Characterizing the temporal dynamics of intrinsic brain activities in depressed adolescents with prior suicide attempts.

Converging evidence has revealed disturbances in the corticostriatolimic system are associated with suicidal behaviors in adults with major depressive disorder. However, the neurobiological mechanism that confers suicidal vulnerability in depressed adolescents is largely unknown. A total of 86 depressed adolescents with and without prior suicide attempts (SA) and 47 healthy controls underwent resting-state functional imaging (R-fMRI) scans. The dynamic amplitude of low-frequency fluctuations (dALFF) was measured using sliding window approach. We identified SA-related alterations in dALFF variability primarily in the left middle temporal gyrus, inferior frontal gyrus, middle frontal gyrus (MFG), superior frontal gyrus (SFG), right SFG, supplementary motor area (SMA) and insula in depressed adolescents. Notably, dALFF variability in the left MFG and SMA was higher in depressed adolescents with recurrent suicide attempts than in those with a single suicide attempt. Moreover, dALFF variability was capable of generating better diagnostic and prediction models for suicidality than static ALFF. Our findings suggest that alterations in brain dynamics in regions involved in emotional processing, decision-making and response inhibition are associated with an increased risk of suicidal behaviors in depressed adolescents. Furthermore, dALFF variability could serve as a sensitive biomarker for revealing the neurobiological mechanisms underlying suicidal vulnerability.

Parsimonious clinical prediction model for the diagnosis of complicated appendicitis.

Objective: To develop a logistic regression model that combines clinical and radiological parameters for prediction of complicated appendicitis. Methods: 248 patients with histologically proven uncomplicated (n = 214) and complicated (n = 34) acute appendicitis were analyzed retrospectively. All patients had undergone a presurgical abdominal and/or pelvic computed tomography (CT) scan, assessed by two radiologists. A model using univariate and multivariate logistic regression analyses was developed, and the strength of association between independent predictors and complicated acute appendicitis was evaluated by adjusted odds radio. Clinical parameters were gender, age, anorexia, vomiting, duration of symptoms, right lower abdominal quadrant (RLQ) tenderness, rebound tenderness, body temperature, white blood cell (WBC) count, and neutrophil ratio. Radiological parameters were appendix diameter, appendicolith, caecal wall thickening, mesenteric lymphadenopathy, extraluminal air, abscess, fat stranding, and periappendicular fluid. Results: Four features (body temperature＞37.2 °C, vomiting, appendicolith, and periappendiceal fluid) were included in the logistic regression model, and yielded an area under the curve (AUC) of 0.87 (95% confidence interval (CI), 0.80-0.93), sensitive of 88%, and specificity of 74%. Conclusion: The logistic regression model makes an accurate and simple prediction of complicated appendicitis possible.

Synthesis and in vitro antiproliferative activities of lupanol derivatives towards human esophageal squamous carcinoma cells.

A series of lupanol derivatives were synthesized and evaluated in vitro for their inhibitory activities against three human esophageal squamous carcinoma cells lines, Eca-109, TE-1 and EC-9706. Among lupanol derivatives, seven were new compounds, and lupanol cinnamate analogues 5 and 6, hydrazone analogues 9 and 10 presented high activities towards all the tested tumour cells, even higher activities than those of doxorubicine.

Synthesis and in vitro antitumour activities of lupeol derivatives.

Nine lupeol derivatives were synthesised and assayed in vitro for their antitumour activities against three human tumour cells lines, A549, LAC and HepG2. Of lupeol derivaties, six were new compounds, and five compounds against A549 cells, four compounds against HepG2 cells and three compounds against LAC cells were effective in reducing viability, and the most promising compounds 5, 6 and 9 exhibited high activities against lung and liver cancer cells, even higher activities than those of adriamycin.

Adenoviral vector mediated ferritin over-expression in mesenchymal stem cells detected by 7T MRI in vitro.

