L-Carnitine and Acetyl-L-Carnitine: Potential Novel Biomarkers for Major Depressive Disorder.

The lack of biomarkers greatly limits the diagnosis and treatment of major depressive disorder (MDD). Endogenous L-carnitine (LC) and its derivative acetyl-L-carnitine (ALC) play antidepressant roles by improving brain energy metabolism, regulating neurotransmitters and neural plasticity. The levels of ALC in people and rodents with depression are significantly reduced. It is necessary to determine whether serum LC and ALC might be used as novel biomarkers for the diagnosis of MDD. Here, ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to determine the concentration of LC and ALC in the serum of healthy controls and patients with MDD; among the latter, in patients who were responsive (effective group) and non-responsive (ineffective group) after 2 weeks of treatment. The diagnostic value of serum LC and ALC for MDD was assessed. Compared with healthy controls, the serum LC and ALC concentrations in patients with MDD were significantly decreased (P < 0.001). Pearson correlation analysis shows that the HDRS-24 score was negatively associated with serum ALC (r = -0.325, P = 0.007). Receiver operating characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.801 with 83.1% sensitivity and 66.3% specificity for LC, and an AUC of 0.898 with 88.8% sensitivity and 76.4% specificity for ALC, differentiating patients with MDD from healthy controls. Furthermore, the concentration of LC and ALC in patients with depression was significantly increased in the effective treatment group, and no significant change was observed in the ineffective treatment group. These results suggest that serum LC and ALC may be novel biomarkers for the diagnosis of MDD.

A classical but new kinetic equation for hydride transfer reactions.

A classical but new kinetic equation to estimate activation energies of various hydride transfer reactions was developed according to transition state theory using the Morse-type free energy curves of hydride donors to release a hydride anion and hydride acceptors to capture a hydride anion and by which the activation energies of 187 typical hydride self-exchange reactions and more than thirty thousand hydride cross transfer reactions in acetonitrile were safely estimated in this work. Since the development of the kinetic equation is only on the basis of the related chemical bond changes of the hydride transfer reactants, the kinetic equation should be also suitable for proton transfer reactions, hydrogen atom transfer reactions and all the other chemical reactions involved with breaking and formation of chemical bonds. One of the most important contributions of this work is to have achieved the perfect unity of the kinetic equation and thermodynamic equation for hydride transfer reactions.

[Reconstitution of humoral immunity by the transplantation of human umbilical cord blood CD34+ cells into NOD/ SCID mice].

OBJECTIVE: To investigate the immune reconstitution by the transplantation of human umbilical cord blood CD34+ cells in the NOD/SCID mouse. METHODS: Mononuclear cells (MNC) were isolated from human fresh cord blood and CD34+ hematopoietic stem cells were selected by magnetic activated cell sorting method. The selected cells were transplanted via tail vein injection into 16 NOD/SCID mice after sublethal whole-body irradiation. Four mice were sacrificed respectively at 4th, 6th, 8th and 10th week after the transplantation, the harvested spleen and peripheral blood cells were used to cell phenotype analysis and humoral immune analysis, respectively. There were 14 mice in another two groups, 7 mice did not receive the transplantation after irradiation, 7 were used as blank control (no irradiation, no transplantation). RESULTS: The mice without transplantation all died within 2 weeks after irradiation. The survival rate of the mice with transplantation was 37.5% at 6th week after the irradiation, while the survival rate of blank control was 100%. At 4th, 6th, 8th and 10th week, the percentage of human CD45+ cells in transplantation group were 4.7 +/- 1.23, 9.22 +/- 2.07, 12.34 +/- 2.38, 8.14 +/- 2.36, respectively, and the percentage of CD19+ B lymphocytes were 1.07 +/- 0.50, 2.17 +/- 0.95, 3.34 +/- 0.90, 1.67 +/- 0.90, respectively. 10 weeks after the transplantation, human CD19+ B lymphocytes distribution were found in the transplanted mice spleen. CONCLUSION: The human-mouse chimeric immune model can be built in irradiated NOD/ SCID mice by the transplantation of human cord blood CD34+ cells. CD34+ cell differentiation declined with time, which might be due to the lack of appropriate cytokines.

What are the differences between ascorbic acid and NADH as hydride and electron sources in vivo on thermodynamics, kinetics, and mechanism?

Ascorbic acid (AscH(2)) and dihydronicotinamide adenine dinucleotide (NADH) are two very important natural redox cofactors, which can be used as hydride, electron, and hydrogen atom sources to take part in many important bioreduction processes in vivo. The differences of the two natural reducing agents as hydride, hydrogen atom, and electron donors in thermodynamics, kinetics, and mechanisms were examined by using 5,6-isopropylidene ascorbate (iAscH(-)) and ß-D-glucopyranosyl-1,4-dihydronicotinamide acetate (GluNAH) as their models, respectively. The results show that the hydride-donating ability of iAscH(-) is smaller than that of GluNAH by 6.0 kcal/mol, but the electron-donating ability and hydrogen-donating ability of iAscH(-) are larger than those of GluNAH by 20.8 and 8.4 kcal/mol, respectively, which indicates that iAscH(-) is a good electron donor and a good hydrogen atom donor, but GluNAH is a good hydride donor. The kinetic intrinsic barrier energy of iAscH(-) to release hydride anion in acetonitrile is larger than that of GluNAH to release hydride anion in acetonitrile by 6.9 kcal/mol. The mechanisms of hydride transfer from iAscH(-) and GluNAH to phenylxanthium perchlorate (PhXn(+)), a well-known hydride acceptor, were examined, and the results show that hydride transfer from GluNAH adopted a one-step mechanism, but the hydride transfer from iAscH(-) adopted a two-step mechanism (e-H(•)). The thermodynamic relation charts (TRC) of the iAscH(-) family (including iAscH(-), iAscH(•), iAsc(•-), and iAsc) and of the GluNAH family (including GluNAH, GluNAH(•+), GluNA(•), and GluNA(+)) in acetonitrile were constructed as Molecule ID Cards of iAscH(-) and of GluNAH in acetonitrile. By using the Molecule ID Cards of iAscH(-) and GluNAH, the character chemical properties not only of iAscH(-) and GluNAH but also of the various reaction intermediates of iAscH(-) and GluNAH all have been quantitatively diagnosed and compared. It is clear that these comparisons of the thermodynamics, kinetics, and mechanisms between iAscH(-) and GluNAH as hydride and electron donors in acetonitrile should be quite important and valuable to diagnose and understand the different roles and functions of ascorbic acid and NADH as hydride, hydrogen atom, and electron sources in vivo.