Search

Melanoma is one of the most malignant skin tumours with constantly increasing incidence worldwide. Previous studies have demonstrated that microRNA-374 (miR-374) is a novel biomarker for cancer therapy. Therefore, this study explores whether miR-374 targeting tyrosinase (TYR) affects melanoma and its underlying mechanism. We constructed subcutaneous melanoma models to carry out the following experiments. The cells were transfected with a series of miR-374 mimics, miR-374 inhibitors or siRNA against TYR. Dual luciferase reporter gene assay was used for the verification of the targeting relationship between miR-374 and TYR. Reverse transcription quantitative polymerase chain reaction and western blot analysis were conducted to determine the expression of miR-374, TYR, β-catenin, B-cell leukaemia 2 (Bcl-2), Bcl-2 associated X protein (Bax), Low-density lipoprotein receptor-related protein 6 (LRP6), Leucine-rich repeat G protein-coupled receptor 5 (LGR5) and CyclinD1. Cell proliferation, migration, invasion, cell cycle distribution and apoptosis were evaluated using cell counting kit-8 assay, scratch test, transwell assay and flow cytometry respectively. TYR was proved as a putative target of miR-374 as the evidenced by the result. It was observed that up-regulated miR-374 or down-regulated TYR increased expression of Bax and decreased expressions of TYR, β-catenin, LRP6, Bcl-2, CyclinD1 and LGR5, along with diminished cell proliferation, migration, invasion and enhanced apoptosis. Meanwhile, cells with miR-374 inhibitors showed an opposite trend. These findings indicated that up-regulated miR-374 could inhibit the expression of TYR to suppress cell proliferation, migration, invasion and promote cell apoptosis in melanoma cells by inhibiting the Wnt signalling pathway., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Aim: To assess the effect of enteral nutrition (EN) supplemented with glutamine on recovery after ileal pouch-anal anastomosis (IPAA) in rats, to provide an experimental basis for nutritional support in patients with ulcerative colitis (UC) after IPAA., Methods: Male Sprague-Dawley (SD) rats were randomly divided into three groups ( n = 8) after IPAA operation using a microsurgical technique. From the third postoperative day, rats in the control group, EN group, and immune nutrition (IN) group were fed standard rat chow, short peptide EN, and short peptide EN combined with glutamine ad libitum , respectively. The rats' general condition was observed throughout the study. Serum levels of total protein (TP), albumin (ALB), prealbumin (PA), and transferrin (TF) were detected on the 30th postoperative day, using an automatic biochemical analyzer. The ileal pouch mucosa was stained with hematoxylin and eosin (HE), and occludin protein levels were detected by immunohistochemistry., Results: The body weight of rats in the EN group (359.20 ± 10.06 g) was significantly higher than that in the control group (344.00 ± 9.66 g) ( P < 0.05) and lower than that in the IN group (373.60 ± 9.86 g) ( P < 0.05) on the 30th postoperative day. The levels of serum TP, ALB, PA, and TF in the EN group were significantly higher than those in the control group ( P < 0.01 for all) and lower than those in the IN group ( P < 0.05 for all). Histopathological score (EN: 0.80 ± 0.37; IN: 0.60 ± 0.40; control group: 2.29 ± 0.18) and expression level of occludin protein (EN: 0.182 ± 0.054; IN: 0.188 ± 0.048; control group: 0.127 ± 0.032) were significantly lower in the control group compared with the EN and IN groups ( P < 0.05 for all), but there were no significant differences between the latter two groups ( P > 0.05 for all)., Conclusion: EN combined with glutamine may effectively improve nutritional status after IPAA. Our results suggest a benefit of glutamine supplementation in EN for UC patients undergoing IPAA, although human studies are required to confirm this finding., Competing Interests: Conflict-of-interest statement: The authors have no financial or other conflicts of interest to disclose.

