OBJECTIVES: To investigate the effect of a variety of kidney-tonifying Chinese medicines on thymus regeneration after acute degeneration in mice. METHODS: Forty-eight 8-week-old male BALB/c mice were randomly divided into normal control group, model control group, negative control group, positive control group, the fructus of Cnidium monnieri (L.) Cuss. group, the fructus of Psoralea corylifolia (L.) group, the fructus of Rubus chingii Hu group, and the tuber onion seed group, with 6 mice in each group. Except for the normal control group, mice in the other groups received intraperitoneal injections of rapamycin (1 mg·kg^－1·d^－1) for 5 consecutive days followed by 14 h of starvation to induce acute thymus degeneration. After successful modeling, in treatment groups ethanol extract of the fructus of Cnidium monnieri (L.) Cuss. (0.78 g·kg^－1·d^－1), fructus of Psoralea corylifolia (L.) (0.39 g·kg^－1·d^－1), fructus of Rubus chingii Hu (0.78 g·kg^－1·d^－1) or the tuber onion seed(0.39 g·kg^－1·d^－1) was intraperitoneally injected once a day for 5 days; while the negative control group was given equal volume of normal saline, and the positive control group was given metformin (300 mg·kg^－1·d^－1). The grip strength was measured with a grip tester 2 h after the last administration. The pathological changes of thymus were observed by hematoxylin and eosin (HE) staining. The structure and distribution of thymic epithelial cells were observed by multiple immunofluorescence method. The proportion of T cell subsets in thymus and peripheral blood was analyzed by flow cytometry. The level of T cell receptor excision circles (TREC) in the genomic DNA of mouse spleen mononuclear cells was detected by quantitative polymerase chain reaction (PCR) for evaluation of thymic output function. The expression of thymus aging- and function-related factors in the thymus tissue were detected by quantitative reverse transcription PCR. The expression of cyclin-dependent kinase inhibitor 1A (p21) and tumor protein 53 (p53) were verified by immunohistochemistry. RESULTS: Rapamycin induced thymic atrophy and significantly reduced limb grip strength in mice (P<0.01). Compared with the negative control group, the limb grip strength of mice in the fructus of Psoralea corylifolia (L.) group, the fructus of Rubus chingii Hu group and the tuber onion seed group was significantly enhanced (all P<0.05), and the level of TREC in spleen of the mice in each administration group was reduced (all P<0.05). Among Chinese herb medicine-treatment groups, the recovery of thymus function and tissue structure in the tuber onion seed group was most obvious. Further study showed that compared with the negative control group, the proportion of CD4 single positive cells (CD3⁺TCR-β⁺CD4⁺CD8^－) in the thymus of the tuber onion seed group was significantly increased (P<0.01), and the proportion of CD3⁺CD28⁺ T cell and CD3⁺CD8⁺CD28⁺ T cell in peripheral blood was significantly increased (all P<0.01). The mRNA levels of IL-1α, IL-6, p21 and p53 in thymocytes were decreased (all P<0.05). The results of immunohistochemistry further confirmed the decrease in p21 and p53 expression. In normal mice, tuber onion seed was observed to enhance limb grip strength (P<0.01), while suppressing thymus output and change the distribution of T cell subsets, and there was no significant effect on thymus weight and the expression of Foxn1, SIRT1, p21, CXCL2 and PTMα. CONCLUSIONS The tuber onion seed and other kidney-tonifying traditional Chinese medicines can accelerate the regeneration process of mouse thymus after acute degeneration induced by rapamycin in mice, and the tuber onion seed exhibits the most pronounced therapeutic effect.
Animals ; Mice ; Male ; Mice, Inbred BALB C ; Thymus Gland/physiology* ; Drugs, Chinese Herbal/pharmacology* ; Sirolimus/adverse effects* ; Regeneration/drug effects*

