Metabolic profiling in the hypothalamus of aged mice.

Metabolic abnormalities are tightly connected to the perturbation of normal brain functions, thereby causing multiple neurodegenerative diseases. The hypothalamus is the master unit that controls the whole-body energy homeostasis. Thus, altered metabolic activity in the hypothalamus could be a crucial clue to better understand the development of metabolic disorders during aging. The current study aimed to investigate the changes in hypothalamic metabolites according to the aging process using gas chromatography-mass spectrometry. We identified that multiple metabolites and neurotransmitters were effectively reduced in the hypothalamus of aged mice. In addition, we observed increased levels of genes linked to the production and utilization of monocarboxylates in the aged hypothalamus, indicating the initiation of metabolic activity to produce alternative nutrient sources. Lastly, we found a reduced number of astrocytes in the hypothalamus of aged mice, suggesting that reduced nutrient availability in the hypothalamus might be associated with the decreased activity of astrocytes during aging. Collectively, the present study suggests that the deterioration of metabolic activities in the hypothalamus might be a primary cause and/or outcome of metabolic diseases associated with the aging process.

Determination of Branched-Chain Amino Acids in Food Supplements and Human Plasma by a CE-MS/MS Method with Enhanced Resolution.

In the presented study, a capillary electrophoresis-mass spectrometry method combining high separation efficiency and sensitive detection has been developed and validated, for the first time, to quantify branched chain amino acids (valine, isoleucine, leucine) in commercial food and sport supplement samples and human plasma samples. The separations were performed in a bare fused silica capillary. The background electrolyte was composed of 500 mM formic acid with pH 2.0. The plasma sample pretreatment was realized by simple protein precipitation with acetonitrile. Injection of a short zone of highly basic electrolyte before the sample injection and application of the negative pressure on the separation were accompanied by enhanced resolution of the isobaric amino acids-isoleucine and leucine. The developed method was characterized by favorable validation parameters, such as linearity (r2 > 0.99), accuracy and precision, the limit of detection, lower limit of quantification, or robustness. These parameters were more than sufficient for the quantification of branched chain amino acids in various samples. The determined concentrations of branched chain amino acids in food and sports supplements were in very good agreement with the content declared by the manufacturer. The investigated concentrations of branched chain amino acids were in the range 294.68-359.24 µM for valine, 91.76-95.67 µM for isoleucine, and 196.78-251.24 µM for leucine. These concentrations fall within the physiological limits. The developed CE-MS/MS method represents a suitable alternative to traditional approaches used in branched chain amino acid quality control and bioanalysis.

Bone regeneration in both small and large preclinical bone defect models using an injectable polymer-based substitute containing hydroxyapatite and reconstituted with saline or autologous blood.

Microbeads consisting of pullulan and dextran supplemented with hydroxyapatite have recently been developed for bone tissue engineering applications. Here, we evaluate the bone formation in two different preclinical models after injection of microbeads reconstituted with either saline buffer or autologous blood. Addition of saline solution or autologous blood to dried microbeads packaged into syringes allowed an easy injection. In the first rat bone defect model performed in the femoral condyle, microcomputed tomography performed after 30 and 60 days revealed an important mineralization process occurring around and within the core of the microbeads in both conditions. Bone volume/total volume measurements revealed no significant differences between the saline solution and the autologous blood groups. Histologically, osteoid tissue was evidenced around and in contact of the microbeads in both conditions. Using the sinus lift model performed in sheep, cone beam computed tomography revealed an important mineralization inside the sinus cavity for both groups after 3 months of implantation. Representative Masson trichrome staining images showed that bone formation occurs at the periphery and inside the microbeads in both conditions. Quantitative evaluation of the new bone formation displayed no significant differences between groups. In conclusion, reconstitution of microbeads with autologous blood did not enhance the regenerative capacity of these microbeads compared to the saline buffer group. This study is of particular interest for clinical applications in oral and maxillofacial surgery.

