OBJECTIVETo evaluate the expression of PTEN, MMP-2 and MMP-9 in thymomas and their correlation with clinical significance.

METHODSImmunohistochemical S-P assay was used to detect the expression of PTEN, MMP-2 and MMP-9 in 45 thymomas and 16 non-neoplastic thymuses.

RESULTSThe positive rate of PTEN, MMP-2 and MMP-9 expression in 45 thymomas were 53.5%, 48.9% and 62.2%, respectively. There were significant differences between non-neoplastic thymus and thymomas (P < 0.05). The expression of PTEN, MMP-2 correlated with histological type (P < 0.05) and different clinical stage of the thymoma (P < 0.01). The expression of MMP-9 was not correlated with histological type and different clinical stages of thymoma (P > 0.05).

CONCLUSIONPTEN, MMP-2 and MMP-9 may play an important role in the occurrence and development of thymoma. The expression of PTEN and MMP-2 correlates with the malignance and the aggression of thymoma.

Adult ; Aged ; Female ; Humans ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; PTEN Phosphohydrolase ; metabolism ; Paraffin Embedding ; Thymoma ; metabolism ; pathology ; Thymus Gland ; metabolism ; Thymus Neoplasms ; metabolism ; pathology ; Young Adult

Adult ; Antigens, CD1 ; metabolism ; Female ; Histiocytosis, Langerhans-Cell ; complications ; metabolism ; pathology ; surgery ; Humans ; Mediastinoscopy ; Myasthenia Gravis ; complications ; metabolism ; pathology ; surgery ; S100 Proteins ; metabolism ; Thymus Gland ; metabolism ; pathology ; surgery

OBJECTIVETo investigate the influence of induced nitric oxide synthase (iNOS) expression on apoptosis of thymocyte in burn rats, and to explore the relationship between NO and pathological lesion of the thymus gland in burn rats.

METHODSFifty-six male Wistar rats were enrolled in the study and randomized into control( C, n = 8,without treatment) , burn ( B, n = 24) , and S-methylisothiourea( SMT, n = 24) groups. Equal amount of isotonic saline solution and SMT(7. 5 mg/kg) were respectively intravenously infused into the rats in B and SMT groups after being inflicted with 30% TBSA full-thickness burns. The weight of thymus gland in each group were weighed, and thymocyte apoptosis and iNOS expression were determined with TUNEL method and immunohistochemistry, respectively at 6,24,72 postburn hours( PBH) , with 8 rats at each time-point. The number of apoptotic cells and the density of iNOS positive cells in thymus was measured by stereological method.

RESULTSThe weight of thymus in B group at 24 and 72 PBH [ (153+/- 14) , (91+/-22) mg] were obviously heavier than those in C group, but much lighter than those in SMT group ( P < 0.01). A few apoptotic cells and iNOS positive cells were observed in cortex and medulla of thymus in C group, while they were observed in B group at 6 PBH, and the number of cells began to increase at 24 PBH, distributing in medulla,parenchyma, the boundary of cortex, and medulla under capsule. The iNOS positive cells in B group at 24 PBH were distributed around the interlobular septum. A large number of cortical cells with brown staining were observed in B group at 72 PBH, and the number of iNOS positive cells also increased, with scattered distribution and clear cell boundary. Fewer positive cells with uneven distribution, no iNOS positive cells, and few apoptotic foci were observed in SMT group after burns. The density of apoptotic cells in B group at 24 and 72 PBH was (2. 428 +/-0. 728) x 10(-5)/microm(3) and (5. 586 +/- 1.233) x 10(-5)/microm(3), respectively, which was obviously higher than that in C and SMT group. The density of iNOS positive cells in B group was increased in a time-dependent manner( P <0. 05).

CONCLUSIONThe apoptotic rate of thymocyte in severely burn rats increases early after burns. The up-regulation of iNOS expression in thymus can promote apoptosis of thymocytes, while SMT can partially ameliorate this phenomenon.

