method to monitor dynamic changes in tumor metabolism and response to treatment over the course of the disease. To date, numerous original studies have highlighted the application of metabolomics to various aspects of tumor metabolic reprogramming research. In this review, we summarize how metabolomics techniques can help understand the effects that changes in the metabolic profile of the tumor microenvironment on the three major metabolic pathways of tumors. Various non-invasive biofluids are available that produce accurate and useful clinical information on tumor metabolism to identify early biomarkers of tumor development. Similarly, metabolomics can predict individual metabolic differences in response to tumor drugs, assess drug efficacy, and monitor drug resistance. On this basis, we also discuss the application of stable isotope tracer technology as a method for the study of tumor metabolism, which enables the tracking of metabolite activity in the body and deep metabolic pathways. We summarize the multifaceted application of metabolomics in cancer metabolic reprogramming to reveal its important role in cancer development and treatment.

Stable Isotope Tracer Addition Reveals the Trophic Status of Benthic Infauna at an Intertidal Area Adjacent to a Seagrass Bed

Stable isotope tracer addition can enhance the isotopic differences of primary producers for a wider food-web resolution than the use of natural abundance stable isotopes (NASIs) alone, particularly in ecosystems where primary producers have similar NASI values. To investigate the food sources and the trophic status of benthic infauna in an intertidal area near a Halophila minor seagrass bed within inner Tai Tam Bay, Hong Kong, China, a 15N addition experiment was conducted, and the results were compared with those from NASI data. Only benthic microalgae (BMA) were labeled by applying 15N-enriched NH4Cl to the sediment daily for the first 7 days during a 21-day study. In contrast to the NASI results, Bayesian mixing models based on the isotope tracer experiment suggested a larger dietary contribution of BMA for nematode Daptonema sp. and copepods, whereas a higher reliance on phytoplankton and seagrass detritus was noted for polychaete Neanthes sp. However, both NASI and isotope tracer addition demonstrated that seagrass detritus was a major food source for nematode Spilophorella sp. The present isotope tracer experiment also revealed a contrasting result of the relatively lower contribution of meiofauna in the diets of carnivores/omnivores as compared to the results of NASIs. This finding suggested that the isotope values in these consumers may have not reached an equilibrium with the added isotope in the study period. Thus, there is a need for applying NASI coupled with isotope tracer addition in the investigation of ecosystems in which primary producers have similar isotope values, especially in ecosystems with lower tissue turnover rates, in order for a more accurate determination of dietary contribution and trophic status of consumers in the food-web study.

Hydrochemical studies on the transect “Kola meridian” using the d18O isotope tracer

The results of hydrochemical studies at 10 stations of the transect “Kola meridian” opencast performed on the expedition NIS “Dalnye Zelentsy” in April 2019, where hydrochemical studies of phosphate phosphorus, nitrate nitrogen and silicon were performed, are presented. To analyze the data, a technique using the 18O isotope tracer was used. The measure of production and destruction of selected nutrients was determined by the author's method. Two alleged foci of phytoplankton activity were identified: areas in the region of the ice edge in the north of the section and in the waters of the Murmansk coastal course. The state of the waters in the section is defined as late spring.

Elucidation of the Structure of Lignin-Carbohydrate Complexes in Ginkgo CW-DHP by 13C-2H Dual Isotope Tracer

To elucidate the chemical linkages between lignin and carbohydrates in ginkgo cell walls, 13C-2H-enriched cell wall-dehydrogenation polymers (CW-DHP) were selectively prepared with cambial tissue from Ginkgo biloba L. by feeding D-glucose-[6-2H2], coniferin-[α-13C], and phenylalanine ammonia-lyase (PAL) inhibitor. The abundant detection of 13C and 2H confirmed that D-glucose-[6-2H2] and coniferin-[α-13C] were involved in the normal metabolism of ginkgo cambial cells that had been effectively labelled with dual isotopes. In the ginkgo CW-DHP, ketal and ether linkages were formed between the C-α of lignin side chains and carbohydrates, as revealed by solid state CP/MAS 13C-NMR differential spectroscopy. Furthermore, the DMSO/TBAH ionic liquids system was used to fractionate the ball-milled CW-DHP into three lignin-carbohydrate complex (LCC) fractions: glucan–lignin complex (GL), glucomannan–lignin complex (GML), and xylan–lignin complex (XL). The XRD determination indicated that the cellulose type I of the GL was converted into cellulose type II during the separation process. The molecular weight was in the order of Ac-GL > Ac-GML > XL. The 13C-NMR and 1H-NMR differential spectroscopy of 13C-2H-enriched GL fraction indicated that lignin was linked with cellulose C-6 by benzyl ether linkages. It was also found that there were benzyl ether linkages between the lignin side chain C-α and glucomannan C-6 in the 13C-2H-enriched GML fraction. The formation of ketal linkages between the C-α of lignin and xylan was confirmed in the 13C-2H-enriched XL fraction.

