Xuzhou Medical College

About: Xuzhou Medical College is a education organization based out in Xuzhou, China. It is known for research contribution in the topics: Cancer & Cell growth. The organization has 12721 authors who have published 7802 publications receiving 102970 citations.

Glycyrrhizin Prevents Hemorrhagic Transformation and Improves Neurological Outcome in Ischemic Stroke with Delayed Thrombolysis Through Targeting Peroxynitrite-Mediated HMGB1 Signaling

Abstract: Peroxynitrite (ONOO-) and high mobility group box 1 protein (HMGB1) are important cytotoxic factors contributing to cerebral ischemia-reperfusion injury. However, the roles of ONOO- in mediating HMGB1 expression and its impacts on hemorrhagic transformation (HT) in ischemic brain injury with delayed t-PA treatment remain unclear. In the present study, we tested the hypothesis that ONOO- could directly mediate the activation and release of HMGB1 in ischemic brains with delayed t-PA treatment. With clinical studies, we found that plasma nitrotyrosine (NT, a surrogate marker of ONOO-) was positively correlated with HMGB1 level in acute ischemic stroke patients. Hemorrhagic transformation and t-PA-treated ischemic stroke patients had increased levels of nitrotyrosine and HMGB1 in plasma. In animal experiments, we found that FeTmPyP, a representative ONOO- decomposition catalyst (PDC), significantly reduced the expression of HMGB1 and its receptor TLR2, and inhibited MMP-9 activation, preserved collagen IV and tight junction claudin-5 in ischemic rat brains with delayed t-PA treatment. ONOO- donor SIN-1 directly induced expression of HMGB1 and its receptor TLR2 in naive rat brains in vivo and induced HMGB1 in brain microvascular endothelial b.End3 cells in vitro. Those results suggest that ONOO- could activate HMGB1/TLR2/MMP-9 signaling. We then addressed whether glycyrrhizin, a natural HMGB1 inhibitor, could inhibit ONOO- production and the antioxidant properties of glycyrrhizin contribute to the inhibition of HMGB1 and the neuroprotective effects on attenuating hemorrhagic transformation in ischemic stroke with delayed t-PA treatment. Glycyrrhizin treatment downregulated the expressions of NADPH oxidase p47 phox and p67 phox and iNOS, inhibited superoxide and ONOO- production, reduced the expression of HMGB1, TLR2, MMP-9, preserved type IV collagen and claudin-5 in ischemic brains. Furthermore, glycyrrhizin significantly decreased the mortality rate, attenuated hemorrhagic transformation, brain swelling, blood-brain barrier damage, neuronal apoptosis, and improved neurological outcomes in the ischemic stroke rat model with delayed t-PA treatment. In conclusion, peroxynitrite-mediated HMGB1/TLR2 signaling contributes to hemorrhagic transformation, and glycyrrhizin could be a potential adjuvant therapy to attenuate hemorrhagic transformation, possibly through inhibiting the ONOO-/HMGB1/TLR2 signaling cascades.

Efficacy of prophylactic intravenous ondansetron on the prevention of hypotension during cesarean delivery: a dose-dependent study.

Abstract: Objective: This study was to determine the optimal dosage of ondansetron for preventing maternal hypotension during cesarean delivery. Methods: One hundred and fifty parturient women scheduled for elective cesarean section were randomly assigned to five groups (n=30). Five minutes prior to spinal anesthesia, women were injected with 5 ml of physiological saline (S), 2 mg (O2), 4 mg (O4), 6 mg (O6), or 8 mg (O8) of ondansetron in saline, respectively. Maternal blood pressure and heart rate were measured at 2-min intervals for 30 min. The serum parameters in umbilical cord blood were analyzed after delivery. Results: Compared with group S, the incidence of maternal hypotension was significantly lower in groups O4 and O6 (P < 0.05). The umbilical venous pH was significantly higher in group O4 (P < 0.05); while the partial pressure of carbon dioxide (Pco2) was significantly lower in groups O4, O6, and O8 (P < 0.05); and the bicarbonate (Hco3 -) and base excess in extracellular fluid (BEecf) were significantly lower in groups O6 and O8 (P < 0.05). Moreover, minimal changes of systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure were observed in group O4 (P < 0.05). Conclusion: The optimal dose of ondansetron preloading was 4 mg during cesarean delivery.

Long noncoding RNA NEAT1-modulated miR-506 regulates gastric cancer development through targeting STAT3.

