This study evaluated whether arginine (Arg) supplementation could attenuate gut injury induced by Escherichia coli lipopolysaccharide (LPS) challenge through an anti-inflammatory role in weaned pigs. Pigs were allotted to four treatments including: (1) non-challenged control; (2) LPS-challenged control; (3) LPS þ 0·5 % Arg; (4) LPS þ 1·0 % Arg. On day 16, pigs were injected with LPS or sterile saline. At 6 h postinjection, pigs were killed for evaluation of small intestinal morphology and intestinal gene expression. Within 48 h of challenge, 0·5 % Arg alleviated the weight loss induced by LPS challenge (P¼ 0·025). In all three intestinal segments, 0·5 or 1·0 % Arg mitigated intestinal morphology impairment (e.g. lower villus height and higher crypt depth) induced by LPS challenge (P, 0·05), and alleviated the decrease of crypt cell proliferation and the increase of villus cell apoptosis after LPS challenge (P,0·01). The 0·5 % Arg prevented the elevation of jejunal IL-6 mRNA abundance (P¼ 0·082), and jejunal (P¼0·030) and ileal (P¼ 0·039) TNF-a mRNA abundance induced by LPS challenge. The 1·0 % Arg alleviated the elevation of jejunal IL-6 mRNA abundance (P¼ 0·053) and jejunal TNF-a mRNA abundance (P¼ 0·003) induced by LPS challenge. The 0·5 % Arg increased PPARg mRNA abundance in all three intestinal segments (P, 0·10), and 1·0 % Arg increased duodenal PPARg mRNA abundance (P¼ 0·094). These results indicate that Arg supplementation has beneficial effects in alleviating gut mucosal injury induced by LPS challenge. Additionally, it is possible that the protective effects of Arg on the intestine are associated with decreasing the expression of intestinal proinflammatory cytokines through activating PPARg expression.
Purpose To investigate the effect of signal strength on the measurement of the retinal nerve fiber layer (RNFL) using optical coherence tomography (OCT). Methods Eyes with known or suspected glaucoma or non-glaucomatous optic atrophy were scanned twice within the same visit using Stratus OCT's Fast Nerve Fiber Layer Thickness (FNFLT) protocol. Only those eyes with two high quality scans (signal strengths of at least 5 and different from each other, no error messages, and no obvious segmentation errors) were included in the study. The RNFL thickness measurements from the initial and the repeat scans were compared and then correlated with the differences in signal strength. Subgroup analyses were performed similarly among patients with average RNFL thickness less than 90 microns and those with at least 90 microns. Results Scans with higher signal strengths are associated with greater RNFL thickness measurements if the signal strength is less than 7. Scans with signal strength of at least 7 have higher reproducibility. This is true among all patients as well as subgroups divided on the basis of average RNFL thickness. Additionally, we found that the greater the variability between the initial and repeat scans, the greater the variability in the RNFL thickness measurements. Scans with higher signal strengths have less variability, especially when the optic nerve is relatively healthy. Conclusions When measuring the RNFL thickness with the Stratus OCT, it is important to aim for a signal strength of at least 7. Visual field testing may be more reliable in some patients, especially when the optic nerve is significantly compromised.
Human induced pluripotent stem cells (iPSCs) provide a valuable model for regenerative medicine and human disease research. To date, however, the reprogramming efficiency of human adult cells is still low. Recent studies have revealed that cell cycle is a key parameter driving epigenetic reprogramming to pluripotency. As is well known, retroviruses such as the Moloney murine leukemia virus (MoMLV) require cell division to integrate into the host genome and replicate, whereas the target primary cells for reprogramming are a mixture of several cell types with different cell cycle rhythms. Whether cell cycle synchronization has potential effect on retrovirus induced reprogramming has not been detailed. In this study, utilizing transient serum starvation induced synchronization, we demonstrated that starvation generated a reversible cell cycle arrest and synchronously progressed through G2/M phase after release, substantially improving retroviral infection efficiency. Interestingly, synchronized human dermal fibroblasts (HDF) and adipose stem cells (ASC) exhibited more homogenous epithelial morphology than normal FBS control after infection, and the expression of epithelial markers such as E-cadherin and Epcam were strongly activated. Futhermore, synchronization treatment ultimately improved Nanog positive clones, achieved a 15–20 fold increase. These results suggested that cell cycle synchronization promotes the mesenchymal to epithelial transition (MET) and facilitates retrovirus mediated reprogramming. Our study, utilization of serum starvation rather than additional chemicals, provide a new insight into cell cycle regulation and induced reprogramming of human cells.
