[The roles of holothurian glycosaminoglycan combined with cisplatin on proliferation and chemotherapeutic response in A549 human lung adenocarcinoma cell].

Objective: To investigate the effects and mechanism of Holothurian Glycosaminoglycan (hGAG) alone in combination with cisplatin (DDP) on apoptosis of pulmonary adenocarcinoma cell A549. Methods: A549 cells were separately treated with blank, hGAG, DDP and hGAG combined with DDP (hGAG + DDP). The cell morphology in 4 groups was observed using light microscope. CCK8 assay was used to determine the cell viability. Flow cytometry by Hoechst 33258 and AnnexinV-FITC/PI staining was applied to detect cell apoptosis. Western blot was then used to detect the protein expression of Bax, Bcl-2, survivin and caspase-3. Results: After treatment for 24 h, the inhibitory rates of A549 cells in control, hGAG, DDP and hGAG + DDP groups were 0, (19.74±5.39)%, (42.01±2.57)% and (53.89±4.58)%, respectively. Moreover, after treatment for 48 h and 72 h, the inhibitory rates in each group were 0, (23.17±4.78)% and (29.17±4.21 )%, (54.00±7.64)% and (59.35±7.31)%, as well as (77.58±4.26)% and (79.94±4.58)%, respectively. The cell viability was significantly lower in drug treatment groups compared with those in control group at the same time point (P<0.05). Hochest 33258 staining showed that no obvious apoptotic cells were detected in the control group, while apoptotic cells were visible in hGAG, cisplatin and combination groups. Flow cytometry showed that cell apoptotic rates were (2.38±0.59)%, (12.59±4.22)%, (16.36±3.63)% and (44.60±5.45)% in the control, hGAG, DDP and hGAG + DDP groups, respectively. The cell apoptosis was significantly lower in drug treatment groups compared with those in control group at the same time point (P<0.05). Furthermore, western blot results showed that the expression of Bax and caspase-3 protein was increased (P<0.05), whereas Bcl-2 and survivin was decreased (P<0.05) in the hGAG+ DDP group compared with cisplatin alone (P<0.05). Conclusions: HGAG can inhibit the proliferation and promote the apoptosis of human lung adenocarcinoma A549 cells. Meanwhile, it can strengthen the chemosensitivity of A549 cells to DDP via up-regulation of Bax, caspase-3 and down-regulation of Bcl-2 and survivin.

Microstructural and Metabolic Changes in Normal Aging Human Brain Studied with Combined Whole-Brain MR Spectroscopic Imaging and Quantitative MR Imaging.

PURPOSE: This study aimed to detect age-related brain metabolic and microstructural changes in healthy human brains by the use of whole-brain proton magnetic resonance spectroscopic imaging (1H­MRSI) and quantitative MR imaging (qMRI). METHODS: In this study, 60 healthy participants with evenly distributed ages (between 21 and 69 years) and sex underwent MRI examinations at 3T including whole-brain 1H­MRSI. The concentrations of the metabolites N­acetylaspartate (NAA), choline-containing compounds (Cho), total creatine and phosphocreatine (tCr), glutamine and glutamate (Glx), and myo-inositol (mI), as well as the brain relaxation times T2, T2' and T1 were measured in 12 regions of interest (ROI) in each hemisphere. Correlations between measured parameters and age were estimated with linear regression analysis and Pearson's correlation test. RESULTS: Significant age-related changes of brain regional metabolite concentrations and tissue relaxation times were found: NAA decreased in eight of twelve ROIs, Cho increased in three ROIs, tCr in four ROIs, and mI in three ROIs. Glx displayed a significant decrease in one ROI and an increase in another ROI. T1 increased in four ROIs and T2 in one ROI, while T2' decreased in two ROIs. A negative correlation of tCr concentrations with T2' relaxation time was found in one ROI as well as the positive correlations of age-related T1 relaxation time with concentrations of tCr, mI, Glx and Cho in another ROI. CONCLUSION: Normal aging in human brain is associated with coexistent brain regional metabolic alterations and microstructural changes, which may be related to age-related decline in cognitive, affective and psychomotor domains of life in the older population.

