Biomedical subjects

Xin Cheng

Publications and source records attributed to Xin Cheng.

25 records · Page 2Linked to original sources

PubMed2003

An engineered multidomain bactericidal peptide as a model for targeted antibiotics against specific bacteria.

We constructed a peptide consisting of a staphylococcal AgrD1 pheromone fused to the channel-forming domain of colicin Ia and named it pheromonicin. This fusion peptide had bactericidal effects against methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA and MRSA, respectively), but not against Staphylococcus epidermidis or Streptococcus pneumoniae. Growth rates, vital staining and colony forming unit (CFU) counts showed that pheromonicin did not merely suppress growth but killed S. aureus cells. The specificity of pheromonicin was shown by the absence of bactericidal effects against an accessory gene regulator (agr) locus knockout of S. aureus, and a dose-dependent inhibition of the bactericidal effects of pheromonicin by competition with corresponding free AgrD pheromone. In vivo, all pheromonicin-treated mice survived administration of MRSA that was lethal to controls. No toxicity was detectable in human liver or renal cells in culture, or in livers, kidneys or spleens of pheromonicin-treated mice. The results suggest that these types of chimeric peptides may be of value as antibiotics against specific bacterial infections.

Amino Acid Sequence↗

PubMed2003

The TNF receptor superfamily: role in immune inflammation and bone formation.

Tumor necrosis factor (TNF) and TNF receptor (TNFR) family proteins play important roles in many biological processes. Recently, the TNF-family molecule, RANKL (also called TRANCE, ODF, and OPGL), and its receptors, RANK and OPG, were found to be regulators of the development and activation of osteoclasts in bone remodeling. TNFalphaalso activates osteoclasts both by themselves and in synergy with RANKL. We used structure-based design to create peptidomimetics and organic therapeutics that inhibit osteoclastogenesis by inhibiting the interaction of ligands and receptors. Here we show for the first time that blocking TNFalpha by these small molecules effectively inhibited osteoclast formation in vitro. These mimetics can be used as a probe to understand the molecular basis of osteoclastogenesis and also as a platform to create useful therapeutic agent.

Carrier Proteins↗

PubMed2002

KCNQ1 and KCNH2 mutations associated with long QT syndrome in a Chinese population.

The long QT syndrome (LQTS) is a cardiac disorder characterized by prolongation of the QT interval on electrocardiograms (ECGs), syncope and sudden death caused by a specific ventricular tachyarrhythmia known as torsade de pointes. LQTS is caused by mutations in ion channel genes including the cardiac sodium channel gene SCN5A, and potassium channel subunit genes KCNQ1, KCNH2, KCNE1, and KCNE2. Little information is available about LQTS mutations in the Chinese population. In this study, we characterized 42 Chinese LQTS families for mutations in the two most common LQTS genes, KCNQ1 and KCNH2. We report here the identification of four novel KCNQ1 mutations and three novel KCNH2 mutations. The KCNQ1 mutations include L191P in the S2-S3 cytoplasmic loop, F275S and S277L in the S5 transmembrane domain, and G306V in the channel pore. The KCNH2 mutations include L413P in transmembrane domain S1, E444D in the extracellular loop between S1 and S2, and L559H in domain S5. The location and character of these mutations expand the spectrum of KCNQ1 and KCNH2 mutations causing LQTS. Excitement, exercises, and stress appear to be the triggers for developing cardiac events (syncope, sudden death) for LQTS patients with KCNQ1 mutations F275S, S277L, and G306V, and all three KCNH2 mutations L413P, E444D and L559H. In contrast, cardiac events for an LQTS patient with KCNQ1 mutation L191P occurred during sleep or awakening from sleep. KCNH2 mutations L413P and L559H are associated with the bifid T waves on ECGs. Inderal or propanolol (a beta blocker) appears to be effective in preventing arrhythmias and syncope for an LQTS patient with the KCNQ1 L191P mutation.

Cation Transport Proteins↗

PubMed2002

TNFalpha inhibition in MRL/lpr mice ameliorates pulmonary but not renal disease.

