Objective　To investigate the expression of protein tyrosine kinase 2 (MFGE8) in patients with ischemic brain injury (IBI) and its regulation on macrophage polarization.Methods　ELISA was used to detect the expression of MFGE8 protein in peripheral blood of patients with ischemic stroke and middle cerebral artery occlusion (MCAO) rat models;IF was used to detect the localization and expression of MFGE8 in brain;BV-2 microglia was treated with the culture supernatant of N2a neuronal cells (Mfge8CA) stably transformed with Mfge8.The polarization ratio of macrophages was detected by flow cytometry.Western blot detection Mfge8,αv/β 3-integrin,FAK,NF-κB.ERK1/2,JNK1/2,P38,PI3K,AKT,mTOR protein expression.Results　The relative content of MFGE8 in peripheral blood of IBI patients and MCAO model rats was significantly lower than that of the control group (Ctrl,P=0.0446,P=0.0259).MFGE8 was highly co-localized with neuron cell marker (NeuN);the proportion of M1 type (CD45+F4/80+iNOS+Arginase1-) macrophages in the brain tissue of MCAO model was significantly higher than that in the Ctrl (P=0.0004).The proportion of M2 type (CD45+F4/80+iNOS-Arginase1+) macrophages was significantly lower than that of the Ctrl (P<0.0001).The proportion of M1 macrophages of BV-2 microglia after supernatant of N2a (mfge8CA) treatment was significantly lower than that of Wild type (WT,P=0.0230).The proportion of M2 macrophages was significantly higher (P<0.0001).The protein expressions of α v/β3-integrin,FAK,p-P85,P85,p-AKT (Ser473),p-mTOR (Ser2481) and p-mTOR (Ser2488) in BV-2 microglia after supernatant of N2a (mfge8CA) treatment were significantly higher than those in WT group.The expression of p-P65 protein was significantly lower than that in WT group.Conclusion　MFGE8 is highly expressed in peripheral blood of patients with IBI.MFGE8 derived from neuronal cells may promote BV-2 microglia M2 macrophages polarization by activating PI3K/AKT/mTOR signals,and inhibit the polarization of M1 macrophages.

Hyaluronic acid soft-tissue fillers are the second most widely used injectable agents in cosmetic surgery. During the coronavirus disease 2019 (COVID-19) pandemic, a few cases of delayed hypersensitivity reactions to hyaluronic acid filler injections have been reported following COVID-19 infection or vaccination against the virus. A 61-year-old woman visited the emergency room with swelling and redness on the entire face that started on the nasolabial area. She had received hyaluronic acid filler injections in her nasolabial area 8 months previously and had completed the primary series of vaccinations and received a booster dose of the mRNA Pfizer-BioNTech COVID-19 vaccine 1 month before the swelling episode. A corticosteroid was added to the antibiotic regimen because of the nonsignificant effect of the antibiotics. The symptoms then resolved, and corticosteroid use was tapered over the course of 2 weeks. Four months later, swelling and redness recurred on both nasolabial folds and chin, but the symptoms were more localized than before. The renewed symptoms regressed with surgical drainage and corticosteroid and antibiotic treatment. This study discusses this extremely rare case of a recurrent delayed hypersensitivity reaction to a hyaluronic acid soft-tissue filler following COVID-19 vaccination.

Purpose: To investigate the cytokine concentrations of aqueous humor in patients with exudative age-related macular degeneration (AMD) and diabetic macular edema (DME). Methods: Fifty-seven subjects were included in the exudative AMD, DME and control groups, each group has 19 patients. Aqueous levels of cytokines epidermal growth factor (EGF), vascular endothelial growth factor-C (VEGF-C), monocyte chemoattractant protein-1 (MCP-1), hepatocyte growth factor (HGF), interleukin (IL)-3, IL-8, IL-6, IL-12p40, intercellular adhesion molecule 1 (ICAM-1) were investigated in each groups. Kruskal-Wallis test and Mann-Whitney U test were performed to compare cytokine concentrations. Results: Aqueous levels of EGF, VEGF-C, MCP-1, HGF, IL-3, IL-8 were significantly higher in exudative AMD group than control group (p = < 0.0001, < 0.0001, 0.004, 0.015, < 0.0001, 0.014) and EGF, VEGF-C, IL-3, IL-8 were significantly higher in DME group than control group (p = < 0.0001, < 0.0001, < 0.0001, 0.005). In the comparison between the exudative AMD and DME groups, EGF was significantly higher in the exudative AMD group (p = 0.001). Conclusions Various cytokines were increased in patients with exudative AMD and DME. In particular, EGF showed a higher level in exudative AMD than in DME.