Itaconic acid and dimethyl itaconate exert antibacterial activity in carbon-enriched environments through the TCA cycle.

Itaconic acid (IA), a metabolite generated by the tricarboxylic acid (TCA) cycle in eukaryotic immune cells, and its derivative dimethyl itaconate (DI) exert antibacterial functions in intracellular environments. Previous studies suggested that IA and DI only inhibit bacterial growth in carbon-limited environments; however, whether IA and DI maintain antibacterial activity in carbon-enriched environments remains unknown. Here, IA and DI inhibited the bacteria with minimum inhibitory concentrations of 24.02 mM and 39.52 mM, respectively, in a carbon-enriched environment. The reduced bacterial pathogenicity was reflected in cell membrane integrity, motility, biofilm formation, AI-2/luxS, and virulence. Mechanistically, succinate dehydrogenase (SDH) activity and fumaric acid levels decreased in the IA and DI treatments, while isocitrate lyase (ICL) activity was upregulated. Inhibited TCA circulation was also observed through untargeted metabolomics. In addition, energy-related aspartate metabolism and lysine degradation were suppressed. In summary, these results indicated that IA and DI reduced bacterial pathogenicity while exerting antibacterial functions by inhibiting TCA circulation. This study enriches knowledge on the inhibition of bacteria by IA and DI in a carbon-mixed environment, suggesting an alternative method for treating bacterial infections by immune metabolites.

Probiotic characterization and comparison of broiler-derived lactobacillus strains based on technique for order preference by similarity to ideal solution analysis.

A total of 10 lactobacillus strains were isolated from broiler chickens and their probiotic properties including tolerance to gastrointestinal fluids and heat treatment, antimicrobial activity, adhesion capacity to intestinal cells, surface hydrophobicity, autoaggregation, antioxidative activity, and immunomodulatory effects on chicken macrophages were evaluated. The Limosilactobacillus reuteri (LR) was the most frequently isolated species, followed by Lactobacillus johnsonii (LJ) and Ligilactobacillus salivarius (LS). All isolates showed good resistance to simulated gastrointestinal conditions and antimicrobial activity against 4 indicator strains including Escherichia coli, Salmonella typhimurium, Klebsiella pneumoniae, and Proteus mirabilis LR 21 exhibited excellent performances on autoaggregation, hydrophobicity and adhesion capacity to Caco-2 intestinal cells. In the meantime, this strain also possessed considerable tolerance to heat treatment, which indicated great potential to be used in the feed industry. However, LJ 20 strain had the highest free radical scavenging activity compared with the other strains. Furthermore, qRT-PCR results revealed that all isolated strains significantly increased the transcriptional levels of proinflammatory genes and tended to induce the M1-type polarization on HD11 macrophages. Particularly, the technique for order preference by similarity to ideal solution (TOPSIS) was adopted in our study to compare and select the most promising probiotic candidate based on in vitro evaluation tests.

Evidence for neuroinflammation and neuroprotection in HCV infection-associated encephalopathy.

OBJECTIVE: Fatigue, mood disturbances and cognitive dysfunction are frequent in patients infected with hepatitis C virus (HCV) who have mild liver disease. The reason is still unclear. The present study aims to gain more insight into the pathomechanism by combining an extensive neuropsychological examination with magnetic resonance spectroscopy in four different brain regions in a patient group covering the whole spectrum of neuropsychiatric findings in patients afflicted with HCV who have only mild liver disease. METHODS: 53 HCV-positive patients with only mild liver disease and differing degrees of neuropsychiatric symptoms were studied with single-voxel MRS of the parietal white matter, occipital grey matter, basal ganglia and pons. Brain metabolite concentrations were quantitatively analysed by using LCmodel. MRS data were compared to those of 23 healthy controls adjusted for age, and analysed for relationships with the extent of neuropsychiatric symptoms. RESULTS: Choline (p=0.02), creatine (p=0.047) and N-acetyl-aspartate plus N-acetyl-aspartyl-glutamate (NN, p=0.02) concentrations in the basal ganglia and choline concentrations in the white matter (p=0.045) were significantly higher in the patients than in controls. Interestingly, the difference was most evident for the patients with low fatigue scores (eg, white matter: choline: p=0.001, creatine: p=0.003, NN: p=0.031). Myo-inositol differed significantly between groups in the white (p=0.001) and grey matter (p=0.003). Fatigue correlated negatively with white matter NN, choline and creatine and myo-inositol levels in white and grey matter and basal ganglia (p<0.01). CONCLUSION: As the increase of choline, creatine and myo-inositol are usually interpreted to indicate glial activation and macrophage infiltration in chronic inflammation and slow virus infections of the brain the present data endorse the hypothesis, that HCV infection may induce neuroinflammation and brain dysfunction. The concomitant increase of NN and the negative correlation to the extent of fatigue suggest a cerebral compensatory process after HCV infection.