Animals ; Apoptosis ; Burns ; metabolism ; pathology ; Gene Expression Regulation ; Isothiuronium ; analogs & derivatives ; pharmacology ; Male ; Nitric Oxide Synthase Type II ; metabolism ; Organ Size ; Rats ; Rats, Wistar ; Thymus Gland ; cytology ; metabolism

To obtain an initial overview of gene diversity and expression pattern in porcine thymus, 11,712 ESTs (Expressed Sequence Tags) from 100-day-old porcine thymus (FTY) were sequenced and 7,071 cleaned ESTs were used for gene expression analysis. Clustered by the PHRAP program, 959 contigs and 3,074 singlets were obtained. Blast search showed that 806 contigs and 1,669 singlets (totally 5,442 ESTs) had homologues in GenBank and 1,629 ESTs were novel. According to the Gene Ontology classification, 36.99% ESTs were cataloged into the gene expression group, indicating that although the functional gene (18.78% in defense group) of thymus is expressed in a certain degree, the 100-day-old porcine thymus still exists in a developmental stage. Comparative analysis showed that the gene expression pattern of the 100-day-old porcine thymus is similar to that of the human infant thymus.
Animals ; Computational Biology ; Expressed Sequence Tags ; Fetus ; metabolism ; Gene Expression Profiling ; Genetic Variation ; Sequence Analysis, DNA ; Sus scrofa ; genetics ; metabolism ; Thymus Gland ; metabolism

Animals ; Glutamine ; blood ; metabolism ; Male ; Physical Conditioning, Animal ; physiology ; Physical Exertion ; physiology ; Rats ; Rats, Sprague-Dawley ; Sleep Deprivation ; metabolism ; physiopathology ; Thymus Gland ; metabolism ; Time Factors

BACKGROUNDVascular endothelial growth factor (VEGF) in the thymus was mainly produced by the thymic epithelial cells (TECs), the predominant component of the thymic microenvironment. The progression of TECs and the roles of VEGF in the neonatal thymus during sepsis have not been reported. This study aimed to explore the alterations of TECs and VEGF level in the neonatal thymus involution and to explore the possible mechanisms at the cellular level.

METHODSBy establishing a model of clinical sepsis, the changes of TECs were measured by hematoxylin-eosin staining, confocal microscopy, and flow cytometry. Moreover, the levels of VEGF in serum and thymus were assessed based on enzyme-linked immunosorbent assay and Western blotting.

RESULTSThe number of thymocytes and TECs was significantly decreased 24 h after lipopolysaccharide (LPS) challenge, (2.40 ± 0.46)×10 7 vs. (3.93 ± 0.66)×10 7 and (1.16 ± 0.14)×10 5 vs. (2.20 ± 0.19)×10 5 , P < 0.05, respectively. Cortical TECs and medullary TECs in the LPS-treated mice were decreased 1.5-fold and 3.9-fold, P < 0.05, respectively, lower than those in the controls. The number of thymic epithelial progenitors was also decreased. VEGF expression in TECs was down-regulated in a time-dependent manner.

CONCLUSIONVEGF in thymic cells subsets might contribute to the development of TECs in neonatal sepsis.

Animals ; Animals, Newborn ; Cells, Cultured ; Epithelial Cells ; cytology ; drug effects ; metabolism ; Lipopolysaccharides ; toxicity ; Mice ; Thymus Gland ; cytology ; drug effects ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism

