High glucose induces MCP-1 expression partly via tyrosine kinase–AP-1 pathway in peritoneal mesothelial cells

High glucose induces MCP-1 expression partly via tyrosine kinase–AP-1 pathway in peritoneal mesothelial cells.BackgroundHigh glucose in peritoneal dialysis solutions has been implicated in the pathogenesis of peritoneal fibrosis in chronic ambulatory peritoneal dialysis (CAPD) patients. However, the mechanisms are not very clear. Peritoneal macrophages seem to participate in the process of peritoneal fibrosis and monocyte chemoattractant protein-1 (MCP-1) plays a key role in the recruitment of monocytes toward the peritoneal cavity. However, little is known about the effect of high glucose on MCP-1 expression and its signal transduction pathway in human peritoneal mesothelial cells.MethodsMesothelial cells were cultured with glucose (5 to 100 mmol/L) or mannitol chronically for up to seven days. MCP-1 expression of mRNA and protein was measured by Northern blot analysis and enzyme-linked immunosorbent assay (ELISA). Chemotactic activity of high-glucose–conditioned culture supernatant was measured by chemotactic assay. To examine the roles of the transcription factors activator protein-1 (AP-1) and nuclear factor-κB (NF-κB), electrophoretic mobility shift assay (EMSA) was performed.ResultsGlucose induced MCP-1 mRNA expression in a time- and dose-dependent manner. MCP-1 protein in cell culture supernant was also increased. Equivalent concentrations of mannitol had no significant effect. High-glucose–conditioned supernatant possessed an increased chemotactic activity for monocytes, which was neutralized by anti–MCP-1 antibody. EMSA revealed that glucose increased the AP-1 binding activity in a time- and dose-dependent manner, but not NF-κB. Curcumin, an inhibitor of AP-1, dose-dependently suppressed the induction of MCP-1 mRNA by high glucose. Tyrosine kinase inhibitors such as genistein (12.5 to 50 μmol/L) and herbimycin A (0.1 to 1 μmol/L) inhibited the high-glucose–induced MCP-1 mRNA expression in a dose-dependent manner, and also suppressed the high-glucose–induced AP-1 binding activity.ConclusionsHigh glucose induced mesothelial MCP-1 expression partly via the tyrosine kinase-AP-1 pathway

Elimination of Chrysanthemum stunt viroid (CSVd) from Meristem Tip Culture Combined with Prolonged Cold Treatment

Chrysanthemum production in Korea has recently been greatly affected by the spread of Chrysanthemum stunt viroid (CSVd) infection, necessitating the use of CSVd-free stocks to ensure successful chrysanthemum cultivation. We investigated the effects of low temperature (4°C), antiviral chemicals (ribavirin and amantadine) and a combination of these treatments on CSVd elimination by meristem tip cultures using plantlets that originated from CSVd-infected chrysanthemum ‘Ency’. Neither antiviral agents led to CSVd elimination, despite the suppression of meristem tip growth in a concentration dependent manner. However, the CSVd elimination rate increased up to 42.8% when meristem tips were excised after storage at 4°C for two months. The most effective results were obtained from a combination of low temperature for three months at 4°C followed by meristem tip culture on media containing 50 and 100 mgL-1 ribavirin. These results suggest that antiviral agents can also be useful for CSVd elimination if their treatment is combined with prolonged periods of low temperature. This is the first report of eradication of viroids from spray type chrysanthemum bred in Korea

Significance of C4d expression in peritubular capillaries concurrent with microvascular inflammation in for-cause biopsies of ABO-incompatible renal allografts

Background Pathologic diagnosis of antibody-mediated rejection (ABMR) in ABO-incompatible (ABOi) transplantation patients is often challenging because patients without ABMR are frequently immunopositive for C4d. The aim of this study was to determine whether C4d positivity with microvascular inflammation (MVI), in the absence of any detectable donor-specific antibodies (DSAs) in ABOi patients, could be considered as ABMR. Methods A retrospective study of 214 for-cause biopsies from 126 ABOi kidney transplantation patients was performed. Patients with MVI score of ≥2 and glomerulitis score of ≥1 (n = 62) were divided into three groups: the absolute ABMR group (DSA-positive, C4d-positive or C4d-negative; n = 36), the C4d-positive group (DSA-negative, C4d-positive; n = 22), and the C4d-negative group (DSA-negative, C4d-negative; n = 4). The Banff scores, estimated glomerular filtration rates (eGFRs), and graft failure rates were compared among groups. Results C4d-positive biopsies showed higher glomerulitis, peritubular capillaritis, and MVI scores compared with C4d-negative specimens. The C4d-positive group did not show significant differences in eGFRs and graft survival compared with the absolute ABMR group. Conclusion The results indicate that C4d positivity, MVI score of ≥2, and glomerulitis score of ≥1 in ABOi allograft biopsies may be categorized and treated as ABMR cases

Activation of spleen tyrosine kinase is required for TNF-α-induced endothelin-1 upregulation in human aortic endothelial cells

