Defining the molecular dynamics associated with T cell differentiation enhances our understanding of T cell biology and opens up new possibilities for clinical implications. In this study, we investigated the dynamics of CD5 expression in CD8+ T cell differentiation and explored its potential clinical uses. Using PBMCs from 29 healthy donors, we observed a stepwise decrease in CD5 expression as CD8+ T cells progressed through the differentiation stages. Interestingly, we found that CD5 expression was initially upregulated in response to T cell receptor stimulation, but diminished as the cells underwent proliferation, potentially explaining the differentiation-associated CD5 downregulation. Based on the proliferationdependent downregulation of CD5, we hypothesized that relative CD5 expression could serve as a marker to distinguish the heterogeneous CD8+ T cell population based on their proliferation history. In support of this, we demonstrated that effector memory CD8+ T cells with higher CD5 expression exhibited phenotypic and functional characteristics resembling less differentiated cells compared to those with lower CD5 expression. Furthermore, in the retrospective analysis of PBMCs from 30 non-small cell lung cancer patients, we found that patients with higher CD5 expression in effector memory T cells displayed CD8+ T cells with a phenotype closer to the less differentiated cells, leading to favorable clinical outcomes in response to immune checkpoint inhibitor (ICI) therapy. These findings highlight the dynamics of CD5 expression as an indicator of CD8+ T cell differentiation status, and have implications for the development of predictive biomarker for ICI therapy.

Melanogenesis is the production of melanin from tyrosine by a series of enzyme-catalyzed reactions, in which tyrosinase and DOPA oxidase play key roles. The melanin content in the skin determines skin pigmentation. Abnormalities in skin pigmentation lead to various skin pigmentation disorders. Recent research has shown that the expression of EMP2 is much lower in melanoma than in normal melanocytes, but its role in melanogenesis has not yet been elucidated. Therefore, we investigated the role of EMP2 in the melanogenesis of MNT1 human melanoma cells. We examined TRP-1, TRP-2, and TYR expression levels during melanogenesis in MNT1 melanoma cells by gene silencing of EMP2. Western blot and RT-PCR results confirmed that the expression levels of TYR and TRP-2 were decreased when EMP2 expression was knocked down by EMP2 siRNA in MNT1 cells, and these changes were reversed when EMP2 was overexpressed. We verified the EMP2 gene was knocked out of the cell line (EMP2 CRISPR/Cas9) by using a CRISPR/Cas9 system and found that the expression levels of TRP-2 and TYR were significantly lower in the EMP2 CRISPR/Cas9 cell lines. Loss of EMP2 also reduced migration and invasion of MNT1 melanoma cells. In addition, the melanosome transfer from the melanocytes to keratinocytes in the EMP2 KO cells cocultured with keratinocytes was reduced compared to the cells in the control coculture group. In conclusion, these results suggest that EMP2 is involved in melanogenesis via the regulation of TRP-2 expression.

Purpose: To report a case of a successful secondary Descemet membrane endothelial keratoplasty in failed penetrating keratoplasty. Case summary: A 46-year-old male with keratoconus in both of his eyes underwent penetrating keratoplasty in his right eye 30 years ago and in his left eye 14 years ago. From one and a half year ago, the patient’s visual acuity decreased in his left eye due to graft failure. For treatment, secondary Descemet membrane endothelial keratoplasty was performed. Partial detachment of Descemet membrane was observed at 13 days after the operation, and an additional air injection was performed. At 8 months after the operation, the patient’s uncorrected visual acuity improved to 0.5 and the cornea maintained its clearance without rejection. Conclusions Secondary Descemet membrane endothelial keratoplasty was successfully performed in a patient with failed penetrating keratoplasty.

Purpose: To report a case of a successful secondary Descemet membrane endothelial keratoplasty in failed penetrating keratoplasty. Case summary: A 46-year-old male with keratoconus in both of his eyes underwent penetrating keratoplasty in his right eye 30 years ago and in his left eye 14 years ago. From one and a half year ago, the patient’s visual acuity decreased in his left eye due to graft failure. For treatment, secondary Descemet membrane endothelial keratoplasty was performed. Partial detachment of Descemet membrane was observed at 13 days after the operation, and an additional air injection was performed. At 8 months after the operation, the patient’s uncorrected visual acuity improved to 0.5 and the cornea maintained its clearance without rejection. Conclusions Secondary Descemet membrane endothelial keratoplasty was successfully performed in a patient with failed penetrating keratoplasty.