Background: Large cell lung cancer (LCLC) patients have a poor prognosis because their tumors are highly malignant and show resistance to chemotherapy and radiotherapy. Plumbagin has anticancer activity toward several tumor types, but its effects on LCLC are unknown. This study investigated the effects of plumbagin on human L9981 and NL9980 large cell lung cancer cells and the mechanisms underlying its action., Methods: The effects of plumbagin on L9981 and NL9980 cells proliferative activity and invasion were analyzed using MTT and Boyden chamber assays, respectively. Exogenous IL-6 was used to detect the presence of the IL-6/STAT3 signaling pathway in LCLC cell lines. L9981 cells were harvested after plumbagin treatment at 9.0μmol/L (IC 50 ), while NL9980 were harvested after treatment at 7.5μmol/L for 6, 24, and 48h, and the expression of IL-6, IL-6R, gp130, and STAT3 and the downstream genes Bcl-2, VEGF, and CycD1 was assessed by RT-PCR. ELISA was performed to determine secreted IL-6 levels, and intracellular phospho-STAT3 levels were measured by western blotting., Results: After the introduction of exogenous IL-6, the mRNA expression of signaling genes and downstream genes was significantly increased in a concentration-dependent manner. Furthermore, plumbagin significantly inhibited the expression of the above mentioned genes in a dose-dependent and time-dependent manner. The mRNA expression levels of downstream genes were correlated with those of signaling genes., Conclusion: Plumbagin was found to significantly inhibit the proliferation and invasion of L9981 and NL9980 cells, and may be an effective therapy for LCLC through targeting the IL-6/STAT3 signaling pathway., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A convenient and efficient two-stage bioprocess was established for fructo-oligosaccharides (FOSs) production, during which the endo-inulinase was first produced and subsequently the inulin supplemented was directly hydrolyzed by the produced endo-inulinase, in the meantime the generated non-prebiotic saccharides was assimilated by the yeast cells. This process was implemented by an engineered Yarrowia lipolytica strain Enop56, in which an optimized endo-inulinase gene from Aspergillus niger was overexpressed. When the strain Enop56 was fermented with an inulin concentration of 600g/L in a 10-L bioreactor, the inulinase activity, FOSs titer, yield and productivity reached to 551.6U/mL, 546.6g/L, 0.91g FOS /g Inulin , and 15.18g/L/h, respectively. Besides, the hydrolysis products were mainly FOSs with polymerization degrees of 3-5 and the total amount of non-prebiotic mono- and disaccharides was only 4.97% in the final fermentation broth. This study demonstrated that the two-stage bioprocess using the strain Enop56 was a promising strategy to produce FOSs on an industrial scale., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Bone metastases often occur in prostate cancers, lung cancers and breast cancers. Bone alkaline phosphatase (BALP) is one of the most commonly used serological markers for clinical evaluation of bone metabolism. Here, we reported that high concentrations of uric acid (UA) caused decrease of BALP levels and revealed that the effect of high concentrations of UA on the BALP expression was through inhibition of its promoter activity. Our results suggested physicians to think about serum UA status of patients with advanced cancer to avoid misdiagnosis when BALP was used to diagnose or assess the extent of bone metastases., Competing Interests: CONFLICTS OF INTEREST The authors declare no competing financial interests.

Aim: To assess the therapeutic potential of Lactobacillus acidophilus (LA) for the treatment of pouchitis in a rat model., Methods: Sprague Dawley rats underwent proctocolectomy and ileal pouch-anal anastomosis followed by administration of dextran sulfate sodium (DSS) to induce pouchitis. Rats with pouchitis were randomly divided into three groups: no intervention (NI), normal saline (NS, 3 mL/d normal saline for 7 d), and LA (3 mL/d LA at 1× 10 10 colony-forming units for 7 d). General body condition was recorded and pouch specimens were obtained for histological examination. mRNA expression levels of interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor-α were determined by RT-PCR. Zonula occludens protein 1 (ZO-1) levels were measured by immunohistochemistry., Results: LA reduced weight loss associated with pouchitis ( P < 0.05) and improved the symptoms of pouchitis in rats. Compared with the NI and NS groups, rats in the LA group showed earlier disappearance of hematochezia (6.17 ± 0.75, 6.50 ± 0.55, 3.17 ± 0.75, P < 0.05) and higher fecal scores (2.67 ± 0.48, 2.50 ± 0.51, 4.42 ± 0.50, respectively, P < 0.05). Histological scores were also lower in the LA group compared with the other two groups (7.17 ± 0.98, 8.00 ± 0.89, 4.00 ± 0.89, respectively, P < 0.05). mRNA expression levels of IL-1β, IL-6, and tumor necrosis factor-α were significantly reduced, while IL-10 mRNA levels were significantly increased in the LA group ( P < 0.05, respectively). ZO-1 protein levels were also significantly increased after administration of LA ( P < 0.05)., Conclusion: LA alleviates pouchitis induced by DSS after ileal pouch-anal anastomosis by decreasing pro-inflammatory factors and increasing anti-inflammatory factors, and restoring ZO-1 expression in the mucosa., Competing Interests: Conflict-of-interest statement: The authors have no financial or other conflicts of interest to disclose.