Effects of early post-hatch feeding on the growth performance, hormone secretion, intestinal morphology, and intestinal microbiota structure in broilers.

This study aimed to investigate the effects of time access to post-hatch feeding on the growth performance, hormone secretion, intestinal morphology, and intestinal microbiota structure of broilers. A total of 900 broilers were randomly allocated to 3 treatment groups, with 6 replicates of 50 broilers each. The 3 treatments were: immediate feeding (Group 2 h), delayed access to feed for 24 h (Group 24 h), and delayed access to feed for 48 h (Group 48 h). The experiment lasted for 50 d. Results revealed that Group 2 h had a higher average daily gain (ADG) and average daily feed intake (ADFI) as well as a lower feed-to-gain ratio (F/G) than Group 48 h during the starter period (P < 0.05). Compared with Group 48 h, broilers in Group 2 h exhibited significantly elevated villus height (VH) and villus height to crypt depth ratio (VH: CD) in the duodenum, increased Occludin, and Claudin-1 mRNA expression in the jejunum but decreased crypt depth (CD) in the duodenum at 50 d (P < 0.05). Meanwhile, broilers in Groups 2 h and 24 h had increased glycogen (Gn) and protein (Pro) levels in breast muscle and TG levels in the liver, as well as a higher concentration of serum T3, T4, and IGF-1 compared with Group 48 h at 21 d (P < 0.05). Besides, intestinal microbiota consisted primarily of Firmicutes, Bacteroidetes, and Proteobacteria at the phylum level at 21 d and 50 d; at the genus level, broilers in Group 2 h displayed significantly reduced abundance of Escherichia at 21 d and Bacteroides at 50 d compared with Group 48 h (P < 0.05). Collectively, these findings signal that early post-hatch feeding measures, especially at 21 d, improve hormone secretion, intestinal morphology, and the growth performance of broilers by enhancing intestinal health and modulating the intestinal microbiota.

Effects of phytosterol supplementation on growth performance, serum lipid, proinflammatory cytokines, intestinal morphology, and meat quality of white feather broilers.

The aim of this study was to evaluate the effects of dietary phytosterol (PS) addition at different levels on growth performance, serum lipid, proinflammatory cytokines, intestinal morphology, and meat quality in broilers. A total of 600, 1-day-old male broilers were allocated into five groups with six replicates and were fed a basal diet supplemented with 0 (control group), 10, 20, 40, or 80 mg/kg PS for 42 days. Compared with the control group, the administration of PS at doses of 40 and 80 mg/kg significantly increased the average daily feed intake and average daily gain of broilers during the experimental period. Similarly, PS at a dosage of 20 and 40 mg/kg increased the concentrations of interleukin-1ß, interferon-γ, interleukin-2, and interleukin-6 but decreased triglyceride, total cholesterol, and low-density lipoprotein cholesterol content of serum (P < 0.05). Dietary PS at less than or equal to 40 mg/kg level increased (P < 0.05) villus height, and villus height to crypt depth ratio in the duodenum and ileum. Supplementing PS increased the pH value at 45 min post-mortem and decreased drip loss and shear force of breast muscle (P < 0.05). Dietary PS administration at 20 and 40 mg/kg decreased malondialdehyde accumulation but increased total antioxidant capacity and superoxide dismutase activity of breast muscle compared with the control group (P < 0.05). PS increased the concentrations of total amino acids and flavor amino acids as well as eicosapentaenoic acid, docosahexaenoic acid, and total polyunsaturated fatty acids but decreased saturated fatty acids in breast muscle (P < 0.05). It was concluded that dietary PS supplementation, especially at 40 mg/kg, could improve growth performance, serum lipid, proinflammatory cytokines, intestinal morphology, and meat quality in broilers, providing insights into its application as a potential feed additive in broiler production.

