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.

Suppressor of Variegation 3–9 Homolog 2 (SUV39H2) methylates the lysine 9 residue of histone H3 and induces heterochromatin formation, resulting in transcriptional repression or silencing of target genes. SUV39H1 and SUV39H2 have a role in embryonic development, and SUV39H1 was shown to suppress cell cycle progression associated with Rb. However, the function of human SUV39H2 has not been extensively studied. We observed that forced expression of SUV39H2 decreased cell proliferation by inducing G1 cell cycle arrest. In addition, SUV39H2 was degraded through the ubiquitin-proteasomal pathway. Using yeast two-hybrid screening to address the degradation mechanism and function of SUV39H2, we identified translationally controlled tumor protein (TCTP) as an SUV39H2-interacting molecule. Mapping of the interacting regions indicated that the N-terminal 60 amino acids (aa) of full-length SUV39H2 and the C-terminus of TCTP (120–172 aa) were critical for binding. The interaction of SUV39H2 and TCTP was further confirmed by co-immunoprecipitation and immunofluorescence staining for colocalization. Moreover, depletion of TCTP by RNAi led to up-regulation of SUV39H2 protein, while TCTP overexpression reduced SUV39H2 protein level. The half-life of SUV39H2 protein was significantly extended upon TCTP depletion. These results clearly indicate that TCTP negatively regulates the expression of SUV39H2 post-translationally. Furthermore, SUV39H2 induced apoptotic cell death in TCTP-knockdown cells. Taken together, we identified SUV39H2, as a novel target protein of TCTP and demonstrated that SUV39H2 regulates cell proliferation of lung cancer cells.
Amino Acids ; Apoptosis ; Carrier Proteins ; Cell Cycle ; Cell Death ; Cell Proliferation ; Embryonic Development ; Female ; Fluorescent Antibody Technique ; G1 Phase Cell Cycle Checkpoints ; Half-Life ; Heterochromatin ; Histones ; Humans ; Immunoprecipitation ; Lung Neoplasms ; Lysine ; Mass Screening ; Pregnancy ; Repression, Psychology ; RNA Interference ; Up-Regulation ; Yeasts

No abstract available.
Humans ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroid Nodule*

No abstract available.
Humans ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroid Nodule*

PURPOSE: Pediatric-type sarcomas such as rhabdomyosarcoma (RMS), Ewing sarcoma (EWS), primitive neuroectodermal tumor (PNET), and desmoplastic small round-cell tumor (DSRCT) are rare in adults, with limited studies on their prognosis and optimal treatment strategies. We aimed to examine the outcome of children and adult patients with RMS, EWS, PNET, and DSRCT and relevant prognostic factors. MATERIALS AND METHODS: We retrospectively reviewed 220 pediatric-type sarcoma patients at a single institution between 1985 and 2011. Comparisons were made in order to examine differences in demographics, disease characteristics, and survival. Survival analyses were performed using the Kaplan-Meier method with log-rank tests and Cox proportional hazards models. RESULTS: A total of 220 consecutive patients were identified at our institute. Median age was 15.6 years (range, 0 to 81 years) and there were 108 children (49%) and 112 adult patients (51%). According to histological classification, 106 patients (48.2%) had RMS, 60 (27.3%) had EWS, 50 (22.7%) had PNET, and 4 (1.8%) had DSRCT. With a median follow-up period of 6.6 years, the estimated median overall survival (OS) of all patients was 75 months (95% confidence interval [CI], 27.2 to 122.8 months) and median event-free survival (EFS) for all patients was 11 months (95% CI, 8.8 to 13.2 months). No significant difference in OS and EFS was observed between adults and children. In multivariate analysis, distant metastasis (hazard ratio [HR], 1.617; 95% CI, 1.022 to 2.557; p=0.040) and no debulking surgery (HR, 1.443; 95% CI, 1.104 to 1.812; p=0.012) showed independent association with worse OS. CONCLUSION: Metastatic disease and no surgical treatment are poor prognostic factors for OS among pediatric-type sarcomas for both adults and children.
Adult* ; Child* ; Classification ; Demography ; Desmoplastic Small Round Cell Tumor ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Incidence* ; Multivariate Analysis ; Neoplasm Metastasis ; Neuroectodermal Tumors, Primitive ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Rhabdomyosarcoma ; Sarcoma* ; Sarcoma, Ewing

This study surveys the improvement characteristics in old-aged muscular mitochondria by bio-active materials coated fabric (BMCF). To observe the effects, the fabric (10 and 30%) was worn to old-aged rat then the oxygen consumption efficiency and copy numbers of mitochondria, and mRNA expression of apoptosis- and mitophagy-related genes were verified. By wearing the BMCF, the oxidative respiration significantly increased when using the 30% materials coated fabric. The mitochondrial DNA copy number significantly decreased and subsequently recovered in a dose-dependent manner. The respiratory control ratio to mitochondrial DNA copy number showed a dose-dependent increment. As times passed, Bax, caspase 9, PGC-1alpha and beta-actin increased, and Bcl-2 decreased in a dose-dependent manner. However, the BMCF can be seen to have had no effect on Fas receptor. PINK1 expression did not change considerably and was inclined to decrease in control group, but the expression was down-regulated then subsequently increased with the use of the BMCF in a dose-dependent manner. Caspase 3 increased and subsequently decreased in a dose-dependent manner. These results suggest that the BMCF invigorates mitophagy and improves mitochondrial oxidative respiration in skeletal muscle, and in early stage of apoptosis induced by the BMCF is not related to extrinsic death-receptor mediated but mitochondria-mediated signaling pathway.
Actins ; Animals ; Antigens, CD95 ; Apoptosis ; Caspase 3 ; Caspase 9 ; DNA, Mitochondrial ; Mitochondria* ; Mitochondrial Degradation ; Muscle, Skeletal ; Oxygen Consumption ; Rats* ; Respiration ; RNA, Messenger

OBJECTIVECheongseoikki-tang (CIT, Korean), also called Qingshu Yiqi decoction () and Seisho-ekki-to (Japanese), is well known as an effective traditional combination of herbs for treating cardiovascular diseases. This study was to research its effects on bone marrow-derived mast cell (BMMC)-mediated allergy and inflammation mechanisms.