Background: Pouchitis occurs in approximately 50% of patients with ulcerative colitis after ileal pouch-anal anastomosis (IPAA) but the pathogenesis remains unclear. We used a rat model of dextran sulfate sodium (DSS)-induced ileal pouchitis to examine whether intestinal barrier disruption plays a role in the development and progression of the disease., Methods: Rats were randomly divided into DSS (underwent IPAA and administered 5% DSS orally), IPAA (underwent IPAA), and Sham groups (underwent switch abdominal surgery). In the DSS group, levofloxacin intervention and nonintervention subgroups were used to determine the influence of antibiotics on intestinal barrier dysfunction. Hematochezia and fecal scores were recorded. Ileum and pouch specimens were obtained for histological assessment. Immunohistochemistry was performed for myeloperoxidase and occludin protein expression. Levels of interleukin-1β (IL-1β), IL-6, IL-10, and tumor necrosis factor α mRNA were detected by real-time PCR. Plasma D-lactate concentrations were determined with colorimetry., Results: Only rats in the DSS group experienced hematochezia, and their fecal and histological scores significantly increased (P < 0.01). Compared with the IPAA and Sham groups, levels of myeloperoxidase, IL-1β, IL-6, tumor necrosis factor α, and plasma D-lactate significantly increased, whereas occludin and IL-10 reduced in the DSS group (P < 0.01). The levofloxacin subgroup showed increased occludin expression and more balanced inflammatory cytokine levels than the nonintervention subgroup. All differences showed linear correlations., Conclusions: The intestinal barrier was disrupted in this rat model of pouchitis. Increased proinflammatory and decreased anti-inflammatory factors aggravated the intestinal barrier damage. Antibiotics may ameliorate this process.

Stimulator of Interferon Gene (STING) is a key mediator of innate immune signaling. STING plays a pivotal role in the pathogenesis of many diseases including infectious diseases, auto-immune diseases and cancer. Many studies have been carried out recently in the field of STING-regulated pathway, however, rarely of transcriptional mechanisms. To characterize the murine STING (mSTING) promoter, we cloned a series of different nucleotide sequences of the 5'-flanking region of the mSTING gene. Transient transfection of promoter-reporter recombinant plasmids and luciferase assay illustrated the region (-77/+177) relative to the transcription start site (TSS) of the mSTING gene was sufficient for full promoter activity. This region contains GATA1, IK2, Sp1/Sp3 and STAT putative transcription factor binding sites. Mutation of GATA1 or Sp1/Sp3 sites led to obvious decrease of the mSTING promoter activity. Overexpression of GATA1 and Sp3 enhanced the mSTING promoter activity, whereas knockdown of GATA1 and Sp3 by a siRNA strategy significantly reduced the transcription activity. Chromatin immunoprecipitation assays demonstrated that GATA1 and Sp3 interact with the mSTING promoter in vivo. These results provided the first analysis of mSTING promoter and demonstrated that transcription factor GATA1 and Sp3 positively regulate the basal transcription of the mSTING gene.

We report the thermal annealing-induced formation of ring-like structure of Zn(II)-doped magnetite from iron alkoxide leaf-like nanoplate precusor. The phase, structure and morphology of magnetite nanorings were comprehensively characterized by powder X-ray diffraction, X-ray photoelectron spectroscopy, atomic force microscope, scanning electron microscope, and transmission electron microscope. The obtained Zn(II)-doped magnetite nanorings are of 13-20 nm in edge width, 70-110 nm in short axis length and 100-150 nm in long axis length. The growth mechanism was possibly due to a combined effect of decomposition of the organic component and diffusion growth. Zn(II)-doped magnetite nanorings delivered saturation magnetization of 66.4 emu/g and coercivity of 33 Oe at room temperature. In addition, the coatings containing Zn(II)-doped magnetite nanorings as fillers exhibit excellent microwave absorption properties with a maximum reflection loss of -40.4 dB and wide effective absorbing band obtained in coating with thin thickness of 1.50 mm.