In vivo magnetic resonance spectrometry imaging demonstrates comparable adaptation of brain energy metabolism to metabolic stress induced by 72 h of fasting in depressed patients and healthy volunteers.

Major depressive disorder (MDD) is characterized by dysregulation of stress systems and by abnormalities in cerebral energy metabolism. Stress induction has been shown to impact neurometabolism in healthy individuals. Contrarily, neurometabolic changes in response to stress are insufficiently investigated in MDD patients. Metabolic stress was induced in MDD patients (MDD, N = 24) and in healthy individuals (CTRL, N = 22) by application of an established fasting protocol in which calorie intake was omitted for 72 h. Both study groups were comparable regarding age, gender distribution, and body mass index (BMI). Fasting-induced effects on brain high-energy phosphate levels and membrane phospholipid metabolism were assessed using phosphorus-31 magnetic resonance spectroscopy (31P-MRS). Two-way repeated measures ANOVAs did not reveal significant interaction effects (group x fasting) or group differences in adenosine triphosphate (ATP), phosphocreatine (PCr), inorganic phosphate (Pi), phosphomonoesters (PME), phosphodiesters (PDE), or pH levels between MDD and CTRL. Fasting, independent of group, significantly increased ATP and decreased Pi levels and an overall increase in PME/PDE ratio as marker for membrane turnover was observed. Overall these results indicate reactive changes in cerebral energetics and in membrane phospholipid metabolism in response to fasting. The observed effects did not significantly differ between CTRL and MDD, indicating that neurometabolic adaptation to metabolic stress is preserved in MDD patients.

Epidermal growth factor promotes intestinal secretory cell differentiation in weaning piglets via Wnt/ß-catenin signalling.

Small intestinal epithelium homeostasis involves four principal cell types: enterocytes, goblet, enteroendocrine and Paneth cells. Epidermal growth factor (EGF) has been shown to affect enterocyte differentiation. This study determined the effect of dietary EGF on goblet, enteroendocrine and Paneth cell differentiation in piglet small intestine and potential mechanisms. Forty-two weaned piglets were used in a 2 × 3 factorial design; the major factors were time post-weaning (days 7 and 14) and dietary treatment (0, 200 or 400 µg/kg EGF supplementation). The numbers of goblet and enteroendocrine cells were generally greater with the increase in time post-weaning. Moreover, the supplementation of 200 µg/kg EGF increased (P < 0.01) the number of goblet and enteroendocrine cells in villus and crypt of the piglet small intestine as compared with the control. Dietary supplementation with 200 µg/kg EGF enhanced (P < 0.05) abundances of differentiation-related genes atonal homologue 1, mucin 2 and intestinal trefoil factor 3 messenger RNA (mRNA) as compared with the control. Piglets fed 200 or 400 µg/kg EGF diet had increased (P < 0.05) abundances of growth factor-independent 1, SAM pointed domain containing ETS transcription factor and pancreatic and duodenal homeobox 1 mRNA, but decreased the abundance (P < 0.01) of E74 like ETS transcription factor 3 mRNA as compared with the control. Animals receiving 400 µg/kg EGF diets had enhanced (P < 0.05) abundances of neurogenin3 and SRY-box containing gene 9 mRNA as compared with the control. The mRNA abundance and protein expression of lysozyme, a marker of Paneth cell, were also increased (P < 0.05) in those animals. As compared with the control, dietary supplementation with 200 µg/kg EGF increased the abundance of EGF receptor mRNA and the ratio of non-phospho(p)-ß-catenin/ß-catenin (P < 0.05) in villus epithelial cells at days 7 and 14. This ratio in crypt epithelial cells was higher (P < 0.05) on the both 200 and 400 µg/kg EGF groups during the same period. Our results demonstrated that dietary EGF stimulated goblet, enteroendocrine and Paneth cell differentiation in piglets during the post-weaning period, partly through EGFR and Wnt/ß-catenin signalling.

