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Objective: To evaluate the relationship between change of effective lens position (ELP) and toric intraocular lens (IOL) rotation in patients with increasing postoperative refractive astigmatism after successful toric IOL implantation., Methods: The subjects include 61 people (61 eyes) with increasing residual astigmatism >0.5 D 3 months after successful toric IOL implantation. Clinical measurements included preoperative, 1-week, and 1-, 2-, and 3-month postoperative visual acuity; refraction; keratometer; anterior and posterior corneal astigmatism; ELP by Scheimpflug camera imaging; and IOL axis by slit-lamp biomicroscopic photograph with pupil dilation., Results: Residual astigmatism in postoperative month 3 (0.81 ± 0.50 D) is higher than that at postoperative week 1 (0.41 ± 0.38 D; p < 0.05). ELP decreased by 264.44 ± 163.25 μm, and the IOL rotated by 2.91 ± 1.44 degrees from week 1 to month 3 (p < 0.05). The ELP change had a positive correlation with IOL rotation (R 2  = 0.383; p = 0.006), and the postoperative refractive astigmatic change had a positive correlation with ELP change (R 2  = 0.272; p = 0.027) and IOL rotation (R 2  = 0.272; p = 0.0001) from week 1 to month 3., Conclusion: ELP change can influence toric IOL rotation and increase residual astigmatism after toric IOL implantation., (Copyright © 2024 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

This study strategically incorporates epidermal growth factor (EGF) and keratinocyte growth factor (KGF) within a hyaluronic acid (HA) hydrogel to enhance corneal wound healing. The controlled release of EGF and KGF from the HA hydrogel is engineered to promote the regeneration of both the epithelial and stromal layers. Specifically, EGF plays a pivotal role in the regeneration of the epithelial layer, while KGF exhibits efficacy in the regeneration of the stromal layer. The combination of these growth factors facilitates efficient regeneration of each layer and demonstrates the capability to modulate each other's regenerative effects. The interplay between EGF and KGF provides an understanding of their cooperative influence on the dynamics of corneal wound healing. The results of this study contribute to the development of advanced strategies for corneal wound management and offer insights into the complex process of corneal regeneration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background Aims: Corneal inflammation after alkali burns often results in vision loss due to corneal opacification and neovascularization. Mesenchymal stem cells (MSCs) and their secreted factors (secretome) have been studied for their anti-inflammatory and anti-angiogenic properties with encouraging results. However, topical instillation of MSCs or their secretome is often accompanied by issues related to delivery or rapid washout. Polyethylene glycol (PEG) and collagen are well-known biomaterials used extensively in scaffolds for tissue engineering. To effectively suppress alkaline burn-induced corneal injury, the authors proposed encapsulating MSCs within collagen gels cross-linked with multi-functional PEG-succinimidyl esters as a means to deliver the secretome of immobilized MSCs., Methods: Human MSCs were added to a neutralized collagen solution and mixed with a solution of four-arm PEG-N-hydroxysuccinimide. An ex vivo organ culture was conducted using rabbit corneas injured by alkali burn. MSCs were encapsulated within PEG-collagen hydrogels and injected onto the wounded cornea immediately following alkali burn and washing. Photographs of the ocular surface were taken over a period of 7 days after the alkali burn and processed for immunohistochemical evaluation. Samples were split into three groups: injury without treatment, MSCs alone, and MSCs encapsulated within PEG-collagen hydrogels., Results: All corneas in ex vivo organ culture lost their transparency immediately after alkali burn, and only the groups treated with MSCs and MSCs encapsulated within PEG-collagen hydrogels recovered some transparency after 7 days. Immunohistochemical analysis revealed increased expression of vimentin in the anterior corneal stroma of the group without treatment indicative of fibrotic healing, whereas less stromal vimentin was detected in the group containing MSCs encapsulated within the PEG-collagen hydrogels., Conclusions: PEG-collagen hydrogels enable the encapsulation of viable MSCs capable of releasing secreted factors onto the ocular surface. Encapsulating MSCs within PEG-collagen hydrogels may be a promising method for delivering their therapeutic benefits in cases of ocular inflammatory diseases, such as alkali burn injuries., (Published by Elsevier Inc.)

