[Show abstract][Hide abstract] ABSTRACT: Aim:Hematoporphyrin monomethyl ether (HMME), which consists of equal amounts of isomers HMME-1 and HMME-2, is a novel porphyrin-related drug for photodynamic therapy. This study was aimed to investigate the uptake transporter-mediated selective uptake of HMME into the liver and to identify the major uptake transporter isoforms involved.Methods:Adult SD rats were intravenously injected with a single dose of HMME (5 mg/kg) with or without rifampicin (an inhibitor of organic anion transporting polypeptides OATP1B1 and OATP1B3, 25 mg/kg). Blood samples were collected, and HMME concentrations were measured using LC-MS/MS. Rat hepatocytes, human hepatocytes and HEK293 cells expressing OATP1B1, OATP1B3, or OATP2B1 were used to investigate the uptake of HMME or individual isomers in vitro.Results:Co-administration of rifampicin significantly increased the exposure of HMME isomers, and decreased the AUC ratio of HMME-1 to HMME-2 from 1.98 to 1.56. The uptake of HMME-2 into human hepatocytes and the HEK293 cells expressing OATP1B1 or OATP2B1 in vitro was 2-7 times greater than that of HMME-1, whereas OATP1B3 mediated a higher HMME-1 uptake. OATP1B1 exhibited a higher affinity for HMME-2 than for HMME-1 (the Km values were 0.63 and 5.61 μmol/L, respectively), which were similar to those in human hepatocytes. By using telmisartan (a non-specific OATP inhibitor) and rifampicin, OATP2B1 was demonstrated to account for <20% of hepatic HMME uptake.Conclusion:OATP1B1 is the major transporter involved in the rapid hepatic uptake of HMME, and the greater uptake of HMME-2 by OATP1B1 may lead to a lower exposure of HMME-2 than HMME-1 in humans.
[Show abstract][Hide abstract] ABSTRACT: Eudaimonic well-being (EWB) is the fulfillment of human potential and a meaningful life. Previous studies have shown that personality traits, especially extraversion, neuroticism, and conscientiousness, significantly contribute to EWB. However, the neurobiological pathways linking personality and EWB are not understood. Here, we used resting-state functional magnetic resonance imaging (rs-fMRI) to investigate this issue. Specifically, we correlated individuals' EWB scores with the regional fractional amplitude of low-frequency fluctuations (fALFF) of the brain, and then examined how personality traits predicted EWB-related spontaneous brain activity. We found that EWB was positively correlated with the fALFF in the right posterior superior temporal gyrus (pSTG) and thalamus, and negatively correlated with the strength of the thalamic-insular connectivity. More importantly, we found that personality traits influenced EWB in different ways. At the regional level, the fALFF in the pSTG and thalamus mediated the effects of neuroticism and extraversion on EWB, whereas the thalamus mediated the effect of conscientiousness on EWB. At the functional connectivity level, the thalamic-insular connectivity only mediated the effect of neuroticism on EWB. Taken together, our study provides the first evidence that EWB is associated with personality traits through different neural substrates.
[Show abstract][Hide abstract] ABSTRACT: Although much attention has been directed towards life satisfaction that refers to an individual's general cognitive evaluations of his or her life as a whole, little is known about the neural basis underlying global life satisfaction. In the present study, we used voxel-based morphometry to investigate the structural neural correlates of life satisfaction in a large sample of young healthy adults (n = 299). We showed that individuals' life satisfaction was positively correlated with the regional gray matter volume (rGMV) in the right parahippocampal gyrus (PHG), and negatively correlated with the rGMV in the left precuneus and left ventromedial prefrontal cortex (VMPFC). This pattern of results remained significant even after controlling for the effect of general positive and negative affect, suggesting a unique structural correlates of life satisfaction. Furthermore, we found that self-esteem partially mediated the association between the PHG volume and life satisfaction as well as that between the prec
Social Cognitive and Affective Neuroscience 11/2014; · 5.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Social well-being reflects the appraisal of one's circumstance and functioning in society, which is crucial for individuals’ mental and physical health. However, little is known about the neural processes associated with social well-being. In this study, we used voxel-based morphometry (VBM) to identify the brain regions underlying individual differences in social well-being, as measured by the Social Well-being Scale (SWBS), in a large sample of young healthy adults. We found that social well-being was negatively correlated with gray matter volume in left mid-dorsolateral prefrontal cortex (mid-DLPFC) that is implicated in executive functioning, emotional regulation and social reasoning. The results remained significant even after controlling for the effect of socioeconomic status. Furthermore, although basic personality factors such as neuroticism, extraversion, and conscientiousness (as measured by the NEO Personality Inventory) all contributed to social well-being, only extraversion acted as a mediational mechanism underlying the association between the left mid-DLPFC volume and social well-being. Together, our findings provide the first evidence for the structural basis of individual differences in social well-being, and suggest that the personality trait of extraversion might play an important role in the acquisition and process of social well-being.