Investigation of Dissimilatory Nitrate Reduction to Ammonium (DNRA) Microbial Communities in Sediments of Urban River Network Along the Huangpu River, china

Dissimilatory nitrate reduction to ammonium (DNRA) is an essential intermediate step in the nitrogen cycle, linking the oxidation and reduction processes of nitrogen compounds. But the detailed research on the environmental nitrogen cycling in urban river networks based on DNRA communities and the functional gene nrfA is lacking. In this study, the flow line of the Huangpu River in Shanghai was analyzed using isotope tracer, quantitative real-time PCR, and high-throughput sequencing techniques to evaluate the role of DNRA on the stability of the river network and marine. The significant positive correlation between the rate of DNRA and sediment organic carbon was identified. At the genus level, Anaeromyxobacter is the most dominant. Notably, both heterotrophic and autotrophic DNRA species were discovered. This study added diversity to the scope of urban freshwater river network ecosystem studies by investigating the distribution of DNRA bacteria along the Huangpu River.

Ecohydrological travel times derived from in situ stable water isotope measurements in trees during a semi-controlled pot experiment

Tree water uptake processes and ecohydrological travel times have gained more attention in recent ecohydrological studies. In situ measurement techniques for stable water isotopes offer great potential to investigate these processes but have not been applied much to tree xylem and soils so far. Here, we used in situ probes for stable water isotope measurements to monitor the isotopic signatures of soil and tree xylem water before and after two deuterium-labeled irrigation experiments. To show the potential of the method, we tested our measurement approach with 20-year-old trees of three different species (Pinus pinea, Alnus incana and Quercus suber). They were planted in large pots with homogeneous soil in order to have semi-controlled experimental conditions. Additional destructive sampling of soil and plant material allowed for a comparison between destructive (cryogenic vacuum extraction and direct water vapor equilibration) and in situ isotope measurements. Furthermore, isotope-tracer-based ecohydrological travel times were compared to travel times derived from sap flow measurements. The time to first arrival of the isotope tracer signals at 15 cm stem hight were ca. 17 h for all tree species and matched well with sap-flow-based travel times. However, at 150 cm stem height tracer-based travel times differed between tree species and ranged between 2.4 and 3.3 d. Sap-flow-based travel times at 150 cm stem hight were ca. 1.3 d longer than tracer-based travel times. The isotope signature of destructive and in situ isotope measurements differed notably, which suggests that the two types of techniques sampled water from different pools. In situ measurements of soil and xylem water were much more consistent between the three tree pots (on average standard deviations were smaller by 8.4 ‰ for δ2H and by 1.6 ‰ for δ18O for the in situ measurements) and also among the measurements from the same tree pot in comparison to the destructive methods (on average standard deviations were smaller by 7.8 ‰ and 1.6 ‰ for δ2H and δ18O, respectively). Our study demonstrates the potential of semi-controlled large-scale pot experiments and very frequent in situ isotope measurements for monitoring tree water uptake and ecohydrological travel times. It also shows that differences in sampling techniques or sensor types need to be considered when comparing results of different studies and within one study using different methods.

Bioequivalence Assessment of High-Capacity Polymeric Micelle Nanoformulation of Paclitaxel and Abraxane® in Rodent and Non-Human Primate Models Using a Stable Isotope Tracer Assay

The in vivo fate of nanoformulated drugs is governed by the physicochemical properties of the drug and the functionality of nanocarriers. Nanoformulations such as polymeric micelles, which physically encapsulate poorly soluble drugs, release their payload into the bloodstream during systemic circulation. This results in three distinct fractions of the drug-nanomedicine: encapsulated, protein-bound, and free drug. Having a thorough understanding of the pharmacokinetic (PK) profiles of each fraction is essential to elucidate mechanisms of nanomedicine-driven changes in drug exposure and PK/PD relationships pharmacodynamic activity. Here, we present a comprehensive preclinical assessment of the poly(2-oxazoline)-based polymeric micelle of paclitaxel (PTX) (POXOL hl-PM), including bioequivalence comparison to the clinically approved paclitaxel nanomedicine, Abraxane®. Physicochemical characterization and toxicity analysis of POXOL hl-PM was conducted using standardized protocols by the Nanotechnology Characterization Laboratory (NCL). The bioequivalence of POXOL hl-PM to Abraxane® was evaluated in rats and rhesus macaques using the NCL’s established stable isotope tracer ultrafiltration assay (SITUA) to delineate the plasma PK of each PTX fraction. The SITUA study revealed that POXOL hl-PM and Abraxane® had comparable PK profiles not only for total PTX but also for the distinct drug fractions, suggesting bioequivalence in given animal models. The comprehensive preclinical evaluation of POXOL hl-PM in this study showcases a series of widely-applicable standardized studies by NCL for assessing nanoformulations prior to clinical investigation.GRAPHICAL ABSTRACT