Whole blood or plasma: what is the ideal matrix for pharmacokinetic-driven drug candidate selection?

In the present era of drug development, quantification of drug concentrations following pharmacokinetic studies has preferentially been performed using plasma as a matrix rather than whole blood. However, it is critical to realize the difference between measuring drug concentrations in blood versus plasma and the consequences thereof. Pharmacokinetics using plasma data may be misleading if concentrations differ between plasma and red blood cells (RBCs) because of differential binding in blood. In this review, factors modulating the partitioning of drugs into RBCs are discussed and the importance of determining RBC uptake of drugs for drug candidate selection is explored. In summary, the choice of matrix (plasma vs whole blood) is an important consideration to be factored in during drug discovery.

An explicitly multi-component arterial gas embolus dissolves much more slowly than its one-component approximation.

We worked out the growth and dissolution rates of an arterial gas embolism (AGE), to illustrate the evolution over time of its size and composition, and the time required for its total dissolution. We did this for a variety of breathing gases including air, pure oxygen, Nitrox and Heliox (each over a range of oxygen mole fractions), in order to assess how the breathing gas influenced the evolution of the AGE. The calculations were done by numerically integrating the underlying rate equations for explicitly multi-component AGEs, that contained a minimum of three (water, carbon dioxide and oxygen) and a maximum of five components (water, carbon dioxide, oxygen, nitrogen and helium). The rate equations were straight-forward extensions of those for a one-component gas bubble. They were derived by using the Young-Laplace equation and Dalton's law for the pressure in the AGE, the Laplace equation for the dissolved solute concentration gradients in solution, Henry's law for gas solubilities, and Fick's law for diffusion rates across the AGE/arterial blood interface. We found that the 1-component approximation, under which the contents of the AGE are approximated by its dominant component, greatly overestimates the dissolution rate and underestimates the total dissolution time of an AGE. This is because the 1-component approximation manifestly precludes equilibration between the AGE and arterial blood of the inspired volatile solutes (O2, N2, He) in arterial blood. Our calculations uncovered an important practical result, namely that the administration of Heliox, as an adjunct to recompression therapy for treating a suspected N2-rich AGE must be done with care. While Helium is useful for preventing nitrogen narcosis which can arise in aggressive recompression therapy wherein the N2 partial pressure can be quite high (e.g.∼5 atm), it also temporarily expands the AGE, beyond the expansion arising from the use of Oxygen-rich Nitrox. For less aggressive recompression therapy wherein nitrogen narcosis is not a significant concern, Oxygen-rich Nitrox is to be preferred, both because it does not temporarily expand the AGE as much as Heliox, and because it is much cheaper and more conservation-minded.

Risk profiling using metabolomic characteristics for susceptible individuals of drug-induced liver injury caused by Polygonum multiflorum.

Idiosyncratic drug-induced liver injury (IDILI) is a rare but potentially severe adverse drug reaction. To date, identifying individuals at risk for IDILI remains challenging. This is a prospective study, where a nested case-control (1:5) design was adopted. For six patients who had abnormalities in liver function test after Polygonum multiflorum Thunb. (PM) ingestion (susceptible group), 30 patients with normal liver function were matched (tolerant group). Based on liquid chromatography-mass spectrometry, metabolomics analysis was done on serum samples prior to PM ingestion, to screen the differential metabolites and characterize metabolomic profiles of patient serum in the two groups. Multivariate analysis showed that there were remarkable separations between susceptible and tolerant groups. A total of 25 major differential metabolites were screened out, involving glycerophospholipid metabolism, sphingolipid metabolism, fatty acid metabolism, histidine metabolism and aromatic amino acid metabolism. Wherein, the area under the curve of the receiver operating characteristic curves of metabolites PE 22:6, crotonoyl-CoA, 2E-tetradecenoyl-CoA, phenyllactic acid, indole-5,6-quinone, phosphoribosyl-ATP were all greater than 0.9. The overall serum metabolic profile comprising of 25 metabolites could clearly distinguish susceptible and tolerant groups. This proof-of-concept study used metabolomics to characterize the metabolic profile of IDILI risk individuals before drug ingestion for the first time. The metabolome characteristics in patient serum before PM ingestion may predict the risk of liver injury after PM ingestion.

