Neuroprotective Effect of NO-Delivery Dinitrosyl Iron Complexes (DNICs) on Amyloid Pathology in the Alzheimer’s Disease Cell Model

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-amyloid1-42(Aβ1-42) 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 Aβ1-42. This study found that DNIC-COOH protected neuronal cells from Aβ-induced cytotoxicity, potentiated neuronal functions, and facilitated Aβ1-42 degradation through the NO-sGC-cGMP-AKT-GSK3β-CREB/MMP-9 pathway.

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

112學年度陽明交通大學生物科技學院碩士班考試入學備取通知

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112學年度陽明交通大學生物科技學院碩士班考試入學備取通知(7/19更新)

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二、報到登記時需攜帶以下資料:大學成績單正本、畢業證書正本(如為應屆畢業生,請填寫切結書)

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Oxygen-loaded microbubble-mediated sonoperfusion and oxygenation for neuroprotection after ischemic stroke reperfusion

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.

Conjugation of bone grafts with NO-delivery dinitrosyl iron complexes promotes synergistic osteogenesis and angiogenesis in rat calvaria bone defects

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

Craniofacial/jawbone deformities remain a significant clinical challenge in restoring facial/dental functions and esthetics. Despite the reported therapeutics for clinical bone tissue regeneration, the bioavailability issue of autografts and limited regeneration efficacy of xenografts/synthetic bone substitutes, however, inspire continued efforts towards functional conjugation and improvement of bioactive bone graft materials. Regarding the potential of nitric oxide (NO) in tissue engineering, herein, functional conjugation of NO-delivery dinitrosyl iron complex (DNIC) and osteoconductive bone graft materials was performed to optimize the spatiotemporal control over the delivery of NO and to activate synergistic osteogenesis and angiogenesis in rat calvaria bone defects. Among three types of biomimetic DNICs, [Fe2(μ-SCH2CH2COOH)2(NO)4] (DNIC-COOH) features a steady kinetics for cellular uptake by MC3T3-E1 osteoblast cells followed by intracellular assembly of protein-bound DNICs and release of NO. This steady kinetics for intracellular delivery of NO by DNIC-COOH rationalizes its biocompatibility and wide-spectrum cell proliferation effects on MC3T3-E1 osteoblast cells and human umbilical vein endothelial cells (HUVECs). Moreover, the bridging [SCH2CH2COOH] thiolate ligands in DNIC-COOH facilitate its chemisorption to deproteinized bovine bone mineral (DBBM) and physisorption onto TCP (β-tricalcium phosphate), respectively, which provides a mechanism to control the kinetics for the local release of loaded DNIC-COOH. Using rats with calvaria bone defects as an in vivo model, DNIC-DBBM/DNIC-TCP promotes the osteogenic and angiogenic activity ascribed to functional conjugation of osteoconductive bone graft materials and NO-delivery DNIC-COOH. Of importance, the therapeutic efficacy of DNIC-DBBM/DNIC-TCP on enhanced compact bone formation after treatment for 4 and 12 weeks supports the potential for clinical application to regenerative medicine.

OPRM1 A118G polymorphism modulating motor pathway for pain adaptability in women with primary dysmenorrhea

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.

A Low-Cost Fertilizer Medium Supplemented with Urea for the Lutein Production of Chlorella sp. and the Ability of the Lutein to Protect Cells against Blue Light Irradiation

林志生教授研究團隊發表研究成果於Bioengineering

連結網址:https://www.mdpi.com/2306-5354/10/5/594

Abstract

This study aimed to investigate the use of organic fertilizers instead of modified f/2 medium for Chlorella sp. cultivation, and the extracted lutein of the microalga to protect mammal cells against blue-light irradiation. The biomass productivity and lutein content of Chlorella sp. cultured in 20 g/L fertilizer medium for 6 days were 1.04 g/L/d and 4.41 mg/g, respectively. These values are approximately 1.3- and 1.4-fold higher than those achieved with the modified f/2 medium, respectively. The cost of medium per gram of microalgal biomass reduced by about 97%. The microalgal lutein content was further increased to 6.03 mg/g in 20 g/L fertilizer medium when supplemented with 20 mM urea, and the cost of medium per gram lutein reduced by about 96%. When doses of ≥1 μM microalgal lutein were used to protect mammal NIH/3T3 cells, there was a significant reduction in the levels of reactive oxygen species (ROS) produced by the cells in the following blue-light irradiation treatments. The results show that microalgal lutein produced by fertilizers with urea supplements has the potential to develop anti-blue-light oxidation products and reduce the economic challenges of microalgal biomass applied to carbon biofixation and biofuel production.

DDX3 suppresses hepatocellular carcinoma progression through modulating the secretion and composition of exosome

麥如村助理教授研究團隊發表研究成果於Am J Cancer Res

連結網址:https://pubmed.ncbi.nlm.nih.gov/37293175/

Abstract

This study aimed to investigate the use of organic fertilizers instead of modified f/2 medium for Chlorella sp. cultivation, and the extracted lutein of the microalga to protect mammal cells against blue-light irradiation. The biomass productivity and lutein content of Chlorella sp. cultured in 20 g/L fertilizer medium for 6 days were 1.04 g/L/d and 4.41 mg/g, respectively. These values are approximately 1.3- and 1.4-fold higher than those achieved with the modified f/2 medium, respectively. The cost of medium per gram of microalgal biomass reduced by about 97%. The microalgal lutein content was further increased to 6.03 mg/g in 20 g/L fertilizer medium when supplemented with 20 mM urea, and the cost of medium per gram lutein reduced by about 96%. When doses of ≥1 μM microalgal lutein were used to protect mammal NIH/3T3 cells, there was a significant reduction in the levels of reactive oxygen species (ROS) produced by the cells in the following blue-light irradiation treatments. The results show that microalgal lutein produced by fertilizers with urea supplements has the potential to develop anti-blue-light oxidation products and reduce the economic challenges of microalgal biomass applied to carbon biofixation and biofuel production.

112學年度陽明交通大學生物科技學院碩士班考試入學備取通知

112學年度陽明交通大學生物科技學院碩士班考試入學備取通知

112學年度碩士班考試入學備取生名單及報到注意事項

即日起至112年7月6日(四)下午3點前 (不含六、日、國定假日)完成報到手續

一、報到地點:新竹市博愛街75號賢齊館325室。

二、報到登記時需攜帶以下資料:大學成績單正本、畢業證書正本(如為應屆畢業生,請填寫切結書)

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