The influence of leg positioning on the appearance and quantification of 1H magnetic resonance muscle spectra obtained from calf muscle

Purpose: To study proton magnetic resonance spectra (1H-MRS) of the muscle metabolite of a leg muscle in neutral (NEU), internal rotation (INT), and external rotation (EXT) leg positioning. Material and methods: The volunteers were selected for this study. The tibialis anterior (TA), soleus (SOL), and gastrocnemius (GAS) muscles of a non-dominate leg were determined by using single-voxel spectroscopy 8 × 8 × 20 mm3 in size. 1H-MRS measurements were performed on a 1.5-Tesla magnetic resonance imaging (MRI) scanner. Results: The results showed that metabolite spectrum of muscle in each NEU, INT, and EXT of leg positioning were not similar. Additionally, the quantification of IMCL (CH3) and EMCL (CH3) is significantly different in SOL. Conclusions: Our study showed that leg positioning influences the appearance and quantification of 1H-MRS in the calf muscle. Hence, it is necessary to pay close attention to positioning because it interferes with spectral fitting and quantification

Proteomic Profiling of Hematopoietic Stem/Progenitor Cells after a Whole Body Exposure of CBA/CaJ Mice to Titanium (48Ti) Ions

Myeloid leukemia (ML) is one of the major health concerns from exposure to radiation. However, the risk assessment for developing ML after exposure to space radiation remains uncertain. To reduce the uncertainty in risk prediction for ML, a much increased understanding of space radiation-induced changes in the target cells, i.e., hematopoietic stem/progenitor cells (HSPCs), is critically important. We used the label-free quantitative mass spectrometry (LFQMS) proteomic approach to determine the expression of protein in HSPC-derived myeloid colonies obtained at an early time-point (one week) and a late time-point (six months) after an acute whole body exposure of CBA/CaJ mice to a total dose of 0, 0.1, 0.25, or 0.5 Gy of heavy-ion titanium (48Ti ions), which are the important component of radiation found in the space environment. Mice exposed to 0 Gy of 48Ti ions served as non-irradiated sham controls. There were five mice per treatment groups at each harvest time. The Trans-Proteomic Pipeline (TPP) was used to assign a probability of a particular protein being in the sample. A proof-of-concept based Ingenuity Pathway Analysis (IPA) was used to characterize the functions, pathways, and networks of the identified proteins. Alterations of expression levels of proteins detected in samples collected at one week (wk) post-irradiation reflects acute effects of exposure to 48Ti ions, while those detected in samples collected at six months (mos) post-irradiation represent protein expression profiles involved in the induction of late-occurring damage (normally referred to as genomic instability). Our results obtained by using the IPA analyses indicate a wide array of signaling pathways involved in response to 1 GeV/n 48Ti ions at both harvest times. Our data also demonstrate that the patterns of protein expression profiles are dose and time dependent. The majority of proteins with altered expression levels are involved in cell cycle control, cellular growth and proliferation, cell death and survival, cell-to-cell signaling and interaction. The IPA analyses indicate several important processes involved in responses to exposure to 48Ti ions. These include the proteosme/ubiquination, protein synthesis, post-translation modification, and lipid metabolism. The IPA analyses also indicate that exposure to 1 GeV/n 48Ti ions affects the development and function of hematological system, immune cell trafficking, including the cytoskeleton. Further, the IPA analyses strongly demonstrate that the NF-κB and MAPKs (ERKs, JNKs, and p38MAPK) pathways play an essential role in signal transduction after exposure to 1 GeV/n 48Ti ions. At an early time-point (1 week), the top networks identified by the IPA analyses are related to metabolic disease, lipid metabolism, small molecule biochemistry, and development disorder. In contrast, the top networks identified in samples collected at a late time-point (6 mos post-irradiation) by the IPA analyses are related to cancer, hematological disorders, and immunological diseases. In summary, the proteomic findings from our study provide a foundation to uncover compounds potentially be highly effective in radiation countermeasures

A Novel Drug Modulator Diarylheptanoid (trans-1,7-Diphenyl-5-hydroxy-1-heptene) from Curcuma comosa Rhizomes for P-glycoprotein Function and Apoptosis Induction in K652/ADR Leukemic Cells

