Orai1 inhibitor STIM2?? regulates myogenesis by controlling SOCE dependent transcriptional factors

Store-operated Ca2+ entry (SOCE), the fundamental Ca2+ signaling mechanism in myogenesis, is mediated by stromal interaction molecule (STIM), which senses the depletion of endoplasmic reticulum Ca2+ stores and induces Ca2+ influx by activating Orai channels in the plasma membrane. Recently, STIM2??, an eight-residue-inserted splice variant of STIM2, was found to act as an inhibitor of SOCE. Although a previous study demonstrated an increase in STIM2?? splicing during in vitro differentiation of skeletal muscle, the underlying mechanism and detailed function of STIM2?? in myogenesis remain unclear. In this study, we investigated the function of STIM2?? in myogenesis using the C2C12 cell line with RNA interference-mediated knockdown and CRISPR-Cas-mediated knockout approaches. Deletion of STIM2?? delayed myogenic differentiation through the MEF2C and NFAT4 pathway in C2C12 cells. Further, loss of STIM2?? increased cell proliferation by altering Ca2+ homeostasis and inhibited cell cycle arrest mediated by the cyclin D1-CDK4 degradation pathway. Thus, this study identified a previously unknown function of STIM2?? in myogenesis and improves the understanding of how cells effectively regulate the development process via alternative splicing

Complete response to FOLFOX4 therapy in a patient with advanced urothelial cancer: a case report

No standard has been established for salvage therapy in gemcitabine refractory advanced urothelial cancer. We report the complete response to FOLFOX4 therapy of a metastatic urothelial cancer patient, for whom adjuvant gemcitabine plus cisplatin combination chemotherapy had failed. A 54-year-old male patient with urothelial cancer (transitional cell carcinoma) in the right kidney underwent three rounds of adjuvant gemcitabine-cisplatin chemotherapy after extensive radical nephrectomy. However, he had new liver, lung metastases and synchronous two separate primary colon cancer. The lung metastasis lesion was confirmed as a metastatic urothelial cancer via percutaneous transthoracic needle biopsy (PTNB). Liver and lung metastasis lesions disappeared after the 4th cycle of FOLFOX4 chemotherapy. In addition, colon cancer also disappeared after the 8th cycle of FOLFOX4 chemotherapy. The patient was still showing a complete response after 4 months. Clinical trials using the FOLFOX regimen as salvage therapy for gemcitabine-refractory advanced urothelial cancer are warranted

Antinociceptive and Anti-Inflammatory Effects of Ethanolic Extracts of Glycine max (L.) Merr and Rhynchosia nulubilis Seeds

The aim of this study was to assess the in vivo potential of ethanolic extracts of Glycine max (L.) Merr. (SoRiTae) and Rhynchosia nulubilis (Yak-Kong) seeds as natural anti-nociceptive and anti-inflammatory agents. To assess the anti-nociceptive and anti-inflammatory potential, the ethanolic extracts of SoRiTae and Yak-Kong seeds were tested in arachidonic acid-induced ear edema, carrageenan induced paw edema, formalin-induced licking time, acetic acid induced writhing and hot plate-induced thermal stimulation in mice. The administration of ethanolic extracts of SoRiTae and Yak-Kong seeds evoked a significant effect of anti-nociceptive and anti-inflammatory activities as compared to standards aminopyrine and indomethacin. The ear edema, paw edema, paw licking time, pain and writhes in mice were significantly reduced (p < 0.05) as compared to the control. The results obtained in this study indicate that both SoRiTae and Yak-Kong soybeans possesses potential anti-nociceptive and anti-inflammatory activities

Differential associations of central and brachial blood pressure with carotid atherosclerosis and microvascular complications in patients with type 2 diabetes

BACKGROUND: We examined the relationship between central blood pressure (BP), brachial BP with carotid atherosclerosis and microvascular complications in type 2 diabetes mellitus (T2DM). METHODS: We recruited 201 patients who were evaluated for central BP, brachial BP, carotid ultrasonography, brachial-ankle pulse wave velocity (baPWV), ankle-brachial index (ABI) and microvascular complications. Central BP were calculated using a radial automated tonometric system. RESULTS: Agreement between central BP and brachial BP was very strong (concordance correlation coefficient between central and brachial SBP = 0.889, between central and brachial PP = 0.816). Central pulse pressure (PP) was correlated with mean carotid intima-media thickness (CIMT), baPWV and ABI, whereas brachial PP was borderline significantly correlated with CIMT. The prevalence of nephropathy(DN) and retinopathy(DR) according to the brachial PP tertiles increased, the prevalences of microvascular complications were not different across central PP tertiles. In multivariate analysis, the relative risks (RRs) for the presence of DR were 1.2 and 4.6 for the brachial PP tertiles 2 and 3 when compared with the first tertile. Also, the RRs for the presence of DN were 1.02 and 3 for the brachial PP tertiles 2 and 3 when compared with the first tertile. CONCLUSIONS: Agreement of central BP and brachial BP was very strong. Nonetheless, this study showed that higher brachial PP levels are associated with increased probability for the presence of microvascular complications such as DR/DN. However, there are no associations with central SBP and central PP with microvascular complications. Central BP levels than brachial BP are correlated with surrogate marker of macrovascular complications

Multislice B₁ Mapping Method Using Magnetic Resonance Composite Spin Echo Sequences and Simultaneous Echo Refocusing

Radiofrequency (RF) transmit field (B1) mapping is a promising method in mitigating the B1 inhomogeneity in various magnetic resonance imaging (MRI) applications. Although several phase- or magnitude-based B1 mapping methods have been proposed, these methods often require complex modeling, long acquisition time, or specialized MRI sequences. A recently introduced simultaneous echo refocusing (SER) technique can be applied in the B1 mapping method to extend the three-dimensional (3D) spatial coverage only without long data acquisition. Therefore, in this study, a multislice B1 mapping method using composite spin echo sequences and SER techniques is proposed to obtain more accurate B1 mapping with short data acquisition time. To evaluate the performance of the proposed B1 mapping method, computational simulations were performed and compared with Morrell’s method, double angle method, and Yarnykh’s method. These results showed that the angle-to-noise ratio of the proposed B1 mapping method has wider B1 range compared to that of other B1 mapping methods. In addition, the proposed B1 mapping methods were compared to the multislice iterative signal intensity mapping method in both phantom and in vivo human experiments, and there was no remarkable difference between the two methods regarding the flip angle distribution in these experiments. Based on these results, this study demonstrated that the proposed B1 mapping method is suitable for accurately measuring B1 propagation under the condition providing reduced scan time and wider 3D coverage of B1 mapping by applying composite RF pulse and SER techniques into the phase-sensitive method