During the coronavirus disease 2019 (COVID-19) pandemic, vaccines help control the spread of infection. To date, 47 vaccines have been approved, with another 227 candidates in various stages of development. In the short period of time since the beginning of their use, evidence has begun to emerge of complications following vaccination in the form of the development or exacerbation of a number of pathological conditions (Block et al., 2022; Haseeb et al., 2022). For example, a population-based study in France identified 1612 cases of myocarditis and 1613 cases of pericarditis requiring hospital treatment within five months of vaccination (le Vu et al., 2022).
Humans ; COVID-19/prevention & control* ; COVID-19 Vaccines/adverse effects* ; Vaccination/adverse effects* ; Vitiligo/etiology* ; Thymus Gland/physiopathology*

BACKGROUND: Endotoxin tolerance (ET) is a protective phenomenon in which pre-treatment with a tolerance dose of lipopolysaccharide (LPS) leads to dramatically elevated survival. Accumulating evidence has shown that peripheral T cells contribute to the induction of ET. However, what happens to T cell development in the thymus under ET conditions remains unclear. The purpose of this study was to analyze the alterations in thymocyte populations (double-positive [DP] and single-positive [SP] cells) under ET conditions. METHODS: Mice were intraperitoneally injected with LPS at a concentration of 5 mg/kg to establish an LPS tolerance model and were divided into two groups: a group examined 72 h after LPS injection (72-h group) and a group examined 8 days after LPS injection (8-day group). Injection of phosphate-buffered saline was used as a control (control group). Changes in thymus weight, cell counts, and morphology were detected in the three groups. Moreover, surface molecules such as CD4, CD8, CD44, CD69, and CD62L were analyzed using flow cytometry. Furthermore, proliferation, apoptosis, cytokine production, and extracellular signal-regulated kinase (ERK) pathway signaling were analyzed in thymocyte populations. The polymorphism and length of the T-cell receptor (TCR) β chain complementarity-determining region 3 (CDR3) were analyzed using capillary electrophoresis DNA laser scanning analysis (ABI 3730). RESULTS: Thymus weight and cell counts were decreased in the early stage but recovered by the late stage in a murine model of LPS-induced ET. Moreover, the proportions of DP cells (control: 72.130 ± 4.074, 72-h: 10.600 ± 3.517, 8-day: 84.770 ± 2.228), CD4+ SP cells (control: 15.770 ± 4.419, 72-h: 44.670 ± 3.089, 8-day: 6.367 ± 0.513), and CD8+ SP cells (control: 7.000 ± 1.916, 72-h: 34.030 ± 3.850, 8-day: 5.133 ± 0.647) were obviously different at different stages of ET. The polymorphism and length of TCR β chain CDR3 also changed obviously, indicating the occurrence of TCR rearrangement and thymocyte diversification. Further analysis showed that the expression of surface molecules, including CD44, CD69, and CD62L, on thymocyte populations (DP and SP cells) were changed to different degrees. Finally, the proliferation, apoptosis, cytokine production, and ERK pathway signaling of thymocyte populations were changed significantly. CONCLUSION These data reveal that alterations in thymocyte populations might contribute to the establishment of ET.
Animals ; CD4-Positive T-Lymphocytes ; Cell Differentiation ; Endotoxins/toxicity* ; Flow Cytometry ; Mice ; Signal Transduction ; Thymocytes ; Thymus Gland

