Blood-brain barrier (BBB) disruption and dysfunction result in brain edema, which is responsible for more than half of all deaths after severe traumatic brain injury (TBI). Fibroblast growth factor 21 (FGF21) has a potential neuroprotective function in the brain. However, the effects and underlying possible mechanism of action on BBB integrity following TBI remain unknown. The purpose of the current study was to determine the effects of FGF21 on BBB protection and TBI treatment. The effects of recombinant human FGF21 (rhFGF21) on BBB integrity and on tight junction (TJ) and adhesion junction (AJ) proteins were investigated both in a TBI mouse model and an in vitro BBB disruption model established with tumor necrosis factor alpha (TNF-α)-induced human brain microvascular endothelial cells (HBMECs). The ability of rhFGF21 to form an FGF21/FGFR1/β-klotho complex was confirmed by in vitro β-klotho small interfering RNA (siRNA) transfection and FGFR1 co-immunoprecipitation. In addition, the specific FGFR1 and peroxisome proliferator-activated receptor gamma (PPARγ) inhibitors PD173074 and GW9662, respectively, were applied to further explore the possible mechanism of rhFGF21 in BBB maintenance after TBI. rhFGF21 markedly reduced neurofunctional behavior deficits and cerebral edema degree, preserved BBB integrity, and recued brain tissue loss and neuron apoptosis in the mouse model after TBI. Both in vivo and in vitro, rhFGF21 upregulated TJ and AJ proteins, thereby preserving the BBB. Moreover, rhFGF21 activated PPARγ in TNF-α-induced HBMECs through formation of an FGF21/FGFR1/β-klotho complex. rhFGF21 protected the BBB through FGF21/FGFR1/β-klotho complex formation and PPARγ activation, which upregulated TJ and AJ proteins.
Wound healing, especially for diabetic wounds, is a lengthy and complicated process involving interactions and responses at the protein, cell, and tissue levels. Loading of growth factors into a hydrogel to construct a sustained‐release system is considered a promising approach to improve wound healing. The present study investigates the effect of thermosensitive heparin‐poloxamer (HP) hydrogel–encapsulated recombinant human fibroblast growth factor 21 (rhFGF21) on wound healing in mice with streptozotocin‐induced diabetes mellitus. First, we studied the in vitro release of rhFGF21 from the rhFGF21‐HP coacervate. The results showed that HP might control the release of rhFGF21. Next, we examined the effect of rhFGF21‐HP on skin wound healing in diabetic mice. Our data showed that rhFGF21‐HP significantly improved wound closure; promoted granulation, collagen deposition, and re‐epithelialization; and enhanced the expression of CD31. Moreover, rhFGF21‐HP had obvious advantages in diabetic wound healing. Therefore, the results suggest that the rhFGF21‐HP hydrogel polymer plays an important role in skin wound healing. This work provides a suitable sustained‐release delivery system that can continuously release rhFGF21 and presents a promising therapeutic strategy for wound healing in patients with diabetes.—Liu, H., Zhao, Y., Zou, Y., Huang, W., Zhu, L., Liu, F., Wang, D., Guo, K., Hu, J., Chen, J., Ye, L., Li, X., Lin, L. Heparin‐poloxamer hydrogel–encapsulated rhFGF21 enhances wound healing in diabetic mice. FASEB J. 33, 9858–9870 (2019). http://www.fasebj.org
This new discovery suggests the potential therapeutic role of nmFGF1 for the treatment of ischemic strokes.
Background Bee pollen (BP) has been used as a traditional medicine and food diet additive due to its nutritional and biological properties. The potential biological properties of bee pollen vary greatly with the botanical and geographical origin of the pollen grains. This study was conducted to characterize the botanical origin and assess the antioxidant effects of ethanol extracts of 18 different bee pollen (EBP) samples from 16 locations in South Korea and their inhibitory activities on human β-amyloid precursor cleavage enzyme (BACE1), acetylcholinesterase (AChE), human intestinal bacteria, and 5 cancer cell lines. Methods The botanical origin and classification of each BP sample was evaluated using palynological analysis by observing microscope slides. We measured the biological properties, including antioxidant capacity, inhibitory activities against human BACE1, and AChE, and antiproliferative activities toward five cancer cell lines, of the 18 EBPs. In addition, the growth inhibitory activities on four harmful intestinal bacteria, six lactic acid-producing bacteria, two nonpathogenic bacteria, and an acidulating bacterium were also assessed. Results Four samples (BP3, BP4, BP13 and BP15) were found to be monofloral and presented four dominant pollen types: Quercus palustris , Actinidia arguta , Robinia pseudoacacia , and Amygdalus persica . One sample (BP12) was found to be bifloral, and the remaining samples were considered to be heterofloral. Sixteen samples showed potent antioxidant activities with EC 50 from 292.0 to 673.9 μg mL − 1 . Fourteen samples presented potent inhibitory activity against human BACE1 with EC 50 from 236.0 to 881.1 μg mL − 1 . All samples showed antiproliferative activity toward the cancer cell lines PC-3, MCF-7, A549, NCI-H727 and AGS with IC 50 from 2.7 to 14.4 mg mL − 1 , 0.9 to 12.7 mg mL − 1 , 5.0 to > 25 mg mL − 1 , 2.7 to 17.7 mg mL − 1 , and 2.4 to 8.7 mg mL − 1 , respectively. In addition, total phenol and flavonoid contents had no direct correlation with antioxidant, anti-human BACE1, or antiproliferative activities. Conclusion Fundamentally, Korean bee pollen-derived preparations could be considered a nutritional addition to food to prevent various diseases related to free radicals, neurodegenerative problems, and cancers. The botanical and geographical origins of pollen grains could help to establish quality control standards for bee pollen consumption and industrial production.
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