DNA-encoded chemical library (DEL) links the power of amplifiable genetics and the non-self-replicating chemical phenotypes, generating a diverse chemical world. In analogy with the biological world, the DEL world can evolve by using a chemical central dogma, wherein DNA replicates using the PCR reactions to amplify the genetic codes, DNA sequencing transcripts the genetic information, and DNA-compatible synthesis translates into chemical phenotypes. Importantly, DNA-compatible synthesis is the key to expanding the DEL chemical space. Besides, the evolution-driven selection system pushes the chemicals to evolve under the selective pressure, i.e., desired selection strategies. In this perspective, we summarized recent advances in expanding DEL synthetic toolbox and panning strategies, which will shed light on the drug discovery harnessing in vitro evolution of chemicals via DEL.

Since China enters the aging society, there are several apparent trends, such as large elderly population base, rapid growth, aging, dysfunctional andempty nest. These phenomenon leads to a huge economic and social burden for our country and individuals. To meet the health demand of elderly population, our society urgently needs more professional and more comprehensive geriatri-cians. However, the current education methods, to some extent, limit the possibility of the graduates becoming a good geriatric medicine physician in relatively short period. Therefore, it is necessary to reform the geriatrics education methods. Systematic learning method, mutual complementarily method and Problem-based Learning (PBL) method can be used to help geriatrics graduate students master the theoretical knowledge and practical skills before working and lay a solid founding for becoming a good geriatric medicine physician in relatively short period.

Recent studies have shown that brain natriuretic peptide ( BNP ) may be the link between cardiovascular disease and metabolic system. The role for BNP in metabolic pathways has already been the subject of intense interest. This article reviews the evidence of the linkage between BNP and metabolic system.

Objective To investigate the influence of sodium selenite on the expression of adiponectin and nephrin in the kidney of rats with diabetic nephropathy, the relation of sodium selenite with adiponectin and nephrin, and to study the roles played by these factors in diabetic nephropathy. Methods Rat models of diabetic nephropathy were established by injecting intraperitoneally streptozocin combined with high fat diet. Three groups of rats were employed: control group, diabetic nephropathy group, and selenite-treated group. The selenite-treated rats were given selenite solution by intragastric administration every day, and other groups were given same volume of saline. After 10 weeks, all rats were sacrificed, blood and urine samples were collected. The kidneys were used to observe pathological changes with light microscope, and to locate protein expression with immunohistochemistry analysis. The mRNA and protein expressions of adiponectin and nephrin were analyzed via real-time PCR, RT PCR, and Western blot. Results The basic condition, biochemical parameters, and pathological images in selenite-treated group were better than those in diabetic nephropathy group. Immunohistochemistry analysis showed that the expression of adiponectin was in both glomeruli and renal tubules in selenite-treated group, and the coloration was enhanced as compared with diabetic nephropathy group. The mRNA and protein expressions of adiponectin in selenite-treated group were significantly higher than those in diabetic nephropathy group and the control group (all P＜0. 05 ). Nephrin expression in selenite-treated group was also higher than that in diabetic nephropathy group, but lower than that in control group. Conclusion Sodium selenite can enhance the mRNA and protein expressions of adiponectin and nephrin in kindey of rats with diabetic nephropathy. Sodium selenite,adiponectin, and nephrin may play important roles in delaying and preventing the development of diabetic nephropathy.

Objective To investigate the relationship among p38 mitogen-activated protein kinase (p38MAPK), NF-KB and monocyte chemoattractant protein-1 (MCP-1), and to study the role of p38MAPK, NF-κB and MCP-1 in diabetic nephropathy. Methods Protein expressions of p38MAPK and NF-κB, and mRNA expression of MCP-1 were initially investigated in rat mesangial cell line HBZY-1, which were incubated separately with 25mmol/L glucose, 100nmol/L insulin, 100 μmol/L H2 O2 and 100mg/L advanced glycosylation end products (AGEs). The relationship among p38MAPK, NF-κB and MCP-1 expression Was observed by usingSB203580, a specific inhibitor of p38MAPK. Results The expressions of p38MAPK, NF-κB and MCP-1 were increased in HBZY-1 cells incubated separately with 25mmol/L glucose, 100nmol/L insulin, 100μmol/L H2 O2and 100 mg/L AGEs. Expressions of NF-κB and MCP-1 were significantly reduced when p38MAPK was inhibited by SB203580. Conclusion p38MAPK, NF-κB and MCP-1 are involved in development of diabetic nephropathy, and p38MAPK stimulation is essential for the expressions of NF-κB and MCP-1.

