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To investigate the mechanisms underlying the protective effects of sodium tanshinone IIA sulfonate (STS) in an ischemia-reperfusion (I/R)-induced rat myocardial injury model.Male SD rats were iv injected with STS, STS+LY294002 or saline (NS) for 15 d. Then the hearts were subjected to 30 min of global ischemia followed by 2 h of reperfusion. Cardiac function, infarction size and area at risk were assessed. Cell apoptosis was evaluated with TUNEL staining, DNA laddering and measuring caspase-3 activity. In addition, isolated cardiomyocytes of neonatal rats were pretreated with the above drugs, then exposed to H2O2 (200 mol/L) for 1 h. Cell apoptosis was detected using flow cytometric assay. The levels of p-Akt, p-FOXO3A and Bim were examined with immunoblotting.Compared to NS group, administration of STS (20 mg/kg) significantly reduced myocardial infarct size (40.28%±5.36% in STS group vs 59.52%±7.28% in NS group), and improved the myocardial function as demonstrated by the increased values of dp/dtmax, LVDP and coronary flow at different reperfusion time stages. Furthermore, STS significantly decreased the rate of apoptotic cells (15.11%±3.71% in STS group vs 38.21%±7.83% in NS group), and reduced caspase-3 activity to nearly a quarter of that in NS group. Moreover, STS significantly increased the phosphorylation of Akt and its downstream target FOXO3A, and decreased the expression of pro-apoptotic gene Bim. Co-treatment with the PI3K inhibitor LY294002 (40 mg/kg) partially countered the protective effects induced by STS treatment. In isolated cardiomyocytes, STS exerted similar protective effects as shown in the ex vivo I/R model.STS pretreatment reduces infarct size and improves cardiac function in an I/R-induced rat myocardial injury model via activation of Akt/FOXO3A/Bim-mediated signal pathway.

We have determined the various haplotypic combinations between alleles as well as restriction fragment length polymorphisms of two linked genetic markers, albumin and vitamin D-binding protein or group-specific component, in a number of Asian-Pacific populations. Using the partial maximum likelihood method, we constructed a phylogenetic network from the haplotype frequencies to assess relationships among the populations sampled. No systematic linkage disequilibrium was detected between most of the combinations, suggesting a lack of operation of any selection pressure at the two loci. The phylogenetic analysis confirmed the known interrelationships among various populations in the Asian-Pacific region. The Australian aborigines clustered closely with the non-Austronesian-speaking highlanders from Papua New Guinea, as expected. Similarly, the Austronesian-speaking Polynesians, Micronesians, and the Southeast Asians branched off together as a separate group. The position of the Austronesian-speaking Tolais from New Britain with respect to other populations from the Southwest Pacific was anomalous. The Tolais revealed a strong affinity with the Australian aborigines, which is inexplicable. The populations from China formed a tight cluster with other populations from the Asian-Pacific region. Genetic interrelationships of these populations with the white Australians were remote, which is in accordance with the known affinities of various human racial groups.

Four plasmid sub-clones, phDBP 140, phDBP 310, phDBP 505 and phDBP 776 that make up the full-length human DBP cDNA, were pooled and used simultaneously as probes. Beside the previously reported Bam HI, Bcl I (T/GATCA) detects a two allele polymorphism with bands at 14.3 kb (a) and 12.6 kb (b). Invariant bands of 17, 11.5, 9.2, 3 kb were also detected. The variant bands are detected by the 5{prime} sub-clone phDBP 140. The hDBP gene has been localized to bands 4q11-4q13. Co-dominant segregation was demonstrated in 4 families, 3 generations and 26 individuals.

During population genetic studies in Korea a new variant in the 6-phosphogluconate (6-PGD) system preliminary called 6-PGDKorea was observed.

Fig. 1. Physical map of the human renin gene, exons 1-9 are shown above. The 2 fragments subcloned from )~V (Hardman et al. 1984) are: a phREN 3k and b phREN 886 (the numbers refer to the approximate number of bases in each subcloned EcoRI insert into plasmid pUC18) Restriction enzyme used. BgIII detected a single two-allele polymorphism with approximately 27kb (allele 1) and 21kb (allele 2) variant bands (Fig. 2). No invariant bands were observed. Both probes revealed the same restriction fragment pattern.

The beta-globin haplotypes of 852 chromosomes from 12 populations in the Asia-Pacific region are described. These data are combined with those from other populations in an investigation of the affinities of regional human populations. Both partial maximum-likelihood and distance Wagner methods indicate that Africans are the most divergent group, with the remaining populations branching in the following order: Australian Aborigines, Highland Melanesians, Lowland Melanesians, Indonesians and Micronesians, Polynesians, east Asians, Indians, and Europeans. This pattern of relationship is consistent with that indicated by other data. Analysis of the evolution and distribution of haplotype occurrence provides some limited support for an origin of modern humans in Africa. Otherwise, however, it was not useful in further elucidating the evolutionary history of human populations.