Immunomodulatory and antioxidant effects of carboxymethylpachymaran on the mice infected with PCV2

The objective of the current study is to investigate the protective effect of carboxymethylpachymaran (CMP) on the immune system of mice via multiple infections with porcine circovirus type 2 (PCV2). The in vivo results showed that CMP administration significantly improved the spleen or thymus index, promoted the proliferation activities of T or B lymphocytes, and increased the production of glutathione, the superoxidase dismutase capacity, and the total antioxidant capacity in the spleen or thymus of PCV2-infected mice. The administration of different CMP doses to PVC2-inoculated mice resulted in the upregulation of IL-2 and IFN-α or the downregulation of IL-10 levels in the serum. These findings suggest that CMP has potential applications in regulating immunological functions to overcome the immunosuppresion caused by PCV2 infection in mice. The findings may also prove useful in designing effective therapies against PCV2 infection.     

Thymus cell population exerting a regulatory function in the immune response of mice to polyvinyl pyrrolidone

An increased response to PVP was observed after adult thymectomy and was partially reversed either by thymus implantation or by a single injection of thymic cells. In addition, an injection of thymic cells was found to reduce the response to PVP in normal recipients. An enhanced response to PVP was measured in B mice compared to that of normals. In such mice reduction of the response to PVP was observed when repeated doses of thymus cells were administered. Lower doses of HC resistant thymus cells strongly inhibited the response to PVP. The cells involved in the thymus regulatory function appear to be radiosensitive, since it was shown that radiation by itself resulted in an increased response to PVP. This inhibitory function of the thymus seems to disappear relatively early in progression of life, as seen by an increased response to PVP in elder mice. These results indicate that a T cell population exerts a regulatory function in the immunological response to PVP that was previously considered to be thymus independent.     

Comparison of the ease of tolerance induction in thymus and bone marrow of three strains of mice

Three strains of mice which vary in their susceptibility to induction of immune tolerance with human gamma-globulin were studied to evaluate the cellular basis for their sensitivity to induction of the unresponsive state. Tolerance induction in BALB/c mice was difficult to establish, while tolerance induction was easily achieved in C57BL/6 and CBF₁ (BALB/c × C57BL/6) mice. The degree of unresponsiveness obtained with various tolerogen doses in intact C57BL/6 and CBF₁ mice was reflected in the sensitivity of their thymocytes to the production of the unresponsive state. In the BALB/c mouse strain slight immune suppression observed at low tolerogen doses was correlated with bone marrow cell unresponsiveness while significant levels of tolerance observed at a high tolerogen dose was due to suppression of thymus cells. It was apparent that CBF₁ mice had inherited both thymus cells and bone marrow cells which exhibited the sensitivity to induction of immune tolerance characteristic of those same cells of their C57BL/6 parent.     

Radiation effects on regeneration and T-cell-inducing function of the thymus

Radiation effects on regeneration and T-cell-inducing function of the thymus were studied in three sets of experiments. When TXB mice were grafted with 1-week-old thymus which had been previously irradiated at various doses, an exponential decrease was observed in the morphological regeneration of the thymus grafts and in their T-cell-inducing function at doses of 600 R and over, showing about 10% that of the control at 1500 R. When in situ thymus of adult mice was locally irradiated, the radiation effect on T-cell-inducing function was less pronounced as compared with the first experiment; i.e., about 40% of the control at 1797 R. When in situ thymus of 1-day-old newborn mice was locally irradiated, regeneration potential of 1-day-old newborn thymus was highly resistant to radiation exposure and no effect on immunologjcal functions was observed even by local irradiation of 2000 R.     

Effects of chorionic gonadotropin on the hematopoietic stem cells

It was shown on the exogenic colony-forming unit (CFU) assay that the chorionic gonadotropin (CG) administration to female mice CBA in doses correlating with its concentration in different stages of woman pregnancy stimulated (depending upon the doses) the CFU formation of bone marrow, but not spleen origin. Injections of CG to the ovariectomized mice has the opposite (inhibited) effect on the CFU contents in bone marrow and spleen. CG-administration in the dose of 40 U1 to the ovariectomized and non-castrated irradiated recipients bone marrow cells stimulates (statistically significant) colonies formation. As for 200 U1 dose hormone has the similar effect only on the non-castrated animals.     