OBJECTIVE: The aim of the present work was to verify whether adenoviral vector mediated ferritin over-expression in mesenchymal stem cells could be detected by 7T MRI device, and to explore the relationship between ferritin content and MRI signal intensities. METHODS: A recombined adenoviral vector (rAdV) encoding ferritin heavy chain (FTH1) subunit was specially designed for the aim of infecting bone marrow mesenchymal stem cells (BMSCs). Ferritin over-expression in BMSCs was determined by cell immunocytochemistry and the ferritin content in cells was determined by ELISA assay. BMSCs were subjected to cell viability, proliferation and multi-differentiation analyses as well as 7T MRI test using fast spin-echo pulse sequence. The R2 value andδR2 were calculated according to T2 mapping images. RESULTS: As was confirmed by cell immunocytochemistry and ELISA assay, rAdV mediated ferritin was over-expressed in BMSCs. Ferritin over-expression did not interfere with stem cell viability or pluripotent differentiation but slowed cell proliferation. The R2 value of BMSCs-FTH1 vs control BMSCs from 1-4 weeks was16.65±1.28 s-1 vs 13.99±0.80 s-1, (t = 3.94, p = 0.004), 15.63±1.37 s-1 vs 13.87±0.83 s-1 (t = 2.47, p = 0.039), 15.53±0.88 s-1 vs 14.25±0.53 s-1 (t = 2.80, p = 0.023) and 14.61±1.28 s-1 vs 13.69±1.03 s-1 (t = 1.25, p = 0.24), respectively. δR2 gradually decreased from 1-4 weeks and the difference between the groups had statistical significance (F = 12.45, p<0.01).δR2 was positively correlated with OD value (r = 0.876, p<0.01) and ferritin concentration (r = 0.899, p<0.01) as determined by Pearson correlation. CONCLUSIONS: Our study confirms that ferritin could be over-expressed in BMSCs as a result of rAdV mediated infection and could be quantitatively detected by 7T MRI device. The differences in T2 signal intensities and R2 values stem from internal contrast generated by endogenous ferritin over-expression. The correlation between δR2, OD and ferritin concentration suggests that MRI can detect ferritin signal change accurately.

Alterations in brain metabolism and function following administration of low-dose codeine phosphate: 1H-magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging studies.

The aim of the present study was to identify alterations in brain function following administration of a single, low-dose of codeine phosphate in healthy volunteers using resting-state functional magnetic resonance imaging (fMRI). In addition, the metabolic changes in the two sides of the frontal lobe were identified using 1H-magnetic resonance spectroscopy (1H-MRS). A total of 20 right-handed healthy participants (10 males, 10 females) were evaluated, and a Signa HDx 1.5T MRI scanner was used for data acquisition. An echo planar imaging sequence was used for resting-state fMRI, whereas a point resolved spectroscopy sequence was used for 1H-MRS. Regional Saturation Technique, Data Processing Assistant for Resting-State fMRI, and Statistical Parameter Mapping 8 were used to analyze the fMRI data. The 1H-MRS data were analyzed using LCModel software. At 1 h after oral administration of codeine phosphate (1.0 mg/kg), the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity were altered in different brain areas. The choline content was significantly increased in the right and left frontal lobes following codeine phosphate administration (P=0.02 and P=0.03, respectively), whereas the inositol content was significantly decreased in the left frontal lobe (P=0.02). There was no change in the glutamic acid content in the frontal lobes. In conclusion, the functions of different brain regions can be affected by a single, low-dose administration of codeine phosphate. The alterations in metabolite content in the two frontal lobes may be associated with changes in brain function, whereas the ALFF in the globus pallidus may have an effect on codeine phosphate addiction. Finally, glutamic acid may be useful in the estimation of codeine dependence.

7.0 T high-resolution 1H-MR spectroscopy of metabolic changes induced by chronic codeine phosphate in rat hippocampus.

Codeine phosphate is used widely to treat cough and pain. It is actually a sedative, but is known to cause codeine dependence. The exact mechanisms of codeine dependence are not fully understood, but are generally believed to be related to drug-induced neuroadaptation. Metabolites changes can provide information for pathological processes and mechanisms before the shape change. It is very useful for the diagnosis and treatment of drug addiction. We used H NMR spectroscopy in vivo to measure the concentrations of cerebral metabolites in the hippocampus of rats subjected to repeated codeine treatment. After 2 months of codeine treatment, the concentration of N-acetylaspartate was significantly decreased in hippocampi, as was that of glutamate, choline, and taurine. Our study highlights the potential use of metabolic profiling to enhance our understanding of metabolite alteration associated with codeine dependence.

