Interleukin-13 promotes cellular senescence through inducing mitochondrial dysfunction in IgG4-related sialadenitis

Immunoglobulin G4-related sialadenitis(IgG4-RS)is an immune-mediated fibro-inflammatory disease and the pathogenesis is still not fully understood.The aim of this study was to explore the role and mechanism of interleukin-13(IL-13)in the cellular senescence during the progress of IgG4-RS.We found that the expression of IL-13 and IL-13 receptorα1(IL-13Rα1)as well as the number of senescent cells were significantly higher in the submandibular glands(SMGs)of IgG4-RS patients.IL-13 directly induced senescence as shown by the elevated activity of senescence-associatedβ-galactosidase(SA-β-gal),the decreased cell proliferation,and the upregulation of senescence markers(p53 and p16)and senescence-associated secretory phenotype(SASP)factors(IL-1βand IL-6)in SMG-C6 cells.Mechanistically,IL-13 increased the level of phosphorylated signal transducer and activator of transcription 6(p-STAT6)and mitochondrial-reactive oxygen species(mt ROS),while decreased the mitochondrial membrane potential,ATP level,and the expression and activity of superoxide dismutase 2(SOD2).Notably,the IL-13-induced cellular senescence and mitochondrial dysfunction could be inhibited by pretreatment with either STAT6 inhibitor AS1517499 or mitochondria-targeted ROS scavenger Mito TEMPO.Moreover,IL-13 increased the interaction between p-STAT6 and c AMP-response element binding protein(CREB)-binding protein(CBP)and decreased the transcriptional activity of CREB on SOD2.Taken together,our findings revealed a critical role of IL-13 in the induction of salivary gland epithelial cell senescence through the elevated mitochondrial oxidative stress in a STAT6–CREB–SOD2-dependent pathway in IgG4-RS.

One Case about the Diagnosis and Treatment of Right-Sided Infective Endocarditis without Any Inducement

We present a case of Staphylococcus aurous tricuspid valve endocarditis without any risk factors (intravenous drug users, with pacemaker or central venous lines and with congenital heart disease). Transthoracic echocardiography, as first line examination, showed the vegetations on tricuspid valve. In our case, the diagnosis and treatment of right-sided infective endocarditis without any inducement were extremely difficult. Therefore, once a patient comes out with fever, the blood culture remains positive for gram-positive bacterium, and the infectious location still unknown, then the infective endocarditis should be considered. In addition, surgical measure is also an important therapy for right-sided infective endocarditis.

Flow imbalance in MHD flows in splitting ducts with locally different electric conductivities of the walls

In this study, three-dimensional liquid-metal magnetohydrodynamic splitting flows in a duct with one inflow channel and two outflow channels with locally different wall electric conductivities（different conductance ratios） are computationally examined. The numerical calculation is achieved with the use of CFX code, with a structured grid system chosen after a series of mesh independence tests. The detailed features of the MHD flows are depicted in a case where the electric conductivities of the two outflow ducts are quite different. Also, the interdependency among the current, fluid velocity, pressure and electric potential is elucidated in order to describe the electromagnetic characteristics of the liquid-metal flows. The result shows that the imbalance of the mass flow rate in the two outflow channels strongly depends on the wall conductivity（i.e., conductance ratio） of each outflow channel.