Breakdown of tolerance and abnormal activation in B cells is an important mechanism in the pathogenesis of Graves’ disease (GD) and high levels of thyroid hormones (THs) can drive the progression of ...GD. However, the interactions between THs and abnormal activation of B cells in the context of GD are not well understood. The aim of this study was to investigate B cell-activating factor (BAFF) mediating the cross talk between THs and B cells and the possible underlying mechanisms. A high-level triiodothyronine (T3) mouse model was used to verify T3-mediated induction of overexpression of BAFF and B cell abnormal differentiation. The possible promotion of BAFF overexpression in the mice spleen macrophages during polarization to M1 by T3 was also studied. We showed that high levels of T3 can induce BAFF overexpression and lead to abnormal differentiation of B cells in the mice. While the overexpression of BAFF was observed across many tissue types in the mice, high levels of T3 could induce M1 macrophages polarization by IFN (interferon-gamma)-γ in the spleen of the mice, which in turn generated BAFF overexpression. Our findings provide a novel insight into the interactions between the endocrine and immune systems, as well as provide insight into the role of TH in the pathogenesis of GD.
We aimed to investigate the association between glycemic variability (GV) and the abnormal differentiation of T-cell subpopulations in patients with type 2 diabetes mellitus (T2DM).
In total, 108 ...hospitalized patients with T2DM were enrolled and divided into two subgroups (normal glycemic excursion (NGE) and high glycemic excursion (HGE)) according to their mean amplitude of glycemic excursion (MAGE) level. The MAGE was evaluated via continuous glucose monitoring for 72 h consecutively. Flow cytometry was used to determine the proportions of T cell subpopulations.
The T helper (Th) 1 cell/Th2 cell ratio was significantly higher, and the proportion of regulatory T cells (Tregs) was significantly lower in the NGE group than in the HGE group (all P < 0.05). After fully adjusting for confounders, the MAGE was positively associated with the Th1 cell/Th2 cell ratio (β = 0.370; P = 0.009) and negatively associated with the proportion of Tregs (β = −0.554; P = 0.001).
The MAGE was an independent risk factor for abnormally high Th1 cell/Th2 cell ratio and proportion of Tregs. Abnormal differentiation of T cell subpopulations induced by GV may impair β-cell function, aggravate insulin resistance, and contribute to the development of diabetic complications.
•Glycemic variability impacts T-cell differentiation.•Mean amplitude of glycemic excursion positively correlates with TH1/TH2 ratios and negatively correlates with Treg proportions.•Increased glycemic variability may impair β-cell function by immune alterations.
Activated B cells contribute to heart diseases, and inhibition of B‐cell activating factor (BAFF) expression is an effective therapeutic target for heart diseases. Whether activated B cells ...participate in the development and progression of hyperthyroid heart disease, and what induces B cells activation in hyperthyroidism are unknown. The present study aimed to determine the roles of BAFF overexpression induced by high concentrations of triiodothyronine (T3) in the pathogenesis of hyperthyroid heart disease. Female C57BL/6J mice were subcutaneously injected with T3 for 6 weeks, and BAFF expression was inhibited using shRNA. Protein and mRNA expression of BAFF in mouse heart tissues evaluated via immunohistochemistry, western blotting and polymerase chain reaction (PCR). Proportions of B cells in mouse cardiac tissue lymphocytes were quantified via flow cytometry. Morphology and left ventricle function were assessed using pathological sections and echocardiography, respectively. Here, we demonstrate that compared with the control group, the proportion of myocardial B cells was larger in the T3 group; immunohistochemistry, western blotting and PCR analyses revealed increased protein and mRNA expression levels of TNF‐α and BAFF in heart tissues of the T3 group. Compared with the normal controls group, in the T3 group, the diameter of myocardial cells and some echocardiographic values significantly increased and hypertrophy and structural disorder were noticeable. Our results revealed that elevated levels of circulating T3 can promote the expression of BAFF in myocardial cells and can lead to B‐cell activation, an elevated inflammatory response and ventricular remodelling.
To investigate the pathogenesis of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM), we evaluated the effects of short-term glycemic variability (GV) on the profile of T cell ...subpopulations.
A total of 47 T2DM patients with normoalbuminuria, 47 microalbuminuria, and 49 macroalbuminuria were enrolled. The continuous glucose monitoring (CGM) determined the GV of enrolled patients. Flow cytometry was used to determine the proportion of T cell subpopulations.
The frequency of T helper (Th) 17 and Th1 cells significantly increased while regulatory T cells (Tregs) significantly decreased in the macroalbuminuria group compared to normoalbuminuria and microalbuminuria groups (
< 0.01). The suppressive function of Tregs was significantly lower in the macroalbuminuria group than the normoalbuminuria group (
< 0.05). Compared with the normoalbuminuria group, the mean amplitude of glucose excursions (MAGE) of the macroalbuminuria group was significantly higher (
<0.05). Furthermore, there were negative associations between the proportion of Tregs and MAGE.
Increased GV could decrease the proportion of Tregs and may impair their function. This may lead to increases in Th1 and Th17 cells, and some inflammatory cytokines, which might contribute to the development and progression of DKD in T2DM.
