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Biomedical subjects

Xing-Hua Zhang

Publications and source records attributed to Xing-Hua Zhang.

5 recordsLinked to original sources

Multivalent cations stabilize DNA duplexes beyond charge neutralization.

Multivalent cations are abundant in cells and play essential roles in DNA duplex stability, genome packaging, and DNA-protein interactions. They can also condense DNA, making it challenging to determine their influence on DNA duplex stability. To overcome this challenge, we studied DNA unpeeling at equilibrium under high tension using magnetic tweezers, thereby preventing condensation. Experiments show that DNA duplex stability first increases and then decreases as cation concentration increases and the maximum DNA duplex stability increases with cation valence. The maximum free energy change of DNA was 3.33 k B T/bp for Na+ and increased to 3.98 k B T/bp for protamine, which is a small arginine-rich protein with a highly positive charge (≈21 for salmon sperm), corresponding to a relative increase of 19.5%. Consistently, all-atom molecular dynamics simulations show that higher-valent cations preferentially embed in the minor groove of DNA and clamp the minor groove, in contrast to the major-groove clamping reported for RNA, thereby stabilizing the helix more efficiently. These findings establish a single-molecule framework for quantifying DNA thermodynamics in complex ionic environments, which contributes to understanding ionic control of genome stability and to designing ion-tunable DNA-based nanostructures and delivery systems.

Journal Article↗

Compaction dynamics of single DNA molecules under tension.

Using transverse magnetic tweezers, we studied the dynamics of DNA compaction induced by hexaammine cobalt chloride under constant forces. Discontinuous DNA compaction events were found for forces ranging from 0.5 to 1.7 pN, with approximately 270 nm DNA adsorbed in each compaction event. Forces larger than 6 pN were found able to unravel the toroid in a similar intermittent stepwise manner. The observations indicate that the folding/unfolding events are transitions between two metastable structural states which are separated by a tension-dependent energy barrier. Analysis of the waiting time revealed that the degree of the package ordering of DNA in a toroid depends on the compaction kinetics.

Bacteriophage lambda↗

Limb ischemic postconditioning protects myocardium from ischemia-reperfusion injury.

OBJECTIVE: To test the hypothesis that limb ischemic postconditioning protects the myocardium from reperfusion injury, and examine the mechanism involved. DESIGN: Forty rabbits were randomly divided into four groups: Control, Ischemic Preconditioning, Ischemic Postconditioning and Remote Postconditioning. Myocardial infarct size and tissue myeloperoxidase activity were determined at the end of the experiment. Plasma creatine kinase and malondialdehyde activity were measured at baseline, the end of ischemia, and after 3 h of reperfusion respectively. RESULTS: Myocardial infarct size was significantly reduced in Ischemic Preconditioning, Ischemic Postconditioning and Remote Postconditioning as compared to Control (p < 0.01). Results were confirmed by plasma creatine kinase activity. Plasma malondialdehyde was significantly less at 3 h of reperfusion in Ischemic Preconditioning, Ischemic Postconditioning and Remote Postconditioning than that in Control (p < 0.01). Neutrophil accumulation (myeloperoxidase activity) in the area at risk was less in Ischemic Preconditioning, Ischemic Postconditioning and Remote Postconditioning than that in Control (p < 0.01). CONCLUSION: Remote postconditioning reduces myocardial infarction in rabbits. The mechanism involved might be reduced oxygen radical-induced injury and improved antioxidant action.

Animals↗

Effect of postconditioning on coronary blood flow velocity and endothelial function in patients with acute myocardial infarction.

OBJECTIVES: To observe the effect of postconditioning on coronary blood flow velocity and endothelial function in acute myocardial infarction (AMI). METHODS: We recruited patients with AMI who underwent primary PCI. The patients were randomized to an ischemic-reperfusion group (IR group) and a postconditioning group. Corrected TIMI frame count (CTFC), Wall motion score index (WMSI), Creatine phosphokinase (CK), CK-MB, malondialdehyde (MDA) were measured. Arterial endothelial function was studied non-invasively by echo Doppler technique. RESULTS: Patients with postconditioning had much faster CTFC. After 8 weeks, the WMSI in Postcond group was significantly larger. There was a significant negative correlation between WMSI and CTFC in IR group and Postcond group(r = - 0.90, p < 0.01; r = - 0.79, p < 0.01). The peaks of CK and CK-MB of Postcond group were much lower than those of the IR group, and MDA-reactive products were significantly lower than those of the IR group after PCI. The endothelium-dependent vasodilatory function was improved in the Postcond group. CONCLUSION: Postconditioning is a simple interventional procedure for salvage of the coronary endothelial function and increasing coronary blood flow velocity.

Adult↗

Effects of granulocyte-macrophage colony stimulating factor on the repair of vessel intima damaged by balloon.

BACKGROUND: The dysfunction of vascular endothelial cells plays a key role in starting and facilitating restenosis. The acceleration of intima repair and the recovery of endothelial function would reduce the restenosis rate. This study was undertaken to assess the effect of granulocyte-macrophage colony stimulating factor (GM-CSF) on the repair of damaged iliac arteries. METHODS: Twenty-four male New Zealand white rabbits undergoing primary iliac artery deendothelization were randomly divided into two groups (GM-CSF group and control group). The GM-CSF group received a subcutaneous injection of GM-CSF [10 microg x kg(-1) x d(-1)], and the control group was given a subcutaneous injection of equivalent saline. The iliac arteries of all animals were damaged by balloon after 7 days. The levels of nitric oxide (NO) were detected before, 1 week, 2 weeks and 4 weeks after angioplasty. The repair and hyperplasia of the intima were observed microscopically and the indices of stenosis were evaluated by computerized planimetry after 4 weeks of angioplasty. RESULTS: The NO levels of the GM-CSF group were higher than those of the control group 2 weeks and 4 weeks after angioplasty [(91.92 +/- 11.57) micromol/L vs. (81.67 +/- 12.18) micromol/L; (97.67 +/- 10.13) micromol/L vs. (83.16 +/- 12.64) micromol/L]. Four weeks after balloon damage, histological examination showed that neointima formation, vascular smooth muscle cells and fibrous tissue of the GM-CSF group were less than those of the control group. The endothelium of the GM-CSF group was more integrated, and stenosis of lumen was slighter than that of the control group. Morphometry showed the lumen area of the GM-CSF group was larger than that of the control group [(1.27 +/- 0.31) mm(2) vs. (0.92 +/- 0.24) mm(2)], the neointimal area and percent of intima hyperplasia were significantly smaller than those of the control group [(0.85 +/- 0.34) mm(2) vs. (1.18 +/- 0.38) mm(2); (40 +/- 7)% vs. (55 +/- 6)%]. CONCLUSION: GM-CSF could facilitate the repair of the intima, reduce neointima formation, better the function of the endothelium, and decrease the rate of restenosis.

Angioplasty, Balloon↗