TNFalpha inhibition has a clearly beneficial effect in a number of arthritides and in Crohn's disease. The exact mechanism of action is uncertain with studies showing inhibition of chemokines, inhibition of adhesion molecule expression, and improved T-cell function. Unlike most therapeutic interventions for autoimmune disease, TNFalpha inhibition appears to act on specific pathologic processes. It is not known how wide-spread these TNFalpha-mediated pathologic processes are. Efforts to expand the use of TNFalpha inhibition have had notable successes but have been disappointing in other disorders. We hypothesized that TNFalpha-mediated pathologic processes might play a significant role in the end-organ effects seen in SLE. We modeled SLE by using MRL/lpr mice and treated with two types of TNFalpha inhibitor. Pulmonary disease was significantly improved in the treated groups compared to controls. In contrast, renal disease was unaffected suggesting that in lupus, where multiple organs are affected, different pathologic processes may be mediating the end-organ damage. This has important implications for designing therapeutics for SLE.

Animals↗

PubMed2002

[Synthesis and preliminary studies of O-(2-[18F] fluoroethyl)-L-tyrosine as a positron emission tomography imaging agent].

OBJECTIVE: To develop a 18F-labeled amino acid, O-(2-[18F]fluoroethyl) - L-tyrosine(18F-FET), as a positron emission tomography (PET) tracer for imaging cerebral tumors. METHODS: 18F-FET was synthesized. Preclinical studies including sterility, endotoxin, and toxicity tests were performed. Two brain tumor cases were studied using 18F-FET and compared with 18F-FDG. RESULTS: Radiochemical purity of 18F-FET was over 95% which remained stable for 6 hours. The 18F-FET injection was sterile and its endotoxin content accorded with the standards of Chinese Pharmacopoeia. The uptake of 18F-FET in the normal brain tissues was significantly lower than that of the tumor, and the images of the brain tumor were clearer than those of 18F-FDG. CONCLUSION: 18F-FET can accumulate in the tumor tissues to give high quality images. It suggests that 18F-FET may be a safe and effective tracer for brain tumor imaging.

Adult↗

PubMed2000

Purification and Characterization of a Platelet Agglutinating Inhibiting Protein (Agkisacutacin) from Agkistrodon acutus Venom.

A platelet agglutinating inhibiting protein (agkisacutacin) was isolated from the venom of Agkistrodon acutus by DEAE Sepharose Fast Flow and size exclusion chromatography. The purified product was a 29 kD protein composed of two disulfide bond-linked polypeptide chains of molecular weight of 14 kD, 15 kD, respectively. It completely inhibited ristocetin-induced platelet agglutination with an IC(50) value of 18.5 mg/L. It also inhibited thrombin-induced platelet aggregation with an IC(50) value of 1.22 g/L, but it did not affect the platelet aggregation induced by collagen and ADP. No fibrinolytic activity, phospholipase A(2) activity, anticoagulant activity, haemorrhagic activity or lethal activity were detected in agkisacutacin. Therefore this protein may offer considerable therapeutic potential in treatment of platelet-rich thrombosis.

Journal Article↗

PubMed2000

Molecular Cloning and Sequence Analysis of cDNA Encoding Acutolysin C, a Hemorrhagic Metalloproteinase, from Agkistrodon acutus.

A full-length cDNA of 1 650 bp was amplified from the snake venom gland cDNA library of Agkistrodon acutus. Analysis of the nucleotide sequence indicated that the amplified cDNA contained a complete open reading frame encoding 417 amino acid residues including signal peptide sequence, zymogen sequence and proteinase domain. The zymogen sequence contained CGVT motif that was highly conserved in almost all venom metalloproteinases. The metalloproteinase domain contained a conserved signature zinc-binding motif HEXXHXXGXXH in the catalytic region and the CIM turn. It shares high similarity with the sequence of acutolysin C deduced from crystallographic data, and with other class P-I snake venom hemorrhagic toxins.

Journal Article↗