ABSTRACT
Fibroblast growth factor 21 (FGF21) is a growth factor with endocrine function in the fibroblast growth factor family. Previous reports have shown that FGF21 is involved in the regulation of energy metabolism and plays a protective role in cardiovascular diseases such as coronary heart disease, diabetes, non-alcoholic fatty liver disease and so on. Recent studies have found that FGF21 can induce autophagy in a variety of tissues and organs, and autophagy is involved in many pathological processes of cardiovascular diseases, including vascular calcification, atherosclerosis, and myocardial ischemia-reperfusion injury. Therefore, FGF21 may play a protective role in a variety of cardiovascular diseases by regulating autophagy. This article reviews the research progress on the protective role of FGF21 in cardiovascular diseases by inducing autophagy.
Subject(s)
Autophagy , Cardiovascular Diseases , Fibroblast Growth Factors , Autophagy/genetics , Autophagy/physiology , Cardiovascular Diseases/genetics , Cardiovascular Diseases/metabolism , Fibroblast Growth Factors/genetics , Fibroblast Growth Factors/metabolism , Humans , Myocardial Reperfusion Injury/genetics , Myocardial Reperfusion Injury/metabolismABSTRACT
In the study, we used functional magnetic resonance imaging associated with behavioral assessment to observe the effects of venlafaxine on the modulation of human motor cortex activation and to provide preliminary data for further assessing its influence on motor functional reorganization after stroke injury. In a randomized, double-blind, crossover study, 8 right-handed subjects received 75 mg of either venlafaxine or a placebo daily over a period of 7 days separated by 3 washout days. The volunteers were asked to execute motor tasks, which included the dynamometer and finger-tapping test. In addition, laboratory tests and functional magnetic resonance imaging examination, before the start of the experiment and after administration of placebo and venlafaxine, were performed. It was shown that the finger-tapping rate of each hand in the venlafaxine stage was significantly improved compared with that observed in the placebo stage (n = 8, F left hand = 57.69, F right hand = 184.48, P < 0.001). The changes in the recorded grip strengths of both hands were not significant between the stages (n = 8, F = 2.63, P > 0.05). In the venlafaxine stage, the activations of the contralateral primary sensorimotor cortex, contralateral premotor cortex, and contralateral supplementary motor area were enhanced significantly, whereas the activation of the bilateral parietal cortices was decreased when compared with the placebo stage. Meanwhile, the enhancement of contralateral primary sensorimotor cortex activation had a positive correlation with the improvement of the finger-tapping rate. It was concluded that venlafaxine could modulate the cortical excitability and improve finger dexterity and reaction speed, which greatly related to the increase of contralateral motor cortical excitability.
Subject(s)
Adrenergic Uptake Inhibitors/pharmacology , Antidepressive Agents/pharmacology , Brain Waves/drug effects , Cyclohexanols/pharmacology , Motor Activity/drug effects , Motor Cortex/drug effects , Selective Serotonin Reuptake Inhibitors/pharmacology , Administration, Oral , Adrenergic Uptake Inhibitors/administration & dosage , Adult , Antidepressive Agents/administration & dosage , Brain Mapping/methods , China , Cross-Over Studies , Cyclohexanols/administration & dosage , Double-Blind Method , Drug Administration Schedule , Functional Laterality , Hand Strength , Healthy Volunteers , Humans , Magnetic Resonance Imaging , Male , Motor Cortex/physiology , Pilot Projects , Reaction Time/drug effects , Selective Serotonin Reuptake Inhibitors/administration & dosage , Time Factors , Venlafaxine HydrochlorideABSTRACT
The application of drug-loaded microbubbles (MBs) in combination with ultrasound (US), which results in an increase in capillary permeability at the site of US-sonication-induced MB destruction, may be an efficient method of localized drug delivery. This study investigated the mechanism underlying the US-mediated release of luciferin-loaded MBs through the blood vessels to targeted cells using an in vivo bioluminescence imaging (BLI) system. The luciferin-loaded MBs comprised an albumin shell with a diameter of 1234 ± 394 nm (mean ± SD) and contained 2.48 × 109 bubbles/mL; within each MB, the concentration of encapsulated luciferin was 1.48 × 10⻹° mg/bubble. The loading efficiency of luciferin in MBs was only about 19.8%, while maintaining both the bioluminescence and acoustic properties. In vitro and in vivo BLI experiments were performed to evaluate the US-mediated release of luciferin-loaded MBs. For in vitro results, the increase in light emission of luciferin-loaded albumin-shelled MBs after destruction via US sonication (6.24 ± 0.72 × 107 photons/s) was significantly higher than that in the luciferin-loaded albumin-shelled MBs (3.11 ± 0.33 × 107 photons/s) (p < 0.05). The efficiency of the US-mediated release of luciferin-loaded MBs in 4T1-luc2 tumor-bearing mice was also estimated. The signal intensity of the tumor with US destruction at 3 W/cm² for 30 s was significantly higher than without US destruction at 3 (p = 0.025), 5 (p = 0.013), 7 (p = 0.012) and 10 (p = 0.032) min after injecting luciferin-loaded albumin-shelled MBs. The delivery efficiency was, thus, improved with US-mediated release, allowing reduction of the total injection dose of luciferin.