Liver transplantation has been regarded as the definitive curative approach for pathologic liver conditions from the acute stage to the chronic end stage for decades. Recently, translational research has been focused on liver stem cell transplantation, using various cell therapies, due to the potential benefit of natural host liver regeneration. Many studies are ongoing utilizing and evaluating the use of either fetal-liver-derived stem cells or oval cells, however many obstacles still remain. Extensive research identifying and characterizimg stem/progenitor cells for potential application to in vitro cell therapy, whereas many questions remain concerning the isolation and identification of adult liver stem cells with adequate capacity for proliferation and the regeneration of injured liver. Recent approaches to liver regeneration include the production of hepatocyte-like cells from other stem cell sources such as mesenchymal stem cells and embryonic stems cells. Another major target for liver regeneration studies include the generation of liver stem cells from induced pluripotent stem cells (IPSC) We review the current data concerning characterization of stem cells and progenitor cells for their capacity to support their potential for re-population and regeneration of normal adult liver from liver damaged due to injury and/or disease.
Adult ; Cell Transplantation ; Cell- and Tissue-Based Therapy ; Humans ; Induced Pluripotent Stem Cells ; Liver Regeneration ; Liver Transplantation ; Liver* ; Mesenchymal Stromal Cells ; Regeneration ; Stem Cell Transplantation ; Stem Cells* ; Translational Medical Research

Background: Verruca vulgaris is a common cutaneous viral infectious disease caused by human papilloma virus (HPV). The main treatment modalities are cryotherapy, immunotherapy, laser therapy, intralesional injection of bleomycin, and salicylic acid therapy. However, there is no definitive tool for predicting clinical improvement or treatment response. Objective: This study was designed to evaluate clinical treatment response according to the hardness of verruca vulgaris skin lesions. We developed a new prediction tool called the “hardening sign” that divides the course of treatment into four categories based on inspection and palpation. Methods: We conducted a retrospective medical chart review of patients who visited Hanyang University Guri Hospital between January 2016 and January 2017 and were clinically diagnosed with verruca vulgaris. We divided the patients into four groups according to the grade of rigidity of their lesions. Results: Forty-seven patients (24 male and 23 female) were identified. The mean age at diagnosis was 17.2±8.5 years, and the mean duration of treatment was 28.8±27.7 weeks. The mean number of hospital visits was 16.5±12.4. Eleven patients underwent only cryotherapy, while 36 patients underwent combined cryotherapy and immunotherapy. We observed significantly shorter durations of treatment for patients with higher grades of hardening. There was no correlation between the hardening grade and the number of treatments required for patients to be completely cured. Conclusion This study suggests that the therapeutic response of verruca vulgaris warts to cryotherapy can be easily predicted by careful consideration of the “hardening sign”.

No abstract available.
Breast ; Carcinoma, Ductal ; Neoplasm Metastasis

Purpose: To report a case of massive retinal hemorrhage during epiretinal membrane (ERM) peeling in a patient with iron deficiency anemia (IDA).Case summary: A 59-year-old female presented with gradually decreasing visual acuity and dysmorphopsia in the right eye for several months. She had a history of chronic IDA due to subtotal gastrectomy from gastric cancer 20 years prior. The patient was diagnosed as having macular ERM and underwent vitrectomy. During ERM peeling with intraocular forceps, we found a massive retinal hemorrhage which was presumed to have originated from the superotemporal branched retinal artery. After hemostasis, the operation was completed without critical complications. However, 2 months after surgery, the patient presented with decreased visual acuity once again. In fundus examination, diffuse macular tractional ERM was evident in the proximity of the previous intraoperative hemorrhage site. The patient underwent tractional membrane and internal limiting membrane removal surgery. The patient is currently undergoing follow-up without complications to date following the second surgery. Conclusions Our case study describes a patient having experienced massive retinal hemorrhage presumably having originated from a superotemporal branched retinal artery during ERM peeling. We speculate that the endothelial cells of retinal vessels are more vulnerable than normal in patients with severe chronic IDA.

