The history of the Newborn Screening Program in Mainland China begins in 1981, when a pilot plan was developed that demonstrated the feasibility of its implementation. It has so far focused on the detection of congenital hypothyroidism (CH) and phenylketonuria (PKU) to prevent or reduce mental and physical developmental retardation in children. Throughout this period, a total of 35,795,550 dried blood samples (DBS) of newborns (NB) have been analyzed for PKU, and 35,715,988 for CH. During this period, 3,082 cases with PKU have been diagnosed, resulting in an incidence of 1 case per 11,614 (95% confidence interval 11,218-12,039) live births. In relation to CH, 17,556 cases have been confirmed, arriving at an incidence of 1 case per 2,034(95% confidence interval 2,005-2,065) live births. The biggest challenge for universal newborn screening is still to increase coverage to midwestern area. In Mainland China, MS/MS newborn screening started in 2004. In a pilot study, 371,942 neonates were screened, and 98 cases were detected with one of the metabolic disorders, and the collective estimated prevalence amounted to 1 in 3795 (95% confidence interval 3,168-4,732) live births, with a sensitivity of 98.99%, a specificity of 99.83%, and a positive predictive value of 13.57%.

Stem cell senescence is an important and current hypothesis accounting for organismal aging, especially the hematopoietic stem cell (HSC). Ginsenoside Rg1 is the main active pharmaceutical ingredient of ginseng, which is a traditional Chinese medicine. This study explored the protective effect of ginsenoside Rg1 on Sca-1+ hematopoietic stem/progenitor cells (HSC/HPCs) in a mouse model of d-galactose-induced aging. The mimetic aging mouse model was induced by continuous injection of d-gal for 42 days, and the C57BL/6 mice were respectively treated with ginsenoside Rg1, Vitamin E or normal saline after 7 days of d-gal injection. Compared with those in the d-gal administration alone group, ginsenoside Rg1 protected Sca-1+ HSC/HPCs by decreasing SA-β-Gal and enhancing the colony forming unit-mixture (CFU-Mix), and adjusting oxidative stress indices like reactive oxygen species (ROS), total anti-oxidant (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-px) and malondialdehyde (MDA). In addition, ginsenoside Rg1 decreased β-catenin and c-Myc mRNA expression and enhanced the phosphorylation of GSK-3β. Moreover, ginsenoside Rg1 down-regulated advanced glycation end products (AGEs), 4-hydroxynonenal (4-HNE), phospho-histone H2A.X (r-H2A.X), 8-OHdG, p16Ink4a, Rb, p21Cip1/Waf1 and p53 in senescent Sca-1+ HSC/HPCs. Our findings indicated that ginsenoside Rg1 can improve the resistance of Sca-1+ HSC/HPCs in a mouse model of d-galactose-induced aging through the suppression of oxidative stress and excessive activation of the Wnt/β-catenin signaling pathway, and reduction of DNA damage response, p16Ink4a-Rb and p53-p21Cip1/Waf1 signaling.

BackgroundGinsenoside Rg1 (Rg1) is one of the most active ingredients in Panax ginseng and has been proven to have anti-oxidative and anti-aging properties. However, there have been few reports concerning the anti-aging effects of Rg1 on the hematopoietic microenvironment and bone marrow stromal cells (BMSCs).MethodsThirty Sprague-Dawley rats were randomly divided into four groups (control, D-galactose (D-gal)-administration, Rg1-treatment, and D-gal-administration + Rg1-treatment groups). After D-gal and Rg1 treatment, BMSCs were extracted from femoral bone marrow for culture. After three passages, BMSCs were tested by senescence-associated β-galactosidase (SA-β-gal) staining, flow cytometric cell cycle phase distribution assay, CCK-8 cell proliferation assay, oxidative stress (reactive oxygen species [ROS], superoxide dismutase [SOD], and malondialdehyde [MDA]) assays, inflammatory marker (interleukin (IL)-2, IL-6, and tumor necrosis factor (TNF)-α) enzyme-linked immunosorbent assay (ELISA), stem cell factor (SCF) ELISA, and senescence-associated protein (p16, p21, and p53) Western blotting.ResultsCompared to the D-gal-administration group, the D-gal-administration + Rg1-treatment group showed significantly decreased levels of SA-β-gal + cell %, ROS, MDA, inflammatory marker expression, and senescence-associated protein expression as well as significantly increased levels of S-phase %, cell proliferation, SOD activity, and SCF expression. Compared to controls, the Rg-1-treatment group displayed significantly reduced levels of SA-β-gal + cell %, G1 phase %, ROS, MDA, inflammatory marker expression, senescence-associated protein expression, and SCF expression as well as significantly increased levels of S-phase %, cell proliferation, and SOD activity.ConclusionsRg1 improves the anti-aging ability of hematopoietic microenvironment through enhancing the anti-oxidant and anti-inflammatory capacities of BMSCs.