METHODSIn this study, the biological effect of Cheongseoikki-tang ethanol extract (CITE) was evaluated, focusing on its effects on the production of allergic mediators by phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 (A23187)-stimulated BMMCs. These allergic mediators included interleukin-6 (IL-6), prostaglandin D2 (PGD2), leukotriene C4 (LTC4), and β-hexosaminidase (β-hex).

RESULTSOur data revealed that CITE inhibited the production of IL-6, PGD2, LTC4, and β-hex induced by PMA plus A23187 (P<0.05).

CONCLUSIONThese findings indicate that CITE has the potential for use in the treatment of allergy.

Animals ; Anti-Inflammatory Agents ; pharmacology ; therapeutic use ; Bone Marrow Cells ; pathology ; Calcimycin ; pharmacology ; Cell Degranulation ; drug effects ; Cell Survival ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hypersensitivity ; drug therapy ; pathology ; Interleukin-6 ; secretion ; Leukotriene C4 ; pharmacology ; Male ; Mast Cells ; drug effects ; pathology ; physiology ; Mice ; Mice, Inbred BALB C ; Prostaglandin D2 ; biosynthesis ; Tetradecanoylphorbol Acetate ; pharmacology ; beta-N-Acetylhexosaminidases ; metabolism

PURPOSE: The aim of this study was to assess the feasibility and safety of laparoscopic resection following the insertion of self-expanding metallic stents (SEMS) for the treatment of obstructing left-sided colon cancer. METHODS: Between October 2006 and December 2012, laparoscopic resection following SEMS insertion was performed in 54 patients with obstructing left-sided colon cancer. RESULTS: All 54 procedures were technically successful without the need for conversion to open surgery. The median interval from SEMS insertion to laparoscopic surgery was 9 days (range, 3-41 days). The median surgery time was 200 minutes (range, 57-444 minutes), and estimated blood loss was 50 mL (range, 10-3,500 mL). The median time to soft diet was 4 days (range, 2-8 days) and possible length of stay (hypothetical length of stay according to the discharge criteria) was 7 days (range, 4-22 days). The median total number of lymph nodes harvested was 23 (range, 8-71) and loop ileostomy was performed in 2 patients (4%). Six patients (11%) developed postoperative complications: 2 patients with anastomotic leakages, 1 with bladder leakage, and 3 with ileus. There was no mortality within 30 days. CONCLUSION: The present study shows that the presence of a SEMS does not compromise the laparoscopic approach. Laparoscopic resection following stent insertion for obstructing left-sided colon cancer could be performed with a favorable safety profile and short-term outcome. Large-scale comparative studies with long-term follow-up are needed to demonstrate a significant benefit of this approach.
Anastomotic Leak ; Colon* ; Colonic Neoplasms* ; Conversion to Open Surgery ; Diet ; Humans ; Ileostomy ; Ileus ; Laparoscopy ; Length of Stay ; Lymph Nodes ; Mortality ; Postoperative Complications ; Stents* ; Urinary Bladder

PURPOSE: This experimental study verified the effect of adipose-tissue-derived stem cells (ASCs) on the healing of ischemic colonic anastomoses in rats. METHODS: ASCs were isolated from the subcutaneous fat tissue of rats and identified as mesenchymal stem cells by identification of different potentials. An animal model of colonic ischemic anastomosis was induced by modifying Nagahata's method. Sixty male Sprague-Dawley rats (10-week-old, 370 +/- 50 g) were divided into two groups (n = 30 each): a control group in which the anastomosis was sutured in a single layer with 6-0 polypropylene without any treatment and an ASCtreated group (ASC group) in which the anastomosis was sutured as in the control group, but then ASCs were locally transplanted into the bowel wall around the anastomosis. The rats were sacrificed on postoperative day 7. Healing of the anastomoses was assessed by measuring loss of body weight, wound infection, anastomotic leakage, mortality, adhesion formation, ileus, anastomotic stricture, anastomotic bursting pressure, histopathological features, and microvascular density. RESULTS: No differences in wound infection, anastomotic leakage, or mortality between the two groups were observed. The ASC group had significantly more favorable anastomotic healing, including less body weight lost, less ileus, and fewer ulcers and strictures, than the control group. ASCs augmented bursting pressure and collagen deposition. The histopathological features were significantly more favorable in the ASC group, and microvascular density was significantly higher than it was in the control group. CONCLUSION: Locally-transplanted ASCs enhanced healing of ischemic colonic anastomoses by increasing angiogenesis. ASCs could be a novel strategy for accelerating healing of colonic ischemic risk anastomoses.
Anastomotic Leak ; Animals ; Body Weight ; Collagen ; Colon ; Constriction, Pathologic ; Humans ; Ileus ; Ischemia ; Male ; Mesenchymal Stromal Cells ; Models, Animal ; Polypropylenes ; Rats ; Rats, Sprague-Dawley ; Stem Cells ; Subcutaneous Fat ; Transplants ; Ulcer ; Wound Infection