The thymus is a pivotal immune organ of the human body, and it is the place where T cells differentiate and mature. The damage of thymus would easily induce autoimmune diseases and even malignant tumors. For years, researchers have been exploring the process of T cell development and revealing the mechanism of thymic injury and regeneration generally through the monolayer culture system of T cells in vitro. However, the classic monolayer culture system could neither reproduce the unique three-dimensional epithelial reticular structure of the thymus, nor provide the cytokines and growth factors required for the directed differentiation of hematopoietic stem cells into T cells. Thymic organoid technology utilizes cells with stem cell potential to simulate the anatomical structure of the thymus and the signaling pathway mediated by thymic epithelial cells in vitro through three-dimensional culture, which is particularly close to the microenvironment of the thymus in vivo. Thymic organoids show great potential in the study of T cell differentiation and development, thymus-related diseases, reconstruction of immune function, and cell therapy. This paper summarizes the methods for culturing thymic organoids, followed by comparing the advantages and disadvantages of the scaffolds used for culturing. The applications of thymic organoids in the disease model, tumor-targeting therapy, regenerative medicine, and organ transplantation were also discussed, with possible future research directions prospected.
Cell Differentiation ; Epithelial Cells ; Hematopoietic Stem Cells ; Humans ; Organoids ; Regenerative Medicine ; Thymus Gland

Thymus is an encapsulated organ having its bilateral origin from the third pharyngeal pouch. It appears to be a single organ but actually it is bilobed. It attains its maximum development at puberty and then it begins to involute. The parenchyma is replaced by adipocytes and lymphocyte production declines. Here we present a large thymus with a small area of persistent active tissue in it which was obtained during routine undergraduate dissection class. Tissues taken from different quadrants of the large thymic mass were processed, embedded in paraffin and sections were taken for hematoxylin and eosin staining which showed presence of thymic tissue in only one quadrant. Further sections from that quadrant was treated with cytokeratin to confirm its epithelial origin. Therefore knowledge of a large persistent thymus will be helpful to the radiologists and surgeons for making differential diagnosis and in avoiding unnecessary surgical intervention.
Adipocytes ; Adolescent ; Aged ; Cadaver ; Diagnosis, Differential ; Eosine Yellowish-(YS) ; Hematoxylin ; Humans ; Immunohistochemistry ; Keratins ; Lymphocytes ; Paraffin ; Puberty ; Surgeons ; Thymus Gland

Invariant NKT (iNKT) cells are a small subset of thymus-generated T cells that produce cytokines to control both innate and adaptive immunity. Because of their very low frequency in the thymus, in-depth characterization of iNKT cells can be facilitated by their enrichment from total thymocytes. Magnetic-activated cell sorting (MACS) of glycolipid antigen-loaded CD1d-tetramer-binding cells is a commonly used method to enrich iNKT cells. Surprisingly, we found that this procedure also dramatically altered the subset composition of enriched iNKT cells. As such, NKT2 lineage cells that express large amounts of the transcription factor promyelocytic leukemia zinc finger were markedly over-represented, while NKT1 lineage cells expressing the transcription factor T-bet were significantly reduced. To overcome this limitation, here, we tested magnetic-activated depletion of CD24⁺ immature thymocytes as an alternative method to enrich iNKT cells. We found that the overall recovery in iNKT cell numbers did not differ between these 2 methods. However, enrichment by CD24⁺ cell depletion preserved the subset composition of iNKT cells in the thymus, and thus permitted accurate and reproducible analysis of thymic iNKT cells in further detail.
Adaptive Immunity ; Cytokines ; Leukemia ; Methods ; Natural Killer T-Cells ; Receptors, Antigen, T-Cell ; T-Lymphocytes ; Thymocytes ; Thymus Gland ; Transcription Factors ; Zinc Fingers

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a well-established treatment modality for a variety of diseases. Immune reconstitution is an important event that determines outcomes. The immune recovery of T cells relies on peripheral expansion of mature graft cells, followed by differentiation of donor-derived hematopoietic stem cells. The formation of new T cells occurs in the thymus and as a byproduct, T cell receptor excision circles (TRECs) are released. Detection of TRECs by PCR is a reliable method for estimating the amount of newly formed T cells in the circulation and, indirectly, for estimating thymic function. The aim of this study was to determine the role of TREC quantitation in predicting outcomes of human leucocyte antigen (HLA) identical allogenic HSCT.METHODS: The study was conducted on 100 patients receiving allogenic HSCT from an HLA identical sibling. TREC quantification was done by real time PCR using a standard curve.RESULTS: TREC levels were inversely related to age (P=0.005) and were significantly lower in patients with malignant diseases than in those with benign diseases (P=0.038). TREC levels could predict relapse as an outcome but not graft versus host disease (GvHD) and infections.CONCLUSION: Age and nature of disease determine the TREC levels, which are related to relapse.
Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Methods ; Polymerase Chain Reaction ; Real-Time Polymerase Chain Reaction ; Receptors, Antigen, T-Cell ; Recurrence ; Siblings ; T-Lymphocytes ; Thymus Gland ; Transplants