Studies examining the association of hemochromatosis (HFE) gene polymorphisms and susceptibility to alcoholic liver disease (ALD) yielded inconsistent results. Thus, we performed a metaanalysis to investigate whether the variations in HFE gene increase the risk of ALD. The studies published up to Feb. 2014 were identified by searching PubMed/MEDLINE, ISI Web of Science, EMBASE and China National Knowledge Infrastructure databases, which was complemented by screening the references of the retrieved studies. For all genotypes and alleles, the odds ratios (ORs) with 95% confidence intervals (CIs) according to the heterogeneity were pooled using fixed-effect model. Sixteen studies with 1933 cases and 9874 controls were included for this meta-analysis. C282Y/C282Y, C282Y/wild type, H63D/wild type and C282Y/H63D were found not to be associated with susceptibility to ALD, but increased risk of H63D/H63D (OR: 1.52, 95% CI: 1.05-2.22, P=0.029) was observed for ALD when compared to total control. Comparison of ALD patients with alcoholics without liver damage revealed a significant association of D allele, as well as a marginal association of H63D/wild type with ALD, while H63D/H63D was not significantly associated with ALD although increased value of OR was obtained. The presence of Y allele and other genotypes yielded insignificant findings when ALD patients were compared with alcoholics without liver damage. No evident publication bias or significant heterogeneity among studies was detected in this meta-analysis. In conclusion, our metaanalysis showed a marginal higher prevalence of H63D variant in ALD but did not support an increased risk of C282Y mutation.

Objective: To investigate expressional changes of brain derived neurotrophic factor (BDNF) in the trachea of rats with acrolein inhalation., Methods: Twenty two SD rats were divided into 2 groups: the rats in experimental group were subjected to acrolein inhalation for the induce of trachea inflammatory injury, while the rats with saline (NS) inhalation were as control. All the rats were sacrificed in 1,3,6 weeks after acrolein (n = 11 at each time point) or saline inhalation (n = 11 at each time point), the samples of trachea epithelium were harvested. The immunohistochemistry and in situ hybridization was performed to detect the location of BDNF protein and mRNA in trachea. The expression of BDNF mRNA in the trachea tissues were determined by RT-PCR., Results: There are positive cells in epithelium of trachea for BDNF protein and mRNA, with cytoplasm staining. The expression of BDNF mRNA in the trachea was increased at 1 week after acrolein inhalation (P < 0.05, vs. control group), then decreased along with the time and reached to the same level as control group at 3 weeks, then last to 6 weeks (P > 0.05)., Conclusion: The inflammatory injury in trachea induced by acrolein exposure could be associated with the increased expression of BDNF. BDNF may be one of the crucial inflammatory factors in the process of inflammatory reaction in trachea with acrolein stimulation.

Excellent perchlorate reduction was obtained under various initial concentrations in a non-membrane microbial electrolysis cell with polyaniline (PANI) modified graphite cathode as sole electron donor. PANI modification is conducive to the formation of biofilm due to its porous structure and good electrocatalytic performance. Compared with cathode without biofilm, over 12% higher reduction rates were acquired in the presence of biocathode. The study demonstrates that, instead of perchlorate reduction, the main contribution of biofilm is involved in facilitate electron transfer from cathode to electrolyte. Interestingly, hairlike structure, referred as to pili-like, was observed in the biofilm as well as in the electrolyte. Additionally, the results show that pili were prone to formation under the condition of external electron field as sole electron donor. Analysis of microbial community suggests that perchlorate reduction bacteria community was most consistent with Azospiraoryzae strain DSM 13638 in the subdivision of the class Proteobacteria., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: To investigate the relationship between p53, COX-2, Bax, c-myc genes and colorectal carcinoma complicated with chronic schistosomiasis., Methods: One hundred and sixty patients with colorectal carcinoma were selected and divided into two groups; a schistosomiasis group (colorectal carcinoma complicated with chronic schistosomiasis, n = 80) and a non-schistosomiasis group (colorectal carcinoma uncomplicated with chronic schistosomiasis, n = 80). The tissue microarray techniques and immunohistochemistry method were used in all the patients to detect the expressions of p53, COX-2, Bax and c-myc proteins., Results: The positive rate and level of p53 protein expression in the schistosomiasis group were lower than those in the non-schistosomiasis group, but there were no significant differences between the two groups (both P > 0.05). The COX-2 protein in both groups was positive, but the positive expression level of COX-2 in the schistosomiasis group was higher than that in the nonschistosomiasis group, and there was a significant difference between the two groups (P < 0.01). The positive rate and level of Bax protein expression were not significantly different between the two groups (both P > 0.05). The positive rate of c-myc expression in the schistosomiasis group was higher than that in the non-schistosomiasis group, with a significant difference (P < 0.01), but the positive expression level was lower than that in the non-schistosomiasis group, and there was a significant difference between the two groups (P < 0.01)., Conclusions: Schistosome infection may impact on the deficiency of p53 of human colorectal cancer cells. It may promote the excessive expression of COX-2 protein, which is an indirect carcinogenic factor. The expression of Bax gene has no correlation with schistosome infection. The schistosome chronic infection may cause a persistent low level expression of c-myc gene.