Purpose-To compare macular thickness measurements using time domain optical coherence tomography (OCT) and Fourier domain OCT (FD OCT).Methods-Thirty-two eyes from 32 normal patients underwent complete ophthalmic evaluation. Macular scanning using the StratusOCT and the RTVue-100 OCT were performed for a total of 3 times each on the same visit. The average retinal thicknesses of the 9 macular sectors as defined by the Early Treatment Diabetic Retinopathy Study (ETDRS), along with the foveal center point and macular volume, were recorded. The standard deviation, the coefficient of variation, and the intraclass correlation coefficient were calculated for each parameter studied. Comparisons were made between the two OCTs in terms of retinal thicknesses measurements, their reproducibility, and macular regional differences. Correlations between retinal thickness and demographic variables (age and gender) were also investigated. Due to known differences in segmentation algorithms of the two OCTs, software calipers were used to measure the distance from the internal limiting membrane to the photoreceptor inner segment--outer segment junction at the foveal center point on all RTVue scans in order to allow a more fair comparison. Results-TheRTVue yielded greater retinal thickness measurements in nearly all macular subfields compared to the StratusOCT. Even after accounting for differences in segmentation algorithms, significant disparities were still evident with the RTVue measurements less than those of the StratusOCT at the foveal center. On both machines, the macula was thinnest at the fovea and thickest within the 3mm ring. There were some consistent regional variations in macular thickness evident on both OCTs. Compared to the StratusOCT, the RTVue generally had lower coefficients of variation and higher intraclass coefficients, suggesting better reproducibility. Age and gender also appeared to be important determinants in some macular thickness parameters. The evolution of OCT has been a step-wise process, starting from the prototype through the development of the first, second, and third generations of commercially available instruments. Each successor had been an improvement over the predecessor in terms of imaging speed and resolution, but the underlying concepts had largely remained the same. In these so-called time domain OCTs (TD OCT), a mechanical moving mirror is crucial for extracting depth information for light reflected from the retina. Therefore, data acquisition speed is limited by the relatively slow mechanical movement. Conclusion-ComparedThe latest time domain model in widespread use, the StratusOCT (Carl Zeiss Meditec, Dublin, CA), has an axial resolution of 8 to 10 μm and a maximum of 512 transverse and 1024 axial data points per image acquired over 1.25 seconds, according to the user's manual. Because eye movement may induce significant errors in measurement, the StratusOCT also allows the user to choose scanning protocols that may increase the image acquisition speed at the expense of tr...
Choroidal neovascularization (CNV) is an important characteristic of advanced wet age‐related macular degeneration (AMD) and leads to severe visual impairment among elderly patients. Previous studies have demonstrated that melatonin induces several biological effects related to antioxidation, anti‐inflammation, and anti‐angiogenesis. However, the role of melatonin in CNV, and its underlying mechanisms, has not been investigated thus far. In this study, we found that melatonin administration significantly reduced the scale and volume of CNV lesions, suppressed vascular leakage, and inhibited the capacity of vascular proliferation in the laser‐induced mouse CNV model. Additionally, the results also show that the melatonin‐treated retinal microglia in the laser‐induced mice exhibited enhanced expression of M1‐type markers, such as iNOS, CCL‐3, CCL‐5, and TNF‐α, as well as decreased production of M2‐type markers, such as Arg‐1, Fizz‐1, IL‐10, YM‐1, and CD206, indicating that melatonin switched the macrophage/microglia polarization from pro‐angiogenic M2 phenotype to anti‐angiogenic M1 phenotype. Furthermore, the RhoA/ROCK signaling pathway was activated during CNV formation, yet was suppressed after an intraperitoneal injection of melatonin. In conclusion, melatonin attenuated CNV, reduced vascular leakage, and inhibited vascular proliferation by switching the macrophage/microglia polarization from M2 phenotype to M1 phenotype via inhibition of RhoA/ROCK signaling pathway in CNV. This suggests that melatonin could be a novel agent for the treatment of AMD.
Thickness measurements are not interchangeable among different OCT devices because of the poor-to-moderate interdevice measurement agreement. FD instruments yield more reproducible macular but not RNFL thickness measurements.
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