A total of 1 116 middle-aged and elderly men and 1 442 postmenopausal women were recruited in this study. Whether bisphenol A exposure was associated with circulating sex hormone concentrations was ...studied. Univariate analysis revealed that the urinary bisphenol A concentration was negatively correlated with the serum levels of luteinizing hormone （B=-0.061, P〈0.0001） and follicle-stimulating hormone （B=-0.086, P〈0.0001） in men, and with the serum levels of follicle-stimulating hormone （B=-0.037, P=0.018） and sex hormone-binding globulin （B=-0.043, P=0.006） in women. However, no significant association was observed between the serum levels of urinary bisphenol A and circulating sex hormone after adjustment for the potential confounders.
Although gastroduodenal ulcers are common in solid organ transplant patients, there are few reports on multiple giant ulcers in the distal ileum and ileocecal valve caused by immunosuppressants ...Herein, we report on a liver transplant recipient and a renal transplant recipient with multiple large ulcers in the distal ileum and ileocecal valve who rapidly achieved ulcer healing upon withdrawal of sirolimus or tacrolimus and administration of thalidomide. In case 1, a 56-yearold man with primary hepatocellular carcinoma had received a liver transplantation. Tacrolimus combined with sirolimus and prednisolone was used as the anti-rejection regimen. Colonoscopy was performed because of severe abdominal pain and diarrhea at postoperative month 10. Multiple giant ulcers were found at the ileocecal valve and distal ileum. The ulcers healed rapidly with withdrawal of sirolimus and treatment with thalidomide. There was no recurrence during 2 years of follow-up. In case 2, a 34-year-old man with end-stage kidney disease received kidney transplantation and was put on tacrolimus combined with mycophenolate mofetil and prednisolone as the anti-rejection regimen. Twelve weeks after the operation, the patient presented with hematochezia and severe anemia. Colonoscopy revealed multiple large ulcers in the ileocecal valve and distal ileum, with massive accumulation of fresh blood. The bleeding ceased after treatment with intravenous somatostatin and oral thalidomide. Tacrolimus was withdrawn at the same time. Colonoscopy at week 4 of follow-up revealed remarkable healing of the ulcers, and there was no recurrence of bleeding during 1 year of follow-up. No lymphoma, tuberculosis, or infection of cytomegalovirus, Epstein-Barr virus, or fungus wasfound in either patient. In post-transplantation cases with ulcers in the distal ileum and ileocecal valve, sirolimus or tacrolimus should be considered a possible risk factor, and withdrawing them or switching to another immunosuppressant might be effective to treat these ulcers.
Endoscopic variceal obturation of gastric varices with tissue glue is considered the first choice for management of gastric varices, and is usually safe and effective. However, there is still a low ...incidence of complications and some are even fatal. Here, we present a case in which endoscopic variceal ligation caused laceration of the esophageal varicose vein with tissue glue emboli and massive bleeding after 3 mo. Cessation of bleeding was achieved via variceal sclerotherapy using a cap-fitted gastroscope. Methods of recognizing an esophageal varicose vein with tissue glue plug are discussed.
Usually, the teaching courseware that based on Web having a tree menu and can easily browse and links chapter and section. We study the development of a software system that can automatically ...generate courseware framework system with the menu tree. Here to generate static pages with dynamic page technology method, the key code of software framework system with the general characteristics stored in the database, and identify the dynamic location will be update. During the background program, according to the user input the information of chapter and section header, create the object code that can generate the directory tree structure; Finally, the teaching courseware framework system will be created that based on user input basic information and choose the courseware page template with the program stored in advance.
Aluminum-doped zinc oxide （ZnO：AI） films were deposited by direct current magnetron sputtering in incorporating hydrogen in sputtering gas at room temper- ature. The influences of hydrogen content in ...sputtering gas on the structural, optical, and electrical properties of ZnO：A1 films were systematically investigated. It is found that hydrogen incorporated into ZnO lattice forms shallow donors in ZnO：A1 films and plays an important role in the properties of ZnO：A1 films. The electrical conductivity and infrared （IR） reflectance are improved due to the increase of electron carrier concentration, and the average trans- mittance decreases, which is ascribed to the strong scat- tering from the hydrogen incorporated and oxygen vacancies in ZnO：A1 films. In this study, the resistivity of 5.5 × 10-4 Ω.cm is obtained, the average transmittance of the wavelength in the range of 400-900 nm is almost 86 %, and the IR reflectance reaches 75 % at 2,500 nm, which is higher than that of reported TCO films. The band gap determined by optical absorption is a result of com- petition between Burstein-Moss effect and many-body perturbation effect. However, the hydrogen content in sputtering gas is above 10 %, and the optical band gap shift is independent of hydrogen content in sputtering gas.
Surveying ionizing radiations of the surrounding with a smartphone provides a low-cost and convenient utility for the general public. We developed a smartphone application (App) that uses the ...built-in camera with a CMOS sensor and a radiation signal extraction algorithm. After a calibration through a series of radiation exposures,the App could display radiation dose rate and cumulative dose in real time without requiring covering the camera lens. A smartphone with this App can be used as a fast survey tool for ionizing radiations.
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