The growth performance, intestinal digestive and absorptive capabilities in piglets with different lengths of small intestines.

The small intestine is an important digestive organ and plays a vital role in the life of a pig. We tested the hypothesis that the length of the small intestine is related to growth performance and intestinal functions of piglets. A total of 60 piglets (Duroc × Landrace × Yorkshire), weaned at day 21, were fed an identical diet during a 28-day trial. At the end of the study, all piglets were sacrificed, dissected and grouped according to small intestine lengths (SILs), either short small intestine (SSI), middle small intestine (MSI) or long small intestine (LSI), respectively. Positive relationships between SIL and BW, average daily gain (ADG), average daily feed intake (ADFI) and gain-to-feed ratios (G : F) were observed. Final BW, ADG, ADFI and G : F significantly increased (P < 0.05) in MSI and LSI piglets compared with SSI piglets. Short small intestine and MSI had greater jejunal mucosa sucrase and alkaline phosphatase activities (P < 0.05) than LSI piglets. The mRNA level of solute carrier family 2 member 2 (Slc2a2) in the jejunal mucosa of SSI piglets was the greatest. The MSI piglets had a greater (P < 0.05) ileal villus height than other piglets and greater (P < 0.05) villus height-to-crypt depth ratios than LSI piglets. However, the LSI piglets had a greater (P < 0.05) ileal crypt depth than SSI piglets. No significant differences in duodenal, jejunal, caecal and colonic morphologies were detected among the groups. Moreover, luminal acetate, propionate, butyrate and total short-chain fatty acid contents were greater (P < 0.05) in SSI and MSI piglets than those in LSI piglets. In addition, there was greater serum glucose concentration in MSI piglets than other piglets. Serum albumin concentration in SSI piglets was the lowest. In conclusion, these results indicate that SIL was significantly positively associated with growth performance, and in terms of intestinal morphology and mucosal digestive enzyme activity, the piglets with a medium length of small intestine have better digestion and absorption properties.

[Efficacy and safety of eltrombopag in aplastic anemia: A multi-center survey in China].

Objective: To evaluate the safety and efficacy of eltrombopag combined with immunosuppressive therapy in patients with aplastic anemia (AA) in China. Methods: We investigated and analyzed the clinical data of AA patients from 14 hematological treatment centers who were treated with oral eltrombopag for at least 3 mon. Results: We enrolled 56 AA patients, including 19 treatment-naïve patients and 37 IST-refractory patients. The median administration period for eltrombopag was 7 (3-31) months, and the median maximum stable dosage was 75 mg/d (50-150 mg/d) . The 3-month hematological response (HR) rate was 60%, and the complete response (CR) rate was 30% in 10 SAA patients who were treated with first-line eltrombopag and standard IST (ATG+CsA) . Eight of 9 eltrombopag and CsA ± androgen first-line treated SAA patients responded (8/9, 89%) and 4 (44%) gave CR. The overall HR and CR rates were 79% and 52.6%, respectively, among these 19 patients by the end of the follow-up period. Of the 19 AA patients who were refractory to CsA ± androgen, 11 achieved HR (57.9%) at 3 mon, and the best HR rate was 44% in standard IST (ATG+CsA) refractory 18 patients after eltrombopag treatment. Fifty-one percent of the patients experienced mild or moderate adverse events, and gastrointestinal discomfort was the most common adverse effect reported by the study subjects. Conclusion: Adding Eltrombopag in first-line IST can accelerate the acquisition and improve the quality of hematological responses in AA patients. AA with relatively more residual hematopoietic cells may be well treated with eltrombopag and non-ATG IST. Eltrombopag can be used as salvage therapy for CsA±androgen refractory patients. Eltrombopag was generally safe and well tolerated by AA patients in China.

Research on protective mechanism of ibuprofen in myocardial ischemia-reperfusion injury in rats through the PI3K/Akt/mTOR signaling pathway.