2D-1H proton magnetic resonance spectroscopic imaging study on brain metabolite alterations in patients with diabetic hypertension.

The aim of the present study was to investigate the possible metabolic alterations in the frontal cortex and parietal white matter in patients with diabetic hypertension (DHT) using proton magnetic resonance (MR) spectroscopic imaging. A total of 33 DHT patients and 30 healthy control subjects aged between 45 and 75 were included in the present study. All subjects were right­handed. The spectroscopy data were collected using a GE Healthcare 1.5T MR scanner. The multi­voxels were located in the semioval center (repetition time/echo time=1,500 ms/35 ms). The area of interest was 8x10x2 cm in volume and contained the two sides of the frontal cortex and the parietal white matter. The spectra data were processed using SAGE software. The ratios of brain metabolite concentrations, particularly for N­acetylaspartate (NAA)/creatine (Cr) and Choline (Cho)/Cr were calculated and analyzed. Statistical analyses were performed using SPSS 17.0. The NAA/Cr ratio of the bilateral prefrontal cortex of the DHT group was significantly lower than that of the control group (left t=­7.854, P=0.000 and right t=­5.787, P=0.000), The Cho/Cr ratio was also much lower than the control group (left t=2.422, P=0.024 and right t=2.920, P=0.007). NAA/Cr ratio of the left parietal white matter of the DHT group was extremely lower than that of the control group (t=­4.199, P=0.000). Therefore, DHT may result in metabolic disorders in the frontal cortex and parietal white matter but the metabolic alterations are different in various regions of the brain. The alteration in cerebral metabolism is associated with diabetes and hypertension. The ratios of NAA/Cr and Cho/Cr are potential metabolic markers for the brain damage induced by DHT.

Magnetic Resonance Spectroscopy Study of Amnestic Mild Cognitive Impairment and Vascular Cognitive Impairment With No Dementia.

Amnestic mild cognitive impairment (aMCI) and vascular cognitive impairment with no dementia (VCIND) are highly predictive of Alzheimer's disease and vascular dementia. In this study, a 2-dimensional magnetic resonance spectroscopy was performed in 25 patients with aMCI, 28 patients with VCIND, and 32 normal controls (NCs). The concentrations of N-acetyl aspartate (NAA), choline (Cho), myoinositol (MI), and creatine (Cr) were measured, and their ratios were calculated. The patients with aMCI displayed significantly lower NAA/MI bilaterally in the posterior cingulate gyrus (PCG) and white matter of occipital lobe (OLWM) than NC participants or patients with VCIND , whereas patients with VCIND displayed markedly lower NAA/Cho bilaterally in the white matter of frontal lobe (FLWM) and left OLWM, and right dorsal thalamus (DT) than patients with NC or aMCI. Compared with the controls, patients with aMCI displayed lower NAA and NAA/Cr in bilateral PCG, left precuneus, and DT, whereas patients with VCIND displayed lower NAA/Cr in bilateral DT and FLWM. In addition, increased MI in right PCG of patients with aMCI and increased Cho in left FLWM of patients with VCIND were also observed. The results might help guide a clinical differentiation between the 2 disorders.

Behavioral deficits, abnormal corticosterone, and reduced prefrontal metabolites of adolescent rats subject to early life stress.

The present study investigated the effect of early life stress in adolescent rats on brain metabolites, serum corticosterone, and depressive-like behavior. A group of rats was subject to early life stress from postnatal day (PND) 1 to 14. A matched control group was studied. Behavioral tests, serum corticosterone and high-resolution proton magnetic resonance spectroscopy were conducted between PND 30 and 40. In this study, adolescent rats exposed to early life stress demonstrated depressive-like behavior and increased serum corticosterone during adolescence. They also showed reduced glutamate, glutamine, and N-acetylaspartate (NAA) levels in the prefrontal cortex. A reduced myo-inositol level, consistent with astroglial deficits, was observed but was not statistically significant. Together, these findings characterize the effect of early life stress on adolescent animals and underscore the long-lasting and detrimental effects of childhood adversities.