Curcuma comosa has been used in traditional Thai medicine to treat menstrual cycle-related symptoms in women. This study aims to evaluate the diarylheptanoid drug modulator, trans-1,7-diphenyl-5-hydroxy-1-heptene (DHH), in drug-resistant K562/ADR human leukemic cells. This compound was studied due to its effects on cell cytotoxicity, multidrug resistance (MDR) phenotype, P-glycoprotein (P-gp) expression, and P-gp function. We show that DHH itself is cytotoxic towards K562/ADR cells. However, DHH did not impact P-gp expression. The impact of DHH on the MDR phenotype in the K562/ADR cells was determined by co-treatment of cells with doxorubicin (Dox) and DHH using an MTT assay. The results showed that the DHH changed the MDR phenotype in the K562/ADR cells by decreasing the IC50 of Dox from 51.6 to 18.2 µM. Treating the cells with a nontoxic dose of DHH increased their sensitivity to Dox in P-gp expressing drug-resistant cells. The kinetics of P-gp mediated efflux of pirarubicin (THP) was used to monitor the P-gp function. DHH was shown to suppress THP efflux and resulted in enhanced apoptosis in the K562/ADR cells. These results demonstrate that DHH is a novel drug modulator of P-gp function and induces drug accumulation in the Dox-resistant K562 leukemic cell line

An evaluation of the antioxidant properties of iodinated radiographic contrast media: An in vitro study

This study reveals the antioxidant properties of iodinated radiographic contrast media to be used in diagnostic radiology. Di(phenyl)-(2,4,6-trinitrophenyl) iminoazanium (DPPH), ferric reducing ability of plasma (FRAP), and 2,2′-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) assays were used for determining in vitro the antioxidant properties of five iodinated radiographic contrast media such as iobitridol (xenetix), iodixanol (visipaque), iohexol (omnipaque), ioxaglate (hexabrix), and isovue (iopamiro). An ascorbic acid and Trolox solution served as a positive control. The absorbance intensity of the colored product was recorded using a spectrophotometer. For DPPH and ABTS assay, the absorbance intensity at 533 and 752 nm, respectively was decreased when compared to control; it indicated an increase in antioxidant activity. For FRAP assay, the absorbance intensity at 593 nm was increased when compared to control; it indicated an increase in antioxidant activity. The results showed that five iodinated radiographic contrast media did not differ in DPPH• radical-scavenging activity when compared to a corresponding control. The ferric reducing ability of all of these iodinated radiographic contrast media also did not differ when compared to a corresponding control, except for iobitridol at 200 mgI/mL and ioxaglate at 50–200 mgI/mL. All iodinated radiographic contrast media showed ABTS•+ radical-scavenging activity. This finding suggested that iobitridol, iodixanol, iohexol, ioxaglate, and isovue exhibited weak in vitro antioxidant properties. The antioxidant ability depended on the type of free radical production and the concentration of iodinated radiographic contrast media. Keywords: Antioxidant property, Radiographic contrast media, Free radica

Effects of obesity on the lipid and metabolite profiles of young adults by serum 1H-NMR spectroscopy

Background Overweight (OW) is considered a risk for various metabolic diseases. However, its effects as a mechanism that alters the metabolite profiles remain unclear. The purpose of this study is to investigate the effects that OW has on the lipid and metabolite profiles in young adults. Methods The serum metabolite profiles of 46 young adults of normal weight and those considered OW were studied by Proton nuclear magnetic resonance spectroscopy (1H NMR) technique. Results 1H NMR metabolite analysis shows the alteration of metabolic levels and increased levels of CH2 lipids and CH3 lipids, which are used as unique biomarkers to identify OW subjects from the normal weight groups. Conclusion This present study reveals that OW contributes to the systemic metabolism and the metabolite alteration among young adults. The alteration in serum lipids level could shed the light on metabolic syndrome pathogenesis in young adults and needs further elucidation

Late Effects of Low-Dose Radiation on the Bone Marrow, Lung, and Testis Collected From the Same Exposed BALB/cJ Mice