The nomenclature "embryonic lymphoid tissue inducer (LTi) cell" reflects the fundamental role of the cell in secondary lymphoid tissue organization. In addition, it is equally important in primary lymphoid tissue development as it regulates central tolerance to self-antigens in the thymus. An adult LTi cell constitutively expresses two sets of tumor necrosis factor (TNF) family members, whereas its embryonic counterpart expresses only one. The first set is lymphotoxin (LT)alpha, LTbeta, and TNFalpha, which are essential for the secondary lymphoid organogenesis during embryogenesis and for maintaining an organized secondary lymphoid structure during adulthood. The second set is OX40- and CD30-ligands, which are critical for memory T cell generation. Adult LTi cells regulate adaptive immune responses by providing LTbetaR signals to stromal cells to maintain secondary lymphoid tissue structure, and determine adaptive immune responses by providing OX40 and CD30 survival signals to activated T cells in memory T cell generation. Along with the consideration of the roles of embryonic LTi cells in primary and secondary lymphoid tissues, this review highlights the roles of adult LTi cells in secondary lymphoid tissue function.
Adult ; Animals ; Humans ; Lymphoid Tissue/cytology/embryology/*immunology ; Lymphokines/immunology/metabolism ; T-Lymphocytes, Helper-Inducer/cytology/*immunology/metabolism ; Thymus Gland/cytology/embryology/*immunology

The aim of the present study was to investigate the modulatory role of activated 5-HT(3) receptors in the central amygdala (CeA) on mitogen concanavalin A (ConA)-stimulated proliferative response of thymocytes in rats and the underlying neuroendocrine regulation circuits. 1-phenylbiguanide (PBG), a putative selective 5-HT(3) receptor agonist, was administered by intraperitoneal (i.p.), bilateral intracerebroventriclular (i.c.v.), and bilateral intracentral amygdala (i.c.a.) injection. In addition, thymocytes isolated from untreated rats were incubated with PBG (at a range of concentrations of 1x10(-8)-1x10(-5) mol/L) in vitro in the presence and absence of ConA, in order to investigate any direct effect of PBG on the proliferation in vitro. MTT method was applied to demonstrate the effect of PBG on the proliferative response of thymocytes. An immunohistochemical SABC assay was used to describe the expression profiles of c-Fos-positive cells in different brain regions including the CeA, hippocampus, cortex, hypothalamus and periaqueductal gray (PAG) at 1, 2, 4 and 8 h after bilateral single-administration of PBG by i.c.a. (1.0 microg/side). Results showed that PBG (1x10(-8)-1x10(-5) mol/L) had no significant influence on the proliferative responses of the isolated thymocytes in vitro, no matter ConA was present or not. The proliferation of thymocytes stimulated by ConA was not significantly changed when PBG was administered by i.p. (0.5 mg/kg per day, for consecutive 5 d), whereas it was remarkably enhanced after bilateral i.c.v. injection of PBG (10 microg/side per day, for consecutive 5 d). Similarly, when PBG was injected bilaterally by i.c.a. (1.0 microg/side per day, for 1 d or consecutive 3, 5 and 7 d), a significantly enhanced proliferation occurred on the 1st day and continued until reaching its peak on the 5th day before decreasing on the 7th day. All of the promoting effects of PBG on the ConA-stimulated proliferation of thymocytes were reversed by pretreatment with the 5-HT(3) receptor antagonist tropisetron (TRP) 5 min prior to the administration of PBG. Interestingly, compared to the treatment with normal saline or TRP + PBG, after a bilateral single-administration of PBG (1.0 microg/side) by i.c.a., the number of c-Fos-positive cells in different brain regions significantly increased at 1 h in the CeA, 1-2 h in the hippocampus, 1-2 h in the cortex, 4 h in the hypothalamus and 8 h in the PAG, respectively, with each maximum response at 1 h in the CeA, 2 h in the hippocampus and cortex, and 4 h in the hypothalamus. Subsequently, the number of cells expressing c-Fos gradually reduced to the minimum at 4 h in the CeA, and at 8 h in the hippocampus, cortex and hypothalamus. In conclusion, the 5-HT(3) receptors in the CeA of rats mediate the modulation of thymus function, at least partly, through the neuroendocrine circuit of the limbic system-cortex-hypothalamus-PAG.
Amygdala ; metabolism ; physiology ; Animals ; Male ; Neuroimmunomodulation ; physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, Serotonin, 5-HT3 ; metabolism ; physiology ; Thymus Gland ; cytology ; physiology