Synthesis and in vitro antitumor activities of lupeol dicarboxylic acid monoester derivatives.

Ten lupeol dicarboxylic acid monoester derivatives as new potent antitumor agents were synthesized and evaluated for in vitro antitumor activities against A549, LAC, HepG2 and HeLa cell lines. Among them, compounds 1-5 showed excellent antitumor activities against all tested tumor cell lines and compounds 6-10 exhibited high activities against A549, HepG2 and HeLa cells, exceeded lupeol, lupanol and doxorubicin. Compound 2 displayed the highest potent antitumor activities with IC50 values of 5.78 µM against A549 cell, 2.38 µM against LAC cell, 6.14 µM against HepG2 cell and 0.00842 µM against HeLa cell.

Nuclear magnetic resonance spectroscopy is highly sensitive for lipid-soluble metabolites.

Although the water-soluble metabolite profile of human mesenchymal stem cells is known, the lipid profile still needs further investigation. In this study, methanol-chloroform was used to extract pid-soluble metabolites and perchloric acid was used to extract water-soluble metabolites. Furthermore, a dual phase extraction method using methanol-chloroform and water was used to obtain both water and lipid fractions simultaneously. All metabolite extractions were analyzed on a 9.4T high-resolution nuclear magnetic resonance spectrometer. Metabolite resonance peaks were assigned in the acquired spectra according to the chemical shift, and the extraction efficiency of ferent methods was compared. Results showed that in the spectra of water-soluble extracts, major metabolites comprised low molecular weight metabolites, including lactate, acetic acid, fatty acids, threonine, glutamic acid, creatine, choline and its derivatives, while in the spectra of lipid-soluble extracts, most metabolites were assigned to fatty acids. Among the different extraction procedures, perchloric acid was more efficient in extracting water-soluble metabolites and methanol-chloroform was efficient in extracting organic components compared with the dual phase extraction method. Nuclear magnetic resonance spectroscopy showed that as low as 0.7 mg organic yield was enough to obtain clear resonance peaks, while about 6.0 mg water-soluble yield was needed to obtain relatively favorable spectral lines. These results show that the efficiency of extracting water and lipid fractions is higher using perchloric acid and methanol-chloroform compared with dual phase extraction and that nuclear magnetic resonance spectroscopy is highly sensitive for analyzing lipid-soluble extracts.

Quantification of choline concentration following liver cell apoptosis using 1H magnetic resonance spectroscopy.

AIM: To evaluate the feasibility of quantifying liver choline concentrations in both normal and apoptotic rabbit livers in vivo, using 1H magnetic resonance spectroscopy (1H-MRS). METHODS: 1H-MRS was performed in 18 rabbits using a 1.5T GE MR system with an eight-channel head/neck receiving coil. Fifteen rabbits were injected with sodium selenite at a dose of 10 µmol/kg to induce the liver cell apoptosis. Point-resolved spectroscopy sequence-localized spectra were obtained from 10 livers once before and once 24 h after sodium selenite injection in vivo. T1 and T2 relaxation time of water and choline was measured separately in the livers of three healthy rabbits and three selenite-treated rabbits. Hematoxylin and eosin and dUTP-biotin nick end labeling (TUNEL) staining was used to detect and confirm apoptosis. Choline peak areas were measured relative to unsuppressed water using LCModel. Relaxation attenuation was corrected using the average of T1 and T2 relaxation time. The choline concentration was quantified using a formula, which was tested by a phantom with a known concentration. RESULTS: Apoptosis of hepatic cells was confirmed by TUNEL assay. In phantom experiment, the choline concentration (3.01 mmol/L), measured by 1H-MRS, was in good agreement with the actual concentration (3 mmol/L). The average T1 and T2 relaxation time of choline was 612 ± 15 ms and 74 ± 4 ms in the control group and 670 ± 27 ms and 78 ± 5 ms in apoptotic livers in vivo, respectively. Choline was quantified in 10 rabbits, once before and once after the injection with sodium selenite. The choline concentration decreased from 14.5 ± 7.57 mmol/L before sodium selenite injection to 10.8 ± 6.58 mmol/L (mean ± SD, n = 10) after treatment (Z = -2.395, P < 0.05, two-sample paired Wilcoxon test). CONCLUSION: 1H-MRS can be used to quantify liver choline in vivo using unsuppressed water as an internal reference. Decreased liver choline concentrations are found in sodium selenite-treated rabbits undergoing liver cell apoptosis.