Large cell neuroendocrine carcinoma is a rare epithelial neuroendocrine malignancy and is preferentially located in gastrointestinal tract and pancreas. Cases of large cell neuroendocrine carcinoma have been reported in many other locations, including the thymus, gallbladder, prostate, larynx, salivary glands, nasopharynx, tonsil and mastoid. However, primary sinonasal large cell neuroendocrine carcinoma never have been reported in Korea. We experienced a case of primary large cell neuroendocrine carcinoma arising from left maxillary sinus recently. A 82-year-old male patient presented with nasal obstruction and epistaxis. The biopsy revealed large cell neuroendocrine carcinoma with poor differentiation. After a general evaluation, the patient was staged as cT3N0M0. The patient was treated by combined radiotherapy and chemotherapy. We report this rare case with literature review.
Aged, 80 and over ; Biopsy ; Carcinoma, Neuroendocrine ; Drug Therapy ; Epistaxis ; Gallbladder ; Gastrointestinal Tract ; Humans ; Korea ; Larynx ; Male ; Mastoid ; Maxillary Sinus ; Nasal Obstruction ; Nasopharynx ; Palatine Tonsil ; Pancreas ; Prostate ; Radiotherapy ; Salivary Glands ; Thymus Gland

Extraskeletal osteosarcoma (ESOS) is a malignant soft tissue neoplasm producing osteoid, without any continuity with the bone or periosteum. Primary ESOS presenting in the mediastinum is an extremely rare, yet aggressive malignant tumor associated with a poor prognosis. We report a case of primary ESOS arising from the thymus in a 63-year-old male patient.
Humans ; Male ; Mediastinum ; Middle Aged ; Osteosarcoma ; Periosteum ; Prognosis ; Soft Tissue Neoplasms ; Thymus Gland

Melatonin or N-acetyl-5-methoxytryptamine, the fascinating molecule secreted by the pineal gland. Melatonin has a close interaction with hypothalamic-pituitary-gonadal axis. In non-seasonal breeders like rat its exact role in reproduction is controvertible. So it is worth to explore the possible role of melatonin on the onset of puberty in male albino rats. Two groups of male rats aged 5 and 10 days were used for the study. In each group, there were three subgroups, each receiving melatonin for 5 days, 10 days or till the day of descent of testes. Similar subgroups were used as controls. Without handling, animals were observed daily for the onset of puberty. On the day of descent of testes, body weight of the animal was noted, blood was collected, serum was separated and used for radio immunoassay. For histomorphometric analysis, all morphometric measurements were done using an occular micrometer. Volume fraction of seminiferous tubules, intertubular connective tissue of testes, cortex and medulla of thymus were estimated by point count method. In both the age groups melatonin advanced the age on descent of testes, increased the body weight, organ weight. It also increased the serum hormone levels. So, in conclusion this study indicates that exogenous melatonin advances the onset of puberty in male albino wistar rats and this effect is more pronounced in the younger animals.
Adolescent ; Animals ; Body Weight ; Connective Tissue ; Humans ; Immunoassay ; Male ; Melatonin ; Methods ; Organ Size ; Pineal Gland ; Puberty ; Rats ; Rats, Wistar ; Reproduction ; Seminiferous Tubules ; Testis ; Thymus Gland