[Show abstract][Hide abstract] ABSTRACT: With the increasing knowledge for the topography of brain function, neuroimaging studies are moving away from traditional brain mapping towards investigating the response properties of specific brain regions. As a result, region of interest (ROI) approach, which allows one to ask how a region responds to a range of situations and tasks, become an important methodology in neuroimaging. The FreeROI is designed to help ROI analysis by providing versatile tools for defining/manipulating ROIs and calculating a summary time course from the region data. A pipeline for handling big dataset is also included.
The 17th National Academic Congress of Psychology (China); 10/2014
[Show abstract][Hide abstract] ABSTRACT: Neuropsychological impairment has long been established as a fundamental characteristic of depression, but a generally accepted, specific pattern of neuropsychological impairment has not been summarized. In this study, we examined the classic neuropsychological paradigm of self-face recognition, to explore whether the self was impaired in major depressive disorder (MDD). Eighteen MDD patients and 20 healthy subjects were recruited to participate in this study. By using a face morphing technique, we measured the size of processing bias in MDD patients during different face discrimination tasks relative to controls. Results of analysis of variance (ANOVA) showed a significant main effect of Group (F (1, 36) = 7.388, P = 0.01). Subsequent independent t-tests further revealed that self bias (t = 2.636, P = 0.012) and self-recognition bias (t = 2.190, P = 0.035) observed in self-famous task and self-stranger task respectively for patients were significantly greater than that for controls. Both self-processing and self-recognition were impaired in patients with MDD, indicating that MDD individuals might exist level of self-abnormalities. These findings provide a new perspective for further study on the etiological and pathological mechanisms of MDD.
Chinese Science Bulletin 10/2014; 59(28). · 1.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Histamine is an important mediator of anaphylactic reactions. Although several methods have been developed to measure histamine levels, each has its limitations. In this study, we developed and validated a convenient bioanalytical method for the qualitative and quantitative determination of histamine in plasma samples from humans, beagle dogs, Sprague–Dawley rats, and imprinting control region mice. A simple plasma protein precipitation method using acetonitrile was selected, and hydrophilic interaction liquid chromatography coupled with mass spectrometry was used for sample separation and detection. Histamine was subjected to gradient elution with acetonitrile, ammonium acetate buffer, and formic acid. A mass spectrometer equipped with an electrospray ionization source was operated in the positive-ion multiple reaction monitoring mode for the detection of histamine and the internal standard. The [M + H]+ transitions were m/z 112 → 95 for histamine and m/z 116 → 99 for d4-histamine, which was used as the internal standard. The lower limit of quantification was 0.2 μg/L and the calibration range was 0.2–500 μg/L. The overall recovery ranged from 93.6% to 102.8%. The intra- and inter-run precision and accuracy were <15% for plasma samples from all four species. The method was validated by measuring the plasma histamine concentrations in five healthy human volunteers. In conclusion, we have developed and validated a novel bioanalytical method for the quantification of histamine levels in plasma samples from various mammalian species.
Journal of Chromatography B 09/2014; 971:35–42. · 2.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although local features of brain morphology have been widely investigated in neuroscience, the inter-regional relations in brain morphology have rarely been investigated, especially not for individual participants.
In this paper, we proposed a novel framework for investigating this relation based on an individual's magnetic resonance imaging (MRI) data. The key idea was to estimate the probability density function (PDF) of local morphological features within a brain region to provide a global description of this region. Then, the inter-regional relations were quantified by calculating the similarity of the PDFs for pairs of regions based on the Kullback–Leibler (KL) divergence.
For illustration, we applied this approach to a pre-post intervention study to investigate the longitudinal changes in morphological relations after long-term sleep deprivation. The results suggest the potential application of this new method for studies on individual differences in brain structure.
The current method can be employed to estimate individual morphological relations between regions, which have been largely ignored by previous studies.
Our morphological relation metric, as a novel quantitative biomarker, can be used to investigate normal individual variability and even within-individual alterations/abnormalities in brain structure.