Discovery of quality-marker ingredients of Panax quinquefolius driven by high-throughput chinmedomics approach.

BACKGROUND: Quality control of traditional Chinese medicine (TCM) has always been a hot issue to TCM. However, due to the complexity of TCM ingredients, the current quality standards of TCM have problems that are difficult to guarantee clinical efficacy. American ginseng, the dried roots of Pawajc quinquefolium L. (Araliaceae), is a valuable herbal medicine due to various pharmacological effects and huge health benefit, which are associated with numerous active ingredients such as ginsenosides. Although a large number of studies have investigated the active ingredients of American ginseng, Q-markers reflecting comprehensive review on its efficacies has yet been unrevealed. PURPOSE: The study aims to discover the Q-markers of Panax quinquefolius (American ginseng), provides a powerful method to clarify the significant ingredents of TCM and help further discovering extensive quality evaluation model,contributing to a significant improvement of TCM quality standard. METHODS: Mice general status, biochemical indexes assay, urine metabolic profile, and serum metabolic profile were utilized for model replication and efficacy evaluation. The in vitro and in vivo constituents of American ginseng using ultra-high performance liquid chromatography coupled with mass spectrometry (UPLC-MS) with Serum Pharmacochemistry of TCM were in-depth investigated. Q-markers that were associated with core markers of therapeutic effects were excavated by a plotting of correlation between marker metabolites and serum constituents (PCMS) approach. RESULTS: Correlation analysis of 41 blood and urine labeled metabolites with 14 serum components showed that 24-methyl-7-cholesten-3ß-ol, zizybeoside II, betulin, ginsenoside Rd, cinnamyl alcohol, pseudoginsenoside F11 is highly correlated with the therapeutic effects of Compound Zaofan Pill (CZP), while pseudoginsenoside F11 and ginsenoside Rd are highly correlated with the therapeutic effects of American ginseng. The six absorbed blood compounds can be considered as potential Q-markers for compound, of which two compounds, such as pseudoginsenoside F11 and ginsenoside Rd, can be considered as potential Q-markers for American ginseng. CONCLUSION: The study has demonstrated that the Chinmedomics is an effective, comprehensive and fire-new method for discovering the Q-markers of TCM, and it may be more reasonable choices to establish quality standards of TCM.

[Pharmacokinetics of skin and blood of Tripterygium wilfordii and Paeonia lactiflora micro-emulsion gel based on micro-dialysis technology].

