Interleukin-1α Activity in Necrotic Endothelial Cells Is Controlled by Caspase-1 Cleavage of Interleukin-1 Receptor-2: IMPLICATIONS FOR ALLOGRAFT REJECTION*

Inflammation is a key instigator of the immune responses that drive atherosclerosis and allograft rejection. IL-1α, a powerful cytokine that activates both innate and adaptive immunity, induces vessel inflammation after release from necrotic vascular smooth muscle cells (VSMCs). Similarly, IL-1α released from endothelial cells (ECs) damaged during transplant drives allograft rejection. However, IL-1α requires cleavage for full cytokine activity, and what controls cleavage in necrotic ECs is currently unknown. We find that ECs have very low levels of IL-1α activity upon necrosis. However, TNFα or IL-1 induces significant levels of active IL-1α in EC necrotic lysates without alteration in protein levels. Increased activity requires cleavage of IL-1α by calpain to the more active mature form. Immunofluorescence and proximity ligation assays show that IL-1α associates with interleukin-1 receptor-2, and this association is decreased by TNFα or IL-1 and requires caspase activity. Thus, TNFα or IL-1 treatment of ECs leads to caspase proteolytic activity that cleaves interleukin-1 receptor-2, allowing IL-1α dissociation and subsequent processing by calpain. Importantly, ECs could be primed by IL-1α from adjacent damaged VSMCs, and necrotic ECs could activate neighboring normal ECs and VSMCs, causing them to release inflammatory cytokines and up-regulate adhesion molecules, thus amplifying inflammation. These data unravel the molecular mechanisms and interplay between damaged ECs and VSMCs that lead to activation of IL-1α and, thus, initiation of adaptive responses that cause graft rejection.     

Adiponectin promotes human jaw bone marrow mesenchymal stem cell chemotaxis via CXCL1 and CXCL8

Adiponectin (APN) is known to promote the osteogenic differentiation of human jaw bone marrow mesenchymal stem cells (h‐JBMMSCs). However, the underlying mechanism has not been fully elucidated. Previously, we showed that APN could promote h‐JBMMSC osteogenesis via APPL1‐p38 by up‐regulating osteogenesis‐related genes. Here, we aimed to determine whether APN could promote h‐JBMMSC chemotaxis through CXCL1/CXCL8. The CCK‐8, wound healing and transwell assays were used to evaluate the proliferation, migration and chemotaxis of h‐JBMMSCs with or without APN treatment. Chemotaxis‐related genes were screened using RNA‐seq, and the results were validated using real‐time PCR and ELISA. We also performed Western blot using the AMPK inhibitor, WZ4003, and the p38 MAPK inhibitor, SB203580, to identify the signalling pathway involved. We found that APN could promote h‐JBMMSC chemotaxis in the co‐culture transwell system. CXCL1 and CXCL8 were screened and confirmed as the up‐regulated target genes. The APN‐induced CXCL1/8 up‐regulation to promote chemotaxis could be blocked by CXCR2 inhibitor SB225002. Western blot revealed that the phosphorylation of AMPK and p38 MAPK increased in a time‐dependent manner with APN treatment. Additionally, WZ4003 and SB203580 could suppress the APN‐induced overexpression of CXCL1 and CXCL8. The results of the transwell chemotaxis assay also supported the above results. Our data suggest that APN can promote h‐JBMMSC chemotaxis by up‐regulating CXCL1 and CXCL8.     

Multistep Photoluminescence Decay Reveals Dissociation of Geminate Charge Pairs in Organolead Trihalide Perovskites

Charge carrier dynamics in organolead iodide perovskites is analyzed by employing time‐resolved photoluminescence spectroscopy with several ps time resolution. The measurements performed by varying photoexcitation intensity over five orders of magnitude enable separation of photoluminescence components related to geminate and nongeminate charge carrier recombination and to address the dynamics of an isolated geminate electron–hole pair. Geminate recombination dominates at low excitation fluence and determines the initial photoluminescence decay. This decay component is remarkably independent of the material structure and experimental conditions. It is demonstrated that dependences of the geminate and nongeminate radiative recombination components on excitation intensity, repetition rate, and temperature, are hardly compatible with carrier trapping and exciton dissociation models. On the basis of semiclassical and quantum mechanical numerical calculation results, it is argued that the fast photoluminescence decay originates from gradual spatial separation of photogenerated weakly bound geminate charge pairs.     

