The phenotypic and functional characteristics of fetal lymphocytes are of considerable interest for our understanding of the development of the immune system. Recent advances demonstrate that prenatal contact of allergens and other antigens is possible and also that the fetal T and B cells might be able to response to various stimuli during gestation [1][2][3][4][5][6]. A potential link between prenatal contact with allergens and allergic disease in future life has also been proposed [1]. Mononuclear cells in the human umbilical cord blood collected after delivery at term have been thoroughly studied in the last two decades [7][8][9][10][11][12][13][14] and it is generally accepted that T cells from the neonates are phenotypically and functionally immature. However, currently little is known about the maturational process of fetal T cells during human gestation, due to the difficulties in obtaining, and also ethical dilemmas of working with, human fetal tissues. So far, only a handful of reports documented the phenotypes of T lymphocytes in human fetuses [15][16][17][18][19][20][21], few covered the functional status of these cells [1,2,6].T cells are identified by monoclonal Ab against CD3 and are further divided into CD4 + (helper) and CD8 + (cytotoxic) subsets. The majority of peripheral T cells express ab-TCR, while a small proportion (about 10%) express gd-TCR. CD16 and CD56 are commonly used for the identification of NK cells that do not have T cell surface markers. In the present study, we collected blood samples by ultrasound-guided cordocentesis from umbilical cord of human fetuses at early second-and third-trimester. Phenotypes of the T cell subsets were quantitatively determined by flow cytometry and their functional status analysed in proliferation and cytokine (IL-2, IL-4, IL-16, IL-10, TNF-a and IFN-g) assays.Term cord blood, maternal and healthy unrelated male adult peripheral blood samples were also included as controls. MATERIALS AND METHODS Subjects and blood samples SUMMARYThis study was undertaken to investigate the phenotypic and functional status of T lymphocytes of human fetuses from early second-to third-trimester. Cord blood samples were obtained from 19 healthy human fetuses (gestation weeks: 18-36), by cordocentesis, and 16 term newborns (gestation weeks 37-42). Maternal and unrelated male blood samples were also taken as controls. Percentage of lymphocytes in fetal white blood cells was 79·3%, reducing to 40% by term birth, much higher than that of adults. Cord blood mononuclear cells (CBMC), prepared by density gradient centrifugation followed by lysis of erythrocytes, were stained using PE-or FITC-labelled monoclonal Abs and analysed by flow cytometry. The frequencies of CD3 + T cells in fetal (40·1%) and neonatal (42·4%) CBMC were significantly lower than that of men (59·6%) and pregnant women (53·6%). Proportions of CD8 + T cells (9·5%), gd-T cells (0·5%) and NK cells (4·8%) in fetal CBMC were also lower than that of neonates (except gd-T cells) and adults. A negative linear corr...

Methamphetamine (METH) has already been a serious problem all over the world. The identification of related biomarkers and pathways is helpful to evaluate the degree of METH addiction, develop appropriate treatment during abstinence, and explore the mechanism. Here, it is the first time to perform metabolomics profiling of METH addicted human serum and three regions of METH-induced conditioned place preference (CPP) rat brain by using UHPLC-MS/MS and matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI), respectively. Untargeted metabolomics analysis demonstrated clear differences between METH abusers and the healthy control by finding 35 distinct expressed metabolites in serum, including 5 TCA intermediates, 17 amino acids and 13 other biomolecules, 15 of which were newly identified following METH exposure. By using MALDI-MSI, the relative quantification and distribution of 14 metabolites were investigated in the nucleus accumbens (NAc), dorsal hippocampus (dHPC) and ventral hippocampus (vHPC) of CPP rat brain. Taken together, METH addiction could influence energy metabolism, amino acids metabolism, and phospholipids metabolism. A multi-parameter model consisting of these related metabolites can be established as a METH addiction biomarker in the future. The mapping of phospholipids provided new insights into the mechanism of METH addiction. Notably, the trend of metabolite changes in NAc and dHPC was almost the same, while it was opposite between dHPC and vHPC. It seems that NAc and dHPC were the two regions more susceptible to METH administration in the brain. And dHPC and vHPC play different roles in METH addiction proved by metabolites mapping.