To further investigate the metabolism of Tripterygium wilfordii and Paeonia lactiflora micro-emulsion gel in vivo,an LCMS/MS method was established for the determination of triptolide and paeoniflorin in T. wilfordii and P. lactiflora micro-emulsion gel.The extracorporeal recovery rate of blood probe was measured by concentration difference methods( incremental method and decremental method). Meanwhile,the skin and blood micro-dialysis methods of tripterine and paeoniflorin were established,and the pharmacokinetics of T. wilfordii microemulsion gel in skin and blood was studied by micro-dialysis combined with LC-MS/MS quantitative analysis. The results showed that the established method for the determination of triptolide and paeoniflorin in T. wilfordii microemulsion gel was well linear within the required range,and the specificity,recovery rate and degree of precision of the chromatography all conformed to the research requirements of micro-dialysis samples. The stability of freeze-thawing and the residual effect all conformed to the criteria of biological sample methodology. The probe recovery rates measured by incremental method and decremental method were almost consistent with the extracorporeal recovery rate test. The recovery rates of paeoniflorin in skin and blood micro-dialysis were( 30. 60±1. 09) % and( 28. 01± 1. 75) %,respectively. And the recovery rates of skin and blood micro-dialysis were( 26. 79 ± 2. 78) % and( 25. 39±1. 86) %,respectively. The intraday recovery rate of probes was stable within 11 h. The results of pharmacokinetic study showed that the Cmaxvalues of triptolide in skin and blood were( 148. 03±41. 51) and( 76. 77±15. 27) µg·L-1,respectively. And the Tmaxvalues were( 2. 33±0. 29) and( 3. 00± 0) h,respectively. The AUC0-11 hvalues were( 2 814. 05± 1 070. 37) and( 1 580. 63±208. 27) µg·h·L-1,respectively. The MRT0-11 hvalues were( 4. 20± 0. 33) and( 4. 54± 0. 34) h,respectively. The T1/2 values were( 4. 61±4. 11) and( 1. 07± 0. 13) h,respectively. The Cmaxvalues of paeoniflorin in skin and blood were( 991. 88 ± 152. 22) and( 407. 02±120. 06) µg·L-1,respectively. The Tmaxvalues were( 2. 00±0) h and( 2. 83±0. 29) h,respectively. The AUC0-11 hvalues were( 18 430. 27±3 289. 35) and( 6 338. 59 ± 1 659. 32) µg·h·L-1,respectively. The MRT0-11 hvalues were( 4. 29 ± 0. 16) and( 4. 00±0. 05) h,respectively. The T1/2 values were( 2. 16±0. 43) and( 1. 78±0. 48) h,respectively. The results suggested that micro-emulsion gel played a role in forming skin reservoir through percutaneous penetration. It not only could improve drug transdermal efficiency,but also control the sustained release of drug and form a long-term effect.

Ameliorative effect of Bacillus subtilis, Saccharomyces boulardii, oregano, and calcium montmorillonite on growth, intestinal histology, and blood metabolites on Salmonella-infected broiler chicken.

This study evaluated the effects of Bacillus subtilis, Saccharomyces boulardii, oregano, and calcium montmorillonite on the physical growth, intestinal histomorphology, and blood metabolites in Salmonella-challenged birds during the finisher phase. In this study, a total of 600 chicks (Ross 308) were randomly distributed into the following dietary treatments: basal diet with no treatment; infected with Salmonella; T1, infected + avilamycin; T2, infected + Bacillus subtilis; T3, Saccharomyces boulardii; T4, infected + oregano; T5, infected + calcium montmorillonite. Our results indicated that feed consumption, body weight gain, total body weight, and feed conversion ratio increased significantly (P < 0.01) in T1 and T2. Villus width increased significantly (P < 0.01) in T1 while the total area was significantly (P < 0.01) higher in T1 and T2 among the treatment groups. Blood protein was significantly (P < 0.01) high in T3 and T4; however, the glucose concentration was significantly (P < 0.01) high in T2, T3, and T4. The treatments increased significantly (P< 0.01) in the treatment groups compared to the negative control. Aspirate aminotransferase (AST) was significantly (P < 0.05) low in T3 compared to the positive control. In conclusion, the results indicated that supplementation of Bacillus subtilis and calcium montmorillonite improved the production performance compared to other feed additives in broiler chicks infected with Salmonella during the finisher phase.

Blood, sweat, and tears: Red Blood Cell-Omics study objectives, design, and recruitment activities.

