Thymic epithelial cells (TECs) play a critical role in thymic development and thymopoiesis. As individuals age, TECs undergo various changes that impact their functions, leading to a reduction in cell numbers and impaired thymic selection. These age-related alterations have been observed in both mice and humans. However, the precise mechanisms underlying age-related TEC dysfunction remain unclear. Furthermore, there is a lack of a comprehensive study that connects mouse and human biological processes in this area. To address this gap, we conducted an extensive transcriptome analysis of young and old TECs in mice, complemented by further analysis of publicly available human TEC single-cell RNA sequencing data. Our analysis revealed alterations in both known and unknown pathways that potentially contribute to age-related TEC dysfunction. Specifically, we observed downregulation of pathways related to cell proliferation, T cell development, metabolism, and cytokine signaling in old age TECs. Conversely, TGF-β, BMP, and Wnt signaling pathways were upregulated, which have been known to be associated with age-related TEC dysfunctions or newly discovered in this study. Importantly, we found that these age-related changes in mouse TECs were consistently present in human TECs as well. This cross-species validation further strengthens the significance of our findings. In conclusion, our comprehensive analysis provides valuable insight into the biological and immunological characteristics of aged TECs in both mice and humans. These findings contribute to a better understanding of thymic involution and age-induced immune dysfunction.
Park, Min-Hee;Boo, Hee-Ock;Kim, Hong-Sub;Lee, Sook-Young
Plant Resources
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v.3
no.3
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pp.163-172
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2000
We compared microstructural features of the ordered cell and disordered leaves in Citrus junos Sieb. by electron microscopy. In the cell of the ordered leaves, many chloroplasts and large vacuoles were particularly observed. Also a lot of vessel, companion cell and big nucleus were presented in vascular bundle regions. The mitochondria and the other organelles were interspersed among the chloroplasts in a thin, peripheral layer of cytoplasm. The chloroplast possessed typical grana and intergranal lamellae, numerous starch grains and a few small osmophilic globules. Besides, microbodies were closely associated with the mitochondria and the chloroplast. The process of the formation of the secondary cell wall from primary cell wall was observed the vessel elements, the tonoplast wall and the secondary cell wall. It was observed that the oil sac with the unique perfume distributed the adjacent cell wall. In the cell of disordered leaves, the all of the organelles were thrust toward the cell wall due to the fusion of vacuoles in the cells. It was observed that a lot of the very small particles spreaded in the cytoplasm. The loss of unique perfume of the leaves was resulted in the destruction of the oil sac. Also, there was not observed grana, lamellae, starch and osmophillic globules in the chloroplast. The small distributed organelles was not observed but the elongation of the cell wall was proceed no longer. Therefore, the plasma membrane diverged from the cell wall. All of organelles in the cell had poor function and deformation. A massive vacuole was fulfilled in single cell and the vacuole contains a lot of large and small particles. The organelles were presented on the side of the cell wall according to the enlargement of vacuole and they were observed to be breakdown.
Background: Factors associated with the prognosis of patients with small cell lung cancer (SCLC) is relatively unknown, than of those with non-small cell lung cancer. This study was undertaken to identify the prognostic factors of SCLC. Methods: The medical records of 333 patients diagnosed with SCLC at tertiary hospital from January 1, 2008, to December 31, 2012 were retrospectively reviewed. Patients were categorized by age (${\leq}65$ years vs. >65 years) and by extent of disease (limited disease [LD] vs extensive disease [ED]). Overall survival and progression free survival rates were determined. Factors associated with prognosis were calculated using Cox's proportional hazard regression model. Results: Most baseline characteristics were similar in the LD and ED groups. Eastern Cooperative Oncology Group (ECOG) performance status (PS), first chemotherapy regimen, and prophylactic cranial irradiation (PCI) differed significantly in patients with LD and ED. Mean ECOG PS was significantly lower (p<0.001), first-line chemotherapy with etoposide-cisplatin was more frequent than with etoposide-carboplatin (p<0.001), and PCI was performed more frequently (p=0.019) in LD-SCLC than in ED-SCLC. Prognosis in the LD group was better in younger (${\leq}65$ years) than in older (>65 years) patients, but prognosis in the ED group was unrelated to age. Conclusion: This study showed that overall survival (OS) was significantly improved in younger than in older patients with LD-SCLC. Univariate and multivariate analyses showed that age, PCI and the sum of cycles were significant predictors of OS in patients with LD-SCLC. However, prognosis in the ED group was unrelated to age.