OBJECTIVE: To study the protective mechanism of ibuprofen (Ib) in myocardial ischemia-reperfusion (I/R) injury in rats, and to analyze its regulatory effect on the phosphatidylinositol 3-hydroxy kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway. MATERIALS AND METHODS: The rat model of myocardial I/R injury was established via ligation of the left main coronary artery (LCA) for 30 min and then reperfusion for 120 min. A total of 36 Sprague-Dawley (SD) rats were randomly divided into sham group (S group, n=12), model group (I/R group, n=12) and Ib group (n=12). The levels of serum creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in each group were detected. The rats were executed, the heart was isolated and the area of myocardial infarction was determined via 2,3,5-triphenyltetrazolium chloride (TTC) staining. The expression levels of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1 (HIF-1) and apoptosis-related proteins in myocardial tissues in each group were detected via Western blotting. Moreover, the content of inflammatory factors in myocardial tissues in each group was detected using the enzyme-linked immunosorbent assay (ELISA) kit. The expression levels of related proteins in the PI3K/Akt/mTOR signaling pathway in myocardial tissues were further analyzed. RESULTS: Compared with those in S group, the levels of CK-MB and LDH were significantly increased (p<0.01), the area of myocardial infarction was significantly increased (p<0.01), the VEGF, HIF-1 and Cleaved caspase-3 protein levels in myocardial tissues were increased (p<0.01), while Bcl-2/Bax declined (p<0.01), the content of interleukin-1 (IL-1), IL-6 and tumor necrosis factor-α (TNF-α) in myocardial tissues was increased (p<0.01), while the content of IL-10 declined (p<0.01), and the expression levels of PI3K, p-Akt and p-mTOR proteins in myocardial tissues were significantly decreased (p<0.01) in I/R group. Compared with those in I/R group, the levels of CK-MB and LDH were significantly decreased (p<0.01), the area of myocardial infarction was significantly decreased (p<0.01), the VEGF, HIF-1 and Cleaved caspase-3 protein levels in myocardial tissues were decreased (p<0.01), while Bcl-2/Bax was increased (p<0.01), the content of IL-1, IL-6 and TNF-α in myocardial tissues declined (p<0.01), while the content of IL-10 was significantly increased (p<0.01), and the expression levels of PI3K, p-Akt and p-mTOR proteins in myocardial tissues were significantly increased (p<0.01) in Ib group. CONCLUSIONS: Ib can activate the PI3K/Akt/mTOR signaling pathway, reduce the release of inflammatory factors and apoptosis, and alleviate the myocardial I/R injury in myocardial cells in rats.

Interaction between bone marrow-derived dendritic cells and miR-21 of tubular renal epithelial cells under hypoxia.

OBJECTIVE: To investigate the intracellular response and role of microRNA 21 in the regulation of dendritic cell maturation and function. MATERIALS AND METHODS: Bone marrow-derived DCs (BMDCs) isolated from male C57BL/6J mice and primary renal tubular epithelial cells were used as primary cells to perform this study. Flow cytometry was used to determine BMDCs and analyze the apoptosis effect. Transmission electron microscopy was used for the identification of the diameter of exosomes. Reverse transcription-Polymerase Chain Reaction (RT-PCR) and Western blotting were used to detect the effect after cells were transfected with oligo. ELISA was used to determine the tumor necrosis factor-α (TNF-α), interleukin-12 (IL-12), and IL-1beta in DC supernatants. RESULTS: We found that the upregulation of microRNA 21 in dendritic cells induced by physical hypoxia contributed to decreased expressions of CD80 (cluster of differentiation 80), CD86 (cluster of differentiation 86), and MHCII (major histocompatibility complex class II molecules) of dendritic cells and suppressed secretion of inflammatory cytokines and chemokine receptor type 7. Co-culture with tubular epithelial cells or hypoxia-pretreated tubular epithelial cell-derived conditional medium promoted bone marrow-derived dendritic cell maturation. Exosomes purified from the supernatant of cultured marrow-derived dendritic cells showed upregulated microRNA 21 under hypoxia, whereas anti-microRNA 21 treated tubular epithelial cells promoted co-cultured marrow-derived dendritic cell maturation. CONCLUSIONS: Both oxygen concentration and tubular epithelial cells participate in regulating dendritic cell maturation, directly or indirectly through the microRNA 21 signal pathway.

Early anisotropy changes in the corpus callosum of patients with optic neuritis.