Curcumin shows effective anti-inflammatory activities but is seldom used in clinic because of its poor solubility in water and vulnerablity to sunshine ultraviolet effect. Novel lipid vesicles have been developed as carriers for skin delivery. In this paper, lipid vesicles-propylene glycol liposomes (PGL), Ethosomes and traditional liposomes, were prepared as curcumin carriers respectively. Their morphology, particle size and encapsulation efficiency and drug release behavior in vitro were evaluated. Transdermal efficiency and deposition quantity in abdominal skin were also measured with Franz diffusion device. Carrageenan-induced paw edema was established to evaluate the anti-inflammatory effect. From the result, the particle size order of lipid vesicles was: PGL (182.4 ± 89.2 nm)Ethosomes>traditional liposomes. PGL had the best encapsulation efficiency of 92.74 ± 3.44%. From anti-inflammatory experiment, PGL showed the highest and longest inhibition on the development of paw edema, followed by Ethosomes and Traditional liposomes. With the elevated entrapment efficiency, good transdermic ability and sustained-release behavior, PGL may represent an efficient transdermal lipid vesicle for skin delivery., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: To study the optimum enzyme extraction process of total flavonoids from Cryptotaenia japonica., Methods: The process was optimized by single factor experiments and orthogonal, the yield of total flavonoids was used as index., Results: The optimum extraction technology was as follows: enzyme dosage: 1U/mL, pH value: 6.0, enzymatic hydrolysis temperature: 60%, enzymatic hydrolysis time: 1 h, the rate of material to liquid: 1 : 30, extraction temperature: 70 degrees C, extraction time: 1 h, the average extraction rate of total flavonoids from Cryptotaenia japonica was 4.76%., Conclusion: The method is an effective way to extract total flavonoids from Cryptotaenia japonica with high extract rate.

Angiotensin II (ANG II)-induced inflammatory and oxidative stress responses contribute to the pathogenesis of hypertension. In this study, we determined whether renin-angiotensin system (RAS) activation in the hypothalamic paraventricular nucleus (PVN) contributes to the ANG II-induced hypertensive response via interaction with neurotransmitters in the PVN. Rats underwent subcutaneous infusion of ANG II or saline for 4 weeks. These rats were treated for 4 weeks through bilateral PVN infusion with either vehicle or losartan (LOS), an angiotensin II type 1 receptor (AT1-R) antagonist, via osmotic minipump. ANG II infusion resulted in higher levels of glutamate, norepinephrine (NE), AT1-R and pro-inflammatory cytokines (PIC), and lower level of gamma-aminobutyric acid (GABA) in the PVN. Rats receiving ANG II also had higher levels of mean arterial pressure, plasma PIC, NE and aldosterone than control animals. PVN treatment with LOS attenuated these ANG II-induced hypertensive responses. In conclusion, these findings suggest that the RAS activation in the PVN contributes to the ANG II-induced hypertensive response via interaction with PIC and neurotransmitters (glutamate, NE and GABA) in the PVN.