BACKGROUND: The Red Blood Cell (RBC)-Omics study was initiated to build a large data set containing behavioral, genetic, and biochemical characteristics of blood donors with linkage to outcomes of the patients transfused with their donated RBCs. STUDY DESIGN AND METHODS: The cohort was recruited from four US blood centers. Demographic and donation data were obtained from center records. A questionnaire to assess pica, restless leg syndrome, iron supplementation, hormone use, and menstrual and pregnancy history was completed at enrollment. Blood was obtained for a complete blood count, DNA, and ferritin testing. A leukocyte-reduced RBC sample was transferred to a custom storage bag for hemolysis testing at Storage Days 39 to 42. A subset was recalled to evaluate the kinetics and stability of hemolysis measures. RESULTS: A total of 13,403 racially/ethnically diverse (12% African American, 12% Asian, 8% Hispanic, 64% white, and 5% multiracial/other) donors of both sexes were enrolled and ranged from 18 to 90 years of age; 15% were high-intensity donors (nine or more donations in the prior 24 mo without low hemoglobin deferral). Data elements are available for 97% to 99% of the cohort. CONCLUSIONS: The cohort provides demographic, behavioral, biochemical, and genetic data for a broad range of blood donor studies related to iron metabolism, adverse consequences of iron deficiency, and differential hemolysis (including oxidative and osmotic stress perturbations) during RBC storage. Linkage to recipient outcomes may permit analysis of how donor characteristics affect transfusion efficacy. Repository DNA, plasma, and RBC samples should expand the usefulness of the current data set.

Betaine or folate can equally furnish remethylation to methionine and increase transmethylation in methionine-restricted neonates.

Methionine partitioning between protein turnover and a considerable pool of transmethylation precursors is a critical process in the neonate. Transmethylation yields homocysteine, which is either oxidized to cysteine (i.e., transsulfuration), or is remethylated to methionine by folate- or betaine- (from choline) mediated remethylation pathways. The present investigation quantifies the individual and synergistic importance of folate and betaine for methionine partitioning in neonates. To minimize whole body remethylation, 4-8-d-old piglets were orally fed an otherwise complete diet without remethylation precursors folate, betaine and choline (i.e. methyl-deplete, MD-) (n=18). Dietary methionine was reduced from 0.3 to 0.2 g/(kg∙d) on day-5 to limit methionine availability, and methionine kinetics were assessed during a gastric infusion of [13C1]methionine and [2H3-methyl]methionine. Methionine kinetics were reevaluated 2 d after pigs were rescued with either dietary folate (38 µg/(kg∙d)) (MD + F) (n=6), betaine (235 mg/(kg∙d)) (MD + B) (n=6) or folate and betaine (MD + FB) (n=6). Plasma choline, betaine, dimethylglycine (DMG), folate and cysteine were all diminished or undetectable after 7 d of methyl restriction (P<.05). Post-rescue, plasma betaine and folate concentrations responded to their provision, and homocysteine and glycine concentrations were lower (P<.05). Post-rescue, remethylation and transmethylation rates were~70-80% higher (P<.05), and protein breakdown was spared by 27% (P<.05). However, rescue did not affect transsulfuration (oxidation), plasma methionine, protein synthesis or protein deposition (P>.05). There were no differences among rescue treatments; thus betaine was as effective as folate at furnishing remethylation. Supplemental betaine or folate can furnish the transmethylation requirement during acute protein restriction in the neonate.

Exploration of the Relationship between Intestinal Colostrum or Milk, and Serum Metabolites in Neonatal Calves by Metabolomics Analysis.

In contrast to colostral immunoglobulins, changes in metabolite composition of ingested colostrum in the gut have received little attention. Here, we characterized the metabolite profiles of colostrum and milk, ingested colostrum and milk, and serum of neonatal calves by liquid chromatography tandem-mass spectrometry and gas chromatography-mass spectrometry metabolomics approaches. Colostrum and milk underwent similar changes in metabolite profiles in the gut after being ingested. These changes were characterized by increases in methionine, glutamate, thymine, and phosphorylcholine. After ingestion, colostrum concentrations of several metabolites, such as γ-aminobutyric acid, glutamate, cinnamic acid, and thymine increased, whereas concentrations of d-ribose, and arginine decreased. These increases and decreases occurred in a time-dependent manner and were associated with alanine, aspartate, glutamate, and pyrimidine metabolism, and valine, leucine, and isoleucine biosynthesis, respectively. Meanwhile, similar changes in serum metabolites were also observed in neonatal calves fed colostrum, which implies that colostrum metabolites are transported across the small intestine and into the bloodstream. In addition, several metabolites of ingested milk were detected in the gut, and were also transferred to the bloodstream. These metabolites were related to phenylalanine, tyrosine, tryptophan, valine, leucine, and isoleucine biosynthesis, the citrate cycle, and histidine metabolism. These findings reveal that the serum metabolome of neonatal calves' changes as a result of ingesting colostrum, which can provide health-related benefits in early life.