The neurobiological causes underlying suicidal behaviors in major depressive disorder (MDD) have not been identified. This study was performed to investigate the differences in brain cortical thickness, surface area, and volume between suicide attempters and non-attempters with MDD. We performed magnetic resonance imaging (MRI) in 38 MDD patients (18-65 years old; 18 male, 20 female) with and without a history of suicide attempts. FreeSurfer software was used to compare the cortical thickness, surface area, and volume of 19 suicide attempters with MDD and 19 suicide non-attempters with MDD, while controlling for age, sex, mean area (or volume), and severity of depression. Compared with suicide non-attempters, suicide attempters with MDD exhibited a larger surface area in the left postcentral area and left lateral occipital area and a larger cortical volume in the left postcentral area and left lateral orbitofrontal area. Suicide attempters exhibited a smaller surface area in the left superior frontal area than suicide non-attempters. The present findings provide evidence for neuroanatomical risk factors of suicide in MDD. Further research to replicate these results and determine the mechanisms underlying these findings is needed., Competing Interests: Declaration of Competing Interest The authors have indicated no financial conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The therapeutic effects of secreted factors (secretome) produced by bone marrow-derived human mesenchymal stem cells (MSCs) were evaluated as a function of their growth in 2D culture conditions and on 3D electrospun fiber scaffolds. Electrospun fiber scaffolds composed of polycaprolactone and gelatin were fabricated to provide a 3D microenvironment for MSCs, and their mechanical properties were optimized to be similar to corneal tissue. The secretome produced by the MSCs cultured on 3D fiber matrices versus 2D culture dishes were analyzed using a Luminex immunoassay, and the secretome of MSCs cultured on the 3D versus 2D substrates showed substantial compositional differences. Concentrations of factors such as HGF and ICAM-1 were increased over 5 times in 3D cultures compared to 2D cultures. In vitro proliferation and scratch-based wound healing assays were performed to compare the effects of the secretome on corneal fibroblast cells (CFCs) when delivered synchronously from co-cultured MSCs through a trans-well co-culture system versus asynchronously after harvesting the factors separately and adding them to the media. Cell viability of CFCs was sustained for 6 days when co-cultured with MSCs seeded on the fibers but decreased with time under other conditions. Scratch assays showed 95% closure at 48 h when CFCs were co-cultured with MSCs seeded on fibers, while the control group only exhibited 50% closure at 48 h. Electrospun fibers seeded with MSCs were then applied to a rabbit corneal organ culture system, and MSCs seeded on fibers promoted faster epithelialization and less scarring. Corneas were fixed and stained for alpha smooth muscle actin (α-SMA), and then analyzed by confocal microscopy. Immunostaining showed that expression of α-SMA was lower in corneas treated with MSCs seeded on fibers, suggesting suppression of myofibroblastic transformation. MSCs cultured on electrospun fibers facilitate wound healing in CFCs and on explanted corneas through differential secretome profiles compared to MSCs cultured on 2D substrates. Future work is merited to further understand the nature and basis of these differences and their effects in animal models. STATEMENT OF SIGNIFICANCE: Previous studies have shown that the secretome of bone marrow-derived mesenchymal stem cells (MSC) is promotes corneal wound healing by facilitating improved wound closure rates and reduction of scarring and neovascularization. The present research is significant because it provides evidence for the modulation of the secretome as a function of the MSC culture environment. This leads to differential expression of therapeutic factors secreted, which can impact corneal epithelial and stromal healing after severe injury. In addition, this article shows that co-continuous delivery of the MSC secretome improves cell migration and proliferation over aliquoted delivery, and that MSCs grown on three-dimensional electrospun fiber constructs may provide a favorable microenvironment for cultured MSCs and as a carrier to deliver their secreted factors to the ocular surface., (Copyright © 2019. Published by Elsevier Ltd.)

