[Supplemental Fuzhenghuayu capsule therapy for improving liver fibrosis markers in patients with chronic hepatitis B following unsatisfactory outcome of nucleos(t)ide analogue monotherapy].

OBJECTIVE: To investigate the ability of Fuzhenghuayu capsule to improve markers of liver fibrosis when provided as supplemental therapy in patients with chronic hepatitis B (CHB) who achieved complete virological response but unsatisfactory resolution of fibrosis markers with nucleos(t)ide analog (NAs) monotherapy. METHODS: One-hundred-and-ten patients with CHB-related liver fibrosis who had received NA for more than or equal to 2 years and achieved sustained virological response (SVR) but no improvement in liver fibrosis index were randomly divided into two equal groups: experimental group, continued oral NAs (one tablet, 1 time/day) with simultaneous Fuzhenghuayu capsule (1.5 g, 3 times/day) for 48 weeks; control group, continued oral NAs only for 48 weeks. Serum fibrosis markers (hyaluronic acid (HA), laminin (LN), amino terminal propeptide of type III procollagen (PIIIP) and IV collagen (IV-C)), liver fibrosis stages, B ultrasonic wave, and liver function were observed before (baseline) and after treatment and compared by statistical analysis. RESULTS: The baseline levels of fibrosis markers were not significantly different between the experimental and control groups. After treatment, the levels of all of the fibrosis markers were lower in the experimental group (P less than 0.05 vs. control group; HA t = 19.548, LN t = 2.264, PIIIP t = 2.230, and IV-C t = 6.649) and lower than the baseline levels (P less than 0.01; HA t = 12.458, LN t = 7.402, PIIIP t = 4.620, IV-C t = 8.937). The control group also showed a significant reduction in HA and LN levels after treatment (P less than 0.01 vs. baseline; t = 5.202 and 3.444), but PIIIP and IV-C were unaffected. The baseline liver fibrosis stages were not significantly different between the experimental and control groups. After treatment, only the experimental group showed significant improvement in liver fibrosis stages (P less than 0.01). The rates of excellent therapeutic outcome, effectiveness, and non-effectiveness were significantly different between the experimental group (11.3%, 43.4%, and 45.3%) and the control group (1.0%, 22.2%, and 75.6%) (x2 = 9.408, P less than 0.01). Similar trends were observed for improvements in B ultrasonic wave for liver and spleen and in markers of liver function. Finally, neither treatment group experienced adverse effects. CONCLUSION: For CHB patients who achieve SVR by antiviral treatment with NAs, but unsatifactory improvement in liver fibrosis indices, administration of supplemental Fuzhenghuayu capsule with continued NAs therapy may represent a safe and effective treatment.

Effect of exogenously applied molybdenum on its absorption and nitrate metabolism in strawberry seedlings.

Molybdenum (Mo)-an essential element of plants-is involved in nitrogen (N) metabolism. Plants tend to accumulate more nitrate and show lower nitrogen use efficiency (NUE) under Mo-deficient conditions. Improving NUE in fruits reduces the negative effect of large applications of chemical fertilizer, but the mechanisms underlying how Mo enhances NUE remain unclear. We cultivated strawberry seedlings sprayed with 0, 67.5, 135, 168.75, or 202.5 g Mo·ha-1 in a non-soil culture system. The Mo concentration in every plant tissue analyzed increased gradually as Mo application level rose. Mo application affected iron, copper, and selenium adsorption in roots. Seedlings sprayed with 135 g Mo·ha-1 had a higher [15N] shoot:root (S:R) ratio, and 15NUE, and produced higher molybdate transporter type 1 (MOT1) expression levels in the roots and leaves. Seedlings sprayed with 135 g Mo·ha-1 also had relatively high nitrogen metabolic enzyme activities and up-regulated transcript levels of nitrate uptake genes (NRT1.1; NRT2.1) and nitrate-responsive genes. Furthermore, there was a significantly lower NO3- concentration in the leaves and roots, a higher NH4+ concentration in leaves, and a higher glutamine/glutamate (Gln/Glu) concentration at 135 g Mo·ha-1. Seedlings sprayed with 202.5 g Mo·ha-1 showed the opposite trend. Taken together, these results suggest that a 135 g Mo·ha-1 application was optimal because it enhanced NO3- transport from the roots to the shoots and increased NUE by mediating nitrogen metabolic enzyme activities, nitrate transport, and nitrate assimilation gene activities.

The flavor and nutritional characteristic of four strawberry varieties cultured in soilless system.