Background: This study aimed to investigate the recent prevalence, management, and comorbidities of diabetes among Korean adults aged ≥30 years by analyzing nationally representative data. Methods: This study used data from the Korea National Health and Nutrition Examination Survey from 2016 to 2018, and the percentage and total number of people ≥30 years of age with diabetes and impaired fasting glucose (IFG) were estimated. Results: In 2018, 13.8% of Korean adults aged ≥30 years had diabetes, and adults aged ≥65 years showed a prevalence rate of 28%. The prevalence of IFG was 26.9% in adults aged ≥30 years. From 2016 to 2018, 35% of the subjects with diabetes were not aware of their condition. Regarding comorbidities, 53.2% and 61.3% were obese and hypertensive, respectively, and 72% had hypercholesterolemia as defined by low-density lipoprotein cholesterol (LDL-C) ≥100 mg/dL in people with diabetes. Of the subjects with diabetes, 43.7% had both hypertension and hypercholesterolemia. With regard to glycemic control, only 28.3% reached the target level of <6.5%. Moreover, only 11.5% of subjects with diabetes met all three targets of glycosylated hemoglobin, blood pressure, and LDL-C. The percentage of energy intake from carbohydrates was higher in diabetes patients than in those without diabetes, while that from protein and fat was lower in subjects with diabetes. Conclusion The high prevalence and low control rate of diabetes and its comorbidities in Korean adults were confirmed. More stringent efforts are needed to improve the comprehensive management of diabetes to reduce diabetes-related morbidity and mortality.

Methods: In total, 55 patients with SIFs were retrospectively investigated in this study. The study population was divided into lumbosacral fusion (n=20) and non-fusion (n=35) groups. Subsequently, the patients’ demographic characteristics, comorbidities, medication history, results of diagnostic imaging studies, and bone mineral density were assessed. The fracture patterns were classified either according to the five typical types (H-pattern bilateral vertical plus horizontal component, unilateral vertical only, bilateral vertical only, unilateral vertical plus horizontal component, and horizontal only fracture) or atypical types. Results: In total, 44 of 55 patients (80%) suffered from more than one senile disease and received corresponding medications that caused secondary osteoporosis. A total of 12 patients had S1 lumbosacral fixation. Moreover, three of these 12 patients who developed a SIF immediately after a lumbosacral fracture had an unstable sacral U fracture. The remaining nine patients showed fracture patterns similar to the non-fusion patients. Single-photon emission computed tomography (SPECT)/computed tomography (CT) can identify fracture recurrence in previously healed fractures. In total, 24 patients (43.6%) had fractures of the pelvis, femur, and thoracolumbar spine. Conclusions SIF develops in elderly patients with multiple adult diseases that can induce secondary osteoporosis. Such fractures may occur in the patients with instrumented lumbosacral fusion. Importantly, some patients showed stress fractures after multilevel instrumented lumbosacral fusion, whereas others showed insufficiency fractures. The different fracture patterns correspond to different grades of SIF, and SPECT/CT can easily identify the fracture status.

Purpose: Adenosine A2A receptor agonist polydeoxyribonucleotide (PDRN) possesses an anti-inflammatory effect and suppress apoptotic cell death in several disorders. In this current study, the effect of PDRN on inflammation and apoptosis in rats with Achilles tendon injury was investigated. Methods: von Frey filament test and plantar test were conducted for the determination of pain threshold. Analysis of histological alterations was conducted by hematoxylin and eosin staining. Immunohistochemistry for cleaved caspase-3-positive cells and cleaved caspase-9-positive cells was done. Enzyme-linked immunoassay was used to detect the concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and cyclic adenosine-3’,5’-monophosphate (cAMP). Western blot was conducted to detect the protein levels of cAMP response element-binding protein (CREB), protein kinase A (PKA), Bcl-2-associated X (Bax), and B-cell lymphoma 2 (Bcl-2). Results: PDRN treatment relieved mechanical allodynia and alleviated thermal hyperalgesia after Achilles tendon injury. TNF-α and IL-6 concentrations were decreased by PDRN application. PDRN injection significantly enhanced cAMP concentration and phosphorylated CREB versus CREB ratio, showing cAMP-PKA-CREB pathway was activated by PDRN application. PDRN treatment inhibited percentages of cleaved caspase-3-positive cells and caspase-9-posiive cells and the suppressed Bax versus Bcl-2 ratio in Achilles tendon injury rats. Conclusions PDRN is probably believed to have a good effect on pain and inflammation in the urogenital organs. PDRN may be used as a new treatment for Achilles tendon injury.