Abstract: Accumulating evidence has indicated that long noncoding RNA NEAT1 exerts critical roles in cancers. So far, the detailed biological role and mechanisms of NEAT1, which are responsible for human gastric cancer (GC), are still largely unknown. Here, we observed that NEAT1 and STAT3 expressions were significantly upregulated in human GC cells including BGC823, SGC-7901, AGS, MGC803, and MKN28 cells compared with normal gastric epithelial cells GES-1, while miR-506 was downregulated. We inhibited NEAT1 and observed that NEAT1 inhibition was able to repress the growth, migration, and invasion of GC cells. Conversely, overexpression of NEAT1 exhibited an increased ability of GC progression in BGC823 and SGC-7901 cells. Bioinformatics analysis, dual luciferase reporter assays, RIP assays, and RNA pull-down tests validated the negative binding correlation between NEAT1 and miR-506. In addition, it was found that miR-506 can modulate the expression of NEAT1 in vitro. STAT3 was predicted as a messenger RNA (mRNA) target of miR-506, and miR-506 mimics can suppress STAT3 mRNA expression. Subsequently, it was observed that downregulation of NEAT1 can restrain GC development by decreasing STAT3, which can be reversed by miR-506 inhibitors. Therefore, it was hypothesized in our study that NEAT1 can be recognized as a competing endogenous RNA to modulate STAT3 by sponging miR-506 in GC. In conclusion, we implied that NEAT1 can serve as an important biomarker in GC diagnosis and treatment.

Hypoxia-Inducible Factor-2α Limits Natural Killer T Cell Cytotoxicity in Renal Ischemia/Reperfusion Injury

Abstract: Natural killer T (NKT) cells are the major early-acting immune cell type and fundamental immune modulators in ischemia-reperfusion injury (IRI). Because lymphocytes are exposed to various oxygen tensions under pathophysiologic conditions, we hypothesize that hypoxia-inducible factors (HIFs) have roles in NKT cell activation, and thus determine the final outcome of renal IRI. In this study, we used Lck-Cre transgenic mice to specifically disrupt HIF-2α in T/NKT cells and found that HIF-2α knockout led to upregulated Fas ligand expression on peripheral NKT cells, but not on conventional T cells. HIF-2α knockout promoted infiltration of NKT cells into ischemic kidneys and exacerbated IRI, which could be mitigated by in vivo NK1.1(+) cell depletion or Fas ligand blockade. Compared with wild-type NKT cells, HIF-2α(-/-) NKT cells adoptively transferred to Rag1-knockout mice elicited more severe renal injury, and these mice were not protected by CGS21680, an adenosine A2A receptor agonist. Mechanistically, hypoxia-induced expression of adenosine A2A receptor in NKT cells and CGS21680-induced cAMP production in thymocytes were HIF-2α-dependent. Hydrogen peroxide-induced Fas ligand expression on thymic wild-type NKT cells was significantly attenuated by CGS21680 treatment, but this effect was lost in HIF-2α(-/-) NKT cells. Finally, CGS21680 and LPS, an inducer of HIF-2α in endothelium, synergistically reduced renal IRI substantially, but this effect was absent in Mx1-Cre-induced global HIF-2α-knockout mice. Taken together, our results reveal a hypoxia/HIF-2α/adenosine A2A receptor axis that restricts NKT cell activation when confronted with oxidative stress and thus protects against renal IRI.

Enzyme-assisted peptide folding, assembly and anti-cancer properties.

Abstract: The α-helix is the most prevalent conformation in proteins. However, formation of the α-helical conformation remains a challenge for short peptides with less than 5 amino acids. We demonstrated in this study that enzyme-instructed self-assembly (EISA) provides a unique pathway to assist the self-assembly of peptides into the α-helical conformation, while a heating–cooling process leads to a conformation more similar to a β-sheet. The same peptide with different conformations self-assembled into different nanostructures. The peptide with α-helical conformation self-assembled into stable nanofibers and hydrogels, while the other one assembled into an unstable nanoparticle suspension. The nanofiber solution exhibited better stability against proteinase K digestion and an enhanced cellular uptake compared to the nanoparticle solution. Therefore, the nanomedicine formed by the α-helical peptide showed a better inhibition capacity against cancer cells in vitro and significantly inhibited tumor growth in vivo compared to the one formed by the β-sheet peptide. Our study demonstrates the unique advantages of EISA to assist peptide folding and self-assembly into biofunctional nanomaterials.