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Objectives: We aimed to evaluate the effect of Shenfu injection in a rat model of ischemic heart failure and explore its mechanism. Methods: A rat model of ischemic heart failure after myocardial infarction was established by ligating the left anterior descending coronary artery. Forty-eight hours after surgery, the rats were intraperitoneally administered Shenfu injection for 7 weeks. Then, left ventricular fractional shortening and left ventricular ejection fraction were measured using transthoracic echocardiography, whereas heart rate and left ventricular end-diastolic pressure were measured using a MD3000 biosignal acquisition and processing system. The hearts and lungs of the rats were excised and weighed to measure the heart and lung weight indexes. In addition, cardiac histopathological changes were observed via hematoxylin–eosin and Masson’s trichrome staining, and serum cardiac troponin content was detected using a cardiac troponin ELISA kit. Furthermore, matrix-assisted laser desorption/ionization–mass spectrometry imaging was used to detect the levels and distribution of small molecules in the hearts of rats with ischemic heart failure. Results: We found that Shenfu injection can significantly increase left ventricular fractional shortening and left ventricular ejection fraction in rats with ischemic heart failure and significantly reduce the left ventricular end-diastolic pressure, heart and lung weight indexes, and cardiac troponin content; improve cardiac tissue morphology; and reduce infarct size. In addition, the matrix-assisted laser desorption/ionization–mass spectrometry imaging results demonstrated that 22:6 phospholipids were predominately distributed in the non-infarct zone, whereas 20:4 phospholipids tended to concentrate in the infarct zone. Shenfu injection significantly reduced taurine, glutathione, and phospholipids levels in the hearts of rats with ischemic heart failure and primarily changed the distribution of these molecules in the non-infarct zone. Conclusion: Shenfu injection induced obvious myocardial protective effects in rats with ischemic heart failure by stimulating antioxidation and changing the phospholipid levels and distribution.

Radix Aconiti Lateralis Preparata (fuzi) is the processed product of Aconitum carmichaelii Debeaux tuber, and has great potential anti-myocardial infarction effects, including improving myocardial damage and energy metabolism in rats. However, the effects of Radix Aconiti Lateralis Preparata extracts in a rat model of myocardial infarction have not yet been fully illustrated. Herein, Radix Aconiti Lateral Preparata was used to prepare Radix Aconiti Lateralis Preparata extract (RAE), fuzi polysaccharides (FPS), and fuzi total alkaloid (FTA). Then, we aimed to compare the effects of RAE, FPS, and FTA in MI rats and further explore their influence on small molecules in the heart. We reported that Radix Aconiti Lateralis Preparata extract (RAE) and fuzi total alkaloid (FTA) significantly improved left ventricular function and structure, and reduced myocardial damage and infarct size in rats with myocardial infarction by the left anterior descending artery ligation. In contrast, fuzi polysaccharides (FPS) was less effective than RAE and FTA, indicating that alkaloids might play a major role in the treatment of myocardial infarction. Moreover, via matrix-assisted laser desorption/ionization–mass spectrometry imaging (MALDI–MSI), we further showed that RAE and FTA containing alkaloids as the main common components regulated myocardial energy metabolism-related molecules and phospholipids levels and distribution patterns against myocardial infarction. In particular, it was FTA, not RAE, that could also regulate potassium ions and glutamine to play a cardioprotective role in myocardial infarction, which revealed that an appropriate dose of alkaloids generated more obvious cardiotonic effects. These findings together suggested that Radix Aconiti Lateralis Preparata extracts containing an appropriate dose of alkaloids as its main pharmacological active components exerted protective effects against myocardial infarction by improving myocardial energy metabolism abnormalities and changing phospholipids levels and distribution patterns to stabilize the cardiomyocyte membrane structure. Thus, RAE and FTA extracted from Radix Aconiti Lateralis Preparata are potential candidates for the treatment of myocardial infarction.