Anti­inflammatory effects of Nypa fruticans Wurmb via NF­κB and MAPK signaling pathways in macrophages.

The inflammatory defense response of macrophages is a natural protective reaction in the immune system. Antioxidant and anti-inflammatory activities are closely related. In addition, the cell signaling pathway regulating inflammation is associated with MAPK and NF-κB signaling pathway phosphorylation. The present study aimed to evaluate whether the ethyl acetate fraction from N. fruticans (ENF) has a modulatory role in the MAPK signaling pathway and inhibition of the IκB/NF-κB signaling pathways, including translocation of NF-κB p65. Antioxidant and anti-inflammatory activities are closely related. In addition, the cell signaling pathway regulating inflammation is associated with MAPK and NF-κB signaling pathway phosphorylation. The results revealed that ENF exhibited antioxidant capacity, attenuated the cytokine levels and blocked nitric oxide production. ENF downregulated cyclooxygenase-2 and inducible nitric oxide synthase expression. We hypothesized that ENF treatment alleviated the various proinflammatory mediators via IκB phosphorylation and transcription of NF-κB compared with the untreated control. In conclusion, the present study demonstrated that the inhibitory effect of ENF treatment was attributed to the inhibition of MAPK and Akt/IκB/NF-κB signaling pathways.

Nypa fruticans Wurmb inhibits melanogenesis in isobutylmethylxanthine­treated melanoma via the PI3K/AKT/mTOR/CREB and MAPK signaling pathways.

Malignant melanoma is responsible for 3.0 and 1.7% of cases of tumor incidence and tumor-associated mortality, respectively, in the Caucasian population. Melanoma is a type of skin cancer that occurs when melanocytes mutate and divide uncontrollably. Nypa fruticans Wurmb (NF) is abundant in phytochemicals (polyphenols and flavonoids) and is traditionally used to treat diseases of the respiratory tract. The present study investigated the inhibitory effect of the ethyl acetate fraction of NF (ENF) on melanogenesis-related factors in isobutylmethylxanthine-treated B16F10 melanoma cells. Phenolics and flavonoids (caffeic acid, catechin, epicatechin and hirsutine) in ENF were analyzed via liquid chromatography-mass spectrometry. In addition, the main factors involved in melanogenesis were identified using immunoblotting, reverse transcription-polymerase chain reaction (RT-PCR), RT-quantitative PCR and immunofluorescence. ENF significantly suppressed the expression of tyrosinase (TYR) and TYR-related proteins 1 and 2 (TYRP-1/2), which are the main factors involved in melanogenesis. ENF also inhibited the expression of microphthalmia-associated transcription factor (MITF) by phosphorylating the related cell signaling proteins (protein kinase B, mammalian target of rapamycin, phosphoinositide 3-kinase and cAMP response element-binding protein). Furthermore, ENF inhibited the phosphorylation of extracellular signal-regulated kinase and thereby downregulated melanogenesis. In conclusion, ENF inhibited melanogenesis by suppressing MITF, which controls TYRP-1/2 and TYR. These results suggested that ENF may be a natural resource that can inhibit excessive melanin expression by regulating various melanogenesis pathways.

Improvement of Liver Fibrosis after Long-Term Antiviral Therapy Assessed by Fibroscan in Chronic Hepatitis B Patients With Advanced Fibrosis.

OBJECTIVES: Performing repeated liver biopsies to assess the improvement of liver fibrosis is impractical. The purpose of this prospective cohort study was to assess the improvement of liver fibrosis during antiviral treatment by serial liver stiffness (LS) measurement using Fibroscan in chronic hepatitis B (CHB) patients with advanced fibrosis. METHODS: Nucleos(t)ide analog-naive CHB patients with advanced fibrosis in histological findings (stage ≥F3), high viral load (hepatitis B virus DNA ≥2,000 IU/ml), and normal liver enzyme levels (<2 × upper normal limit) before starting antiviral treatment were included in this study. LS measurement was performed at baseline and annually for 5 years during antiviral treatment. Five-year fibrosis improvement was defined as LS value <7.2 kPa (

Measurement of donor kidney functional renal volume and glomerular filtration rate to predict allograft function during the post-transplantation period.

