Enterotoxin-related genes PPFIA4 and SCN3B promote colorectal cancer development and progression.

To identify the role of enterotoxin-related genes in colorectal cancer (CRC) development and progression. Upregulated differentially expressed genes shared by three out of five Gene Expression Omnibus (GEO) data sets were included to screen the key enterotoxin-induced oncogenes (EIOGs) according to criteria oncogene definition, enrichment, and protein-protein interaction (PPI) network analysis, followed by prognosis survival, immune infiltration, and protential drugs analyses was performed via integration of RNA-sequencing data and The Cancer Genome Atlas-derived clinical profiles. We screened nine common key EIOGs from at least three GEO data sets. A Cox proportional hazards regression models verified that more alive cases, decreased overall survival, and highest 4-year survival prediction in CRC patients with high-risk score. Protein tyrosine phosphatase receptor type F polypeptide-interacting protein alpha-4 (PPFIA4), STY11, SCN3B, and SPTBN5 were shared in the same PPI network. Immune infiltration results showed that SCN3B and synaptotagmin 11 expression were obviously associated with B cell, macrophage, myeloid dendritic cell, neutrophils, and T cell CD4+ and CD8+ in both colon adenocarcinoma and rectal adenocarcinoma. CHIR-99021, MLN4924, and YK4-279 were identified as the potential drugs for treatment. Finally, upregulated EIOGs genes PPFIA4 and SCN3B were found in colon adenocarcinoma and PPFIA4 and SCN3B were proved to promote cell proliferation and migration in vitro. We demonstrated here that EIOGs promoting a malignancy phenotype was related with poor survival and prognosis in CRC, which might be served as novel therapeutic targets in CRC management.

Ectomycorrhizal synthesis between two Tuber species and six tree species: are different host-fungus combinations having dissimilar impacts on host plant growth?

Truffle cultivation has drawn more and more attention for its high economic and ecological values in the world. To select symbionts suitable for cultivation purposes, we conducted greenhouse-based mycorrhization trials of two Tuber species (T. formosanum and T. pseudohimalayense) with five broad-leaved tree species (Corylus yunnanensis, Quercus aliena var. acutiserrata, Q. acutissima, Q. robur, Q. variabilis) and one conifer species (Pinus armandii). Axenically germinated seedlings of all tree species were either inoculated, or not, with spore suspensions of these two truffles in the greenhouse. Eight months after inoculation, T. formosanum or T. pseudohimalayense ectomycorrhizae were successfully formed on these six tree species, as evidenced by both morphological and molecular analyses. All selected trees showed good receptivity to mycorrhization by both fungi, with average colonization rates visually estimated at 40-50%. Plant growth, photosynthesis, and nutrient uptake were assessed 2 years after inoculation and were mainly affected by host species. Mycorrhization by both fungi significantly improved P uptake of the hosts, and the interaction between truffle species and host plant species had significant effects on leaf water and leaf K concentrations. In addition, a significantly negative correlation between leaf Ca and leaf C concentration was found across all the seedlings. In addition, mycorrhization had slightly increased plant stem and canopy, but had no significant effects on plant photosynthesis. Overall, these results suggest that the effects of these two Tuber ECMF on plant growth and nutrient acquisition depend on the identity of the host species. Moreover, all selected plant species could be symbiotic partners with either T. pseudohimalayense or T. formosanum for field cultivation purposes.

Identification of dysregulated microRNAs involved in arachidonic acid metabolism regulation in dilated cardiomyopathy-mediated heart failure patients.

