[The progress, challenges and opportunities of neonatal genome screening].

Neonatal screening is one of the crucial parts of the tertiary prevention strategy to reduce congenital disability. Traditional neonatal screening, mainly focusing on genetic metabolic diseases, has limitations in disease types and requires genetic testing for further validation and accurate typing. Currently, conducting genetic screening based on biochemical metabolite screening has become the trend in neonatal screening. This article synthesizes the current state of neonatal genome screening at home and abroad. Herein, the comprehensive concepts of "SNV Plus" (single nucleotide variation plus) and "CNV Plus" (copy number variation plus) have been proposed to develop a new technology that can detect the gene structure of SNV and CNV simultaneously and improve the level of neonatal genome screening based on characteristics of the pathogenic gene structure.

LncRNA DBH-AS1 facilitates the tumorigenesis of melanoma by targeting miR-233-3p via IGF-1R/Akt signaling.

OBJECTIVE: While Long Noncoding RNAs (LncRNAs) are well-known to modulate human cancer progression, the specific function of DBH-AS1 in melanoma remains to be fully established. The study will investigate the role of DBH-AS1 in melanoma cell. PATIENTS AND METHODS: The expression profiles of DBH-AS1, miR-223-3p, and IGF-1R in melanoma tissues and cell lines were determined by RT-qPCR analysis. CCK-8 assay, colony assays and transwell assay were employed to analyze the effects of DBH-AS1 on the proliferation, migration, and invasion in GC cells. Bioinformatics analysis and Dual-Luciferase reporter assay determined the direct binding relation between DBH-AS1, miR-223-3p and IGF-1R in GC. RESULTS: Herein, we observed significant reductions in DBH-AS1 expression in melanoma tumor tissues and cell lines. Knockdown DBH-AS1 in melanoma cells impaired their proliferative, migratory, and invasive potential. We determined that DBH-AS1 was able to modulate insulin growth factor receptor (IGF-1R) expression as a competing endogenous RNA for DBH-AS1. In line with this finding, the knockdown DBH-AS1 was associated with decreases in the expression of glucose transporter (GLUT)-1 and a consequent inhibition of glucose uptake, lactate production, and ATP generation by melanoma cells. CONCLUSIONS: These findings therefore suggest that DBH-AS1 can enhance glycolytic activity in melanoma cells, thereby disrupting melanoma progression via miR-223-3p/EGFR/AKT axis. As such this signaling axis may be a viable therapeutic target for melanoma treatment in human patients.

The effect of selenium supplementation on coronary heart disease: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Selenium is a crucial mineral with antioxidant and immune functions, and selenium deficiency may increase the risk of coronary heart disease (CHD). However, the effect of selenium supplementation on CHD is still controversial according to numerous randomized controlled trials (RCTs). The aim of our meta-analysis study was to investigate the impact of selenium on CHD. METHODS: PUBMED, EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials databases were systematically searched to identify RCTs evaluating the effect of selenium supplementation on CHD mortality, blood lipid profile (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol), serum C-reactive protein (CRP), and the level of glutathione peroxidase (GSH-PX) from inception until September 20, 2016. Odds ratio of CHD mortality and the associated 95% confidence intervals (CIs) were calculated using the fixed effect model. Weighted mean difference or standardized mean difference (SMD) and 95% confidence intervals (CIs) were calculated to determine the lipid profile, serum CRP, and GSH-PX using fixed effect or random effect models depending on the observed heterogeneity. RESULTS: A total of 16 eligible RCTs with 43998 participants were included. Significant effects were observed for serum CRP (SMD=-0.48; 95% CI, -0.96 to 0; p=0.049) and GSH-PX (SMD=0.5; 95% CI, 0.36-0.64; p<0.001) after selenium supplementation. However, selenium supplementation was not statistically associated with CHD mortality and an aberrant lipid profile. CONCLUSION: Selenium supplementation decreased serum CRP and increased the GSH-PX level, suggesting a positive effect on reducing oxidative stress and inflammation in CHD. However, selenium supplementation is not sufficient to reduce mortality and to improve the lipid status.

Comparative study of 13 candidate genes applying multi-reference normalization to detect the expression of different fineness in skin tissues of wool sheep.

Fiber diameter is a useful indicator of wool traits and it is the main determinant of wool quality and value. A comparative study was conducted to analyze the abundance and expression of 13 candidate genes using expression profile microarray analysis and to identify novel molecular markers associated with wool traits to provide a molecular basis for improving wool quality in sheep. Genes associated with fineness of skin tissue were identified using a real-time reverse transcriptase-polymerase chain reaction method with 18SrRNA, ß-Actin, and GAPDH used for multi-reference normalization. The results indicated that the expression levels of TXNIP, TFDP1, and FAIM genes in super-fine type wool sheep were higher than those in fine-type wool sheep; the corresponding expression ratios of super-fine to fine wool sheep were 1.45, 1.57, and 2.55, respectively. The expression levels of PIK3CA, ADAM9, and FZD3 genes were lower in super-fine wool sheep compared with fine-type wool sheep; the corresponding expression ratios were 0.61, 0.65, and 0.52, respectively. The other genes tested (RPS6KA, ABCG2, GSTA1, PTPN13, GJB3, PPARD, and LAMB1) were similarly expressed in both types of wool sheep. These results infer that lower expression of PIK3CA, ADAM9, and FZD3 genes was associated with lower fiber diameter, whereas lower expression of TXNIP, TFDP1, and FAIM genes was associated with higher fiber diameter.

