The aim of this case control study was to evaluate the prognostic value of automatically quantified retinal vessel tortuosity from fundus images and vessel density from OCT-A in Fabry disease and to evaluate the correlation of these with systemic disease parameters.
Methods
Automatically quantified perimacular retinal vessel tortuosity (MONA REVA software), acquired by fundus imaging, and perifoveal retinal vessel density, acquired by optic coherence tomography angiography (OCT-A) were compared between 26 FD patients and 26 controls. Gender and FD phenotype were analyzed to the obtained retinovascular data and correlated to the Mainz severity score index (MSSI) and plasma lyso-Gb3.
Results
Automatically quantified retinal vessel tortuosity indices of FD patients were significantly lower, reflecting an increased vessel tortuosity, compared to controls (p = 0.008). Males with a classical phenotype showed significantly lower retinal vessel tortuosity indices compared to males with an oligosymptomatic phenotype and females with a classical or oligosymptomatic phenotype (p < 0.001). The retinal vessel tortuosity index correlated significantly with systemic disease severity parameters [global MSSI (r = − 0.5; p < 0.01), cardiovascular MSSI (r = − 0.5; p < 0.01), lyso-Gb3 (r = − 0.6; p < 0.01)].
Conclusion
We advocate fundus imaging based automatically quantified retinal vessel tortuosity index over OCT-A imaging as it is a quick, non-invasive, easily assessable, objective and reproducible marker.
Hundreds of millions of people worldwide are affected by Chagas’ disease caused by Trypanosoma cruzi. Since the current treatment lack efficacy, specificity, and suffers from several side-effects, novel therapeutics are mandatory. Natural products from endophytic fungi have been useful sources of lead compounds. In this study, three lactones isolated from an endophytic strain culture were in silico evaluated for rational guidance of their bioassay screening. All lactones displayed in vitro activity against T. cruzi epimastigote and trypomastigote forms. Notably, the IC50 values of (+)-phomolactone were lower than benznidazole (0.86 vs. 30.78 μM against epimastigotes and 0.41 vs. 4.88 μM against trypomastigotes). Target-based studies suggested that lactones displayed their trypanocidal activities due to T. cruzi glyceraldehyde-3-phosphate dehydrogenase (TcGAPDH) inhibition, and the binding free energy for all three TcGAPDH-lactone complexes suggested that (+)-phomolactone has a lower score value (−3.38), corroborating with IC50 assays. These results highlight the potential of these lactones for further anti-T. cruzi drug development. 相似文献
Apoptosis - Around three out of one hundred thousand people are diagnosed with glioblastoma multiforme, simply called glioblastoma, which is the most common primary brain tumor in adults. With a... 相似文献
Biological Invasions - Oystershell scale (OSS; Lepidosaphes ulmi) is an emerging invasive insect that poses a serious threat to conservation of quaking aspen (Populus tremuloides) in the... 相似文献
Since the identification of the apolipoprotein E (apoE) *ε4 allele as a major genetic risk factor for late-onset Alzheimer's disease, significant efforts have been aimed at elucidating how apoE4 expression confers greater brain amyloid-β (Aβ) burden, earlier disease onset and worse clinical outcomes compared to apoE2 and apoE3. ApoE primarily functions as a lipid carrier to regulate cholesterol metabolism in circulation as well as in the brain. However, it has also been suggested to interact with hydrophobic Aβ peptides to influence their processing in an isoform-dependent manner. Here, we review evidence from in vitro and in vivo studies extricating the effects of the three apoE isoforms, on different stages of the Aβ processing pathway including synthesis, aggregation, deposition, clearance and degradation. ApoE4 consistently correlates with impaired Aβ clearance, however data regarding Aβ synthesis and aggregation are conflicting and likely reflect inconsistencies in experimental approaches across studies. We further discuss the physical and chemical properties of apoE that may explain the inherent differences in activity between the isoforms. The lipidation status and lipid transport function of apoE are intrinsically linked with its ability to interact with Aβ. Traditionally, apoE-oriented therapeutic strategies for Alzheimer's disease have been proposed to non-specifically enhance or inhibit apoE activity. However, given the wide-ranging physiological functions of apoE in the brain and periphery, a more viable approach may be to specifically target and neutralise the pathological apoE4 isoform. 相似文献
The deleterious effects of reactive oxygen species (ROS), including singlet oxygen (1O2), on biological systems have cultivated widespread interest in fields ranging from therapeutic techniques to sterilization materials. Researchers have, for example, sought to capitalize on the oxidative damage from singlet oxygen to treat tumors as well as to kill antibiotic resistant bacteria. To generate 1O2 in a controllable manner, photosensitizers are optimized to generate 1O2 from ground state oxygen (3O2) when excited by light. When considering applications of photosensitization, favorable properties include high 1O2 yield, low synthetic complexity, and minimal cost. Previously, studies have shown that plasmonic nanoparticles are able to amplify the photosensitization of 1O2 from small molecule photosensitizers in a mechanism similar to metal-enhanced fluorescence (MEF), thereby improving yield. A recent study from our lab has demonstrated that brominated carbon nanodots, which are an inexpensive and simple-to-collect as a hydrocarbon combustion byproduct, generate reactive oxygen species that can be used for antimicrobial photodynamic inactivation of bacteria. Herein we investigate the combination of these advantageous properties. Using the turn-on fluorescent probe Singlet Oxygen Sensor Green™ to detect 1O2, we report the metal-enhanced photosensitization of 1O2 by brominated dots in silvered Quanta Plate™ wells. These results provide a promising direction for the potential optimization of carbon nanodot-based agents in light-activated antimicrobial materials.
Clathrin-mediated endocytosis has long been viewed as a process driven by core endocytic proteins, with internalized cargo proteins being passive. In contrast, an emerging view suggests that signaling receptor cargo may actively control its fate by regulating the dynamics of clathrin-coated pits (CCPs) that mediate their internalization. Despite its physiological implications, very little is known about such “cargo-mediated regulation” of CCPs by signaling receptors. Here, using multicolor total internal reflection fluorescence microscopy imaging and quantitative analysis in live cells, we show that the μ-opioid receptor, a physiologically relevant G protein–coupled signaling receptor, delays the dynamics of CCPs in which it is localized. This delay is mediated by the interactions of two critical leucines on the receptor cytoplasmic tail. Unlike the previously known mechanism of cargo-mediated regulation, these residues regulate the lifetimes of dynamin, a key component of CCP scission. These results identify a novel means for selectively controlling the endocytosis of distinct cargo that share common trafficking components and indicate that CCP regulation by signaling receptors can operate via divergent modes. 相似文献
Cenozoic bird tracks are known largely from North America, Europe, and the Middle East. There have been no reports of Cenozoic bird tracks from East Asia. This paper describes a series of two trackways produced by a galliform-like or gruiform-like bird from the Oligocene to Early Miocene of Tibet. The tracks are represented by tracings collected from a coal mine in Shigatse, Tibet, during the late 1970s. The tracks are comparable to Ornithoformipes and Pavoformipes and likely represent a medium-sized to large cursorial or flightless bird. In relation to modern bird tracks, the tracks bear a striking resemblance to those produced by the North American Wild Turkey (Meleagris gallopavo) except that M. gallopavo tracks often possess a small, elevated hallux impression. Due to the fact that these are tracings, however, a hallux may have been present and simply have been overlooked. The Shigatse trackways were, unfortunately, lost when the mine was closed and then backfilled during the 1980s, and there is little to no likelihood of recovery. Casts can be catalogued as holotype specimens but tracings cannot; however, all the original tracings have been donated to a public institution by their discoverer, Yimin Wu. 相似文献