Thyroid Dysfunction, Neurological Disorder and Immunosuppression as the Consequences of Long-term Combined Stress.

Stress is a powerful modulator of neuroendocrine, behavioral, and immunological functions. So far, the molecular mechanisms of response to stressors still remain elusive. In the current study, after 10 days of repeated chronic stress (hot-dry environment and electric foot-shock), a murine model of combined-stress (CS) was created in the SPF Wistar rats. Meanwhile, we established an ulcerative-colitis (UC) rat model induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS)/ethanol enema according to previous studies. The blood, hypothalamus, and colon tissues of these rats from CS, normal control (NC), UC and sham (SH) groups, were collected for further investigations. Comparing to the NC group, the serum levels of T3, T4, fT3 and fT4 were obviously decreased in the CS group after chronic stress, indicating that thyroid dysfunction was induced by long-term combined stress. Moreover, the application of RNA-seq and subsequent analyses revealed that neurological disorder and immunosuppression were also caused in the hypothalamus and colon tissues, respectively. Comparing with SH group, besides the induced colon inflammation, thyroid dysfuntion and neurological disorder were also produced in the UC group, suggesting that hypothalamic-pituitary-thyroid (HPT) axis and gastrointestinal system might not function in isolation, but rather, have intricate crosstalks.

Effect of vitamin D treatments on plasma metabolism and immune parameters of healthy dairy cows.

The objective of this study was to investigate the possible beneficial effect of vitamin D repletion on certain immune parameters of vitamin D insufficient dairy cows. Twenty dairy cows in late lactation were treated daily with vitamin D in five different ways: sunlight exposure (SUN), D2 supplementation combined with sunlight exposure (D2SUN), D2 supplementation (D2), D3 supplementation (D3), and D2 and D3 supplementation combined (D2D3). The cows had very low vitamin D levels at d 0 because of the vitamin D deprivation before the study. After 1 month of vitamin D repletion, all cows had plasma 25(OH)D levels within the normal range. Total 25(OH)D concentration was significantly higher in SUN, D2SUN and D2D3 than D2 or D3 at the end of the study. However, milk yield, as well as protein and fat content of the milk, was not influenced by vitamin D treatments. There was no difference obtained in the measured immune parameters: Leucocyte populations, somatic cell count, immunoglobulin concentrations in plasma and milk, and antigen-stimulated cytokine productions did not change in response to vitamin D repletion or difference in vitamin D sources, and no relations to plasma 25(OH)D levels were identified. Despite the fact that plasma 25(OH)D increased from a very low level to normal range, the present study did not show any effect of vitamin D repletion on the tested immune parameters of healthy dairy cows. Therefore, in this study, it was concluded that repletion to physiologically normal plasma 25-hydroxyvitamin D levels of vitamin D-depleted healthy dairy cows had no influence on immune parameters.

Laser stimulating ST36 with optical fiber induce blood component changes in mice: a Raman spectroscopy study.