Many studies have revealed that the oxytocin receptor gene (OXTR) is associated with emotional salience and depression among females. Hippocampus is closely associated with the pathophysiology of major depressive disorder (MDD). However, little is known of the interaction effects of OXTR and MDD on hippocampal volume. We sought to investigate the interaction effects of OXTR (rs53576) allelic variants and MDD on hippocampal volumes which also including subfield volumes. The OXTR rs53576 genotype groups were categorized as minor G allele carriers and A allele homozygotes. A total of 47 female patients with depression and 30 healthy females were included in this study. There were significant interactions between OXTR allele type and diagnosis of MDD on the 7 hippocampal subfield volumes, such as left presubiculum, left subiculum, left molecular, right cornus ammonis 1, right granule cells in the molecular layer of the dentate gyrus, right molecular layer, and right subiculum. There were no differences in the hippocampal volumes between MDD vs healthy controls or OXTR A vs G alleles. Our results demonstrate the importance of the interactions between OXTR and MDD on hippocampal volume. Future studies with large sample size should expand those interactions in the whole brain volumes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: The postdischarge suicide rate in children and adolescents ever hospitalized for a psychiatric illness is much higher than that of children and adolescents in the general population. We aimed to investigate the postdischarge death and suicide among children and adolescents hospitalized for a psychiatric illness using the Korean National Health Insurance database and causes of death statistics from the National Statistics Office., Method: We identified children and adolescents less than 18 years of age who experienced at least one psychiatric hospitalization from 2008 to 2013 with a principal diagnosis of a psychiatric disorder based on the International Classification of Diseases, 10th Revision, Code Fxx.x). Postdischarge deaths (all-cause death or suicide) after the first psychiatric hospitalization were investigated., Results: The total number of patients hospitalized for a psychiatric illness was 14,097, and the numbers of all-cause deaths and suicide deaths after discharge were 93 and 64, respectively. The rates of suicide according by diagnostic group were 440.1 (per 100,000 person-years) for psychosis, 248.8 for depression, 155.4 for conduct disorder, 153.6 for bipolar disorder, 103.4 for posttraumatic stress disorder, 93.0 for anxiety disorder, and 38.4 for attention-deficit/hyperactivity disorder., Conclusion: As suicide is the main cause of postdischarge death, there is an urgent need to develop and implement effective prevention strategies after psychiatric hospitalization., (Copyright © 2018 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the effect of intraoperative complications during iris-claw phakic intraocular lens (pIOL) implantation on endothelial cell survival., Design: Retrospective cohort study., Participants: Fifty-two eyes of 26 patients with high myopia treated with the iris-claw pIOL., Methods: The patients were divided as group 1 (no intraoperative events) and 2 (intraoperative events) according to the intraoperative events such as intraoperative bleeding, postoperative intraocular pressure (IOP) rise, and late resolution of the chamber inflammation. Endothelial cell density was compared at 1, 2, 6, 12, and 24 months after the operation prospectively., Results: Group 1 showed mean percentage of individual change of -0.04%±7.90% at 1 month, -0.01%±8.67% at 2 months, -0.02%±10.33% at 6 months, 0.05%±9.81% at 12 months, and 0.05%±5.33% at 24 months postoperatively. In group 2, mean percentage individual cell change was -0.17%±8.57% at 1 month, -0.13%±12.14% at 2 months, -0.13%±15.07% at 6 months, -0.17%±11.94% at 12 months, and -0.28%±13.54% at 24 months postoperatively. Two groups showed a significant differences in every visit., Conclusions: Even transient events, such as intraoperative bleeding, postoperative IOP rise, and late resolution of the chamber inflammation, would affect the survival of endothelial cells., (Copyright © 2013 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Caspase-3 and caspase-7 are structurally closely related and demonstrate overlapping substrate specificity. However, during apoptosis, they are differentially regulated and show distinct subcellular localizations, implying the presence of specific substrates. In this study, to identify caspase-7 substrates, we treated the lysates derived from caspase-3-deficient MCF-7 cells with purified caspase-7 and analyzed decreased proteins by 2-DE. Intriguingly, several proteasome subunits such as alpha2, alpha6, and Rpt1 are degraded by caspase-7 during apoptosis in vitro and in vivo. Caspase-7 mediated cleavage of proteasome subunits results in the reduction of proteasome activity and thereby increases the accumulation of ubiquitinated proteins in cells. These findings suggest that caspase-7 facilitates the execution of apoptosis through down-regulation of the 26S proteasome, which regulates the turnover of proteins involved in the apoptotic process.

Apoptotic signals are typically accompanied by activation of aspartate-specific cysteine proteases called caspases, and caspase-3 and -7 play crucial roles in the execution of apoptosis. Previously, using the proteomic approach, protein disulfide isomerase (PDI) was found to be a candidate substrate of caspase-7. This abundant 55 kDa protein introduces disulfide bonds into proteins (via its oxidase activity) and catalyzes the rearrangement of incorrect disulfide bonds (via its isomerase activity). PDI is abundant in the ER but is also found in non-ER locations. In this study we demonstrated that PDI is cleaved by caspase-3 and -7 in vitro. In addition, in vivo experiment showed that it is cleaved during etoposide-induced apoptosis in HL-60 cells. Subcellular fractionation showed that PDI was also present in the cytosol. Furthermore, only cytosolic PDI was clearly digested by caspase-3 and -7. It was also confirmed by confocal image analysis that PDI and caspase-7 partially co-localize in both resting and apoptotic MCF-7 cells. Overexpression of cytosolic PDI (ER retention sequence deleted) inhibited cell death after an apoptotic stimulus. These data indicate that cytosolic PDI is a substrate of caspase-3 and -7, and that it has an anti-apoptotic action.