The world faces the serious problem of aging. In this study, we aimed to investigate the effect of chlorogenic acid (CGA) on vascular senescence. C57/BL6 female mice that were 14 ± 3 months old were infused with either Angiotensin II (AngII) or saline subcutaneously for two weeks. These mice were administered CGA of 20 or 40 mg/kg/day, or saline via oral gavage. AngII infusion developed vascular senescence, which was confirmed by senescence associated-β-galactosidase (SA-β-gal) staining. CGA administration attenuated vascular senescence in a dose-dependent manner, in association with the increase of Sirtuin 1 (Sirt1) and endothelial nitric oxide synthase (eNOS), and with the decrease of p-Akt, PAI-1, p53, and p21. In an in vitro study, with or without pre-treatment of CGA, Human Umbilical Vein Endothelial Cells (HUVECs) were stimulated with H2O2 for an hour, then cultured in the absence or presence of 0.5–5.0 μM CGA for the indicated time. Endothelial cell senescence was induced by H2O2, which was attenuated by CGA treatment. Pre-treatment of CGA increased Nrf2 in HUVECs. After H2O2 treatment, translocation of Nrf2 into the nucleus and the subsequent increase of Heme Oxygenase-1 (HO-1) were observed earlier in CGA-treated cells. Furthermore, the HO-1 inhibitor canceled the beneficial effect of CGA on vascular senescence in mice. In conclusion, CGA exerts a beneficial effect on vascular senescence, which is at least partly dependent on the Nuclear factor erythroid 2-factor 2 (Nrf2)/HO-1 pathway.

Background/Aims: It is controversial whether pretreatment with a proton pump inhibitor (PPI) before Helicobacter pylori eradication treatment decreases the eradication rate. To determine the effects of pretreatment with lansoprazole alone, followed by an H. pylori eradication regimen (lansoprazole 30 mg, amoxicillin 750 mg and clarithromycin 200 mg twice daily for 1 week), on the eradication rate and quality of life (QoL) of the patient. Methods: Patients with H. pylori-positive peptic ulcer were randomly assigned to two groups. The patients received either lansoprazole (30 mg) once daily for 6–8 weeks before H. pylori eradication (group A), or eradication treatment and then lansoprazole (30 mg) for 6–8 weeks (group B). To assess the QoL of the patients, the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire was evaluated. Results: A total of 116 patients were enrolled. The cure rates were 78.9% in group A and 78.0% in group B. In both groups, GSRS analysis showed a significant improvement of the overall GSRS score at the assessment of eradication efficacy, compared to baseline; there was no difference between the groups. Conclusion: With this H. pylori eradication regimen, there was no difference in the cure rates and QoL associated with PPI pretreatment.

Objective. We examined whether or not day-to-day variations in lipid profiles, especially triglyceride (TG) variability, were associated with the exacerbation of diabetic kidney disease. Methods. We conducted a retrospective and observational study. First, 527 patients with type 2 diabetes mellitus (DM) who had had their estimated glomerular filtration rate (eGFR) checked every 6 months since 2012 for over 5 years were registered. Variability in postprandial TG was determined using the standard deviation (SD), SD adjusted (Adj-SD) for the number of measurements, and maximum minus minimum difference (MMD) during the first three years of follow-up. The endpoint was a ≥40% decline from baseline in the eGFR, initiation of dialysis or death. Next, 181 patients who had no micro- or macroalbuminuria in February 2013 were selected from among the 527 patients for an analysis. The endpoint was the incidence of microalbuminuria, initiation of dialysis, or death. Results. Among the 527 participants, 110 reached a ≥40% decline from baseline in the eGFR or death. The renal survival was lower in the higher-SD, higher-Adj-SD, and higher-MMD groups than in the lower-SD, lower-Adj-SD, and lower-MMD groups, respectively (log-rank test p = 0.0073 , 0.0059, and 0.0195, respectively). A lower SD, lower Adj-SD, and lower MMD were significantly associated with the renal survival in the adjusted model (hazard ratio, 1.62, 1.66, 1.59; 95% confidence intervals, 1.05-2.53, 1.08-2.58, 1.04-2.47, respectively). Next, among 181 participants, 108 developed microalbuminuria or death. The nonincidence of microalbuminuria was lower in the higher-SD, higher-Adj-SD, and higher-MMD groups than in the lower-SD, lower-Adj-SD, and lower-MMD groups, respectively (log-rank test p = 0.0241 , 0.0352, and 0.0474, respectively). Conclusions. Postprandial TG variability is a novel risk factor for eGFR decline and the incidence of microalbuminuria in patients with type 2 DM.

In IgA nephropathy (IgAN), IgA1 molecules are characterized by galactose deficiency in O-glycans. Here, we investigated the association between urinary glycosylation profile measured by 45 lectins at baseline and renal prognosis in 142 patients with IgAN. The primary outcome was estimated glomerular filtration rate (eGFR) decline (> 4 mL/min/1.73 m2/year), or eGFR ≥ 30% decline from baseline, or initiation of renal replacement therapies within 3 years. During follow-up (3.4 years, median), 26 patients reached the renal outcome (Group P), while 116 patients were with good renal outcome (Group G). Multivariate logistic regression analyses revealed that lectin binding signals of Erythrina cristagalli lectin (ECA) (odds ratio [OR] 2.84, 95% confidence interval [CI] 1.11–7.28) and Narcissus pseudonarcissus lectin (NPA) (OR 2.32, 95% CI 1.11–4.85) adjusted by age, sex, eGFR, and urinary protein were significantly associated with the outcome, and they recognize Gal(β1-4)GlcNAc and high-mannose including Man(α1-6)Man, respectively. The addition of two lectin-binding glycan signals to the interstitial fibrosis/tubular atrophy score further improved the model fitness (Akaike’s information criterion) and incremental predictive abilities (c-index, net reclassification improvement, and integrated discrimination improvement). Urinary N-glycan profiling by lectin array is useful in the prediction of IgAN prognosis, since ECA and NPA recognize the intermediate glycans during N-glycosylation of various glycoproteins.

SynopsisThe derivatives of poly(chloromethy1styrene) resin (PCMS) with N-methyl-N-carboxylmethyldithiocarbamate (l), N,N-di(B-hydroxyethy1)dithiocarbamate (2), N-methyl-N-carboxylmethylamino (3), and di(P-hydroxyethy1)amino (4) groups were prepared, and the metal ion reactivity of the polymer resins with these functional groups were investigated. Additionally, the effect of y irradiation on the reaction with metal ion was also investigated. In the reaction of PCMS under the same conditions, the substitution ratio order is as follows: (2) > (1) > (4) > (3). In the reaction of the resins with cupric ion, the reaction amount reached a maximum of 4.17 mequiv/g for resin (1) and 4.75 mequiv/g for (2). The polymers containing sulfur atom have a large reactivity toward metal ion in comparison to the polymers without sulfur atom. The reactivity of polymer (1) toward metal ions decreased in the following order: Ag(1) >> Cu(I1) > Zn(I1) 2 Ni(I1) 2 Co(I1). The other metal ions, except Ag(1) and Cu(II), hardly reacted with polymer (2). Thus, polymer (2) has a remarkable selectivity. It was also found that the reaction amount of polymers containing sulfur after y irradiation is almost the same as that before y irradiation.