INTRODUCTION: Optic neuritis (ON) and any other early manifestation of multiple sclerosis (MS) are referred to as clinically isolated syndrome (CIS) as long as MS is suspected. In this prospective study we aimed to determine whether diffusion tensor imaging (DTI) could quantify structural changes in patients with early MS. METHODS: A total of 24 patients and 15 control subjects were prospectively followed by clinical examinations and MRI. the main inclusion criterion was presentation with ON. Patients underwent serial MRI scans: MRI1 (baseline, n=24), MRI2 (mean 6.6 months, n=24), MRI3 (mean 13.0 months, n=14), MRI4 (mean 39.4 months, n=5). Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps were derived from DTI. Four regions of interest (ROIs) were defined in normal-appearing white matter (NAWM). RESULTS: In the temporal course FA decreased in the genu of the callosal body (GCC) from MRI1 to MRI4 (P=0.005) and in the splenium of the callosal body (SCC) (P=0.006). Patients already had lower FA values in the SCC (P<0.01) on MRI1 compared with the controls. Patients had lower FA values in the GCC (P<0.01) starting from MRI2. Patients with definite MS on follow-up (n=9) showed a correlation between FA in the SCC and time (r=-0.40, P=0.004), whereas patients without progression did not. CONCLUSIONS: Our findings suggest that the corpus callosum is an early site for development of anisotropy changes in MS patients with ON. There seems to be a primary FA decrease in all patients with ON that only deteriorates in the group developing definite MS.

First-principles investigation on electronics characteristics of benzene derivatives with different side groups.

The electronics properties for benzene derivatives with different side groups connected to two gold electrodes with symmetric contacts are investigated by using first-principles methods based on the density functional theory. We have found that a bias can induce a transition from the electron-withdrawing behaviors to the electron-denoting behaviors for the OH side group in a phenoldithiol molecule. The degree of asymmetry of the I-V characteristics and the magnitudes in current depend remarkably on the type and number of attached side groups. The detailed analysis illustrates that the "doping" effect of the side groups and the asymmetry of potential profile in devices under different bias polarities are intrinsic origins leading to such observed phenomena. The results show that it is feasible to import some particular characteristics to a benzene-dithiol molecular device through an attachment of different side groups.

Antitumor effect of miR-27b-3p on lung cancer cells via targeting Fzd7.

OBJECTIVE:   Lung cancer is the most common malignancy with the highest mortality rate among cancers. microRNAs (miRNAs) have been confirmed to be closely related to the physiological disorder, especially the tumor process. This study aimed to investigate the effect of miR-27b-3p on lung tumor cells. MATERIALS AND METHODS: The expressions of miR-27b-3p in lung tumors and adjacent non-tumors lung tissues were compared. We test the bonding effect of miR-27b-3p on the Fzd7 promoter, and miR-27b-3p effects on the Fzd7 expression in both NCI-H446 and A549 cells. Then, effects of miR-27b-3p and Fzd7 on these cells viability, survival and apoptosis were detected, respectively. In addition, the possible mechanism of miR-27b-3p affected these cells apoptosis was explored by analyzing the expression of apoptosis-related factors. RESULTS: We found that miR-27b-3p was low expressed in lung tumors compared to adjacent non-tumorous lung tissues. miR-27b-3p directly targeted Fzd7 promoter and negatively regulated Fzd7 expression. Fzd7 promoted NCI-H446 and A549 cells viability and survival, inhibited cells apoptosis. However, miR-27b-3p effects on these cells were quite the opposite to Fzd7. The expressions of apoptosis-related factors were associated positively with miR-27b-3p and showed a negative correlation with Fzd7 expression. CONCLUSIONS: The miR-27b-3p was lowly expressed in lung cancer tissues, and played the role of a tumor suppressor. It could promote cell apoptosis and suppress cancer cells viability and survival via down-regulating Fzd7. It suggested that miR-27b-3p might be a potential target for the prophylaxis and treatment of lung cancer.

Disarrangement of fiber tracts and decline of neuronal density correlate in glioma patients--a combined diffusion tensor imaging and 1H-MR spectroscopy study.