Strawberry fruits (cv. Benihoppe, Tochiotome, Sachinoka, and Guimeiren) were harvested and evaluated the flavor and nutritional parameters. By principal component analysis and hierarchical clustering analysis, differences were observed based on the volatile compounds composition, sugar and acid concentration, sweetness, and total soluble sugars/total organic acids of the four varieties. A total of 37, 48, 65, and 74 volatile compounds were identified and determined in cv. Benihoppe, Tochiotome, Sachinoka, and Guimeiren strawberry fruits extracted by head-space solid-phase microextraction (HS-SPME), respectively. Esters significantly dominated the chemical composition of the four varieties. Furaneol was detected in cultivars of Sachinoka and Guimeiren, but mesifuran was only found in cv. Tochiotome. Tochiotome and Sachinoka showed higher content of linalool and (E)-nerolidol. Sachinoka showed the highest content of total sugars and total acids. Guimeiren showed higher sweetness index than the other three cultivars. Firmness of Tochiotome was highest among all the varieties. The highest total soluble solids TSS value was found in cv. Sachinoka, followed by the Guimeiren and Tochiotome varieties. Sachinoka had the highest titratable acidity TA value. The content of ascorbic acid (AsA) of cv. Tochiotome was higher than the others, but there was no significant difference in cultivars of Benihoppe, Tochiotome, and Sachinoka. Fructose and glucose were the major sugars in all cultivars. Citric acid was the major organic acid in cv. Tochiotome, cv. Sachinoka, and cv. Guimeiren. Tochiotome had higher ratios of TSS/TA and total sugars/total organic acids than others, arising from its lower acid content. The order of the comprehensive evaluation score was Sachinoka>Guimeiren>Tochiotome>Benihoppe.

Analysis of basic leucine zipper genes and their expression during bud dormancy in peach (Prunus persica).

Dormancy is a biological characteristic developed to resist the cold conditions in winter. The bZIP transcription factors are present exclusively in eukaryotes and have been identified and classified in many species. bZIP proteins are known to regulate numerous biological processes, however, the role of bZIP in bud dodormancy has not been studied extensively. In total, 50 PpbZIP transcription factor-encoding genes were identified and categorized them into 10 groups (A-I and S). Similar intron/exon structures, additional conserved motifs, and DNA-binding site specificity supported our classification scheme. Additionally, chromosomal distribution and collinearity analyses suggested that expansion of the PpbZIP transcription factor family was due to segment/chromosomal duplications. We also predicted the dimerization properties based on characteristic features of the leucine zipper and classified PpbZIP proteins into 23 subfamilies. Furthermore, qRT-PCR results indicated that PpbZIPs genes may be involved in regulating dormancy. The same gene of different species might participate in different regulating networks through interactions with specific partners. Our expression profiling results complemented the microarray data, suggesting that co-expression patterns of bZIP transcription factors during dormancy differed among deciduous fruit trees. Our findings further clarify the molecular characteristics of the PpbZIP transcription factor family, including potential gene functions during dormancy. This information may facilitate further research on the evolutionary history and biological functions of bZIP proteins in peach and other rosaceae plants.

Efficacy of omeprazole and amoxicillin with either clarithromycin or metronidazole on eradication of Helicobacter pylori in Chinese peptic ulcer patients.

AIM: One-week triple therapy with proton pump inhibitors, clarithromycin and amoxicillin has recently been proposed as the first-line treatment for Helicobacter pylori (H. pylori) infection; however, data regarding the effects of this regimen in China are scarce. The aim of this prospective and randomized study was to compare the efficacy of clarithromycin and metronidazole when they were combined with omeprazole and amoxicillin on eradication of H. pylori and ulcer healing in Chinese peptic ulcer patients. METHODS: A total of 103 subjects with H. pylori-positive peptic ulcer were randomly divided into two groups, and accepted triple therapy with omeprazole 20 mg, amoxicillin 1000 mg and either clarithromycin 500 mg (OAC group, n = 58) or metronidazole 400 mg (OAM group, n = 45). All drugs were given twice daily for 7 d. Patients with active peptic ulcer were treated with omeprazole 20 mg daily for 2-4 wk after anti-H. pylori therapy. Six to eight weeks after omeprazole therapy, all patients underwent endoscopies and four biopsies (two from the antrum and two others from the corpus of stomach) were taken for rapid urease test and histological analysis (with modified Giemsa staining) to examine H. pylori. Successful eradication was defined as negative results from both examination methods. RESULTS: One hundred patients completed the entire course of therapy and returned for follow-up. The eradication rate of H. pylori for the per-protocol analysis was 89.3% (50/56) in OAC group and 84.1% (37/44) in OAM group. Based on the intention-to-treat analysis, the eradication rate of H. pylori was 86.2% (50/58) in OAC group and 82.2% (37/45) in OAM group. There were no significant differences in eradication rates between the two groups on either analysis. The active ulcer-healing rate was 96.7% (29/30) in OAC group and 100% (21/21) in OAM group (per-protocol analysis, P>0.05). Six patients in OAC group (10.3%) and five in OAM group (11.1%) reported adverse events (P>0.05). CONCLUSION: One-week triple therapy with omeprazole and amoxicillin in combination with either clarithromycin or metronidazole is effective for the eradication of H. pylori. The therapeutic regimen comprising metronidazole with low cost, good compliance and mild adverse events may offer a good choice for the treatment of peptic ulcers associated with H. pylori infection in China.