Heart failure (HF), a clinical syndrome with high morbidity and mortality, is becoming a growing public health problem. Dilated cardiomyopathy (DCM) is one of the major causes of HF, yet the molecular mechanisms underlying DCM-mediated HF are not completely understood. Previous studies have shown that dysregulation of arachidonic acid (AA) metabolism could contribute to the development of HF. To explore the roles of microRNAs (miRNAs) in regulating AA metabolism in HF, we used two public datasets to analyze the expression changes of miRNAs in the patients of DCM-mediated HF. A total of 101 and 88 miRNAs with significant abundance alterations in the two dataset were obtained, respectively. Around 1/3 of these miRNAs were predicted to target AA metabolic pathway genes. We also investigated the distribution of known single nucleotide polymorphisms (SNPs) within the sequences of miRNAs dysregulated in DCM-mediated HF patients, and identified miRNAs harboring high number of SNPs in either the seed regions or the entire sequences. These information could provide clues for further functional studies of miRNAs in the pathogeny of DCM-mediated HF.

The Global Burden of Atrial Fibrillation and Stroke: A Systematic Review of the Clinical Epidemiology of Atrial Fibrillation in Asia.

BACKGROUND: Our previous review reported great variability in the incidence and prevalence of atrial fibrillation (AF) in non-Western cohorts, especially from Asian countries; in recent years, epidemiologic studies on AF have been increasingly reported from Asia. METHODS: The goal of this updated systematic review was to present the current knowledge base of AF epidemiology in Asian countries since our previous review. We also explored AF incidence and the risk of stroke in AF by using a meta-analysis, with I2 testing the heterogeneity. Third, "real-world" antithrombotic drug use for ischemic stroke (IS) prevention associated with AF was studied. RESULTS: A total of 58 articles from eight countries in Asia were included in the analysis. The summary annual incidence of AF was 5.38 (95% CI, 4.53-6.24; I2 = 99.5%; n = 10) per 1,000 person-years, and the IS annual risk in AF was 3.0% (1.60%-4.95%; I2 = 99.8%; n = 8) when meta-analysis was performed on hospital- and community-based studies. Hospital- and community-based AF prevalence ranged from 0.37% to 3.56% and 2.8% to 15.8%, respectively. IS prevalence in AF ranged from 1.9% to 6.0% and 0.36% to 28.3% in community- and hospital-based studies. Warfarin use in Chinese subjects is relatively low (1.0%-4.1%) compared with Japanese subjects (49.1%-70.0%) in community-based studies. The rate of warfarin use was < 50% in hospital-based studies. CONCLUSIONS: The incidence and prevalence of AF have increased in recent years, although great variability still exists in Asian countries. Variability in annual IS risk in patients with AF was apparent between hospital- and community-based studies. However, the rate of warfarin use was < 50% in hospital studies from Asian countries.

Contrasting responses of root morphology and root-exuded organic acids to low phosphorus availability in three important food crops with divergent root traits.

Phosphorus (P) is an important element for crop productivity and is widely applied in fertilizers. Most P fertilizers applied to land are sorbed onto soil particles, so research on improving plant uptake of less easily available P is important. In the current study, we investigated the responses in root morphology and root-exuded organic acids (OAs) to low available P (1 µM P) and sufficient P (50 µM P) in barley, canola and micropropagated seedlings of potato-three important food crops with divergent root traits, using a hydroponic plant growth system. We hypothesized that the dicots canola and tuber-producing potato and the monocot barley would respond differently under various P availabilities. WinRHIZO and liquid chromatography triple quadrupole mass spectrometry results suggested that under low P availability, canola developed longer roots and exhibited the fastest root exudation rate for citric acid. Barley showed a reduction in root length and root surface area and an increase in root-exuded malic acid under low-P conditions. Potato exuded relatively small amounts of OAs under low P, while there was a marked increase in root tips. Based on the results, we conclude that different crops show divergent morphological and physiological responses to low P availability, having evolved specific traits of root morphology and root exudation that enhance their P-uptake capacity under low-P conditions. These results could underpin future efforts to improve P uptake of the three crops that are of importance for future sustainable crop production.

[Effect of tensile strain on perlecan expression of human periodontal ligament cells].