Polymeric nanoparticles are widely used as targeted carriers for biomacromolecules. In this paper, modified gelatin nanoparticles were prepared and their feasibility as insulin pulmonary administration system was investigated. D: ,L: -glyceraldehyde and poloxamer 188 were used for gelatin nanoparticle preparation. Novel water-in-water emulsion technique was used to prepare insulin-loaded nanoparticles. Morphological examination of insulin-loaded nanoparticles was carried out using scanning electron microscopy (SEM). Intratracheal instillation of insulin-loaded nanoparticles was performed to evaluate animal hypoglycemic effect. With fluorescence labeling of insulin, alveolar deposition and absorption of insulin-loaded nanoparticles were investigated. Histological changes in the lung were also observed to evaluate the safety. From the micromorphology observation, insulin-loaded nanoparticles under gelatin-poloxamer 188 ratio at 1:1 showed smooth and uniform surface, with average particle size 250 nm and Zeta potential -21.1 mV. From animal experiment, insulin-loaded nanoparticles under gelatin-poloxamer 188 ratio at 1:1 promoted insulin pulmonary absorption effectively and showed good relative pharmacological bioavailability. Proved by alveolar deposition result, FITC-insulin-loaded nanoparticle group was characterized by an acute and rapid hypoglycemic effect. In addition, nanoparticles could guarantee the safety of lung by reducing insulin deposition in lung. A transient weak inflammatory response was observed at 1 day after administration. With good physical characterization, high bioavailability, fast and stable hypoglycemic effect, insulin-loaded nanoparticles might be developed as a novel insulin pulmonary system for diabetes therapy.

Objective: To evaluate mesenteric vascular anatomy using 256 multi-slice computed tomography (MSCT) before laparoscopic colorectal surgery., Methods: Eleven patients with colorectal cancer underwent 256 MSCT from February 2010 to December 2010. The evaluation items were visualization of mesenteric artery and vein by 3-dimensional CT angiography, which was compared with findings on laparoscopic surgery., Results: Three-dimensional CT angiography correctly demonstrated variations of the mesenteric artery and vein and were consistent with laparoscopic findings. Of the 3 patients undergoing right hemicolectomy, ileocolic artery (ICA) ran ventrally to the superior mesenteric vein(SMV) in 1 patient, whereas ICA ran dorsally to the SMV in 2 patients; the right colic artery (RCA) branched directly from superior mesenteric artery(SMA) in 2 patients; RCA was absent and the left branch of middle colic artery(MCA) fed the tumor in 1 patient. In the patients who had transverse colon resection, MCA branched from SMA. In 2 of 3 patients who underwent sigmoidectomy, sigmoid artery (SA) branched from left colic artery(LCA); in 1 of 3 patients of sigmoid resection, SA branched from inferior mesenteric artery(IMA). In 4 patients with rectal cancer, the superior rectal artery (SRA) fed the tumor., Conclusion: The 256 MSCT is effective for evaluating mesenteric vascular anatomy variation before laparoscopic surgery for colorectal cancer.

Findings from our laboratory indicate that proinflammatory cytokines and their transcription factor, nuclear factor-kappaB (NF-κB), are increased in the hypothalamic paraventricular nucleus (PVN) and contribute towards the progression of heart failure. In this study, we determined whether NF-κB activation within the PVN contributes to sympathoexcitation via interaction with neurotransmitters in the PVN during the pathogenesis of heart failure. Heart failure was induced in rats by left anterior descending coronary artery ligation. Sham-operated control (SHAM) or heart failure rats were treated for 4 weeks through bilateral PVN infusion with SN50, SN50M or vehicle via osmotic minipump. Rats with heart failure treated with PVN vehicle or SN50M (inactive peptide for SN50) had increased levels of glutamate, norepinephrine (NE), tyrosine hydroxylase (TH), superoxide, gp91(phox) (a subunit of NAD(P)H oxidase), phosphorylated IKKβ and NF-κB p65 activity, and lower levels of gamma-aminobutyric acid (GABA) and the 67-kDa isoform of glutamate decarboxylase (GAD67) in the PVN compared with those of SHAM rats. Plasma levels of cytokines, norepinephrine, epinephrine and angiotensin II, and renal sympathetic nerve activity (RSNA) were increased in heart failure rats. Bilateral PVN infusion of SN50 prevented the decreases in PVN GABA and GAD67, and the increases in RSNA and PVN glutamate, norepinephrine, TH, superoxide, gp91(phox), phosphorylated IKKβ and NF-κB p65 activity observed in vehicle or SN50M-treated heart failure rats. A same dose of SN50 given intraperitoneally did not affect neurotransmitters concentration in the PVN and was similar to vehicle-treated heart failure rats. These findings suggest that NF-κB activation in the PVN modulates neurotransmitters and contributes to sympathoexcitation in rats with ischemia-induced heart failure.