Roles of Helicobacter pylori infection and cyclooxygenase-2 expression in gastric carcinogenesis.

AIM: Cyclooxygenase (COX)-2 is over expressed in gastrointestinal neoplasm. Helicobacter pylori (H pylori) infection is causally linked to gastric cancer. However, the expression of COX-2 in various stages of H pylori-associated gastric carcinogenesis pathway has not been elucidated. Therefore, the aim of this study was to clarify the role of H pylori induced COX-2 expression during carcinogenesis in the stomach. METHODS: Gastric biopsies from 138 subjects (30 cases of chronic superficial gastritis (CSG), 28 cases of gastric glandular atrophy (GA), 45 cases of gastric mucosal intestinal metaplasia (IM), 12 cases of moderate gastric epithelial dysplasia and 23 cases of gastric cancer) were enrolled. H pylori infection was assessed by a rapid urease test and histological examination (modified Giemsa staining). The expression of COX-1 and COX-2 in human gastric mucosa was detected by immunohistochemical staining. RESULTS: H pylori infection rate was 64.3% in GA and 69.5% in gastric cancer, which was significantly higher than that (36.7%) in CSG (P<0.05). The positive expression rates of COX-2 were 10.0%, 35.7%, 37.8%, 41.7% and 69.5% in CSG, GA, IM, dysplasia and gastric cancer, respectively. From CSG to GA, IM, dysplasia and finally to gastric cancer, expression of COX-2 showed an ascending tendency, whereas COX-1 expression did not change significantly in the gastric mucosa. The level of COX-2 expression in IM and dysplasia was significantly higher in H pylori-positive than in H pylori-negative subjects (P<0.01). CONCLUSION: COX-2 expression induced by H pylori infection is a relatively early event during carcinogenesis in the stomach.

Endoplasmic reticulum proteins quality control and the unfolded protein response: the regulative mechanism of organisms against stress injuries.

The endoplasmic reticulum is the cellular compartment in which secretory proteins are synthesized and folded. Perturbations of endoplasmic reticulum homeostasis lead to the accumulation of unfolded proteins. The activation of the unfolded protein response during endoplasmic reticulum stress transmits information about the status of protein folding to the cytosol and nucleus. The unfolded protein response leads to the upregulation of genes encoding endoplasmic reticulum chaperones, attenuation of translation, and initiation of the endoplasmic reticulum quality control system to restore endoplasmic reticulum homeostasis. When the unfolded protein response is insufficient to rebuild the steady state in endoplasmic reticulum, the programmed cell death or apoptosis would be initiated, by triggering cell injuries, even to cell death through apoptosis signals. In this review, we briefly outline research on the chaperones and foldases conserved in eukaryotes and plants, and describe the general principles and mechanisms of the endoplasmic reticulum quality control and the unfolded protein response. We describe the current models for the molecular mechanism of the unfolded protein response in plants, and emphasize the role of inositol requiring enzyme-1-dependent network in the unfolded protein response. Finally, we give a general overview of the directions for future research on the unfolded protein response in plants and its role in the response to environmental stresses.

Roles of endoplasmic reticulum stress and unfolded protein response associated genes in seed stratification and bud endodormancy during chilling accumulation in Prunus persica.

Dormancy mechanisms in seeds and buds arrest growth until environmental conditions are optimal for development. A genotype-specific period of chilling is usually required to release dormancy, but the underlying molecular mechanisms are still not fully understood. To discover transcriptional pathways associated with dormancy release common to seed stratification and bud endodormancy, we explored the chilling-dependent expression of 11 genes involved in endoplasmic reticulum stress and the unfolded protein response signal pathways. We propose that endoplasmic reticulum stress and the unfolded protein response impact on seed as well as bud germination and development by chilling-dependent mechanisms. The emerging discovery of similarities between seed stratification and bud endodormancy status indicate that these two processes are probably regulated by common endoplasmic reticulum stress and unfolded protein response signalling pathways. Clarification of regulatory pathways common to both seed and bud dormancy may enhance understanding of the mechanisms underlying dormancy and breeding programs may benefit from earlier prediction of chilling requirements for uniform blooming of novel genotypes of deciduous fruit tree species.