This study was purposed to investigate the effects of high-dose dexamethasone on structure and function of thymic epithelial cells (TEC). Male C57BL/6 mice aged 6 to 8 weeks were used as experimental animals. The mice were injected intraperitoneally with dexamethasone (20 mg/kg), and the other mice treated with saline were used as controls. Thymus was harvested at day 5 after treatment. The histological changes of the treated thymus were monitored by HE staining and in situ immunofluorescence staining. The ratio of each subset in the thymus were analyzed by using flow cytometry, and quantitative PCR was applied to detect the expression levels of IL-22 and Foxn1, which represent the regenerative function of thymus. The results showed that compared with control mice, the structure of TEC in mice treated with high-dose dexamethasone was damaged and the thymic cell number was declined dramatically (P < 0.05); the ratios of thymus cell subsets were changed, the number of double positive (DP) thymus cells among these subsets declined sharply (P < 0.05); the expression levels of Foxn1 and IL-22 increased by 34 and 8 folds respectively. It is concluded that the use of high-dose dexamethasone can lead to damage of the structure and function of TEC, and induce up-regulation of the expression of genes related to thymus repair.
Animals ; Dexamethasone ; administration & dosage ; adverse effects ; Epithelial Cells ; cytology ; drug effects ; Forkhead Transcription Factors ; metabolism ; Interleukins ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Thymus Gland ; cytology ; drug effects

OBJECTIVETo explore possible mechanism of electroacupuncture (EA) for regulating immune function in anxiety disorder (AD) rats by observing the effect of acupuncture on the histology of thymus and expressions of atrial natriuretic peptide (ANP) and natriuretic peptide receptor type A (NPR- A) in thymus.

METHODSTotally 34 SD healthy rats were randomly divided into the blank control group (n = 10), the model group (n = 12), the EA group (n = 12). Anxiety model was established in rats of the model group and the EA group by using chronic unpredictable stress (CUS) stimulation. EA (15/25 Hz) at Neiguan (PC6) and Shenmen (HT7) was performed in the EA group, with 15-min needle retaining, once every other day, 15 days in total. Needle was fixed at same acupoints for 15 min without electric stimulus in the other two groups. Anxiety-like behavior was measured by elevated plus-maze (EPM) test. Pathological changes of thymus tissue were observed by optical microscope. Expressions of ANP and NPR-A in thymus were measured by immunohistochemical assay.

RESULTSThe thymus tissue in the model group was severely atrophied, with unclear structure of thymic lobules, unclear margin of thymic medulla, loosely arranged lymphocytes ,and obviously enlarged volume of thymic corpuscle. The thymus tissue in the EA group was mildly atrophied, with existent structure of thymic lobules, clear margin of thymic medulla, densely arranged lymphocytes in cortical region, and widened medullary area. Com- pared with the blank control group, the percentage of open-arms entries (OE%) in the total QE times ob- viously decreased in the model group (P < 0.05), ANP expression obviously increased (P < 0.05), and NPR-A expression obviously decreased (P < 0.01). Compared with the model group, OE% was obviously elevated (P < 0.05), ANP expression obviously decreased (P < 0.05), and NPR-A expression obviously increased (P < 0.01) in the EA group.

CONCLUSIONEA not only could reduce anxiety of rats, but also could improve chronic stress induced thymus injury through intervening synthesis and secretion of ANP, as well as the expression of NPR-A (a specific receptor of ANP).

Acupuncture Points ; Animals ; Anxiety Disorders ; therapy ; Atrial Natriuretic Factor ; metabolism ; Electroacupuncture ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Atrial Natriuretic Factor ; metabolism ; Thymus Gland ; pathology