Intraocular Povidone Iodine During Pars Plana Vitrectomy for Severe and Atypical Endophthalmitis.

BACKGROUND AND OBJECTIVE: To describe the experience and clinical outcomes of povidone iodine (PI) infusion in the setting of pars plana vitrectomy for the treatment of endophthalmitis. MATERIALS AND METHODS: This was a retrospective case series of 12 patients with clinical and/or culture evidence of endophthalmitis requiring pars plana vitrectomy with 0.025% PI used in vitreous irrigation solution during vitrectomy. The primary endpoint was clinical resolution of the infection. Secondary endpoints included visual recovery, need for repeat surgery, and ocular toxicity RESULTS: There were 11 eyes that showed clinical or culture evidence of resolution of infection postoperatively (91.7%); 10 eyes had improvement in vision postoperatively (83.3%). Overall uncorrected visual acuity improved from 20/5321 (2.43 ± 0.58 logMAR) to 20/375 (1.27 ± 1.05 logMAR) (P = .0003). No clinical evidence of ocular toxicity or unexplained vision loss due to PI was observed. CONCLUSIONS: PI infusion during pars plana vitrectomy for endophthalmitis appears safe and led to excellent post-surgical results in a traditionally high-risk cohort. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:485-490.].

Effect of Cr on the Mineral Structure and Composition of Cement Clinker and Its Solidification Behavior.

In order to reveal the solidification behavior of Cr in the cement clinker mineral phase, 29Si magic-angle spinning nuclear magnetic resonance, X-ray diffraction, and scanning electron microscopy with energy-dispersive X-ray spectroscopy techniques were used to analyze the morphology and composition of the cement clinker mineral phase doped with Cr. The results showed that the addition of Cr did not change the chemical environment of 29Si in the clinker mineral phase, and it was still an isolated silicon-oxygen tetrahedron. Cr affected the orientation of the silicon-oxygen tetrahedron and the coordination number of calcium, leading to the formation of defects in the crystal structure of the clinker mineral phase, by replacing Ca2+ into the mineral phase lattice to form a new mineral phase Ca3Cr2(SiO4)3. Cr acted as a stabilizer for the formation of ß-C2S in the clinker calcination. As the amount of Cr increased, the relative content of C3S decreased and the relative content of C2S increased. Further, Cr easily dissolved in C2S, while it was not found in C3S. This study is conducive to further research on the mechanism of heavy metal solidification in cement clinker. Furthermore, it is important to evaluate the environmental risk of heavy metals in the process of sludge disposal through cement kiln and promote the utilization of sludge resources and the sustainable development of the cement industry.

Ezh2 Regulates Activation-Induced CD8+ T Cell Cycle Progression via Repressing Cdkn2a and Cdkn1c Expression.

Transition from resting to cell cycle in response to antigenic stimulation is an essential step for naïve CD8+ T cells to differentiate to effector and memory cells. Leaving the resting state requires dramatic changes of chromatin status in the key cell cycle inhibitors but the details of these concerted events are not fully elucidated. Here, we showed that Ezh2, an enzymatic component of polycomb repressive complex 2 (PRC2) catalyzing the trimethylation of lysine 27 on histone 3 (H3K27me3), regulates activation induced naïve CD8+ T cells proliferation and apoptosis. Upon deletion of Ezh2 during thymocyte development (Ezh2fl/flCd4Cre+ mice), naive CD8+ T cells displayed impaired proliferation and increased apoptosis in response to antigen stimulation. However, naive CD8+ T cells only had impaired proliferation but no increase in apoptosis when Ezh2 was deleted after activation (Ezh2fl/flGzmBCre+ mice), suggesting cell cycle and apoptosis are temporally separable events controlled by Ezh2. We then showed that deletion of Ezh2 resulted in the increase in expression of cyclin-dependent kinase inhibitors Cdkn2a (p16 and Arf) and Cdkn1c (p57) in activated naïve CD8+ T cells as the consequence of reduced levels of H3K27me3 at these two gene loci. Finally, with real time imaging, we observed prolonged cell division times of naïve CD8+ T cells in the absence of Ezh2 post in vitro stimulation. Together, these findings reveal that repression of Cdkn1c and Cdkn2a by Ezh2 plays a critical role in execution of activation-induced CD8+ T cell proliferation.

Hyperglycemia-suppressed expression of Serpine1 contributes to delayed epithelial wound healing in diabetic mouse corneas.