BACKGROUND: We measured donor kidney weight (D-KW), functional renal volume (D-FRV), and single-kidney glomerular filtration rate (D-SKGFR), and then evaluated the impact of the indices to recipient body weight (R-BW) on graft function. METHODS: This study included 44 recipients of live donor transplants without delayed graft function or acute rejection within 2 years of transplantation. RESULTS: There was a statistically significant difference in serum creatinine between recipients with a D-KW/R-BW ratio of 4.25, D-FRV/R-BW ratio of >5.14, or D-SKGFR/R-BW ratio of >1.06, respectively. D-KW/R-BW, D-FRV/R-BW, and D-SKGFR/R-BW strongly correlated with serum creatinine at 1 year and 2 years post-transplantation. In multivariate analysis, D-FRV and donor age were statistically significant risk factors which influenced serum creatinine at 1 year and 2 years post-transplantation. CONCLUSION: D-FRV/R-BW and donor age have significant impact on graft function. D-FRV/R-BW can be measured ahead of surgery. Therefore, measuring the D-FRV is useful to select a more optimal donor kidney among otherwise similar candidates during preoperative evaluation to improve posttransplant graft function.

MDM2 and p53 polymorphisms are associated with the development of hepatocellular carcinoma in patients with chronic hepatitis B virus infection.

A single-nucleotide polymorphism (SNP) in the promoter region of MDM2, SNP 309, is associated with hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus infection. The effect of p53 codon 72 polymorphism Arg72Pro on HCC risk remains inconsistent. This study evaluated the association of MDM2 and p53 polymorphisms with the presence and early onset of HCC in Korean patients with chronic hepatitis B virus (HBV) infection. In total, 583 consecutive patients with chronic HBV infection were classified according to the presence (n = 287) or absence (n = 296) of HCC. The MDM2 SNP 309 and p53 Arg72Pro were genotyped using restriction fragment length polymorphism method. The MDM2 G/G and p53 Pro/Pro genotypes were more frequent in HCC group than in non-HCC group (P < 0.001 and P = 0.004, respectively). Multivariate analysis for the presence of HCC revealed that the odds ratio (OR) for MDM2 G/G over T/T was 4.89 (P < 0.001) and that of p53 Pro/Pro over Arg/Arg was 3.03 (P = 0.006). Combined MDM2 G/G and p53 Pro/Pro had a synergistic effect on HCC risk, with an OR of 20.78 (P < 0.001). The mean age of tumor onset in patients with MDM2 G/G genotype was 50.9 years compared with 55.1 with T/T genotype (P = 0.018) and that with p53 Pro/Pro was 49.7 years compared with 52.9 with Arg/Arg (P = 0.040). Thus, MDM2 SNP 309 and p53 Arg72Pro are associated with the early development of HCC in Korean patients with chronic HBV infection.

The level of 2-h post-challenge glucose is an independent risk factor of carotid intima-media thickness progression in Korean type 2 diabetic patients.