Evidence for heat shock protein immunity in a rat cardiac allograft model of chronic rejection.

BACKGROUND: The stress response to injury concept has been proposed as a mechanism of chronic rejection. This hypothesis has been tested with a rat cardiac allograft model in recipients pretreated with donor bone marrow (BM) cells. Chronic rejection is manifested in this BM group by obliterative arteriopathy and the epicardium and endocardium contains lymphocytic infiltrates resembling Quilty lesions. Pretreatment with a liver allograft (the orthotopic liver transplant [OLTx] group) is associated with an absence of chronic rejection in the transplanted heart. METHODS AND RESULTS: . Stress responses in the allograft were assessed by determining heat shock protein (hsp) expression by immunohistology of graft tissues and immunoblot analysis of stromal tissue lysates with monoclonal antibodies (mAb) to mammalian hsp60, the inducible hsp72, the constitutively expressed hsc73, and the grp78 C-terminal sequence KSEKDEL (grp78seq). Immunostaining showed clusters of grp78seq-positive cells in the inflammatory infiltrates of obliterated blood vessels and Quilty lesions in the BM group of cardiac allografts. Such grp78seq-positive cells were not seen in the OLTx group of heart allografts nor in syngrafts. Neither group showed significantly different graft myocyte staining of grp78 or hsp72, whereas hsp60 and hsc73 showed higher expression in the BM group and, to a lesser extent, the OLTx group. The increased expression of hsc73 was seen especially in the obliterated arteries and in myocytes nearby cellular infiltrates. Immunoblot analysis of graft stromal tissue lysates showed additional bands with mAb to hsp60 and hsc73 for the OLTx and especially the BM group. No significant bands were seen for hsp72 and grp78. Lymphocytes isolated from chronically rejecting allografts reacted with irradiated autologous spleen cells in the presence of mycobacterial hsp65 and interleukin-2. Culturing of graft-infiltrating cells with mycobacterial hsp71 and interleukin-2 yielded lymphocyte clones without alloreactivity, but with strong proliferative responsiveness to self-antigen-presenting cells and, only in the presence of mycobacterial hsp71 or murine grp78. This T-cell reactivity seemed to require intact hsp molecules because treatment of hsp71 with proteolytic enzymes, polymyxin, or ATP abrogated this induction of the stimulatory effect of self-antigen-presenting cells. These T cells are similar to the hsp-dependent, autoreactive lymphocytes cloned from acutely rejecting rat allografts. CONCLUSIONS: These findings support the concept that the pathogenesis of chronic rejection involves a stress response and the participation of graft-infiltrating autoreactive T cells that operate under hsp-dependent mechanisms.

Identification of two types of autoreactive T lymphocyte clones cultured from cardiac allograft-infiltrating cells incubated with recombinant mycobacterial heat shock protein 71.

Recent studies in several laboratories have advanced the concept that during cellular rejection, the allograft undergoes a stress response which regulates the expression of stress proteins (or heat shock proteins, hsp) and triggers the recruitment and activation of hsp-reactive lymphocytes. In a rat model of heterotopic heart transplants we have found that allograft-infiltrating lymphocytes respond to recombinant mycobacterial hsp and irradiated syngeneic spleen cells as a source of self-APC (antigen-presenting cells). This report describes T cell clones generated by culturing ACI into Lewis rat cardiac allograft-derived lymphocytes with mycobacterial hsp71, syngeneic spleen cells and IL-2 (interleukin-2). Two groups of self-APC-reactive T cell clones have been distinguished, all of them are CD3+, CD4+, CD8-. One group is referred to as hsp71-dependent, autoreactive T cells because these clones respond to self-APC but only in the presence of hsp71. No reactivity is seen with mycobacterial hsp65 or when hsp71 is tested with allo-PC from ACI donors or third-party APC from Brown Norway (BN) rats. Treatment of hsp71 with trypsin, polymyxin B or ATP-agarose chromatography abrogates the hsp71 effect thus indicating that structurally intact hsp71 must interact with self-APC which then activate hsp71-dependent, autoreactive T cells. The second group of clones reacts to self-APC and while their response does not require the presence of hsp71, their proliferation is often augmented by hsp71 but not by hsp65. These hsp71-independent, autoreactive clones do not respond to allo-APC from ACI donors or third-party APC from BN rats. Polymyxin or trypsin treatment had no significant effect on their proliferative responses. The data with the anti-TCR-alpha beta monoclonal antibody R73 offer additional evidence for two functionally different types of self-APC reactive CD4 cells infiltrating the allograft. R73 inhibits the proliferation of self-APC induced responses of hsp-71-independent clones as well as the allo-APC induced responses of alloreactive T cell clones. In contrast, this antibody augments the responses of hsp71-dependent T cells. Moreover, these clones can also proliferate in response to self-APC when hsp71 is substituted by R73. The hsp71-dependency of self-APC reactive T cell reactivity represents a previously unrecognized mechanism of cellular immunity to allografts. This mechanism might be related to the peptide binding properties of hsp71 and the ability of stress proteins to function as molecular chaperones in antigen processing.