The effect of graded doses of fission neutrons or X rays on the stromal compartment of the thymus in mice

The effect of irradiation on the supportive role of the thymic stroma in T cell differentiation was investigated in a transplantation model using athymic nude mice and transplanted irradiated thymuses. In this model, neonatal CBA/H mice were exposed to graded doses of whole-body irradiation with fast fission neutrons of 1 MeV mean energy or 300 kVp X rays. The doses used varied from 2.75 up to 6.88 Gy fission neutrons and from 6.00 up to 15.00 Gy X rays at center-line dose rates of 0.10 and 0.30 Gy/min, respectively. Subsequently, the thymus was excised and a thymus lobe was transplanted under the kidney capsule of H-2 compatible nude mice. One and two months after transplantation, the T cell composition of the thymic transplant was investigated using immunohistology with monoclonal antibodies directed to the cell surface differentiation antigens Thy-1, Lyt-1, Lyt-2, MT-4, and T-200. Furthermore, the stromal cell composition of the thymic transplant was investigated with monoclonal antibodies directed to MHC antigens and with monoclonal antibodies defining different subsets of thymic stromal cells. To investigate the reconstitution capacity of the thymic transplant, the peripheral T cell number was measured using flow cytofluorometric analysis of nude spleen cells with the monoclonal antibodies anti-Thy-1, anti-Lyt-2, and anti-MT-4. The results of this investigation show that a neonatal thymus grafted in a nude mouse has a similar stromal and T cell composition as that of a normal thymus in situ. In addition, grafting of such a thymus results in a significant increase of the peripheral T cell number. Irradiation of the graft prior to transplantation has no effects on the stromal and T cell composition but the graft size decreases. This reduction of size shows a linear dose-response curve after neutron irradiation. The X-ray curve is linear for doses in excess of 6.00 Gy. The RBE for fission neutrons for the reduction of the relative thymic graft size to 10% was equal to 2.1. Furthermore, the peripheral T cell number decreases with increasing doses of irradiation given to the graft prior to transplantation. The present data indicate that the regenerative potential of thymic stromal cells is radiosensitive and is characterized by D0 values equal to 2.45 and 3.68 Gy for neutrons and X rays, respectively. In contrast, the ability of the thymic stromal cells to support T cell maturation is highly radioresistant.     

Role of cAMP and Neutrophil Cyclooxygenase in Gonadotropin-Dependent Regulation of T Lymphocyte Proliferation

The effect of the main pregnancy hormone, chorionic gonadotropin (CG), on proliferation of peripheral blood mononuclear cells (PBMC) was studied in the presence of autologous neutrophils; also, hormone-dependent regulation of the cAMP levels in T lymphocytes and neutrophils was evaluated. PBMC proliferation in response to a mitogen is suppressed by physiological doses of CG (10, 50, and 100 IU/ml). Autologous neutrophils enhance the suppression induced by the low dose of CG (10 IU/ml), but when cyclooxygenase was inhibited this effect was not observed; this suggests that the anti-proliferative effects of the low dose of CG can be mediated by the products generated by neutrophil cyclooxygenase. The effect of CG was associated with increased cAMP levels in T lymphocytes and neutrophils. Comparison of functional and cAMP-related effects of CG in both cell populations indicates that cAMP is involved in the anti-proliferative effects of CG.     

Developmental abnormalities of terminal deoxynucleotidyl transferase positive bone marrow cells and thymocytes in New Zealand mice: effects of prostaglandin E1