PURPOSE: To investigate the perlecan expression of human periodontal ligament cells (hPDLCs) under cyclic tensile strain in vitro, and learn the molecular mechanism of periodontal remolding during tooth movement. METHODS: hPDLCs isolated by enzyme digestion were loaded with 12% elongation, 1 Hz of uniaxial tensile strain for 12, 24 and 48 h. The unloaded cells were used as control. Real-time PCR and enzyme-linked immune sorbent assay (ELISA) were applied to analyze the mRNA and protein expression of perlecen in each sample respectively. The data was analyzed with SPSS 19.0 software package. RESULTS: Within 12 h, mRNA expression was transiently elevated, but no significant difference was detected compared with the control. After 12 h, the mRNA expression was significantly decreased. It would decreased to (0.28±0.049) at lowest level of control at lowest level at 48 h (P<0.05). The protein expression of perlecan was time-dependently decreased. Specifically, it was downregulated from (14.03±0.71) pg/mL (control) to (11.06±0.15) pg/mL at lowest level at 48 h (P<0.05). CONCLUSIONS: Tensile strain time-dependently down-regulates perlecan expression, indicating perlecan may play a pivot role in PDLCS responding to mechanical loading in vitro.

Phototropins function in high-intensity blue light-induced hypocotyl phototropism in Arabidopsis by altering cytosolic calcium.

Phototropins (phot1 and phot2), the blue light receptors in plants, regulate hypocotyl phototropism in a fluence-dependent manner. Especially under high fluence rates of blue light (HBL), the redundant function mediated by both phot1 and phot2 drastically restricts the understanding of the roles of phot2. Here, systematic analysis of phototropin-related mutants and overexpression transgenic lines revealed that HBL specifically induced a transient increase in cytosolic Ca(2+) concentration ([Ca(2+)]cyt) in Arabidopsis (Arabidopsis thaliana) hypocotyls and that the increase in [Ca(2+)]cyt was primarily attributed to phot2. Pharmacological and genetic experiments illustrated that HBL-induced Ca(2+) increases were modulated differently by phot1 and phot2. Phot2 mediated the HBL-induced increase in [Ca(2+)]cyt mainly by an inner store-dependent Ca(2+)-release pathway, not by activating plasma membrane Ca(2+) channels. Further analysis showed that the increase in [Ca(2+)]cyt was possibly responsible for HBL-induced hypocotyl phototropism. An inhibitor of auxin efflux carrier exhibited significant inhibitions of both phototropism and increases in [Ca(2+)]cyt, which indicates that polar auxin transport is possibly involved in HBL-induced responses. Moreover, PHYTOCHROME KINASE SUBSTRATE1 (PKS1), the phototropin-related signaling element identified, interacted physically with phototropins, auxin efflux carrier PIN-FORMED1 and calcium-binding protein CALMODULIN4, in vitro and in vivo, respectively, and HBL-induced phototropism was impaired in pks multiple mutants, indicating the role of the PKS family in HBL-induced phototropism. Together, these results provide new insights into the functions of phototropins and highlight a potential integration point through which Ca(2+) signaling-related HBL modulates hypocotyl phototropic responses.

Structure of a polysaccharide from Urtica fissa determined by NMR spectra.

A polysaccharide, isolated and purified from the aqueous extract of nettle plant Urtica fissa, was found to consist of D-glucose and D-arabinose. Molecular weight was determined to be Mn 4140. The NMR experiments (¹H, ¹³C, ¹H--¹H COSY, TOCSY, HSQC, NOESY, and HMBC) revealed the structure as the following repeating unit: -->6)-α-D-Glcp-(1-->6)-α-D-Glcp-(1-->6)-ß-D-Glcp--(1-->5)-ß-D-Araf-(1-->3)-ß-D-Glcp-(1-->

Extracellular Ca²+ alleviates NaCl-induced stomatal opening through a pathway involving H2O2-blocked Na+ influx in Vicia guard cells.