AbstractEndothelin-1 (ET-1) promotes atherosclerosis. We tested whether spleen tyrosine kinase (Syk) mediates tumor necrosis factor-α (TNF-α)-induced ET-1 upregulation in human aortic endothelial cells (HAECs) and sought to identify the signal pathways involved. TNF-α-induced reactive oxygen species (ROS) activated Syk and phosphatidylinositol 3-kinase (PI3K), which was required for the activation of AP-1 and subsequent ET-1 gene transcription. ROS mediated c-Jun NH2-terminal kinase (JNK) is also required for AP-1 activation, but Syk and PI3K regulated AP-1 activation independently of JNK. Through regulation of ET-1 production, Syk could be implicated in atherosclerosis

Comparison of Serum Beta 2-Microglobulin and 24 hour Urinary Creatinine Clearance as a Prognostic Factor in Multiple Myeloma

A new staging system for multiple myeloma (MM) has utilized serum concentrations of beta 2-microglobulin (Sβ2M) and albumin as important prognostic factors for survival. Since Sβ2M is an indicator of glomerular filtration rate, we compared the prognostic values of Sβ2M and 24-hr urinary creatinine clearance (Ccr) in patients with MM. We retrospectively reviewed the records of 170 MM patients from January 1996 to November 2003 whose 24-hr urinary Ccr was available at the time of diagnosis. We found that pretreatment Sβ2M was inversely related to Ccr (Spearman's correlation coefficient=-0.787). In univariate analysis, the hazard ratio (HR) of death was 1.043 (p<0.001) for Sβ2M and 0.985 (p<0.001) for Ccr. Multivariate analysis showed that Sβ2M (HR 1.030, p=0.010) and Ccr (HR 0.993, p=0.059) were significant prognostic factors in patients' survival. In conclusion, 24-hr urinary Ccr may be utilized for staging of patients with MM

Expression of RsMYB1 in chrysanthemum regulates key anthocyanin biosynthetic genes

Background: Several MYB genes belonging to R2R3 MYB transcription factors have been used in several plant species to enhance anthocyanin production, and have shown various expression or regulation patterns. This study focused on the effect of ectopic expression of an RsMYB1 isolated from radish ( Raphanus sativa ) on chrysanthemum cv. \u2018Shinma\u2019. Results: The RT-PCR results confirmed that RsMYB1 regulated the expression of three key biosynthetic genes (CmF3H, CmDFR, and CmANS) that are responsible for anthocyanin production in transgenic chrysanthemum, but were not detected in the non-transgenic line. In all transgenic plants, higher expression levels of key biosynthetic genes were observed in flowers than in leaves. However, the presence of RsMYB1 in chrysanthemum did not affect any morphological characteristics, such as plant height, leaf shape or size, and number of flowers. Furthermore, no anthocyanin accumulation was visually observed in the leaves and floral tissue of any of the transgenic lines, which was further confirmed by anthocyanin content estimation. Conclusion: To our knowledge, this is the first time the role of an MYB transcription factor in anthocyanin production has been investigated in chrysanthemum

Possible beneficial association between renin-angiotensin-aldosterone-system blockade usage and graft prognosis in allograft IgA nephropathy: a retrospective cohort study

Background Although immunoglobulin A nephropathy (IgAN) is associated with an increased risk of renal allograft failure, evidences for its treatment, including renin-angiotensin-aldosterone system blockade (RAASB) usage, remain limited. Methods In this bi-center retrospective cohort study, we included patients who were recently diagnosed with IgAN through allograft biopsies. We identified their 6-month antihypertensive medication prescriptions and investigated the association between the medication types, albuminuria changes, and risk of 5-year death-censored-graft-failure (DCGF). The mixed effect model and cox regression analysis were used. Results A total of 464 allograft IgAN patients were included: 272, 38, 33, and 121 patients in the no antihypertensive medication, single agent RAASB, single agent beta blocker (BB)/calcium channel blocker (CCB), and combination therapy groups, respectively. High-degree albuminuria after 6 months of allograft IgAN diagnosis was an important prognostic parameter and a partial mediator for the association between the subgroups and 5-year DCGF. The usage of single RAASB was associated with decrement of albuminuria from allograft IgAN diagnosis (P for interaction = 0.03). The single BB/CCB group demonstrated significantly worse prognosis than the single RAASB group (adjusted hazard ratio, 2.76 [1.09–6.98]; P = 0.03). Conclusions In conclusion, RAASB may be beneficial for graft prognosis in early allograft IgAN patients who require single antihypertensive medication therapy, by means of reducing albuminuria. Further investigation of treatment strategy in allograft IgAN is warranted.This study was supported by a grant from the Ministry of Health and Welfare (No. HI15C2632), a grant from the National Research Foundation of Korea (No. 2019R1A2C2011465), and a grant from the Ministry of Science, ICT and Future Planning of Korea (No. 2015M3C9A2054342). The funder played no role in performing the study; the study was performed independently by the authors