Journal of Neuroscience Methods 09/2014; · 2.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mindfulness is typically defined as nonjudgmental awareness of experiences in the present moment, which is beneficial for mental and physical well-being. Previous studies have identified multiple regions in the default mode network (DMN) that are involved in mindfulness, but little is known about how these regions work collaboratively as a network. Here, we used resting-state functional magnetic resonance imaging to investigate the role of the DMN in trait mindfulness by correlating spontaneous functional connectivity among DMN nodes with self-reported trait mindfulness in a large population of young adults. Among all pairs of the DMN nodes, we found that individuals with weaker functional connectivity between the thalamus and posterior cingulate cortex (PCC) were more mindful of the present. Post-hoc analyses of these two nodes further revealed that graph-based nodal properties of the thalamus, not the PCC, were negatively correlated with trait mindfulness, suggesting that a low involvement of the thalamus in the DMN is relevant for high trait mindfulness. Our findings not only suggest the thalamus as a switch between mind-wandering and mindfulness, but also invite future studies on mechanisms of how mindfulness produces beneficial effects by modulating the thalamus.
[Show abstract][Hide abstract] ABSTRACT: authors have contributed equally to this work. In functional magnetic resonance imaging studies, object selectivity is defined as a higher neural response to an object category than other object categories. Importantly, object selectivity is widely considered as a neural signature of a functionally-specialized area in processing its preferred object category in the human brain. However, the behavioral significance of the object selectivity remains unclear. In the present study, we used the individual differences approach to correlate participants' face selectivity in the face-selective regions with their behavioral performance in face recognition measured outside the scanner in a large sample of healthy adults. Face selectivity was defined as the z score of activation with the contrast of faces vs. non-face objects, and the face recognition ability was indexed as the normalized residual of the accuracy in recognizing previously-learned faces after regressing out that for non-face objects in an old/new memory task. We found that the participants with higher face selectivity in the fusiform face area (FFA) and the occipital face area (OFA), but not in the posterior part of the superior temporal sulcus (pSTS), possessed higher face recognition ability. Importantly, the association of face selectivity in the FFA and face recognition ability cannot be accounted for by FFA response to objects or behavioral performance in object recognition, suggesting that the association is domain-specific. Finally, the association is reliable, confirmed by the replication from another independent participant group. In sum, our finding provides empirical evidence on the validity of using object selectivity as a neural signature in defining object-selective regions in the human brain.
Frontiers in Human Neuroscience 07/2014; 8. · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Thrombotic thrombocytopenic purpura (TTP) requires immediate treatment with plasma exchange (PE) to prevent disease mortality and/or morbidity. Frequently, PE is initiated before blood sample is collected to confirm ADAMTS13 deficiency. However, the effect of PE treatments on the evaluation of ADAMTS13 is uncertain. Moreover, the pertinence of ADAMTS13 activity during PE therapy to prediction of treatment outcomes is unclear. Thus, clarification of the diagnostic and prognostic values of ADAMTS13 activity obtained during PE treatment is an unmet clinical need.Study Design and MethodsA total of 212 sequential samples were obtained during the course of daily PE treatment from 19 patients with acquired TTP. ADAMTS13 activity levels were determined in these longitudinal samples for analysis.ResultsAfter the initial three daily PE procedures, the sensitivities of ADAMTS13 activity in diagnosis of TTP (<10%) were 89, 83, and 78%, respectively. To determine prognostic value, patients with (n = 7) and without (n = 12) a recovery of ADAMTS13 activity to more than 10% within seven sessions of daily PE treatment were compared. Recovery of ADAMTS13 activity to more than 10% within 7 days is significantly associated with a timely achievement of clinical response (p < 0.01). In contrast, the patients without more than 10% ADAMTS13 within 1 week appear at risk for worse treatment outcomes manifested as TTP exacerbation, treatment refractoriness, or death.Conclusion
The data suggest that ADAMTS13 activities measured during the initial period of PE therapy offer both diagnostic and prognostic values in acquired TTP.
[Show abstract][Hide abstract] ABSTRACT: Construction anatomical connections of large-scale brain networks via diffusion magnetic resonance imaging (dMRI) plays an important role in modeling the human connectome (). In practice, one of the important but unsolved issues is the determination of nodes for network construction. Previous studies have demonstrated that significant effects exist on the topological properties if applying different of nodes (e.g., different node scales or different prior atlas) ([2, 3]). However, little is known whether the node refining in anatomical network construction matters? Here, node refining refers to whether to compute the gray matter/white matter boundary (GWB) for each node in the raw prior atlas before being used to construct the whole-brain networks with tractography. Although both methods have been widely used (e.g.,  vs. ), the node-refining effects have yet been studied. According to the procedures of anatomical network construction via dMRI, the node-refining effects appear to be significant in the network construction, as shown in Fig. 1A. In this work, we seek to evaluate the node refining effects on the topological properties of the constructed large-scale anatomical networks with the widely-used automated anatomical labeling (AAL) parcellation atlas ().