PURPOSE: The aim of this study is to investigate the clinical performance and safety of Zimmer® natural nail cephalomedullary nail (ZNN CM nail) in the treatment of proximal femur fractures. MATERIALS AND METHODS: The following research was conducted as a prospective, non-comparative, single center outcome study. Upon providing written informed consent, enrolled patients' data were collected and analyzed. Postoperative follow-up visits were scheduled at 6 weeks, 3 months, 6 months, and 1 year. Follow-up evaluation included radiographic assessment, physical examination, and quality of life and adverse events reports. RESULTS: Thirty-nine patients were available for evaluation at one year postoperative. The patients reported the mean EuroQol-5 Dimension score increased after surgery: from 0.4 points at discharge (n=49) to 0.6 points at 1-year post-surgery (n=39). The mean Harris hip score also increased after surgery: from 56.3 points at discharge (n=49) to 72.1 points at 1 year (n=12). Bone union was seen in 64% (n=16) in 6 months and 95% (n=37) in 1 year. CONCLUSION: The results of this 1-year follow-up study affirmed the effectiveness and safety of the ZNN CM nail in the treatment of proximal femur fractures.
Femoral Fractures ; Femur ; Follow-Up Studies ; Fracture Fixation ; Fracture Fixation, Intramedullary ; Hip ; Hip Fractures ; Humans ; Informed Consent ; Outcome Assessment (Health Care) ; Physical Examination ; Prospective Studies ; Quality of Life

BACKGROUND: Enhancement and maintenance of the stemness of mesenchymal stem cells (MSCs) is one of the most important factors contributing to the successful in vivo therapeutic application of these cells. In this regard, three-dimensional (3D) spheroid formation has been developed as reliable method for increasing the pluripotency of MSCs. Moreover, using a new protocol, we have previously shown that dental tissues of extracted wisdom teeth can be effectively cryopreserved for subsequent use as a source of autologous stem cells. The main purpose of this study is to analyze the stemness and in vitro osteogenic differentiation potential of 3D spheroid dental MSCs compared with conventional monolayer cultured MSCs. METHODS: In this study, MSC-characterized stem cells were isolated and cultured from long-term cryopreserved dental follicles (hDFSCs), and then 2D hDFSCs were cultured under 3D spheroid-forming conditions using a newly designed microchip dish. The spheroids (3D hDFSCs) thus produced were investigated and characterized with respect to stemness, MSC marker expression, apoptosis, cell cycle analysis, extracellular matrix (ECM) production, and osteogenic and adipogenic differentiation properties. RESULTS: In terms of MSC and senescence markers, spheroid cells showed no difference when compared with 2D hDFSCs; however, 3D hDFSCs were observed to have a higher proportion of cell cycle arrest and a larger number of apoptotic cells. Moreover, spheroids showed substantially increased levels of pluripotency marker (early transcription factors) and ECM protein expression. Compared with 2D hDFSCs, there was also a notable enhancement in the osteogenic induction potential of spheroids, although no differences were observed with respect to in vitro adipogenesis. CONCLUSION: To the best of our knowledge, this is the first study to demonstrate the application of a spheroid culture system for dental follicle-derived stem cells using a microchip dish. Although further studies are needed, including in vivo transplantation, the results obtained in this study indicate that spheroid hDFSCs derived from cryopreserved dental follicle tissues could be used as a valuable source of autologous stem cells for bone tissue regeneration.
Adipogenesis ; Aging ; Apoptosis ; Bone and Bones ; Cell Cycle ; Cell Cycle Checkpoints ; Dental Sac ; Extracellular Matrix ; Humans ; In Vitro Techniques ; Mesenchymal Stromal Cells ; Methods ; Molar, Third ; Osteogenesis ; Regeneration ; Stem Cells

No abstract available.
Arthroplasty ; Hip ; Pelvis