We used 3 biological metrics highly relevant to health risks, that is, cell death, inflammation, and global DNA methylation, to determine the late effects of low doses (0.05 or 0.1 Gy) of 137 Cs γ rays on the bone marrow, lung, and testis collected at 6 months post-irradiation from the same exposed BALB/cJ mouse. This integrative approach has not been used for such a purpose. Mice exposed to 0 or 1 Gy of radiation served as a sham or positive control group, respectively. The results could deliver information for better health risk assessment across tissues, including better scientific basis for radiation protection and clinical application. We found no changes in the levels of all studied biological metrics (except a significant increase in the levels of an anti-inflammatory cytokine, ie, interleukin 10) in tissues of 0.05-Gy exposed mice, when compared to those in sham controls. In contrast, significantly increased levels of cell death and inflammation, including a significant loss of global 5-hydroxymethylcytosine, were found in all tissues of the same mice exposed to 0.1 or 1.0 Gy. Our data demonstrated not only no harm but also hormesis in the 0.05-Gy exposed mice. However, the hormetic effect appears to be dependent on biological metrics and tissue

Identification of Metabolic Phenotypes in Young Adults with Obesity by 1H NMR Metabolomics of Blood Serum

(1) Since the obesity prevalence rate has been consistently increasing, it is necessary to find an effective way to prevent and treat it. Although progress is being made to reduce obesity in the young adult population, a better understanding of obesity-related metabolomics and related biochemical mechanisms is urgently needed for developing appropriate screening strategies. Therefore, the aim of this study is to identify the serum metabolic profile associated with young adult obesity and its metabolic phenotypes. (2) Methods: The serum metabolic profile of 30 obese and 30 normal-weight young adults was obtained using proton nuclear magnetic resonance spectroscopy (1H NMR). 1H NMR spectra were integrated into 24 integration regions, which reflect relative metabolites, and were used as statistical variables. (3) Results: The obese group showed increased levels of lipids, glucose, glutamate, N-acetyl glycoprotein, alanine, lactate, 3 hydroxybutyrate and branch chain amino acid (BCAA), and decreased levels of choline as compared with the normal-weight group. Non-hyperlipidemia obese adults showed lower levels of lipids and lactate, glutamate, acetoacetate, N-acetyl glycoprotein, isoleucine, and higher levels of choline and glutamine, as compared with hyperlipidemic obese adults. (4) Conclusions: This study reveals valuable findings in the field of metabolomics and young adult obesity. We propose several serum biomarkers that distinguish between normal weight and obese adults, i.e., glutamine (higher in the normal group, p < 0.05), and lactate, BCAAs, acetoacetate and 3-hydroxybutyrate (higher in the obese group, p < 0.05). In addition, visceral fat and serum TG, glutamate, acetoacetate, N-acetyl glycoprotein, unsaturated lipid, isoleucine, and VLDL/LDL are higher (p < 0.05) in the obese with hyperlipidemia. Therefore, they can be used as biomarkers to identify these two types of obesity

Waist Circumference and BMI Are Strongly Correlated with MRI-Derived Fat Compartments in Young Adults

Young adulthood is increasingly considered as a vulnerable age group for significant weight gain, and it is apparent that there is an increasing number of new cases of metabolic syndrome developing among this population. This study included 60 young adult volunteers (18–26 years old). All participants obtained a calculated total abdominal fat percentage, subcutaneous fat percentage, and visceral fat percentage using a semiautomatic segmentation technique from T1-weighted magnetic resonance imaging (MRI) images of the abdomen. The results show strongest correlation between abdominal fat and BMI (r = 0.824) followed by subcutaneous fat (r = 0.768), and visceral fat (r = 0.633) respectively, (p < 0.001 for all, after having been adjusted for age and gender). Among anthropometric measurements, waist circumference showed strong correlation with all fat compartments (r = 0.737 for abdominal, r = 0.707 for subcutaneous fat, and r = 0.512 for visceral fat; p < 0.001 for all). The results obtained from examining the blood revealed that there was a moderate positive correlation relationship between all fat compartments with triglyceride, high-density lipoprotein, and fasting glucose levels (p < 0.05 for all). This study suggests that both BMI and waist circumference could be used to assess the fat compartments and treatment targets to reduce the risk of metabolic disorders and health risks in the young adult population