Quantitative multivoxel proton MR spectroscopy study of brain metabolites in patients with amnestic mild cognitive impairment: a pilot study.

INTRODUCTION: The purpose of this study is to investigate brain metabolic changes in patients with amnestic mild cognitive impairment (aMCI) using multivoxel proton MR spectroscopy ((1)H-MVS). METHODS: Fourteen aMCI patients and fifteen healthy control subjects participated in this experiment. All MR measurements were acquired using a 1.5-T GE scanner. (1)H-MVS point resolved spectroscopy (2D PROBE-CSI PRESS) pulse sequence (TE = 35 ms; TR = 1,500 ms; phase × frequency, 18 × 18) was used for acquiring MRS data. All data were post-processed using Spectroscopy Analysis by General Electric software and linear combination of model (LCModel). The absolute concentrations of N-acetylaspartate (NAA), choline (Cho), myoinositol (MI), creatine (Cr), and the metabolite ratios of NAA/Cr, Cho/Cr, MI/Cr, and NAA/MI were measured bilaterally in the posterior cingulate gyrus (PCG), inferior precuneus (Pr), paratrigonal white matter (PWM), dorsal thalamus (DT), and lentiform nucleus (LN). RESULTS: Patients with aMCI displayed significantly lower NAA levels in the bilateral PCG (p < 0.01), PWM (p < 0.05), and left inferior Pr (p < 0.05). The metabolite ratio of NAA/MI was decreased in the bilateral PCG (p < 0.01) and PWM (p < 0.05) and in the left DT (p < 0.01). NAA/Cr was decreased in the left PCG (p < 0.01), DT (p < 0.05), right PWM (p < 0.05), and LN (p < 0.05). However, MI/Cr was elevated in the right PCG (p < 0.01) and left PWM (p < 0.05). Significantly increased Cho level was also evident in the left PWM (p < 0.05). CONCLUSIONS: Our observations of decreased NAA, NAA/Cr, and NAA/MI, in parallel with increased Cho and MI/Cr might be characteristic of aMCI patients.

[Study on fMRI brain map in patients undergoing needling at Zusanli (ST36) by reinforcing method].

OBJECTIVE: To observe the characteristic of the fMRI brain map in patients undergoing needling at Zusanli (ST36) by reinforcing method for exploring the essence of Meridian-Collaterals and the mechanisms of acupuncture in treating diseases. METHODS: Twenty-six healthy volunteers were randomly assigned to two groups by double blinded method, 16 in the acupoint group and 10 in the non-acupoint group. Using GE Signa 1. 5 T superconducting MRI system, the fMRI was performed with Gradient echo-EPI sequence. Post-processing of fMRI data was performed using the Functool software (GE-ADW4.0) to generate positive correlation coefficient brain functional activating images and the data was analyzed statistically using SPSS 13.0 software. RESULTS: Brain functional area was elicited in 13 out of the 15 patients in the acupoint group and 10 in the non-acupoint group. Among them, the temporal elicited area in the acupoint group showed specificity (Fisher's Exact test, P = 0.022) and only the difference in contralateral hemisphere activation rate was of statistical significance (McNemer test, P = 0.020). CONCLUSION: Acupoints has its own specific brain activated areas. The therapeutic effect of acupoint might be mediated through brain to treat diseases and regulate functional disorder of organs. There exists special transmission channel of meridian.