The enzyme TdT was used as a marker with which to study the ontogeny of primitive lymphopoietic cells in NZ strain mice. A marked accumulation of abnormally large, rapidly proliferating TdT+ cells was seen in the subcapsular region of the thymus cortex in the NZB and NZB/W mice. This abnormal accumulation of TdT+ thymocytes was most pronounced in the NZB/W hybrid and persisted for at least the first 16 wk of life. In addition, significantly elevated percentages of TdT+ bone marrow cells (presumptive prothymocytes) were present in NZB, NZW, and NZB/W mice between 1 and 4 wk of age, with the highest mean peak levels occurring in the NZB strain. Treatment of both normal and adrenalectomized BALB/c and NZB/W mice with pharmacologic doses (7 to 10 mg/kg) of PGE1 caused a marked, dose-dependent decrease in thymus weight and thymus cell number within 12 to 18 hr. Histologic and cell separation studies showed that this was due to the selective depletion of PNA+ TdT+ cortical thymocytes. Similarly, PGE1 caused a reversible, dose-dependent decrease in the percentage of TdT+ bone marrow cells. In contrast, PGF2 alpha, which is not therapeutically active against autoimmunity in NZB/W mice, had no detectable effect on TdT+ bone marrow cells or thymocytes in BALB/c or NZB/W mice. These results directly document the existence of abnormalities in the development of lymphopoietic precursor cells in the bone marrow and thymus cortex of NZ strain mice prior to the onset of autoimmune phenomena. The results also raise the possibility that the therapeutic efficacy of exogenous PGE1 in autoimmune NZ strain mice may be related, at least in part, to its ability to rectify the abnormal development of these early lymphoid cells.     

DNA-protein cross-links in different organs of mice induced by the combined action of zinc and gamma-irradiation

Fractional whole-body gamma-irradiation of mice at total doses of 0. 5-1.5 Gy induces increased DNA-protein cross-links (DPCs) in thymus, spleen, and brain, whereas in liver no DPCs are detected. Chronic administration of zinc ions in drinking water at concentration 10 mg/liter for 20-30 days increased DPCs in thymus, spleen, brain, and liver of mice. The combined action of zinc ions and gamma-radiation produced a significantly lower amount of DPCs than was induced by the separate action of these agents.     

Pain-induced alteration of glutamate in periaqueductal central gray and its reversal by morphine

Experiments were performed to evaluate alterations of glutamate levels in the periaqueductal central gray matter (CG) of mice following various treatments. Pain, but not stress, significantly reduced CG glutamate levels. Morphine, evaluated at its time of peak analgesic effect, not only reversed pain-induced depression of CG glutamate levels but significantly increased glutamate above control levels. Pentobarbital and chlorpromazine were without effect on CG glutamate levels suggesting a drug-specific response for this brain area. Evidence supporting a CG-specific morphine response is provided by comparison with alterations of glutamate levels in hypothalamus. In hypothalamus, morphine was without effect in reversing a pain-induced depression of glutamate levels.     

Pain-induced alteration of glutamate in periaqueductal central gray and its reversal by morphine

Experiments were performed to evaluate alterations of glutamate levels in the periaqueductal central gray matter (CG) of mice following various treatments. Pain, but not stress, significantly reduced CG glutamate levels. Morphine, evaluated at its time of peak analgesic effect, not only reversed pain-induced depression of CG glutamate levels but significantly increased glutamate above control levels. Pentobarbital and chlorpromazine were without effect on CG glutamate levels suggesting a drug-specific response for this brain area. Evidence supporting a CG-specific morphine response is provided by comparison with alterations of glutamate levels in hypothalamus. In hypothalamus, morphine was without effect in reversing a pain-induced depression of glutamate levels.     