Age-related regression in hematopoietic stem/progenitor cells (HSC/HPCs) limits replenishment of the blood and immune system and hence contributes to hematopoietic diseases and declined immunity. In this study, we employed D-gal-induced aging mouse model and observed the antiaging effects of Angelica Sinensis Polysaccharide (ASP), a major active ingredient in dong quai (Chinese Angelica Sinensis), on the Sca-1+ HSC/HPCs in vivo. ASP treatment prevents HSC/HPCs senescence with decreased AGEs levels in the serum, reduced SA-β-Gal positive cells, and promoted CFU-Mix formation in the D-gal administrated mouse. We further found that multiple mechanisms were involved: (1) ASP treatment prevented oxidative damage as total antioxidant capacity was increased and levels of reactive oxygen species (ROS), 8-OHdG, and 4-HNE were declined, (2) ASP reduced the expression of γ-H2A.X which is a DNA double strand breaks (DSBs) marker and decreased the subsequent ectopic expressions of effectors in p16Ink4a-RB and p19Arf-p21Cip1/Waf senescent pathways, and (3) ASP inhibited the excessive activation of Wnt/β-catenin signaling in aged HSC/HPCs, as the expressions of β-catenin, phospho-GSK-3β, and TCF-4 were decreased, and the cyto-nuclear translocation of β-catenin was inhibited. Moreover, compared with the positive control of Vitamin E, ASP exhibited a better antiaging effect and a weaker antioxidation ability, suggesting a novel protective role of ASP in the hematopoietic system.

The present study investigated the effect and underlying mechanisms of ginsenoside Rg1 (Rg1) in attenuating subacute liver injury induced by D-galactose (D-gal) in mice. Specific Pathogen Free (SPF) male C57BL/6J mice were randomly divided into 3 groups: i) D-gal-administration group (D-gal group), where the mice were intraperitoneally administrated with D-gal (120 mg/kg/day for 42 days); ii) D-gal + Rg1 group where the mice were treated with 120 mg/kg/day D-gal for 42 days and with Rg1 at a dose of 20 mg/kg/day for 35 days. The first dose of Rg1 was administered on the 8th day of treatment with D-gal; and iii) the normal control group, where the mice were injected with an equal volume of saline for 42 days. The day following the final injections in all groups, peripheral blood was collected and serum was prepared to measure the contents of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBiL), advanced glycation end products (AGEs) and 8-hydroxy-2 deoxyguanosine (8-OH-dG). Liver tissue homogenates were prepared to measure the contents of malondialdehyde (MDA) and glutathione (GSH), and the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). Paraffin section were prepared to observe the microscopic structure of the liver. Transmission electron microscopy was used to observe the ultrastructure of hepatocytes. Frozen section were prepared and stained with senescence-associated β-galactosidase to detect the relative optical density value of senescence-associated markers. Compared with the D-gal group, the contents of AST, ALT, TBiL, AGEs and MDA significantly decreased in the D-gal + Rg1 group, while the activities of SOD and GSH-Px markedly increased, and liver injury and degenerative alterations of hepatocytes were reduced. Administration of Rg1 induced a protective effect on D-gal-induced liver injury in mice by inhibiting the oxidative stress, reducing DNA damage and decreasing the AGE content.