Intercross population study reveals that co-mutation of mitfa genes in two subgenomes induces red skin color in common carp ( Cyprinus carpio wuyuanensis).

Common carp are among the oldest domesticated fish in the world. As such, there are many food and ornamental carp strains with abundant phenotypic variations due to natural and artificial selection. Hebao red carp (HB, Cyprinus carpio wuyuanensis), an indigenous strain in China, is renowned for its unique body morphology and reddish skin. To reveal the genetic basis underlying the distinct skin color of HB, we constructed an improved high-fidelity (HiFi) HB genome with good contiguity, completeness, and correctness. Genome structure comparison was conducted between HB and a representative wild strain, Yellow River carp (YR, C. carpio haematopterus), to identify structural variants and genes under positive selection. Signatures of artificial selection during domestication were identified in HB and YR populations, while phenotype mapping was performed in a segregating population generated by HB×YR crosses. Body color in HB was associated with regions with fixed mutations. The simultaneous mutation and superposition of a pair of homologous genes ( mitfa) in chromosomes A06 and B06 conferred the reddish color in domesticated HB. Transcriptome analysis of common carp with different alleles of the mitfa mutation confirmed that gene duplication can buffer the deleterious effects of mutation in allotetraploids. This study provides new insights into genotype-phenotype associations in allotetraploid species and lays a foundation for future breeding of common carp.

Vasculoprotective Effects of Water Extracts of Black, Green and Dark Tea in Vitro.

To investigate the preventive effects of tea on hyperglycemia and vascular complications of diabetes, we report the extraction and composition as well as the vasculoprotective effects of black tea extract (BTE), green tea extract (GTE), and dark tea extract (DTE). High Performance Liquid Chromatography (HPLC) and colorimetric methods were conducted to analyze for tea catechins, caffeine, polyphenols, amino acids and polysaccharides of BTE, GTE and DTE. The inhibitory effects of α-glucosidase, aldose reductase (AR), advanced glycation end-products (AGEs) and glucose uptake promotion effect in BTE, GTE and DTE were explored in vitro. Contents of six major catechin forms and total catechin as well as polyphenols are higher in GTE and DTE than BTE. BTE, GTE, and DTE showed the inhibitory effects of a-glucosidase, AR, and AGEs, but only DTE exhibited the glucose uptake promotion effect in HepG2 cells. The results suggest that regular consumption of tea can help prevent the progression of hyperglycemia and the vascular complications of diabetes.

[Growth and decline of Oncomelania hupensis status in Duchang County at North shore of Poyang Lake, 2005-2012].

OBJECTIVE: To understand the dynamic of Oncomelania hupensis snail status in Duchang County at north shore of Poyang Lake, so as to provide the evidence for formulating the strategy of schistosomiasis control. METHODS: The data about the snail status in Duchang County from 2005 to 2012 were collected, and the change trend of the snail status was analyzed. Results From 2005 to 2012, all the average density of living snails, the occurrence rate of frames with living snails, the density of infected snails and the area with infected snails showed a trend of sharp decline, and stayed at a low level. Compared to 2005, the above 4 indexes in 2008 decreased by 70.06%, 90.33%, 79.48%, and 37.88%, respectively, and those in 2012 decreased by 99.35%, 98.98%, 99.33%, and 93.84%, respectively. The infection rates of snails fluctuated between 0.06% and 0.53%, which showed a trend of first decrease and then increase. The snail area maintained at the level of 2052.5 hm2 since 2007. CONCLUSIONS: Most of the indexes of the snail status in Duchang County have decreased to the lowest level in history since 2012, but the snail area is stable and the infection rate of snails shows a fluctuation trend, which suggests that the risks of schistosomiasis transmission still exist, and the snail control still should be strengthened.

Synthesis, nitric oxide release, and α-glucosidase inhibition of nitric oxide donating apigenin and chrysin derivatives.

α-Glucosidase (AG) play crucial roles in the digestion of carbohydrates. Inhibitors of α-glucosidase (AGIs) are promising candidates for the development of anti-diabetic drugs. Here, five series of apigenin and chrysin nitric oxide (NO)-donating derivatives were synthesised and evaluated for their AG inhibitory activity and NO releasing capacity in vitro. Except for 9a-c, twelve compounds showed remarkable inhibitory activity against α-glucosidase, with potency being better than that of acarbose and 1-deoxynojirimycin. All organic nitrate derivatives released low concentrations of NO in the presence of l-cysteine. Structure activity relationship studies indicated that 5-OH, hydrophobic coupling chain, and carbonyl groups of the coupling chain could enhance the inhibitory activity. Apigenin and chrysin derivatives therefore represents a new class of promising compounds that can inhibit α-glucosidase activity and supply moderate NO for preventing the development of diabetic complications.

Synthesis of organic nitrates of luteolin as a novel class of potent aldose reductase inhibitors.

Aldose reductase (AR) plays an important role in the design of drugs that prevent and treat diabetic complications. Aldose reductase inhibitors (ARIs) have received significant attentions as potent therapeutic drugs. Based on combination principles, three series of luteolin derivatives were synthesised and evaluated for their AR inhibitory activity and nitric oxide (NO)-releasing capacity in vitro. Eighteen compounds were found to be potent ARIs with IC50 values ranging from (0.099±0.008) µM to (2.833±0.102) µM. O(7)-Nitrooxyethyl-O(3'),O(4')-ethylidene luteolin (La1) showed the most potent AR inhibitory activity [IC50=(0.099±0.008) µM]. All organic nitrate derivatives released low concentrations of NO in the presence of l-cysteine. Structure-activity relationship studies suggested that introduction of an NO donor, protection of the catechol structure, and the ether chain of a 2-carbon spacer as a coupling chain on the luteolin scaffold all help increase the AR inhibitory activity of the resulting compound. This class of NO-donor luteolin derivatives as efficient ARIs offer a new concept for the development and design of new drug for preventive and therapeutic drugs for diabetic complications.