莱菔子乙醇提取物对ApoE-/-小鼠血脂血糖及肝脂肪变性的影响*

目的:探讨莱菔子乙醇提取物(AERS)对ApoE^-/-小鼠血脂血糖及肝脂肪变性的影响及其机制。方法:随机将60只ApoE^-/-小鼠分为对照组(CG)、生理盐水组(NG)、罗格列酮组(RG)、AERS治疗组,后者再分成AERS低、中、高剂量组(AERS-L/M/H),每组10只。除CG常规饲料外,其他动物均以高脂高糖高盐饲料饲养9周,CG和NG分别每天以等容量NS灌胃1次,RG每天灌胃罗格列酮(1.33 mg·kg^-1,NS稀释成等容量溶液,每次0.2 ml·10 g^-1),AERS组动物每天分别予AERS灌胃(100、300和900 mg·kg^-1)9周后。肝病理学观察,检测FPG、FIns,计算胰岛素抵抗指数(IRI)和肝系数(LC)。检测血清ALT、AST、瘦素(LEP)、TNF-α及血脂水平(TC、FFA等)。Western blot检测肝脂质代谢相关蛋白表达(HMG-R、LDL-R、LEP-R)。结果:与CG相比,NG和RG肝脏外观(色泽、肿胀情况等)和病理学(脂肪变性、肝细胞坏死等)改变明显,而AERS-M/H与CG相似;与CG相比,血清FPG、Fins、IRI、ALT、AST、TNF-α、LC、TG、LDL-C、FFA、LEP等指标明显升高(P＜0.05);与NG相比,AERS呈现剂量依赖性降低(P＜0.05);与RG相比,AERS-H的FPG、Fins明显升高(P＜0.05),而IRI明显降低(P＜0.05);与NG和RG相比,AERS组的HMG-R和LEP-R蛋白表达呈剂量依赖性减少,而LDL-R蛋白表达呈剂量依赖性增加(P＜0.05)。结论:AERS能阻止高脂高糖饲料诱导ApoE^-/^-小鼠血脂血糖升高及肝脂肪变性,其机制与减少FFA和LEP的生成,抑制TNF-α、HMG-R、LEP-R蛋白表达和促进LDL-R的蛋白表达有关。     

In vivo effect of progesteron and estrogen on thymus mass and T-cell functions in female mice

Progesteron and estradiol, administered in doses equivalent to those used for therapy caused a marked transient reduction of the thymus mass, but did not affect the cellularity of other lymphoid organs. Humoral and cellular immune response of the hormone-treated mice was normal at the time of thymus involution. The same was true for the stem-cell differentiation capacity. The remaining thymus cells after hormone treatment showed increased DNA-synthesis.     

Studies on the recirculating cells in the mouse thymus

The cells in the mouse thymus which respond to PHA and have the distribution characteristics of recirculating lymphocytes upon infusion into isologous recipients are markedly enriched 2 days after treatment of mice with proper doses of cortisone acetate. However, a similar increase is not observed in lymph nodes and spleen. During regeneration of the steroidinvoluted thymus, the proportion of recirculating thymic cells disappeared more rapidly than the relative PHA-responsiveness of the cell population. These findings indicate that all PHA-responsive thymocytes may not have recirculating capacity. The recirculating cells present in the thymus and lymph nodes have no tendency to distribute to the thymus, but tend to accumulate in lymph nodes. This fact, together with the finding that in vitro trypsin treatment of the cells temporarily abolishes their lymph node-seeking capacity, are taken as evidence that the recirculating cells in the thymus have undergone their maturation within this organ whereby they have gained membrane receptors which determine their distribution characteristics.     

The effect of curculigoside on mouse model of perimenopausal depression

ObjectiveTo investigate the effect of curculigoside on mice with simulated perimenopausal depression.MethodGavage with high, medium, small dose of curculigoside once daily for 30 d consecutive days. Record the related behavior index. The wet weights and viscera indexes of the mouse uterus, thymus, and spleen were measured. Half of the brain was homogenized and tested for 5-HT and DA concentrations. The levels of serum E2, T, FSH, and LH were measured as well. Finally, histological changes in the uterus, thymus, spleen, and hypothalamus were observed under a light microscope.Resultcurculigoside can enhance the activity and latency time of the mice, increase mouse memory, and decrease electric shocks and immobility times in the TST and FST experiments. Mice treated with curculigoside showed significantly enhancement in viscera indexes of the thymus, spleen, and uterus; significantly elevated levels of serum E2 and T; significantly increased brain 5-HT and DA concentrations; significantly decreased levels of serum FSH and LH; and improvements in the histopathological lesions of the uterus, hypothalamus, thymus, and spleen. The high dose of curculigoside produced the best results.ConclusionAll doses of curculigoside are associated with reversing hormone (E2, T, FSH, and LH) disorders in perimenopausal syndrome and adjusting imbalanced 5-HT and DA levels, representing a therapeutic effect in perimenopausal depression.     