ST36 is a commonly-used acupoint in traditional Chinese medicine (TCM) for treatment of inflammations, pains and gastrointestinal disturbs. For decades, the low power laser acupuncture has been widely applied as an alternative therapy to traditional metal needle acupuncture and achieved relatively fine therapeutic effect for ST36-related symptoms with reduction of uncomfortableness and infection risks. However its disadvantages of low penetrativity and lack of manipulation skills limit its potential performance. An optical fiber laser acupuncture introduced by the previous study combines traditional needling acupuncture and the laser stimulation together, making a stronger therapeutic effect and showing a potential value in clinical application. To evaluate its acupunctural effect on blood, mice are taken as experimental model and Raman spectroscopic technique is used to analysis the changes of blood components after stimulating on ST36. The results show that both the traditional needling acupuncture and optical fiber acupuncture could lead to some spectral changes of blood in mice. This study explores the optical fiber acupuncture's effect on blood in mice using Raman spectroscopy technique for mechanism of acupuncture therapy.

Metabolomic profiling of the effects of Curcumae rhizoma and Sparganii rhizome on stress-led blood stasis.

Blood stasis (BS) is a complex syndrome with blood flow retardation or cessation. The Traditional Chinese Medicine, Curcumae rhizome (CR) and Sparganii rhizome (SR), showed promising effects on this disease, and especially effective when used in combination. However, the detailed influence of the TCMs on the BSS disturbed metabolic pathways was still unclear. In this study, a BS model was constructed in SD rat and the TCMs were used individually or in combination to assess the effects. As a result, combination of CR and SR led to the improvement in hemorheology parameters of up to 80% in the BS model. Further analyzing using metabolomics showed several metabolic pathways, including center carbon metabolism, amino acid metabolism, etc., recovered to the normal levels after treatment. Informatively, tyrosine and thymidine exhibited potential importance in the BSS and its treatment process. From these results, the metabolic profiles of BS and the SR-CR treatment were provided, which may helpful for better understanding the BSS mechanism and the development of more effective therapies.

¹H-NMR-Based Metabonomics of the Protective Effect of Coptis chinensis and Berberine on Cinnabar-Induced Hepatotoxicity and Nephrotoxicity in Rats.

Coptis chinensis Franch has been used in Traditional Chinese Medicine (TCM) for treating infectious and inflammatory diseases for over two thousand years. Berberine (BN), an isoquinoline alkaloid, is the main component of Coptis chinensis. The pharmacological basis for its therapeutic effects, which include hepatoprotective effects on liver injuries, has been studied intensively, yet the therapy of liver injuries and underlying mechanism remain unclear. We investigated the detoxification mechanism of Coptis chinensis and berberine using metabolomics of urine and serum in the present study. After the treatment with Coptis chinensis and berberine, compared with the cinnabar group, Coptis chinensis and berberine can regulate the concentration of the endogenous metabolites. PLS-DA score plots demonstrated that the urine and serum metabolic profiles in rats of the Coptis chinensis and berberine groups were similar those of the control group, yet remarkably apart from the cinnabar group. The mechanism may be related to the endogenous metabolites including energy metabolism, amino acid metabolism and metabolism of intestinal flora in rats. Meanwhile, liver and kidney histopathology examinations and serum clinical chemistry analysis verified the experimental results of metabonomics.

Living and Training at 825 m for 8 Weeks Supplemented With Intermittent Hypoxic Training at 3,000 m Improves Blood Parameters and Running Performance.

