Biomedical subjects

Hong-Yan Zhang

Publications and source records attributed to Hong-Yan Zhang.

10 recordsLinked to original sources

PubMed2006

RNA Interference with chemically modified siRNA.

siRNA has become an indispensable tool for functional characterization of genes. It has also demonstrated tremendous potential as a new generation of drug candidates. Although the technology works very well to a great panel of cells in vitro, it is still a challenge to translate the success into in vivo target validation easiness and, even more difficult, into therapeutic applications. With a number of chemically modified compounds under initial clinical trial from several commercial entities, the interests in chemical modification of siRNA have become heightened. In this review we have tried to touch on most of the chemical modifications of RNA that have been tested in the siRNA landscape, but maintained a focus on the backbone modifications, and 2'-modifications on the ribose ring. It is anticipated that more modifications and more systematic comparisons between different modifications will be performed to draw more educated conclusions over some of the modifications.

Hydroxylation↗

PubMed2006

[Clinical study on severe acute pancreatitis complicated by hepatic insufficiency].

OBJECTIVE: To investigate the pathogenic factors of severe acute pancreatitis (SAP) complicated by hepatic insufficiency, the prognosis and the effective preventive and therapeutic interventions. METHODS: One hundred and fifty-two patients with SAP (from January 2003 to June 2004) were divided into 2 groups, SAP with hepatic insufficiency group and SAP without hepatic insufficiency group. The related factors such as causes of disease, serum biochemical criteria, complications, mortality and course of disease were observed. RESULTS: The concentrations of serum amylase, creatinine and lactate dehydrogenase were all much higher in the SAP with hepatic insufficiency group than those in the SAP without hepatic insufficiency group (P<0.05). The incidences of complications such as acute renal failure, heart failure, gastrointestinal hemorrhage and infection were also higher in the SAP with hepatic insufficiency group than those in the SAP without hepatic insufficiency group (P<0.05). There was no significant difference in mortality between these two groups, but the course of disease in SAP with hepatic insufficiency group was longer than that in the other group (P<0.05). CONCLUSION: The causes of SAP complicated by hepatic insufficiency are related to the imbalance of internal environment and the characteristics of the liver function. To control the biliary tract diseases, intervene with traditional Chinese medicine, recover the intestinal function in time, reduce the damage of pancreatic enzyme, maintain the stability of internal environment and avoid using drugs that can induce liver injury are all important aspects of reducing the incidence of hepatic insufficiency.

Adult↗

PubMed2006

[Study on the maximum entropy principle and population genetic equilibrium].

A general mathematic model of population genetic equilibrium about one locus was constructed based on the maximum entropy principle by WANG Xiao-Long et al. They proved that the maximum solve of the model was just the frequency distribution that a population reached Hardy-Weinberg genetic equilibrium. It can suggest that a population reached Hardy-Weinberg genetic equilibrium when the genotype entropy of the population reached the maximal possible value, and that the frequency distribution of the maximum entropy was equivalent to the distribution of Hardy-Weinberg equilibrium law about one locus. They further assumed that the frequency distribution of the maximum entropy was equivalent to all genetic equilibrium distributions. This is incorrect, however. The frequency distribution of the maximum entropy was only equivalent to the distribution of Hardy-Weinberg equilibrium with respect to one locus or several limited loci. The case with regard to limited loci was proved in this paper. Finally we also discussed an example where the maximum entropy principle was not the equivalent of other genetic equilibria.

Entropy↗

PubMed2005

A universal plasmid library encoding all permutations of small interfering RNA.

Small interfering RNA (siRNA) is normally designed to silence preselected known genes. Such selections are inevitably prone to bias as a result of limited knowledge about the biological process, transcript identity, and functions. A library that contains all permutations of siRNA could avoid such problems. In this paper, it is shown that 5 x 10(7) siRNA-encoding plasmids can be constructed in a single tube by using vectors with two mutated RNA polymerase III promoters arranged in a convergent manner. Such a library was used to carry out genomewide screening of functional genes in a phenotype-driven manner. Multiple siRNAs that induce a significant increase of cell proliferation speed were identified.

Base Sequence↗

PubMed2004

Locked nucleic acid containing antisense oligonucleotides enhance inhibition of HIV-1 genome dimerization and inhibit virus replication.

We have evaluated antisense design and efficacy of locked nucleic acid (LNA) and DNA oligonucleotide (ON) mix-mers targeting the conserved HIV-1 dimerization initiation site (DIS). LNA is a high affinity nucleotide analog, nuclease resistant and elicits minimal toxicity. We show that inclusion of LNA bases in antisense ONs augments the interference of HIV-1 genome dimerization. We also demonstrate the concomitant RNase H activation by six consecutive DNA bases in an LNA/DNA mix-mer. We show ON uptake via receptor-mediated transfection of a human T-cell line in which the mix-mers subsequently inhibit replication of a clinical HIV-1 isolate. Thus, the technique of LNA/DNA mix-mer antisense ONs targeting the conserved HIV-1 DIS region may provide a strategy to prevent HIV-1 assembly in the clinic.