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) and MR spectroscopy are noninvasive, quantitative tools for the preoperative assessment of gliomas with which the quantitative parameter fractional anisotropy (FA) and the concentration of neurometabolites N-acetylaspartate (NAA), choline (Cho), creatine (Cr) of the brain can be determined. Measurements of FA and NAA reflect the integrity of fiber tracts and the presence of neurons, respectively. This investigation examines changes of FA and NAA and compares these different aspects in architecture of gliomas after spatial coregistration. METHODS: DTI and chemical shift (1)H-MR spectroscopy was performed in 34 healthy volunteers and 69 patients with histologically confirmed (n = 48) or morphologically suspected (n = 21) non-necrotic brain glioma. Volumes of interest (VOIs) were placed in the tumor center (TC), the tumor border (TB), the normal-appearing white matter adjacent to the tumors (TNWM), and in the white matter of the contralateral hemisphere (NWMC). Median FA values and NAA/Cr and NAA/Cho ratios were calculated in the patients' VOIs and the gray and white matter of the volunteers. Correlations of FA values and NAA ratios were calculated. RESULTS: Continuous changes of FA and NAA from the tumor center to the periphery (the adjacent white matter and the contra-lateral hemisphere, respectively) were observed, where median values were: TC: 0.73 +/- 0.45, 0.47 +/- 0.58, 0.17 +/- 0.15 (NAA/Cr, NAA/Cho, FA); TB: 1.06 +/- 0.53, 1.00 +/- 0.15, 0.23 +/- 0.08; TNWM: 1.42 +/- 2.48, 1.21 +/- 0.95, 0.34 +/- 0.09; and NWMC: 1.63 +/- 0.72, 1.56 +/- 1.34, 0.38 +/- 0.08. Correlation of median FA values and NAA ratios in the cumulative group of patients was high (r = 0.99 [NAA/Cr], 0.95 [NAA/ Cho] at P < .01). Correlation between the individual NAA ratios and the FA values was moderate (r = 0.53 [NAA/Cr], 0.51 [NAA/Cho] at P < .01). CONCLUSION: In gliomas, the degree of tissue organization decreases continuously from the surrounding tissue toward the center of the tumor accompanied by a concordant decrease of NAA. This uniform behavior of FA and NAA reflects a decreasing integrity of both neuronal structures and fibers.

Detection of Normal Aging Effects on Human Brain Metabolite Concentrations and Microstructure with Whole-Brain MR Spectroscopic Imaging and Quantitative MR Imaging.

BACKGROUND AND PURPOSE: Knowledge of age-related physiological changes in the human brain is a prerequisite to identify neurodegenerative diseases. Therefore, in this study whole-brain (1)H-MRS was used in combination with quantitative MR imaging to study the effects of normal aging on healthy human brain metabolites and microstructure. MATERIALS AND METHODS: Sixty healthy volunteers, 21-70 years of age, were studied. Brain maps of the metabolites NAA, creatine and phosphocreatine, and Cho and the tissue irreversible and reversible transverse relaxation times T2 and T2' were derived from the datasets. The relative metabolite concentrations and the values of relaxation times were measured with ROIs placed within the frontal and parietal WM, centrum semiovale, splenium of the corpus callosum, hand motor area, occipital GM, putamen, thalamus, pons ventral/dorsal, and cerebellar white matter and posterior lobe. Linear regression analysis and Pearson correlation tests were used to analyze the data. RESULTS: Aging resulted in decreased NAA concentrations in the occipital GM, putamen, splenium of the corpus callosum, and pons ventral and decreased creatine and phosphocreatine concentrations in the pons dorsal and putamen. Cho concentrations did not change significantly in selected brain regions. T2 increased in the cerebellar white matter and decreased in the splenium of the corpus callosum with aging, while the T2' decreased in the occipital GM, hand motor area, and putamen, and increased in the splenium of the corpus callosum. Correlations were found between NAA concentrations and T2' in the occipital GM and putamen and between creatine and phosphocreatine concentrations and T2' in the putamen. CONCLUSIONS: The effects of normal aging on brain metabolites and microstructure are region-dependent. Correlations between both processes are evident in the gray matter. The obtained data could be used as references for future studies on patients.