Diesel Exhaust Particles Impair Therapeutic Effect of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells against Experimental Colitis through ROS/ERK/cFos Signaling Pathway

Background and Objectives@#Epidemiological investigations have shown positive correlations between increased diesel exhaust particles (DEP) in ambient air and adverse health outcomes. DEP are the major constituent of particulate atmospheric pollution and have been shown to induce proinflammatory responses both in the lung and systemically. Here, we report the effects of DEP exposure on the properties of human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs), including stemness, regeneration, and immunomodulation. @*Methods@#and Results: Non-apoptotic concentrations of DEP (10 μg/ml) inhibited the migration and osteogenic differentiation capacity of WJ-MSCs. Gene expression profiling showed that DEP increased intracellular reactive oxygen species (ROS) and expression of pro-inflammatory and metabolic-process-related genes including cFos. Furthermore, WJ-MSCs cultured with DEP showed impaired suppression of T cell proliferation that was reversed by inhibition of ROS or knockdown of cFos. ERK inhibition assay revealed that DEP-induced ROS regulated cFos through activation of ERK but not NF-κB signaling. Overall, low concentrations of DEP (10 μg/ml) significantly suppressed the stemness and immunomodulatory properties of WJ-MSCs through ROS/ERK/cFos signaling pathways. Furthermore, WJ-MSCs cultured with DEP impaired the therapeutic effect of WJ-MSCs in experimental colitis mice, but was partly reversed by inhibition of ROS. @*Conclusions@#Taken together, these results indicate that exposure to DEP enhances the expression of pro-inflammatory cytokines and immune responses through a mechanism involving the ROS/ERK/cFos pathway in WJ-MSCs, and that DEP-induced ROS damage impairs the therapeutic effect of WJ-MSCs in colitis. Our results suggest that modulation of ROS/ERK/cFos signaling pathways in WJ-MSCs might be a novel therapeutic strategy for DEP-induced diseases.

New insights into the transcriptional regulation of aquaporin-2 and the treatment of X-linked hereditary nephrogenic diabetes insipidus

The kidney collecting duct (CD) is a tubular segment of the kidney where the osmolality and final flow rate of urine are established, enabling urine concentration and body water homeostasis. Water reabsorption in the CD depends on the action of arginine vasopressin (AVP) and a transepithelial osmotic gradient between the luminal fluid and surrounding interstitium. AVP induces transcellular water reabsorption across CD principal cells through associated signaling pathways after binding to arginine vasopressin receptor 2 (AVPR2). This signaling cascade regulates the water channel protein aquaporin-2 (AQP2). AQP2 is exclusively localized in kidney connecting tubules and CDs. Specifically, AVP stimulates the intracellular translocation of AQP2-containing vesicles to the apical plasma membrane, increasing the osmotic water permeability of CD cells. Moreover, AVP induces transcription of the Aqp2 gene, increasing AQP2 protein abundance. This review provides new insights into the transcriptional regulation of the Aqp2 gene in the kidney CD with an overview of AVP and AQP2. It summarizes current therapeutic approaches for X-linked nephrogenic diabetes insipidus caused by AVPR2 gene mutations.

The comparison of QTc interval change on the ECG during laparoscopic cholecystectomy under inhalation and total intravenous anesthesia

