The present study was designed to evaluate the potential role of miR-93 in cerebral ischemic/reperfusion (I/R) injury in mice. The stroke model was produced in C57BL/6 J mice via middle cerebral artery occlusion (MCAO) for 1 h followed by reperfusion. And miR-93 antagomir was transfected to down-regulate the miR-93 level. Our results showed that miR-93 levels in the cerebral cortex of mice increased at 24 and 48 h after reperfusion. Importantly, in vivo study demonstrated that treatment with miR-93 antagomir reduced cerebral infarction volume, neural apoptosis and restored the neurological scores. In vitro study demonstrated that miR-93 antagomir attenuated hydrogen peroxide (HO)-induced injury. Moreover, miR-93 antagomir suppressed oxidative stress in I/R brain and HO treated cortical neurons. Furthermore, we founded that down-regulation of miR-93 increased the expression of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1) and the luciferase reporter assay confirmed that miR-93 directly binds to the predicted 3'-UTR target sites of the nrf2 gene. Finally, we found that knockdown of Nrf2 or HO-1 abolished miR-93 antagomir-induced neuroprotection against oxidative stress in HO treated neuronal cultures. These results suggested that miR-93 antagomir alleviates ischemic injury through the Nrf2/HO-1 antioxidant pathway.

No abstract

No abstract

No abstract

No abstract

Bacterial infection has been a considerable obstacle for diabetic wound healing. A multifunctional nanoplatform used as nanozyme for bacterial infected diabetic wound is extremely attractive. Therefore, gold nanoclusters modified zirconium-based porphyrin metal–organic frameworks (Au NCs@PCN) were constructed by an in situ growth method. Through SEM, TEM, and EDS mapping, the surface of ellipsoid-shaped particles around 190 nm was observed to be evenly interspersed with 5–8 nm gold nanoclusters. Notably, Au NCs@PCN exhibits excellent performance in exciting ROS generation and photothermal effects. Under near-infrared (NIR) laser irradiation, Au NCs@PCN can be heated to 56.2 °C and produce ROS, showing an effective killing effect on bacteria. Antibacterial studies showed that Au NCs@PCN inhibited MRSA and Ampr E. coli by destroying membrane structure and inducing protein leakage up to 95.3% and 90.6%, respectively. Animal experiments showed that Au NCs@PCN treated diabetic rats had reduced wound coverage to 2.7% within 21 days. The immunoblot analysis showed that proangiogenic and proepithelial cell proliferation factors were expressed significantly up-regulated. These results prove that Au NCs@PCN with photocatalytic and nanozyme activity has a broad application prospect for promoting diabetic infected wound healing.

Background Healing of MRSA (methicillin-resistant Staphylococcus aureus) infected deep burn wounds (MIDBW) in diabetic patients remains an obstacle but is a cutting-edge research problem in clinical science. Surgical debridement and continuous antibiotic use remain the primary clinical treatment for MIDBW. However, suboptimal pharmacokinetics and high doses of antibiotics often cause serious side effects such as fatal complications of drug-resistant bacterial infections. MRSA, which causes wound infection, is currently a bacterium of concern in diabetic wound healing. In more severe cases, it can even lead to amputation of the patient's limb. The development of bioactive nanomaterials that can promote infected wound healing is significant. Results The present work proposed a strategy of using EGCG (Epigallocatechin gallate) modified black phosphorus quantum dots (BPQDs) as therapeutic nanoplatforms for MIDBW to achieve the synergistic functions of NIR (near-infrared)-response, ROS-generation, sterilization, and promoting wound healing. The electron spin resonance results revealed that EGCG-BPQDs@H had a more vital photocatalytic ability to produce singlet oxygen than BPQDs@H. The inhibition results indicated an effective bactericidal rate of 88.6% against MRSA. Molecular biology analysis demonstrated that EGCG-BPQDs significantly upregulated CD31 nearly fourfold and basic fibroblast growth factor (bFGF) nearly twofold, which were beneficial for promoting the proliferation of vascular endothelial cells and skin epidermal cells. Under NIR irradiation, EGCG-BPQDs hydrogel (EGCG-BPQDs@H) treated MIDBW area could rapidly raise temperature up to 55 °C for sterilization. The MIBDW closure rate of rats after 21 days of treatment was 92.4%, much better than that of 61.1% of the control group. The engineered EGCG-BPQDs@H were found to promote MIDBW healing by triggering the PI3K/AKT and ERK1/2 signaling pathways, which could enhance cell proliferation and differentiation. In addition, intravenous circulation experiment showed good biocompatibility of EGCG-BPQDs@H. No significant damage to major organs was observed in rats. Conclusions The obtained results demonstrated that EGCG-BPQDs@H achieved the synergistic functions of photocatalytic property, photothermal effects and promoted wound healing, and are promising multifunctional nanoplatforms for MIDBW healing in diabetics. Graphical Abstract

Taking into account the effects of multiple pairs of variable delays, this paper deals with the global dynamics for a class of differential neoclassical growth models. We aim to obtain significant insights into better understanding of how the multiple pairs of variable delays essentially affect the stability and attractiveness of the unique positive equilibrium point. First of all, we prove that every solution of the IVP (initial value problem) with respect to the addressed system exists globally and is positive and bounded above. Secondly, with the help of the methods of fluctuation lemma and analytical techniques, two delay-independent criteria and one delay-dependent criterion on the attractivity of the unique positive equilibrium point are established, which improve and complement some published results. Lastly, two examples with the numerical simulation are arranged to illustrate the effectiveness and feasibility of the obtained theoretical results.