The objective of the present study was to develop a novel in vitro system to simulate the process of dissolution and permeation of oral solid dosage forms in vivo, and to establish a correlation between in vitro permeation and in vivo absorption that could predict the bioavailability (BA) and bioequivalence (BE) of congeneric products. The in vitro dissolution and absorption kinetics of four dosage forms of isosorbide mononitrate (ISMN) were evaluated by the USP basket/paddle system and drug dissolution/absorption simulating system (DDASS). The corresponding pharmacokinetic study was performed in beagle dogs. A comparative study was carried out between the classical and the novel method to estimate the effectiveness of the modified DDASS in simulating the course of dissolution and absorption in vivo. Indeed, the correlation coefficients of in vitro dissolution and in vivo absorption obtained from DDASS and dogs were higher. Moreover, a higher level A in vitro-in vivo correlation (IVIVC) between DDASS permeation and dog absorption was established, with correlation coefficients of 0.9968, 0.9872, 0.9921, and 0.9728. The DDASS method was more accurate at modeling the process of dissolution and absorption in vivo for both immediate-release (IR) and sustained-release (SR) dosage forms of ISMN., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objective: To investigate the mechanism of tea polyphenol in inhibiting microsatellite instability (MSI) of colorectal cancer., Methods: Using LoVo cells and SW480 cells treated with aqueous solution of tea polyphenol, cell proliferation was detected by methyl thiazolyl tetrazolium (MTT) method, changes in microsatellite sequences were detected by genescan method and changes in gene expression of LoVo cells were detected by illumina expression arrays and quantitative real-time polymerase chain reaction (PCR)., Results: The proliferation inhibition rates of LoVo and SW480 cells treated with tea polyphenol increased with the increasing of drug concentration and showed an increasing tendency with time. The proliferation inhibition rate of LoVo cells with tea polyphenol was higher than that of SW480 cells, and there was a significant difference in the proliferation inhibition rates at 24 h, 72 h and one week. The microsatellite sequence of LoVo cells treated with tea polyphenol remained stable. The gene expression arrays and quantitative real-time PCR suggested that tea polyphenol inhibited the gene expressions of MT2A, MAFA, HES1 and JAG1 nearly two-fold over controls. It was also found that tea polyphenol inhibited the BAX and p38 genes with a more than two-fold difference but did not significantly inhibit the nuclear factor-κB pathway., Conclusion: Tea polyphenol significantly inhibited the proliferation of MSI colorectal cancer cells and stably maintained the microsatellite state in MSI colorectal cancer. Tea polyphenol inhibited the gene expressions of HES1, JAG1, MT2A and MAFA, up-regulated the gene expression of BAX and down-regulated that of P38. Further research is required to investigate how these pathways are interrelated.

Leptospira interrogans (L. interrogans) genomic DNA was used as template to amplify the full-length gene for ribosomal protein L11 methyltransferase (liPrmA) by PCR. The pET22b-/liprmA expression plasmid was successfully constructed in Escherichia coli (E.coli.) strain TOP10 and confirmed by restriction enzyme digest and sequencing. Through optimizing expression of the recombinant liPrmA-6xHis fusion protein in expression host E. coli. BL21, the yield of soluble target protein reached 40 mg (liter culture)-1. The LiPrmA was purified to apparent homogeneity in a single step using Ni-NTA His Bind chromatography. Amino acid homologous analysis showed that liPrmA shared significant identity with other prokaryotic PrmA and eukaryotic putative PrmA in the catalytic region including AdoMet binding domain. Methylation activity experiments showed purified liPrmA was able to catalyze the ribosomal protein L11 of L. interrogans methylated under the presence of S-adenosyl-methionine (AdoMet).