To gain further insights into the function of extracellular Ca²+ in alleviating salt stress, Vicia faba guard cell protoplasts (GCPs) were patch-clamped in a whole-cell configuration. The results showed that 100 mM NaCl clearly induced Na+ influx across the plasma membrane in GCPs and promoted stomatal opening. Extracellular Ca²+ at 10 mM efficiently blocked Na+ influx and inhibited stomatal opening, which was partially abolished by La³+ (an inhibitor of plasma membrane Ca²+ channel) or catalase (CAT, a H2O2 scavenger), respectively. These results suggest that the plasma membrane Ca²+ channels and H2O2 possibly mediate extracellular Ca²+-blocked Na+ influx in GCPs. Furthermore, extracellular Ca²+ activated the plasma membrane Ca²+ channels under NaCl stress, which was partially abolished by CAT. These results, taken together, indicate that hydrogen peroxide (H2O2) likely regulates Na+ uptake by activating plasma membrane Ca²+ channels in GCPs. In accordance with this hypothesis, H2O2 could mimic extracellular Ca²+ to activate Ca²+ channels and block Na+ influx in guard cells. A single-cell analysis of cytosolic free Ca²+ ([Ca²+](cyt)) using Fluo 3-AM revealed that extracellular Ca²+ induced the accumulation of cytosolic Ca²+ under NaCl stress, but had few effects on the accumulation of cytosolic Ca²+ under non-NaCl conditions. All of these results, together with our previous studies showing that extracellular Ca²+ induced the generation of H2O2 in GCPs during NaCl stress, indicate that extracellular Ca²+ alleviates salt stress, likely by activating the H2O2-dependent plasma membrane Ca²+ channels, and the increase in cytosolic Ca²+ appears to block Na+ influx across the plasma membrane in Vicia guard cells, leading to stomatal closure and reduction of water loss.

[Macrocystic serous adenoma of the pancreas: a report of 5 cases].

OBJECTIVE: To investigate the diagnosis and treatment of macrocystic serous adenoma of the pancreas (MSAP). METHODS: The clinical data of 5 patients with MSAP treated from October 1999 to October 2009 were retrospectively analyzed. There were 5 female and 1 male. RESULTS: Of the 5 patients, 3 patients presented with abdominal pain and fullness, 1 patient with jaundice, 1 patient with asymptomatic. Ultrasonography and CT could manifest macrocystic lesion of the pancreas; all the lesion showed a well-defined border, internal septations, enhanced cyst walls, with no intramural (mural) nodule and papillary projections; the wall was smooth and thin in 4 cases; irregular lobulation could be observed in 3 cases, round or oval in 2 cases; 2 cases had pancreatic duct dilatation, 1 case had biliary duct dilatation. The tumors located in the pancreatic body and tail in 3 cases, the tumors located the pancreatic head in 2 cases. The sizes of the tumors ranged from 6.5 cm to 13.0 cm (mean, 8.8 cm). Five patients all accepted surgical intervention. The main postoperative complication was pancreatic fistula (2 cases); all the fistula was cured. Recurrence or metastasis were not found in 5 patient followed up postoperatively from 8 to 35 months. CONCLUSIONS: MSAP has no specific symptoms. The imaging appearance of MSAP is similar to mucinous cystic neoplasm of the pancreas. The tumor can gradually grow up and produce compression symptoms. MSAP can be cured by complete resection.

Microbial transformation of epothilone A by Aspergillus niger AS 3.739.

The microbiological transformation of epothilone A (1) by Aspergillus niger AS 3.739 afforded four main metabolites. Their structures were elucidated by (1)H, (13)C NMR and HSQC, COSY, HMBC, and NOESY spectra as trans-12,13-hydroxylated epothilone A (2), cis-12,13-hydroxylated epothilone A (3), trans-12,15-epoxidated epothilone A (4), and cis-12,15-epoxidated epothilone A (5). All four compounds were firstly found based on their stereochemistry. These new compounds displayed cytotoxicity against human breast carcinoma cells MCF-7 with IC(50) 9.88 microg/ml of 2, 2.52 microg/ml of 3, 9.88 microg/ml of 4, and 5.68 microg/ml of 5.

Structural characterization of polysaccharides from the roots of Urtica fissa.