OBJECTIVE: To evaluate the relationship between the metabolic abnormalities commonly associated with diabetes and the changes in carotid intima-media thickness (IMT) in Korean type 2 diabetic patients who do not have clinically manifest cardiovascular disease (CVD). DESIGN: In a prospective study, a total of 152 type 2 diabetic patients were recruited from a group of outpatients at the Yonsei University Hospital. MATERIALS AND METHODS: The carotid IMTs of 152 subjects with type 2 diabetes (mean age 63.5+/-7.0 years) were determined at baseline and after a mean follow-up time of 23.7+/-3.7 months. Fasting plasma glucose, serum total cholesterol (TC), serum triglyceride, high-density lipoprotein cholesterol (HDL-C), HbA1c, oral glucose tolerance test (OGTT) results for 2-h post-challenge glucose (2hPG), and blood pressure measurements were collected every 3 months and averaged. RESULTS: The highest quartiles of baseline C-peptide and homeostatic model assessment (HOMA) index showed more IMT progression than the lowest quartiles. The change in the mean IMT correlated with average values of HbA1c (r=.219, P=.007), the 2-h post-challenge glucose (r=.239, P=.003), HDL-C (r=-.228, P=.005), LDL-C (r=.175, P=.033), and non-HDL-C (r=.194, P=.016). Multiple regression analysis demonstrated that the independent risk factor for the mean IMT change in diabetic patients was the average 2hPG level (P=.004). The change in the mean IMT of those in the lowest quartile of average 2hPG (<11.1 mmol/l) was 823+/-176 to 841+/-146 microm (P=.276). In the highest quartile (2hPG >15.3 mmol/l), however, the mean IMT increased from 794+/-127 to 882+/-153 microm (P<.001). CONCLUSION: The 2hPG parameter among the various metabolic parameters exerts the greatest influence upon the prevention of carotid IMT progression in type 2 diabetic subjects. The level of 2hPG is an independent risk factor for the progression of carotid IMT in Korean type 2 diabetic patients.

Haplotype combination of Calpain-10 gene polymorphism is associated with metabolic syndrome in type 2 diabetes.

Patients with metabolic syndrome are at increased risk of developing cardiovascular disease. The combinations of the haplotype created by the alleles of three single nucleotide polymorphisms (SNPs): SNP-43, -19, and -63 of the Calpain-10 gene (CAPN10), have been reported to be associated with the risk of type 2 diabetes in many populations. The aim of this study was to examine the association of the CAPN10 polymorphism with metabolic syndrome in patients with type 2 diabetes in Korea. Overall, 382 patients with type 2 diabetes were enrolled in this study. All the subjects were genotyped according to CAPN10 SNP-43, -19, and -63. The restriction fragment length polymorphism method was used for the three SNPs. The baseline presence of components of metabolic syndrome was determined. Two hundred and sixty-five (69.4%) patients had metabolic syndrome. Patients with the 111/121 haplotype combination showed a higher risk of hypertension than the other haplotype combinations (odd ratio (OR)=2.334, P=0.010). Patients with the 111/121 haplotype combination had a significantly high risk of metabolic syndrome (OR=1.927, P=0.042). The results of this study suggest that a novel 111/121 haplotype combination created by the CAPN10 SNP-43, -19, and -63 increases the susceptibility to the metabolic syndrome in patients with type 2 diabetes.

Chronologically different impacts of immunologic and non-immunologic risk factors on renal allograft function.

INTRODUCTION: Upon analysis of the risk factors affecting renal graft survival and function, the time-dependent effects of each risk factor should be differentiated from their net effects. To evaluate the chronologically different impacts of risk factors on graft renal function, we reviewed 390 recipients who received a kidney from 1-haplotype-matched living-related donors. MATERIALS AND METHODS: Until 5-yr post-transplantation (TX), yearly serum creatinine (Scr), 24-h urinary excretion of protein, and their yearly changes were compared by the episodes of acute rejection within 1 yr, the kidney weight to recipient body weight (KW/BW) ratio, the donor/recipient (D/R) age ratio, and the D/R gender pairing. The Kaplan-Meier method, Cox proportional hazard model, ANOVA, and repeated measures ANOVA were each applied for different purposes. RESULTS: Only the episodes of acute rejection were a significant risk factor affecting graft survival. The episodes of acute rejection, KW/BW ratio, D/R age ratio, and D/R gender pairing consistently and independently had significant influences on Scr. Recipients having the lowest KW/BW ratio (first quartile) or the highest D/R age ratio (fourth quartile) had rapid increments of Scr after 4-yr post-TX. After 3-yr post-TX, there were significant correlations between the number of non-immunologic risk factors present and the yearly changes in Scr. CONCLUSIONS: Non-immunologic factors had a detrimental effect on renal graft function, especially after 3-yr post-TX. If immunologic risks seem to be similar, size matching, age, and gender pairing should be considered for better long-term graft function in renal TX recipients.