BACKGROUND: There can be changes in the cardiac function during laparoscopic cholecystectomy. In this study, QTc interval changes were compared between total intravenous anesthesia (TIVA) group and inhalation anesthesia group during laparoscopic cholecystectomy. METHODS: The study was conducted on adult patients, ages ranging from 20 to 65 years old, and classified as the American Society of Anesthesiologists physical status I or II. At random, the patients were divided into group 1 (TIVA, n = 20) and group 2 (inhalation anesthesia, n = 19). Group 1 patients were induced and maintained with continuous infusion of remifentanil and propofol using a target controlled infusion device. Patients in group 2 were induced with sevoflurane and N2O using mask ventilation, and then anesthesia was maintained with sevoflurane and N2O. The QTc interval, heart rate and mean arterial pressure were measured prior to induction, immediately following intubation, 10 minutes following intubation, following CO2 inflation, immediately following head-up position, 10 minutes following head-up position, following CO2 deflation-supine position respectively. RESULTS: In group 1, the ECG sampling showed no prolongation in the QTc intervals at all measured points. In group 2, QTc interval was significantly longer at all other measured points compared to prior to induction (P < 0.05). Except prior to induction, QTc intervals were significantly longer at all other measure points in group 2 compared to those in group 1 (P < 0.05). CONCLUSIONS: There was no QTc interval prolongation under the TIVA using propofol and remifentanil during laparoscopic cholecystectomy.

Pyomyositis of the iliacus muscle and pyogenic sacroiliitis after sacroiliac joint block: A case report / 대한마취과학회지

Sacroiliac joint block can be performed for the diagnosis and treatment of sacroiliac joint dysfunction. Although sacroiliac joint block is a common procedure, complications have not been reported in detail. We report a case of iliacus pyomyositis and sacroiliac joint infection following a sacroiliac joint block. A 70-year-old female patient received sacroiliac joint blocks to relieve pelvic pain. The patient was admitted to the emergency room two days after the final sacroiliac joint block (SIJB) with the chief complaints of left pelvic pain corresponding to a visual analogue scale (VAS) score of 9 and fever. A pelvic MRI indicated a diagnosis of myositis. After 1 month of continuous antibiotic therapy, the patient's erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level remained elevated. A 67Ga SPECT/CT was done. Abnormal uptake was seen at the left sacroiliac joint (SIJ), and septic sacroiliitis was suspected. The CRP normalized to 0.29 mg/dl and the ESR decreased to 60 mm/hr, and the patient had no fever after 57 days of antibiotic therapy. She was directed for follow up at an outpatient clinic.

Imatinib Mesylate is Effective for Patients Not Only with Chronic Myeloid Leukemia, but Also Rheumatoid Arthritis / 대한내과학회지

Synovial tissue proliferation and inflammation are regarded as possible causes of rheumatoid arthritis. Activation of tyrosine kinase by numerous cytokines and BCR-ABL translocation contribute to synovial tissue inflammation and the development of rheumatoid arthritis, respectively. Imatinib is a tyrosine kinase-blocking agent that is widely used for treating chronic myeloid leukemia. We found several interesting case reports of patients with refractory rheumatoid arthritis who entered remission after initiating imatinib therapy. However, only one case report on treating rheumatoid arthritis with imatinib was found in Korea. Here, we describe the case of a 50-year-old man who showed clinical remission of rheumatoid arthritis and chronic myeloid leukemia after receiving 3 months of imatinib therapy.

Membrane Trafficking of Collecting Duct Water Channel Protein AQP2 Regulated by Akt/AS160

Akt (protein kinase B (PKB)) is a serine/threonine kinase that acts in the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. The PI3K/Akt signaling pathway, triggered by growth factors and hormones including vasopressin, is an important pathway that is widely involved in cellular mechanisms regulating transcription, translation, cell growth and death, cell proliferation, migration, and cell cycles. In particular, Akt and Akt substrate protein of 160 kDa (AS160) are likely to participate in the trafficking of aquaporin-2 (AQP2) in the kidney collecting duct. In this study, we demonstrated that 1) small interfering RNA (siRNA)-mediated gene silencing of Akt1 significantly decreased Akt1 and phospho-AS160 protein expression; and 2) confocal laser scanning microscopy of AQP2 in mouse cortical collecting duct cells (M-1 cells) revealed AS160 knockdown by siRNA increased AQP2 expression in the plasma membrane compared with controls, despite the absence of dDAVP stimulation. Thus, the results suggest that PI3K/Akt pathways could play a role in AQP2 trafficking via the AS160 protein.