Objective To investigate the relationship between p38MAPK and PPAR-?,and to study the role of p38MAPK and PPAR-? for diabetic nephropathy. Methods The expression of p38MAPK protein and PPAR-? mRNA was investigated in rat mesangial cells line HBZY-1 that was incubated respectively with 25 mmol/L glucose,100 nmol/L insulin,100 ?mol/L H_2O_2 and 100 mg/L AGEs. The relationship between p38MAPK and PPAR-? expression was studied by using SB203580,a specific inhibitor of p38MAPK. Results p38MAPK had significantly higher expression,while the expression of PPAR-? was significantly decreased in rat mesangial cells line HBZY-1 incubated with 25 mmol/L glucose,100 nmol/L insulin,100 ?mol/L H_ 2 O_ 2 and 100 mg/L AGEs respectively. PPAR-? activity was significantly reduced when p38MAPK was inhibited by SB203580. Conclusion p38MAPK is involved in development of diabetic nephropathy and may antagonize the expression of PPAR-?. PPAR-? activity might protect the function of kidney.

Objective:To investigate the influence of sodium selenite on adiponectin expression in kidney of rats with diabetic nephropathy and the relation between sodium selenite and adiponectin,so as to investigate the role of sodium selenite and adiponectin in diabetic nephropathy.Methods: Diabetic nephropathy rat models were established by injecting streptozocin intraperitoneally and high fat diet.The study was divided into 3 groups,namely,a control group,a diabetic nephropathy group and a selenite-treated group.Animals in the selenite-treated group were given selenite solution 1 ?g/kg daily via intragastric administration; those in the other 2 groups were given the same dose of saline in the same way.The animals were sacrificed 10 weeks later and the blood and urine samples were used for biochemical examination.Samples of renal cortex were cut quickly and fixed with 4% glutaral for observation under scanning electron microscope.The renal samples were made into paraffin section for observation of the pathological changes under light microscope and for location of protein expression via immunohistochemistry analysis.The expression of adiponectin mRNA and protein was examined by real-time PCR and Western blotting,respectively.Results: The general condition and biochemical parameters of animals in the selenite-treated group were obviously improved and the pathological changes were obviously releived compared with those in the diabetic nephropathy group.Immunohistochemistry analysis showed that the expression of adiponection in the selenite-treated group was obviously stronger than that in the diabetic nephropathy group,and the expression was found in both glomcrulus and renal tubule.The expression of adiponectin mRNA in the selenite-treated group and diabetic nephropathy group was 2.043 and 1.373 folds that of the control group,respectively.The expression of adiponectin protein in the selenite-treated group was significantly higher than those in the control group and diabetic nephropathy group (P

Objective:To investigate the relationship between p38 mitogen-activated protein kinase(p38MAPK) and vascular endothelial growth factor (VEGF),and to study the role of p38 mitogen-activated protein kinase and vascular endothelial growth factor for diabetic nephropathy,and therefore to study the mechanism of sodium selenite in anti-diabetic nephropathy.Methods:We initially investigated protein expression of p38MAPK and VEGF in rat mesangial cells(RMCs)which were incubated respectively with 25 mmol/L glucose,100mg/L BSA-AGEs,100nmol/L insulin and 100 ?mol/L H 2O 2.We also studied the relationship between p38MAPK and VEGF protein expression by using SB203580,a specific inhibitor of p38MAPK.We then evaluated the direct effects of sodium selenite on the regulation of p38MAPK and VEGF protein expression.Results:p38MAPK and VEGF had significantly higher expression in RMCs incubated with 25mmol/L glucose,100mg/L BSA-AGEs,100nmol/L insulin and 100?mol/L H 2O 2 respectively.VEGF activity was significantly reduced when p38MAPK was inhibited by SB203580.Furthermore,both p38MAPK and VEGF protein expression were significantly decreased in RMCs with sodium selenite treatment.Conclusion:p38MAPK and VEGF are involved in development of diabetic nephropathy and p38MAPK stimulation is essential for VEGF expression,and also suggests that sodium selenite may play a role in the prevention of diabetic nephropathy by down-regulation of both p38MAPK and VEGF expression.

Objective:To observe the effect of sodium selenite on expression of Cyclooxygenase-2 (COX-2) mRNA in rat mesangial cells (RGMC), and to study the mechanism of sodium selenite in anti-diabetic nephropathy.Methods:RGMC was incubated with high glucose,advanced glycosylation end products (AGE),high insulin and H_2O_2 respectively;simultaneously,RGMC pre-treated with sodium selenite was incubated with above factors.The expression of COX-2 mRNA was detected and compared.Results:The four factors increased the expression of COX-2 mRNA independently;sodium selenite inhibited the expression of COX-2 mRNA by the four factors distinctly.Conclusion:Sodium selenite suppresses the expression of COX-2 mRNA in RGMC, which suggests that sodium selenite may play a significant role in the prevention of diabetic nephropathy by inhibition of the expression of COX-2 mRNA in RGMC.

The expression of cyclooxygenase-2 (COX-2) mRNA and protein was significantly increased in rat glomerular mesangial cells (RCMC) treated separately with high glucose, high insulin, H2 O2 and advanced glycosylation end products. The expressions of COX-2 mRNA and protein in RCMC induced by above 4 factors were distinctly inhibited by sodium selenite, suggesting that sodium selenite might play a significant role in the prevention of diabetic nephropathy via this mechanism.