PURPOSE: Patients with diabetes mellitus (DM) are at an increased risk for developing corneal complications, including delayed wound healing. The purpose of this study was to characterize the expression and the function of Serpine1 and other components of urokinase plasminogen activator (uPA)-proteolytic system in delayed epithelial wound healing in diabetic mouse corneas. METHODS: Mice of the strain C57BL/6 were induced to develop diabetes by streptozotocin, and wound-healing assays were performed 10 weeks afterward. Gene expression and/or distribution were assessed by real-time PCR, Western blotting, and/or immunohistochemistry. The role of Serpine1 in mediating epithelial wound closure was determined by subconjunctival injections of neutralizing antibodies in either normal or recombinant protein in diabetic corneas. Enzyme assay for matrix metalloproteinase (MMP)-3 was also performed. RESULTS: The expressions of Serpine1 (PAI-1), Plau (uPA), and Plaur (uPA receptor) were upregulated in response to wounding, and these upregulations were significantly suppressed by hyperglycemia. In healing epithelia, Plau and Serpine1 were abundantly expressed at the leading edge of the healing epithelia of normal and, to a lesser extent, diabetic corneas. Inhibition of Serpine1 delayed epithelial wound closure in normal corneas, whereas recombinant Serpine1 accelerated it in diabetic corneas. The Plau and MMP-3 mRNA levels and MMP-3 enzymatic activities were correlated to Serpine1 levels and/or the rates of epithelial wound closure. CONCLUSIONS: Serpine1 plays a role in mediating epithelial wound healing and its impaired expression may contribute to delayed wound healing in DM corneas. Hence, modulating uPA proteolytic pathway may represent a new approach for treating diabetic keratopathy.

Genome-wide transcriptional analysis of differentially expressed genes in diabetic, healing corneal epithelial cells: hyperglycemia-suppressed TGFß3 expression contributes to the delay of epithelial wound healing in diabetic corneas.

Patients with diabetes mellitus (DM) may develop corneal complications and delayed wound healing. The aims of this study are to characterize the molecular signatures and biological pathways leading to delayed epithelial wound healing and to delineate the involvement of TGFß3 therein. Genome-wide cDNA microarray analysis revealed 1,888 differentially expressed genes in the healing epithelia of normal (NL) versus type 1 DM rat corneas. Gene ontology and enrichment analyses indicated TGFß signaling as a major altered pathway. Among three TGFß isoforms, TGF-ß1 and ß3 were upregulated in response to wounding in NL corneal epithelial cells (CECs), whereas the latter was greatly suppressed by hyperglycemia in rat type 1 and 2 and mouse type 1 DM models. Functional analysis indicated that TGF-ß3 contributed to wound healing in NL corneas. Moreover, exogenously added TGF-ß3 accelerated epithelial wound closure in type 2 rat and type 1 mouse DM corneas via Smad and PI3K-AKT signaling pathways, autoregulation, and/or upregulation of Serpine1, a well-known TGFß target gene. Taken together, our study for the first time provides a comprehensive list of genes differentially expressed in the healing CECs of NL versus diabetic corneas and suggests the therapeutic potential of TGF-ß3 for treating corneal and skin wounds in diabetic patients.

Systemic analyses of immunophenotypes of peripheral T cells in non-segmental vitiligo: implication of defective natural killer T cells.

Although it is widely believed that non-segmental vitiligo (NSV) results from the autoimmune destruction of melanocytes, a clear understanding of defects in immune tolerance, which mediate this uncontrolled self-reactivity, is still lacking. In the present study, we systemically evaluated circulating regulatory T (Treg) cells, including CD4(+) CD25(+) FoxP3(+) Treg cells and invariant natural killer T (iNKT) cells, as well as naïve and memory CD4(+) and CD8(+) T cells and their cytokine production, in a cohort of 43 progressive NSV patients with race-, gender-, and age-matched healthy controls. We found that the general immunophenotypes of CD4(+) and CD8(+) T cells and the percentage of CD4(+) CD25(+) FoxP3(+) Tregs were comparable between NSV and healthy controls. However, percentages of peripheral iNKT cells were significantly decreased in NSV patients compared to that in healthy controls. Our data confirm the previous notion that the percentage of peripheral CD4(+) CD25(+) FoxP3(+) Tregs remains unaltered in NSV and suggests the involvement of defective iNKT cells in the pathogenesis of NSV.

Lack of an association of miR-938 SNP in IDDM10 with human type 1 diabetes.

MicroRNAs (miRNAs) are a newly discovered type of small non-protein coding RNA that function in the inhibition of effective mRNA translation, and may serve as susceptibility genes for various disease developments. The SNP rs12416605, located in human type 1 diabetes IDDM10 locus, changes the seeding sequence (UGU[G/A]CCC) of miRNA miR-938 and potentially alters miR-938 targets, including IL-16 and IL-17A. In an attempt to test whether miR-938 may be a susceptibility gene for IDDM10, we assessed the possible association of the miR-938 SNP with T1D in an American Caucasian cohort of 622 patients and 723 healthy controls by TaqMan assay. Our current data do not support the association between the SNP in miR-938 and type 1 diabetes.