王雲銘教授研究團隊發表研究成果於 Bioconjugate Chemistry

連結網址：https://pubmed.ncbi.nlm.nih.gov/37552618/

Abstract

The employment of metal-organic framework (MOF)-based nanomaterials has been rapidly increasing in bioapplications owing to their biocompatibility, drug degradation, tunable porosity, and intrinsic biodegradability. This evidence suggests that the multifunctional bimetallic ions can behave as remarkable candidates for infection control and wound healing. In this study, bimetallic MOFs (Zn-HKUST-1 and FolA-Zn-HKUST-1) embedded with and without folic acid were synthesized and used for tissue sealing and repairing incisional wound sites in mice models. For comparison, HKUST-1 and FolA-HKUST-1 were also synthesized. The Brunauer-Emmett-Teller (BET) surface area measured for HKUST-1, FolA-HKUST-1, Zn-HKUST-1, and FolA-Zn-HKUST-1 from N2 isotherms was found to be 1868, 1392, 1706, and 1179 m2/g, respectively. The measurements of contact angle values for Zn-HKUST-1, FolA-HKUST-1, and Zn-FolA-HKUST-1 were identified as 4.95 ± 0.8, 43.6 ± 3.4, and 60.62 ± 2.0°, respectively. For topical application in wound healing, they display a wide range of healing characteristics, including antibacterial and enhanced wound healing rates. In addition, in vitro cell migration and tubulogenic potentials were evaluated. The significant reduction in the wound gap and increased expression levels for CD31, eNOS, VEGF-A, and Ki67 were observed from immunohistological analyses to predict the angiogenesis behavior at the incision wound site. The wound healing rate was analyzed in the excisional dermal wounds of diabetic mice model in vivo. On account of antibacterial potentials and tissue-repairing characteristics of Cu2+ and Zn2+ ions, designing an innovative mixed metal ion-based biomaterial has wide applicability and is expected to modulate the growth of various gradient tissues.

王雲銘教授及高智飛副教授研究團隊發表研究成果於 ACS Chemical Neuroscience

連結網址：https://pubmed.ncbi.nlm.nih.gov/37533298/

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive impairment, memory loss, and behavioral deficits. β-amyloid_1-42(Aβ_1-42) aggregation is a significant cause of the pathogenesis in AD. Despite the numerous types of research, the current treatment efficacy remains insufficient. Hence, a novel therapeutic strategy is required. Nitric oxide (NO) is a multifunctional gaseous molecule. NO displays a neuroprotective role in the central nervous system by inhibiting the Aβ aggregation and rescuing memory and learning deficit through the NO signaling pathway. Targeting the NO pathway might be a therapeutic option; however, NO has a limited half-life under the biological system. To address this issue, a biomimetic dinitrosyl iron complex [(NO)₂Fe(μ-SCH₂CH₂COOH)₂Fe(NO)₂] (DNIC-COOH) that could stably deliver NO was explored in the current study. To determine whether DNIC-COOH exerts anti-AD efficacy, DNIC-COOH was added to neuron-like cells and primary cortical neurons along with Aβ_1-42. This study found that DNIC-COOH protected neuronal cells from Aβ-induced cytotoxicity, potentiated neuronal functions, and facilitated Aβ_1-42 degradation through the NO-sGC-cGMP-AKT-GSK3β-CREB/MMP-9 pathway.

Keywords: Alzheimer’s disease; amyloid pathology; dinitrosyl iron complexes; nitric oxide.

何奕儒助理教授研究團隊發表研究成果於Biomater Res.

連結網址：https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10324216/

Abstract

Background: Ischemic stroke-reperfusion (S/R) injury is a crucial issue in the protection of brain function after thrombolysis. The vasodilation induced by ultrasound (US)-stimulated microbubble cavitation has been applied to reduce S/R injury through sonoperfusion. The present study uses oxygen-loaded microbubbles (OMBs) with US stimulation to provide sonoperfusion and local oxygen therapy for the reduction of brain infarct size and neuroprotection after S/R.

Methods: The murine S/R model was established by photodynamic thrombosis and thrombolysis at the remote branch of the anterior cerebral artery. In vivo blood flow, partial oxygen pressure (pO2), and brain infarct staining were examined to analyze the validity of the animal model and OMB treatment results. The animal behaviors and measurement of the brain infarct area were used to evaluate long-term recovery of brain function.

Results: The percentage of blood flow was 45 ± 3%, 70 ± 3%, and 86 ± 2% after 60 min stroke, 20 min reperfusion, and 10 min OMB treatment, respectively, demonstrating sonoperfusion, and the corresponding pO2 level was 60 ± 1%, 76 ± 2%, and 79 ± 4%, showing reoxygenation. After 14 days of treatment, a 87 ± 3% reduction in brain infarction and recovery of limb coordination were observed in S/R mice. The expression of NF-κB, HIF-1α, IL-1β, and MMP-9 was inhibited and that of eNOS, BDNF, Bcl2, and IL-10 was enhanced, indicating activation of anti-inflammatory and anti-apoptosis responses and neuroprotection. Our study demonstrated that OMB treatment combines the beneficial effects of sonoperfusion and local oxygen therapy to reduce brain infarction and activate neuroprotection to prevent S/R injury.

王雲銘教授研究團隊發表研究成果於 Journal of Materials Chemistry B

連結網址：https://pubs.rsc.org/en/content/articlelanding/2023/tb/d3tb00587a

 Abstract

謝仁俊教授研究團隊發表研究成果於Frontiers in Neuroscience

連結網址：https://www.frontiersin.org/articles/10.3389/fnins.2023.1179851/full

Introduction: Primary dysmenorrhea (PDM) is a common condition among women of reproductive age, characterized by menstrual pain in the absence of any organic causes. Previous research has established a link between the A118G polymorphism in the mu-opioid receptor (OPRM1) gene and pain experience in PDM. Specifically, carriers of the G allele have been found to exhibit maladaptive functional connectivity between the descending pain modulatory system and the motor system in young women with PDM. This study aims to explore the potential relationship between the OPRM1 A118G polymorphism and changes in white matter in young women with PDM.

Methods: The study enrolled 43 individuals with PDM, including 13 AA homozygotes and 30 G allele carriers. Diffusion tensor imaging (DTI) scans were performed during both the menstrual and peri-ovulatory phases, and tract-based spatial statistics (TBSS) and probabilistic tractography were used to explore variations in white matter microstructure related to the OPRM1 A118G polymorphism. The short-form McGill Pain Questionnaire (MPQ) was used to access participants’ pain experience during the MEN phase.

Results: Two-way ANOVA on TBSS analysis revealed a significant main effect of genotype, with no phase effect or phase-gene interaction detected. Planned contrast analysis showed that during the menstrual phase, G allele carriers had higher fractional anisotropy (FA) and lower radial diffusivity in the corpus callosum and the left corona radiata compared to AA homozygotes. Tractographic analysis indicated the involvement of the left internal capsule, left corticospinal tract, and bilateral medial motor cortex. Additionally, the mean FA of the corpus callosum and the corona radiata was negatively correlated with MPQ scales in AA homozygotes, but this correlation was not observed in G allele carriers. No significant genotype difference was found during the pain-free peri-ovulary phase.

Discussion: OPRM1 A118G polymorphism may influence the connection between structural integrity and dysmenorrheic pain, where the G allele could impede the pain-regulating effects of the A allele. These novel findings shed light on the underlying mechanisms of both adaptive and maladaptive structural neuroplasticity in PDM, depending on the specific OPRM1 polymorphism.