Dimerization↗

PubMed2004

Validating siRNA using a reporter made from synthetic DNA oligonucleotides.

Only a small fraction of all siRNAs are effective in silencing their target genes, and siRNA efficacy can only be determined experimentally. Previously described reporter-based siRNA validation methods all rely on the availability of physical cDNA clones, and this limits the high throughput applicability of the method. In the current report, we used short synthetic DNA fragment containing a siRNA targeting site, instead of cDNA, to fuse with a reporter gene. When targeting such transcripts with different siRNAs, we found that such constructs can faithfully report the efficacy of the corresponding siRNAs in a sequence specific manner, even when the inserted DNA fragment is essentially only long enough to cover the targeting site. The efficacy of both vector-based siRNA and synthetic siRNA can be evaluated using this system. Since only readily available short synthetic DNA fragments are needed for forming the evaluation vector, this method provides an appealing way of validating siRNAs in high throughput.

Animals↗

PubMed2004

Simultaneous pancreas-kidney transplantation with portal-enteric drainage: a case report.

BACKGROUND: Simultaneous pancreas-kidney transplantation (SPK) with portal-enteric drainage is physiological effective in treatment of patients with diabetes mellitus complicated by end-stage renal disease. A case is reported with a review of our clinical experience. METHODS: A patient with type 2 diabetes complicated by renal failure was subjected to SPK transplantation with portal-enteric drainage. Pancreaticoduodenal allograft procured from corpse was transplanted to recipient's right abdomen with donor's portal vein anastomosed to recipient's superior mesenteric vein. Donor's plastic pancreas artery was anastomosed to recipient's right common iliac artery and donor's duodenum anastomosed to recipient's jejunum. The kidney allograft was transplanted ectopically to the contralateral iliac fossa. Postoperative immunosuppression includes tacrolimus (TAC)/mycophenolate mofetil (MMF)-based regimen and methylprednisolone or prednisone. RESULTS: On the 5th postoperative day, the level of blood creatinine decreased from 590 micromol/L to normal. Daily urine volume was about 2500 ml. On the 18th postoperative day, insulin was given up, and the levels of fasting blood-glucose and after meal blood-glucose were kept normal. No acute rejection symptoms or other complications were observed except infection of Pseudomonas aeruginosa. CONCLUSION: Combined pancreas and kidney transplantation with portal-enteric drainage is a physiological effective treatment for diabetic patients with end-stage renal disease.

Adult↗

PubMed2003

mRNA accessible site tagging (MAST): a novel high throughput method for selecting effective antisense oligonucleotides.

A solution-based method, mRNA accessible site tagging (MAST), has been developed to map the accessible sites of any given mRNA in high throughput fashion. mRNA molecules were immobilized and hybridized to randomized oligonucleotide libraries. Oligonucleotides specifically hybridized to the mRNA were sequenced and found to be able to precisely define the accessible sites of the mRNA. A number of ways were used to validate the accessible sites defined by the MAST process. Mapping of rabbit beta-globin mRNA demonstrates the efficacy and advantage of MAST over other technologies in identifying accessible sites. Antisense oligonucleotides designed according to the accessible site map of human RhoA and Renilla luciferase mRNA result in knockdown effects that are in good correlation with the degrees of accessibility. The MAST methodology can be applied to mRNA of any length using a universal protocol.

Animals↗

PubMed2003

Effective small interfering RNAs and phosphorothioate antisense DNAs have different preferences for target sites in the luciferase mRNAs.

Antisense DNA target sites can be selected by the accessibility of the mRNA target. It remains unknown whether a mRNA site that is accessible to an antisense DNA is also a good candidate target site for a siRNA. Here, we reported a parallel analysis of 12 pairs of antisense DNAs and siRNA duplexes for their potency to inhibit reporter luciferase activity in mammalian cells, both of the antisense DNA and siRNA agents in a pair being directed to same site in the mRNA. Five siRNAs and two antisense DNAs turned out to be effective, but the sites targeted by those effective siRNAs and antisense DNAs did not overlap. Our results indicated that effective antisense DNAs and siRNAs have different preferences for target sites in the mRNA.

Animals↗

PubMed2002

[Influence of exogenous RNA upon expression of mouse albumin gene and its sensitivity to DNase I].

Cultured mouse fibroblasts were treated with rabbit liver RNA. Rat liver RNA was injected into mouse prostates. Influence of exogenous RNA upon expression of mouse albumin gene was detected by immunohistochemical staining. Nucleuses of cultured mouse fibroblasts treated with different RNAs were isolated and digested with DNase I. Mouse albumin gene was amplified by PCR to detect levels of its digestion. It was found that exogenous RNAs could increase the sensitivity of mouse albumin gene to DNase I digestion and promote its expression.

Albumins↗