Notch1 is an important mediator for enhancing of B‐cell activation and antibody secretion by Notch ligand

The roles of Notch1 and Notch2 in T‐cell function have been well studied, but the functional roles of Notch in B cells have not been extensively investigated, except for Notch2 involvement in peripheral marginal zone B‐cell differentiation. This study examined the roles of Notch1 in murine primary B cells. During B‐cell activation by B‐cell receptor ligation, Notch1 was up‐regulated while Notch2 was not. In addition, Notch1 up‐regulation itself did not contribute to the further activation of B cells, but the Notch ligand was important for Notch1‐mediated further B‐cell activation. Moreover, Notch1 deficiency significantly decreased B‐cell activation and antibody secretion under the presence of Notch ligand. These data suggest that Notch1 is an important mediator for enhancing B‐cell activation and antibody secretion by Notch ligand.     

Infrared LED light therapy influences the expression of fibronectin and tenascin in skin wounds of malnourished rats—A preliminary study

The aim of this investigation was to evaluate the effect of infrared (λ 846 ± 20 nm) LED irradiation on the expression profile of the extracellular matrix protein components, tenascin and fibronectin on skin wounds induced in well nourished and malnourished rats. Eighteen albino rats (21 days old) were randomly divided into a well-nourished group (standard diet) and a malnourished group (regional basic diet). After receiving the diet for 70 days, skin wounds were created and the animals were subdivided into three groups: well-nourished control (n = 6), malnourished control (n = 6), and malnourished + LED irradiated (λ 846 ± 20 nm, 100 mW, 4 J/cm²) (n = 6). The animals were sacrificed 3 and 7 days after injury and histological sections were immunostained for both proteins. They were examined for the presence, intensity, distribution and pattern of immunolabeling. At 3 days, the distribution of tenascin was shown to be greater in the wound bed of malnourished animals compared to the well-nourished group. The intensity and distribution of tenascin was shown to be lower in the malnourished LED irradiated group compared to the malnourished control. There was a significant difference regarding the presence of fibronectin in the malnourished and well-nourished groups after 7 days (p = 0.03). The intensity of fibronectin was slight (100%) in the irradiated group and moderate to intense in the malnourished control group. The results of the present study indicate that infrared LED irradiation modulates positively the expression of tenascin and particularly fibronectin.     

Stromal interaction molecule 1 (STIM1) regulates sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 1a (SERCA1a) in skeletal muscle

Stromal interaction molecule 1 (STIM1) mediates Ca²⁺ movements from the extracellular space to the cytosol through a store-operated Ca²⁺ entry (SOCE) mechanism in various cells including skeletal muscle cells. In the present study, to reveal the unidentified functional role of the STIM1 C terminus from 449 to 671 amino acids in skeletal muscle, binding assays and quadrupole time-of-flight mass spectrometry were used to identify proteins binding in this region along with proteins that mediate skeletal muscle contraction and relaxation. STIM1 binds to sarcoplasmic/endoplasmic reticulum Ca²⁺-ATPase 1a (SERCA1a) via this region (called STIM1-SBR). The binding was confirmed in endogenous full-length STIM1 in rabbit skeletal muscle and mouse primary skeletal myotubes via co-immunoprecipitation assay and immunocytochemistry. STIM1 knockdown in mouse primary skeletal myotubes decreased Ca²⁺ uptake from the cytosol to the sarcoplasmic reticulum (SR) through SERCA1a only at micromolar cytosolic Ca²⁺ concentrations, suggesting that STIM1 could be required for the full activity of SERCA1a possibly during the relaxation of skeletal muscle. Various Ca²⁺ imaging experiments using myotubes expressing STIM1-SBR suggest that STIM1 is involved in intracellular Ca²⁺ distributions between the SR and the cytosol via regulating SERCA1a activity without affecting SOCE. Therefore, in skeletal muscle, STIM1 could play an important role in regulating Ca²⁺ movements between the SR and the cytosol.     

Modulation of T-type calcium channels by bioactive lipids

T-type calcium channels (T-channels/Ca_V3) have unique biophysical properties allowing a calcium influx at resting membrane potential of most cells. T-channels are ubiquitously expressed in many tissues and contribute to low-threshold spikes and burst firing in central neurons as well as to pacemaker activities in cardiac cells. They also emerged as potential targets to treat cancer and hypertension. Regulation of these channels appears complex, and several studies have indicated that Ca_V3.1, Ca_V3.2, and Ca_V3.3 currents are directly inhibited by multiple endogenous lipids independently of membrane receptors or intracellular pathways. These bioactive lipids include arachidonic acid and ω3 poly-unsaturated fatty acids; the endocannabinoid anandamide and other N-acylethanolamides; the lipoamino-acids and lipo-neurotransmitters; the P450 epoxygenase metabolite 5,6-epoxyeicosatrienoic acid; as well as similar molecules with 18–22 carbons in the alkyl chain. In this review, we summarize evidence for direct effects of these signaling molecules, the molecular mechanisms underlying the current inhibition, and the involved chemical features. The impact of this modulation in physiology and pathophysiology is discussed with a special emphasis on pain aspects and vasodilation. Overall, these data clearly indicate that T-current inhibition is an important mechanism by which bioactive lipids mediate their physiological functions.     

Surgeon Custom-Made Iliac Branch Device to Salvage Hypogastric Artery during Endovascular Aneurysm Repair

Endovascular salvage of the hypogastric artery using iliac branch device (IBD) during endovascular aortic aneurysm repair (EVAR), offers less invasive alternative solution to surgery to prevent pelvic ischemia. We have performed the first Korean surgeon custom-made IBD for this purpose to overcome the limitation of unavailability of the devices in Korea. Four patients with abdominal aortic aneurysm with bilateral common iliac artery aneurysm (CIAA) were treated using custom-made IBDs from October 2013 to December 2013. IBD was created in back table before EVAR operation using TFLE Zenith iliac limb stent graft (Cook Inc.). Three V12 (Atrium, Inc.) one Viabahn (Gore, Inc.) were used for bridging between IBD and target hypogastric artery. With this modification of IBD procedure, exteriorize the guide wire without snare device is possible which offers another benefit in terms of reducing medical costs comparing to commercial IBD. All operations were successful without any device related complications or postoperative endoleaks. During the mean follow up of 3 months, all IBD were patent without clinical complications. Surgeon custom made IBD is feasible and useful to preserve pelvic perfusion especially in the situation of limited commercial IBD availability in many countries. Long-term follow-up is needed to evaluate stent graft patency and IBD-related complications.