Purpose: To report a case of massive retinal hemorrhage during epiretinal membrane (ERM) peeling in a patient with iron deficiency anemia (IDA).Case summary: A 59-year-old female presented with gradually decreasing visual acuity and dysmorphopsia in the right eye for several months. She had a history of chronic IDA due to subtotal gastrectomy from gastric cancer 20 years prior. The patient was diagnosed as having macular ERM and underwent vitrectomy. During ERM peeling with intraocular forceps, we found a massive retinal hemorrhage which was presumed to have originated from the superotemporal branched retinal artery. After hemostasis, the operation was completed without critical complications. However, 2 months after surgery, the patient presented with decreased visual acuity once again. In fundus examination, diffuse macular tractional ERM was evident in the proximity of the previous intraoperative hemorrhage site. The patient underwent tractional membrane and internal limiting membrane removal surgery. The patient is currently undergoing follow-up without complications to date following the second surgery. Conclusions Our case study describes a patient having experienced massive retinal hemorrhage presumably having originated from a superotemporal branched retinal artery during ERM peeling. We speculate that the endothelial cells of retinal vessels are more vulnerable than normal in patients with severe chronic IDA.

Background: and purpose: The anti-aging standard forest healing program (ASFHP), which uses forest therapy, was reported to be effective in improving psychological, physical, and cognitive functions. However, there are several challenges to directly visiting the forest. This study aimed to investigate the impact of multi-session ASFHP with forest visit on the mental and physical health of the older people with visits to forest facilities and compared them with those of the same program conducted indoors. Methods: Individuals aged over 70 years with concerns about cognitive decline were recruited at dementia relief centers and divided into control and experimental groups. A total of 33 people were administered ASFHP under the supervision of a forest therapy instructor. The control group stayed indoors, while the experimental group visited a forest healing center and repeated the program 20 weeks. Results: The multiple-session ASFHP positively affected cognitive impairment screening test (CIST) total scores (p=0.002), memory (p=0.014), Korean version of the Repeatable Battery for the Assessment of Neuropsychological Status total scores (p<0.001), immediate recall (p=0.001), visuospatial/construction (p<0.001), language (p<0.001), forest healing standard questionnaire total scores (p=0.002), and cognitive function (p=0.019), regardless of location. The forest visits during the ASFHP showed positive effects on orientation (p=0.035), delayed recall (p=0.042), emotional stability (p=0.032), physical activity (p=0.005), and health (p=0.022). The CIST scores of the memory domain were the strongest indicator of the multiple-session ASFHP effects. Conclusions The 20-week multi-session ASFHP with forest visit showed effects on cognitive improvement and physical and emotional stability compared to indoor education.

Silent information regulator 2 (Sirtuin2 / SIRT2) is a NAD⁺-dependent deacetylase that regulates the cellular oxidative stress response. It modulates transcriptional silencing and protein stability through deacetylation of target proteins including histones. Previous studies have shown that SIRT2 plays a role in mood disorders and hippocampus-dependent cognitive function, but the underlying neurobiological mechanism is poorly understood. Here, we report that chronic stress suppresses SIRT2 expression in the hippocampus. Molecular and biochemical analyses indicate that the stress-induced decrease in the SIRT2 expression downregulates synaptic plasticity-related genes in the hippocampus through the increase of euchromatic histone-lysine N-methyltransferase 2 (Ehmt2) (also known as G9a). shRNA-mediated knockdown of SIRT2 in the dentate gyrus alters the expression of synaptic plasticity-related genes in a way similar to those induced by chronic stress, and produces depression-like behaviors. Our results indicate that SIRT2 plays an important role in the response to stress, thereby modulating depression-like behaviors.
Cognition ; Dentate Gyrus ; Depression ; Down-Regulation ; Hippocampus ; Histone-Lysine N-Methyltransferase ; Histones ; Mood Disorders ; Neuronal Plasticity ; Oxidative Stress ; Protein Stability ; Up-Regulation