Objective : This is a retrospective review of 22 surgically treated benign and malignant tumors of brachial plexus region to describe clinical presentation, the characteristics of brachial plexus tumor and clinical outcomes with a literature review. Methods : Twenty-one patients with consecutive 22 surgeries for primary brachial plexus tumors were enrolled between February 2002 and November 2011 were included in this study. The medical records of all patients were reviewed. Results : Eleven male and 10 female patients were enrolled. Mean age was 39 years. Three patients had brachial plexus tumor associated with neurofibromatosis (13.6%). Presenting signs and symptoms included parenthesis and numbness (54.5%), radiating pain (22.7%), direct tenderness and pain (27.2%), palpable mass (77.3%). Twelve patients presented preoperative sensory deficit (54.5%) and 9 patients presented preoperative motor deficit (40.9%). Twenty tumors (90.9%) were benign and 2 tumors (9.1%) were malignant. Benign tumors included 15 schwannomas (68.2%), 4 neurofibromas (18.2%) and 1 granular cell tumor (4.5%). There were 1 malignant peripheral nerve sheath tumor (MPNST) and 1 malignant granular cell tumor. Gross total resection was achieved in 16 patients (72.7%), including all schwannomas, 1 neurofibroma. Subtotal resection was performed in 6 tumors (27.3%), including 3 neurofibromatosis associated with brachial plexus neurofibromas, 1 MPNST and 2 granular cell tumor in one patient. Conclusion : Resection of tumor is the choice of tumor in the most of benign and malignant brachial plexus tumors. Postoperative outcomes are related to grade of resection at surgery and pathological features of tumor.
Objectives: The purpose of this study was to determine the relationship between methylation status of the Dact1 gene and MTHFR a1298c polymorphic forms in transitional cell carcinoma tissues in a Chinese population. Methods: Polymorphisms of folate metabolism enzyme gene MTHFR were assessed by restrictive fragment length polymorphism (RFLP) methods and PCR-based DNA methylation analysis was used to determine the CpG island methylation status of the Dact1 gene. Associations between the methylation status of the Dact1 gene and clinical characteristics, as well as MTHFR a1298c polymorphisms, were analyzed. Results: aberrant methylation of the Dact1 gene was found in 68.3% of cancer tissues and 12.4% of normal tissues,. The methylation rate of the Dact1 gene in cancer tissues was significantly higher in patients with lymph node metastasis than in those without lymph node metastasis (46.3% vs. 17.2%, P = 0.018). No association was found between aberrant DNA methylation and selected factors including sex, age, tobacco smoking, alcohol consumption and green tea consumption. After adjusting for potential confounding variables, variant allele of MTHFR a1298c was found to be associated with methylation of the Dact1 gene. Compared with wild type CC, the odds ratio was 4.33 (95% CI: 1.06-10.59) for AC and 4.95 (95% CI: 1.18-12.74) for AA. The N stage in TNM staging and the occurrence of lymph node metastasis were associated with an MTHFR 1298 AA+AC genotype (P<0.05). Conclusion: MTHFR 1298 AC and AA genotypes might help maintain a normal methylation status of the Dact1 gene, aberrant CpG island methylation of which is closely related to the genesis and progression of transitional cell carcinoma.
Kim, Ye-Hwan;Byun, Young Joon;Kim, Won Tae;Jeong, Pildu;Yan, Chunri;Kang, Ho Won;Kim, Yong-June;Lee, Sang-Cheol;Moon, Sung-Kwon;Choi, Yung-Hyun;Yun, Seok Joong;Kim, Wun-Jae
Journal of Korean Medical Science
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v.33
no.47
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pp.303.1-303.10
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2018
Background: Cell division cycle 6 (CDC6) is an essential regulator of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle. CDC6 has been associated with oncogenic activities in human cancers; however, the clinical significance of CDC6 in prostate cancer (PCa) remains unclear. Therefore, we investigated whether the CDC6 mRNA expression level is a diagnostic and prognostic marker in PCa. Methods: The study subjects included 121 PCa patients and 66 age-matched benign prostatic hyperplasia (BPH) patients. CDC6 expression was evaluated using real-time polymerase chain reaction and immunohistochemical (IH) staining, and then compared according to the clinicopathological characteristics of PCa. Results: CDC6 mRNA expression was significantly higher in PCa tissues than in BPH control tissues (P = 0.005). In addition, CDC6 expression was significantly higher in patients with elevated prostate-specific antigen (PSA) levels (> 20 ng/mL), a high Gleason score, and advanced stage than in those with low PSA levels, a low Gleason score, and earlier stage, respectively. Multivariate logistic regression analysis showed that high expression of CDC6 was significantly associated with advanced stage (${\geq}T3b$) (odds ratio [OR], 3.005; confidence interval [CI], 1.212-7.450; P = 0.018) and metastasis (OR, 4.192; CI, 1.079-16.286; P = 0.038). Intense IH staining for CDC6 was significantly associated with a high Gleason score and advanced tumor stage including lymph node metastasis stage (linear-by-linear association, P = 0.044 and P = 0.003, respectively). Conclusion: CDC6 expression is associated with aggressive clinicopathological characteristics in PCa. CDC6 may be a potential diagnostic and prognostic marker in PCa patients.