转基因MSC对放射损伤胸腺组织修复的研究

目的：探讨转基因MSC能否修复放射损伤的胸腺。方法：雌性BALB/C小鼠120只,随机分为4组：对照组30只,予以假照射;照射组30只,60Coγ射线胸腺单次照射,剂量为9Gy;照射＋MSC组30只,9Gy照射后2小时输注转基因MSC;对照＋MSC组30只,假照射后2小时输注转基因MSC。照射后1、7、14、21、28天检测各组小鼠血像、胸腺指数及胸腺病理。结果：照射＋MSC组血像和胸腺指数在各个时间点均优于照射组,胸腺病理显示组织结构恢复明显加快。结论：转基因MSC能归巢至放射损伤胸腺并能促进胸腺的修复,为干细胞的临床应用提供了实验依据。     

Ursolic acid ameliorates thymic atrophy and hyperglycemia in streptozotocin–nicotinamide-induced diabetic mice

The purpose of this study was to assess the effects of low-dose ursolic acid (UA) on glycemic regulation and immune responses in streptozotocin–nicotinamide (STZ/NA)-induced diabetic mice. Diabetic mice were supplemented with two different doses of UA (0.01 and 0.05%, w/w) or metformin (0.5%, w/w) for 4 weeks. Compared with the untreated diabetic group, UA and metformin significantly improved blood glucose, glycosylated hemoglobin, glucose tolerance, insulin tolerance and plasma leptin levels as well as aminotransferase activity. The plasma and pancreatic insulin concentrations were significantly higher in both UA groups than in the untreated diabetic group. Supplementation with metformin increased the pancreatic insulin level without a change in the plasma insulin level. The relative thymus weights were lower in the untreated diabetic group compared to the non-diabetic group; however, the UA or metformin group had significantly improved thymus weights. Mice receiving UA or metformin supplementation had increased CD4⁺CD8⁺ subpopulations in the thymus compared to the untreated diabetic mice. Concanavalin A-stimulated splenic T-lymphocyte proliferation and single-positive (CD4⁺ and CD8⁺) subpopulations were significantly higher in the UA-supplemented diabetic groups than in the untreated diabetic group, but lipopolysaccharide-stimulated B-lymphocyte proliferation and the CD19⁺ subpopulation were not significantly different among the groups. In the STZ/NA-induced diabetic mice, metformin increased the splenic T-lymphocyte CD4⁺ and CD8⁺ cell numbers without any change in T-lymphocyte proliferation. Both doses of UA lowered splenic IL-6 levels, whereas metformin increased IFN-γ, IL-6 and TNF-α levels compared to the untreated diabetic mice. These results suggest that low-dose UA may be used as a hypoglycemic agent and immune modulator in non-obese type 2 diabetic mice.     

Cytokine profiles in mice tissues after irradiation of the thymus projection area with femtosecond laser

The effects of pulsed femtosecond laser irradiation in the near ultraviolet region on the levels of cytokines in the thymus, blood, and skin of irradiated mice have been studied. Irradiation of the thymus projection area with low-intensity laser radiation in the near UV region of the spectrum showed significant changes in cytokine levels in the skin and thymus and, to a lesser extent, in the blood of irradiated mice. Laser irradiation with a power density of 20 mW/cm² affects the cytokine profile in the thymus: IFN-γ, IL-3, IL-4, IL-5, eotaxin, GM-CSF, and chemokine KC–factors that can affect differentiation and proliferation of the cells of the immune system in the gland. Conclusions: It is assumed that changes in the expression of cytokines in the thymus after laser irradiation are explained by the rearrangement of biochemical processes possibly associated with the maturation of cells in the gland.     

Cytofluorimetric study of ploidy in the preleukemic thymus in C57BL/Ka mice under fractionated irradiation

The ploidy of the thymus was studied in C57B1/Ka mice irradiated with 4 weekly X-Ray doses of 1.75 Gy. The determination of nuclear DNA content was performed by flow cytometry of intact thymocytes labeled with propidium iodide in presence of a mixture of chicken and rainbow trout red blood cells as internal reference standards. The method has been tested by detecting the sex difference in DNA content of G0/G1 of normal thymic mouse cells. The mean value was 2.9% higher in female mice. The thymus of almost 60% of irradiated male mice present a slight hypoploidy of 2.6% one month after the last irradiation.