20th Annual Meeting of the Organization for Human Brain Mapping, Hamburg, Germany; 06/2014
[Show abstract][Hide abstract] ABSTRACT: The opinion of mind-body interaction has been increasingly acknowledged in recent years, as exemplified by accumulating evidence indicating that physical health (body) is associated with emotion and emotion regulation (mind). Yet the neural basis linking emotion regulation with physical health remains largely uninvestigated. Here we used magnetic resonance imaging to investigate the neural basis of this pathway in a large population of healthy young adults. With a systematic study revealing the association of self-reported physical health and emotion traits of personality and general affective experiences, we further demonstrated that, for better physical health, individuals needed to regulate their emotion more effectively. Importantly, individuals who had larger gray matter (GM) volume in the amygdala reported not only a higher ability of emotion regulation but also better physical health. Further, GM volume in the amygdala mediated the correlation between emotion regulation ability and physical health. Our findings suggest that the amygdala plays a critical role in the neural circuit through which emotion regulation may influence physical health. Therefore, our study takes the first step towards exploring the neuroanatomical basis for body-mind interaction, and may inform interventions aimed at promoting physical health by augmenting skills of emotion regulation.
Social Cognitive and Affective Neuroscience 06/2014; · 5.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mindfulness is the state of being attentive to and aware of what is taking place in the present, which is beneficial for reducing stress-related symptoms and improving mental and physical health. Previous studies have demonstrated that meditation practice can improve individuals' mindfulness through modifying functions and structures of multiple brain regions, including the anterior cingulate cortex (ACC), insula, fronto-limbic network, posterior cingulate cortex (PCC), and temporal-parietal junction. However, little is known about the neuroanatomical correlates of trait mindfulness. In the current study, we used voxel-based morphometry to investigate the neural correlates of individual differences in trait mindfulness by correlating the gray matter (GM) volume of each voxel across the whole brain with trait mindfulness measured by the Mindful Attention Awareness Scale in a large sample of young adults (N = 247). We found that individuals who were more mindful of the present had greater GM volume in the right hippocampus/amygdala and bilateral ACC and but less GM volume in bilateral PCC and the left orbitofrontal cortex. These results suggest that trait mindfulness is associated with brain regions involved in executive attention, emotion regulation, and self-referential processing, through which mindfulness may exerts its beneficial effects on psychological and physical well-being.
[Show abstract][Hide abstract] ABSTRACT: Cervical cancers/CCs are one of the commonest malignancies and the second leading cause of cancer-related death in women. Resveratrol inhibits CC cell growth but its molecular target(s) remains unclear. Since the signaling pathways mediated by STAT3, Notch1 and Wnt2 play beneficial roles in CC formation and progression, the effects of resveratrol on them in cervical adenocarcinoma (HeLa) and squamous cell carcinoma (SiHa) cells were analyzed. The biological significances of the above signaling for HeLa and SiHa cells were evaluated by treating the cells with STAT3, Wnt or Notch selective inhibitors. The frequencies of STAT3, Notch and Wnt activations in 68 cases of CC specimens and 38 non-cancerous cervical epithelia were examined by tissue microarray-based immunohistochemical staining. The results revealed that HeLa and SiHa cells treated by 100μM resveratrol showed extensive apoptosis, accompanied with suppression of STAT3, Notch and Wnt activations. Growth inhibition and apoptosis were found in HeLa and SiHa populations treated by AG490, a STAT3/JAK3 inhibitor but not the ones treated by Notch inhibitor L-685,458 or by Wnt inhibitor XAV-939. Immunohistochemical staining performed on the tissue microarrays showed that the frequencies of Notch1, Notch2, Hes1, Wnt2, Wnt5a and p-STAT3 detection as well as β-catenin nuclear translocation in CC samples were significantly higher than that of noncancerous group (p<0.01), while the expression rate of PIAS3 was remarkably low in cancer samples (p<0.01). Our results thus demonstrate that STAT3, Wnt and Notch signaling are frequently co-activated in human CC cells and specimens and resveratrol can concurrently inhibit those signaling activations and meanwhile lead cervical squamous cell carcinoma and adenocarcinoma cells to growth arrest and apoptosis. STAT3 signaling is more critical for CC cells and is the major target of resveratrol because selective inhibition of STAT3 rather than Wnt or Notch activation commits SiHa and HeLa cells to apoptosis.
[Show abstract][Hide abstract] ABSTRACT: We proposed an improved approach to measuring regional diffusivity dependency with diffusion MRI. Unlike the original approach, the improved metric can detect all types of regional dependencies. Systematical comparison was done.
2014 IEEE International Symposium on Biomedical Imaging, Beijing; 04/2014