Three polysaccharides were isolated from the roots of Urtica fissa by extraction, ultrafiltration, anion-exchange, and gel-filtration chromatography. The structures were characterized using acetylation, methylation, and spectral methods (GCMS, NMR). All three polysaccharides are mainly composed of D-arabinofuranosyl, D-galactopyranosyl, D-glucopyranosyl residues with different structural characteristics. Polysaccharide A of MW 5.2 x 10(3) contained a linear chain of 1-linked beta-D-glucopyranosyl, 1,6-linked beta-D-glucopyranosyl, 1,6-linked alpha-galactopyranosyl, and 1,5-linked beta-arabinofuranosyl moieties. Polysaccharide B of MW 7.7 x 10(4) possessed a chain consisting of 1,5-linked alpha-D-arabinofuranosyl, 1,3-linked beta-D-mannopyranosyl, 1,6-linked beta-D-glucopyranosyl, and 1,6-linked alpha-D-galactopyranosyl residues, but 4-O of alpha-D-galactopyranosyl residues were branched by terminal beta-D-glucopyranosyl residues. Polysaccharide C of MW 5.3 x 10(4) composed of a chain of 1,5-linked alpha-D-arabinofuranosyl, 1,4-linked beta-D-galactopyranosyl, 1,5-linked beta-D-xylopyranosyl, 1,4-linked beta-D-mannopyranosyl, 1-linked beta-D-glucopyranosyl residues, and the terminal beta-D-glucopyranosyl residues are attached to 3-O positions of 1,6-linked alpha-D-glucopyranosyl residues.

Matrix metalloproteinase and its inhibitor in temporomandibular joint osteoarthrosis after indirect trauma in young goats.

Our aim was to examine the change in expression of matrix metalloproteinases (MMP-13), matrix metalloproteinases-3 (MMP-3), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in the articular cartilage of goats with experimentally-induced osteoarthrosis of the temporomandibular joint (TMJ) at various times. Osteoarthrosis was induced in 20 goats in the bilateral TMJ and 5 goats acted as controls. There were 5 goats in each group, and a group was killed at 7 days, and 1, 3, and 6 months postoperatively. The samples were collected, and the joints evaluated histologically. Immunofluorescence was used to detect the presence of MMPs and TIMP-1 in the articular disc and condylar cartilage. The ultrastructure of the articular disc and condylar surface at 1 month was examined with scanning electron microscopy (SEM). Osteoarthrosis of the TMJ progressed gradually over time. MMP-13, MMP-3, and TIMP-1 were expressed strongly in the TMJ soon after injury; MMP-13 became gradually weakened, and MMP-3 strengthened later. None of these were expressed in the normal condyle. After a month the surface of the arthrotic condyle was uneven, and the underlying collagen fibrils were exposed in irregular fissures on the surface. The secretion of TIMP-1 was related closely to the changes of MMPs during osteoarthrosis of the TMJ. The unbalanced ratio between them caused degradation of the matrix of the cartilage and might be the cause of osteoarthrosis of the TMJ.

The role of bone morphogenetic protein-2 in vivo in regeneration of peripheral nerves.

We investigated the effects of bone morphogenetic protein-2 (BMP-2) and some other BMPs on regeneration of peripheral motor nerves in vivo. The facial nerves of 24 New Zealand rabbits were crushed to examine a series of retrograde changes in the facial nuclei and axons, in what has been called the "axon reaction". The facial nerves of the experimental group were treated with epineurial coaptation and BMP-2 after the injury. Nerves not treated with BMP-2 were regarded as controls. The expression of BMP-2 was investigated by in situ hybridisation in the neurons of facial nuclei. The electrophysiology, image analysis and transmission electron microscopy were used to evaluate the level of the recovery of facial nerves. The results showed that the axons in the experimental group were thicker and denser than those in the control group four weeks later. The expression of BMP-2 in the neurons of facial nuclei increased after injury. The electron microscopic observations showed that the axons' degeneration in the experimental group was less than that in the control group. Despite the morphological difference between the two groups, there was no apparent difference between them in nerve conduction velocity. These findings suggest that BMP-2 might be involved in the regeneration of facial nerves, and might function as a potential neurotrophic factor.