Excitatory amino acids (EAA) are thought to play an important role in producing cell death associated with ischemic and traumatic spinal cord injury. The present study was carried out to determine if the response characteristics of spinal sensory neurons in segments adjacent to degeneration sites induced by EAA are altered following these morphological changes. Intraspinal injections of quisqualic acid (QA) produced neuronal degeneration and spinal cavitation of gray matter. The severity of lesions was significantly attenuated by pretreatment with a non-NMDA antagonist NBQX. In extracellular single unit recordings, dorsal horn neurons in QA injected animal showed the increased mechanosensitivity, which included a shift to the left in the stimulus-response relationship, an increased background activity and an increase in the duration of after-discharge responses. Neuronal responses, especially the C-fiber response, to suprathreshold electrical stimulation of sciatic nerve also increased in most cases. These results suggest that altered functional states of neurons may be responsible for sensory abnormalities, e.g. allodynia and hyperalgesia, associated with syringomyolia and spinal cord injury.
Sciatic nerve (SN) is the thickest and longest nerve of the body. Deviations from the normal anatomical origin and level of bifurcation of SN have been frequently reported. In the present case, we are presenting a unique scenario of origin of terminal branches of the SN-tibial nerve (TN) and common peroneal nerve (CPN) in the pelvic region itself from divisions arising directly from the lumbosacral plexus. This variation was associated with origin of posterior femoral cutaneous nerve from the superior division of CPN with anomalous communicating branches between pudendal nerve and TN. The unique characteristics of the present case are the presence of 'pseudoganglion' found on the inferior division of TN. The present case stands out as the first of its kind to mention such pseudoganglion. Knowledge of some unusual findings like presence of pseudoganglion and intercommunications between nerves have clinical implications in anesthesiology, neurology, sports medicine, and surgery.
In this study, two types of central flow distributor designs are presented and compared to obtain the optimal compact design which has the least flow resistance and the uniform flow distribution in a vehicular fuel cell stack. For effective and reliable prediction on the thermo-flow characteristics of the reactants flow over the entire fuel cell stack domain, open channel flow in the bipolar plates of the power generating cells were simulated by applying a simplified flow resistance model with an empirical porous concept. A number of case studies were performed to figure out an optimal configuration of a central flow distributor device in terms of the time-dependent thermo-flow behavior and load-dependent flow distribution. The results showed that the stable and load-independent thermo-flow uniformity is very design specific, which is closely associated with the design of central manifolding devices in order to achieve the enhanced volumetric power density and the reliable long-lasting operating of fuel cells.
The emergence of multidrug-resistant microorganisms, as well as fungal infectious diseases that further threaten health, especially in immunodeficient populations, is a major global problem. The development of new antifungal agents in clinical trials is inferior to the incidence of drug resistance, and the available antifungal agents are restricted. Their mechanisms aim at certain characteristics of the fungus in order to avoid biological similarities with the host. Synthesis of the cell wall and ergosterol are mainly targeted in clinical use. The need for new approaches to antifungal therapeutic agents or development alternatives has increased. This review explores new perspectives on mechanisms to effectively combat fungal infections and effective antifungal activity. The clinical drug have a common feature that ultimately causes caspase-dependent cell death. The drugs-induced cell death pathway is associated with mitochondrial dysfunction, including mitochondrial membrane depolarization and cytochrome c release. This mechanism of action also reveals antimicrobial peptides, the primary effector molecules of innate systems, to highlight new alternatives. Furthermore, drug combination therapy is suggested as another strategy to combat fungal infection. The proposal for a new approach to antifungal agents is not only important from a basic scientific point of view, but will also assist in the selection of molecules for combination therapy.
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