Identification of cardiac stem cells within mature cardiac myocytes

Cardiac stem cells are described in a number of mammalian species including humans. Cardiac stem cell clusters consisting of both lineage-negative and partially committed cells are generally identified between contracting cardiac myocytes. In the present study, c-kit⁺, Sca⁺, and Isl1⁺ stem cells were revealed to be located inside the sarcoplasm of cardiac myocytes in myocardial cell cultures derived from newborn, 20-, and 40-day-old rats. Intracellularly localized cardiac stem cells had a coating or capsule with a few pores that opened into the host cell sarcoplasm. The similar structures were also identified in the suspension of freshly isolated myocardial cells (ex vivo) of 20- and 40-day-old rats. The results from this study provide direct evidence for the replicative division of encapsulated stem cells, followed by their partial cardiomyogenic differentiation. The latter is substantiated by the release of multiple transient amplifying cells following the capsule rupture. In conclusion, functional cardiac stem cells can reside not only exterior to but also within cardiomyocytes.     

Effects of acupuncture on declined cerebral blood flow,impaired mitochondrial respiratory function and oxidative stress in multi-infarct dementia rats

Brain energy disorders and oxidative stress due to chronic hypoperfusion were considered to be the major risk factors in the pathogenesis of dementia. In previous studies, we have demonstrated that acupuncture treatment improved cognitive function of VaD patients and multi-infarct dementia (MID) rats. Acupuncture therapy also increased the activities of glycometabolic enzymes in the brain. But it is not clear whether acupuncture treatment compensates neuronal energy deficit after cerebral ischemic through enhancing the activities of glucose metabolic enzymes and preserving mitochondrial function, and whether acupuncture neuroprotective effect is associated with activations of mitochondrial antioxidative defense system. So, the effect of acupuncture therapy on cognitive function, cerebral blood flow (CBF), mitochondrial respiratory function and oxidative stress in the brain of MID rats was investigated in this study. The results showed that acupuncture treatment significantly improved cognitive abilities and increased regional CBF of MID rats. Acupuncture elevated the activities of total SOD, CuZnSOD and MnSOD, decreased the level of malondialdehyde (MDA) and superoxide anion, regulated the ratio of reduced glutathione (GSH) and oxidized glutathione (GSSG) in mitochondria, and raised the level of the respiratory control index (RCI) and P/O ratio and the activities of mitochondrial respiratory enzymes of MID rats. These results indicated that acupuncture treatment improved cognitive function of MID rats; and this improvement might be due to increased CBF, which ameliorated mitochondrial dysfunction induced by ischemia and endogenous oxidative stress system of brain.     

The Effects of Mobile Phone Radiofrequency Radiation on Cochlear Stria Marginal Cells in Sprague–Dawley Rats

To investigate the possible mechanisms for biological effects of 1,800 MHz mobile radiofrequency radiation (RFR), the radiation-specific absorption rate was applied at 2 and 4 W/kg, and the exposure mode was 5 min on and 10 min off (conversation mode). Exposure time was 24 h short-term exposure. Following exposure, to detect cell DNA damage, cell apoptosis, and reactive oxygen species (ROS) generation, the Comet assay test, flow cytometry, DAPI (4′,6-diamidino-2-phenylindole dihydrochloride) staining, and a fluorescent probe were used, respectively. Our experiments revealed that mobile phone RFR did not cause DNA damage in marginal cells, and the rate of cell apoptosis did not increase (P > 0.05). However, the production of ROS in the 4 W/kg exposure group was greater than that in the control group (P < 0.05). In conclusion, these results suggest that mobile phone energy was insufficient to cause cell DNA damage and cell apoptosis following short-term exposure, but the cumulative effect of mobile phone radiation still requires further confirmation. Activation of the ROS system plays a significant role in the biological effects of RFR. Bioelectromagnetics. © 2020 The Authors. Bioelectromagnetics published by Wiley Periodicals, Inc.     

Absence of the myelin-associated glycoprotein (MAG) and the neural cell adhesion molecule (N-CAM) interferes with the maintenance,but not with the formation of peripheral myelin

We have previously shown that mice deficient in the gene for the myelin-associated glycoprotein (MAG) develop normal myelin in the peripheral nerves, but show axon and myelin degeneration at eight months of age, suggesting that MAG is involved in the maintenance of axon-Schwann cell integrity. The search for molecules that might replace MAG during myelination revealed an overexpression of the neural cell adhesion molecule (N-CAM) at those aspects where MAG is detectable in wild type mice. To test whether N-CAM might compensate for MAG during myelination in MAG-deficient mice, double mutants deficient in both MAG and N-CAM (MAG⁻/N-CAM⁻mice) were generated by cross-breeding the single mutants. Whereas alterations of myelin development were not detectable in either of the single or double mutants, degeneration of myelin and axons occurred approximately 4 weeks earlier in MAG⁻/N-CAM⁻than in MAG⁻mutants. Furthermore, at 8 weeks of age, single fiber preparation and electron microscopy revealed that the number of profiles indicative of degeneration was substantially increased in MAG⁻/N-CAM⁻mutants when compared to MAG⁻mice. These data suggest that in MAG-deficient mice N-CAM does not compensate for MAG in myelin formation but partially substitutes for it in the maintenance of axon-myelin integrity. Received: 20 May 1996 / Accepted: 19 July 1996