Wonnabussapawich, P, Hamlin, MJ, Lizamore, CA, Manimmanakorn, N, Leelayuwat, N, Tunkamnerdthai, O, Thuwakum, W, and Manimmanakorn, A. Living and training at 825 m for 8 weeks supplemented with intermittent hypoxic training at 3,000 m improves blood parameters and running performance. J Strength Cond Res 31(12): 3287-3294, 2017-We aimed to investigate the effect of an 8-week low-altitude training block supplemented with intermittent hypoxic training, on blood and performance parameters in soccer players. Forty university-level male soccer players were separated into altitude (n = 20, 825 m) or sea-level (n = 20, 125 m) groups. Before (1-2 days ago) and after (1 and 14 days later) training, players were asked to give a resting venous blood sample and complete a series of performance tests. Compared with sea level, the altitude group increased erythropoietin, red blood cell (RBC) count, and hematocrit 1 day after training (42.6 ± 24.0%, 1.8 ± 1.3%, 1.4 ± 1.1%, mean ± 95% confidence limits (CL), respectively). By 14 days after training, only RBC count and hemoglobin were substantially higher in the altitude compared with the sea-level group (3.2 ± 1.8%, 2.9 ± 2.1% respectively). Compared with sea level, the altitude group 1-2 days after training improved their 50-m (-2.9 ± 1.4%) and 2,800-m (-2.9 ± 4.4%) run times and demonstrated a higher maximal aerobic speed (4.7 ± 7.4%). These performance changes remained at 14 days after training with the addition of a likely higher estimated V[Combining Dot Above]O2max in the altitude compared with the sea-level group (3.2 ± 3.0%). Eight weeks of low-altitude training, supplemented with regular bouts of intermittent hypoxic training at higher altitude, produced beneficial performance improvements in team-sport athletes, which may increase the viability of such training to coaches and players that cannot access more traditional high altitude venues.

1H NMR-based Investigation of Metabolic Response to Electro-Acupuncture Stimulation.

Acupuncture is a traditional Chinese medicine therapy that has been found useful for treating various diseases. The treatments involve the insertion of fine needles at acupoints along specific meridians (meridian specificity). This study aims to investigate the metabolic basis of meridian specificity using proton nuclear magnetic resonance (1H NMR)-based metabolomics. Electro-acupuncture (EA) stimulations were performed at acupoints of either Stomach Meridian of Foot-Yangming (SMFY) or Gallbladder Meridian of Foot-Shaoyang (GMFS) in healthy male Sprague Dawley (SD) rats. 1H-NMR spectra datasets of serum, urine, cortex, and stomach tissue extracts from the rats were analysed by multivariate statistical analysis to investigate metabolic perturbations due to EA treatments at different meridians. EA treatment on either the SMFY or GMFS acupoints induced significant variations in 31 metabolites, e.g., amino acids, organic acids, choline esters and glucose. Moreover, a few meridian-specific metabolic changes were found for EA stimulations on the SMFY or GMFS acupoints. Our study demonstrated significant metabolic differences in response to EA stimulations on acupoints of SMFY and GMFS meridians. These results validate the hypothesis that meridian specificity in acupuncture is detectable in the metabolome and demonstrate the feasibility and effectiveness of a metabolomics approach in understanding the mechanism of acupuncture.

Mimicking oxygen delivery and waste removal functions of blood.

In addition to immunological and wound healing cell and platelet delivery, ion stasis and nutrient supply, blood delivers oxygen to cells and tissues and removes metabolic wastes. For decades researchers have been trying to develop approaches that mimic these two immediately vital functions of blood. Oxygen is crucial for the long-term survival of tissues and cells in vertebrates. Hypoxia (oxygen deficiency) and even at times anoxia (absence of oxygen) can occur during organ preservation, organ and cell transplantation, wound healing, in tumors and engineering of tissues. Different approaches have been developed to deliver oxygen to tissues and cells, including hyperbaric oxygen therapy (HBOT), normobaric hyperoxia therapy (NBOT), using biochemical reactions and electrolysis, employing liquids with high oxygen solubility, administering hemoglobin, myoglobin and red blood cells (RBCs), introducing oxygen-generating agents, using oxygen-carrying microparticles, persufflation, and peritoneal oxygenation. Metabolic waste accumulation is another issue in biological systems when blood flow is insufficient. Metabolic wastes change the microenvironment of cells and tissues, influence the metabolic activities of cells, and ultimately cause cell death. This review examines advances in blood mimicking systems in the field of biomedical engineering in terms of oxygen delivery and metabolic waste removal.