Hypoglycemic effect of the water extract of Pu-erh tea.

The water extraction and composition of pu-erh tea, as well as the hypoglycemic effect of the water extract of pu-erh tea (WEPT) in vivo and in vitro, are reported to investigate its hypoglycemic effect on diabetes. High-performance liquid chromatography and colorimetric methods are used to analyze the tea catechins, caffeine, polyphenols, amino acids, and polysaccharides of the WEPT. The effect of the WEPT on glucose uptake by cultured HepG2 cells and the inhibition effect of rat intestinal sucrase, maltase, and porcine pancreatic amylase are determined in vitro. Then, the blood glucose and insulin levels of intragastrically administered WEPT on fasting and oral glucose tolerance test (OGTT) using type 2 diabetic db/db (BKS.Cg-m +/+ Lepr(db)/J) mice are determined in vivo. The results showed that the WEPT dose-dependently and significantly increased glucose uptake by HepG2 cells and inhibited rat intestinal sucrase, maltase, and porcine pancreatic amylase activity. The WEPT intragastrically given for 4 weeks suppressed the increase in blood insulin and glucose levels of db/db mice fasted overnight. In OGTT, the WEPT improved impaired glucose tolerance and ameliorated retarded insulin response at 60 and 120 min in db/db mice. These results suggest that the WEPT has beneficial effects on glucose homeostasis in type 2 diabetes and in amendment of insulin resistance.

Furoxan nitric oxide donor coupled chrysin derivatives: synthesis and vasculoprotection.

A series of furoxan-based nitric oxide-releasing chrysin derivatives were synthesized. Pharmacological assays indicated that all chrysin derivatives exhibited in vitro inhibitory activities against aldose reductase and advanced glycation end-product formation. Some chrysin derivatives were also found to increase the glucose consumption of HepG2 cells. Furthermore, the compounds released a low amount of NO in the presence of L-cysteine (range from 0.20% to 1.89%). These hybrid furoxan-based NO donor chrysin derivatives offer a mutual prodrug design concept for the development of therapeutic or preventive agents for vascular complications due to diabetes.

Synthesis, characterization and vasculoprotective effects of nitric oxide-donating derivatives of chrysin.

Vascular complications are major causes of disability and death in patients with diabetes mellitus. It is often characterized by endothelial dysfunction. Studies have shown that either the loss of nitric oxide bioactivity or the decreased biosynthesis of NO is a central mechanism in endothelial dysfunction. As such, the delivery of exogenous NO is an attractive therapeutic option that has been used to slow the progress of diabetic vascular complications. In this paper, a novel group of hybrid nitric oxide-releasing chrysin derivatives was synthesized. The results indicated that all these chrysin derivatives exhibited in vitro inhibitory activities against aldose reductase and advanced glycation end-products formation. And some of them were even found to increase the glucose consumption of HepG2 cells. Furthermore, all compounds released NO upon incubation with phosphate buffer at pH 7.4. These hybrid ester NO donor prodrugs offer a potential drug design concept for the development of therapeutic or preventive agents for vascular complications due to diabetes.

Asymmetric dimethylarginine impairs glucose utilization via ROS/TLR4 pathway in adipocytes: an effect prevented by vitamin E.

BACKGROUND: Asymmetric dimethylarginine (ADMA), the inhibitor of nitric oxide synthase (NOS), has been reported to be associated with glucose metabolism, but its mechanisms remain unknown. METHODS: In 3T3-L1 adipocytes, we measured the effects of ADMA on glucose transport process under basal or insulin-induced condition, and examined the production of nitric oxide (NO), reactive oxygen species (ROS) and tumor necrosis factor alpha (TNF-alpha), and the expression of toll-like receptor 4 (TLR4). RESULTS: ADMA significantly impaired basal or insulin-stimulated 2-deoxy- [3H] glucose uptake, and decreased the expression of insulin receptor substrate-1 (IRS-1) and glucose transporter-4 (GLUT4). Phosphorylated protein of IRS-1 and translocation of GLUT4 with insulin-stimulation were also inhibited by ADMA. NO decreased, while production of ROS and TNF-alpha, and expression of TLR4 increased after ADMA treatment. Vitamin E reduced the effects of ADMA on glucose transport system, and on NO, ROS and TLR4. Moreover, vitamin E decreased ADMA contents by up-regulating dimethylarginine dimethylaminohydrolase (DDAH) activity in adipocytes. Though L-arginine also increased NO level, but failed to reduce the effects of ADMA. CONCLUSION: ADMA significantly impairs both basal and insulin-stimulated glucose transport in adipocytes, which may relate to activation of the ROS/TLR4 pathway.

Synthesis and promotion angiogenesis effect of chrysin derivatives coupled to NO donors.

Two types of new chrysin derivatives were prepared by coupling NO donors of alkyl nitrate and furazan derivatives and were fully characterized by (1)H NMR and other techniques. These compounds were tested in human umbilical vein endothelial cells (HUVECs-12) and all the compounds exhibited cell proliferation. Notable effects of promoting angiogenesis were observed for all the modified compounds using chick chorioallantoic membrane (CAM) assay.