[Show abstract][Hide abstract] ABSTRACT: Efforts to identify meaningful functional imaging-based biomarkers are limited by the ability to reliably characterize inter-individual differences in human brain function. Although a growing number of connectomics-based measures are reported to have moderate to high test-retest reliability, the variability in data acquisition, experimental designs, and analytic methods precludes the ability to generalize results. The Consortium for Reliability and Reproducibility (CoRR) is working to address this challenge and establish test-retest reliability as a minimum standard for methods development in functional connectomics. Specifically, CoRR has aggregated 1,629 typical individuals’ resting state fMRI (rfMRI) data (5,093 rfMRI scans) from 18 international sites, and is openly sharing them via the International Data-sharing Neuroimaging Initiative (INDI). To allow researchers to generate various estimates of reliability and reproducibility, a variety of data acquisition procedures and experimental designs are included. Similarly, to enable users to assess the impact of commonly encountered artifacts (for example, motion) on characterizations of inter-individual variation, datasets of varying quality are included.
[Show abstract][Hide abstract] ABSTRACT: Mindfulness can be viewed as an important dispositional characteristic that reflects the tendency to be mindful in daily life, which is beneficial for improving individuals' both hedonic and eudaimonic well-being. However, no study to date has examined the brain regions involved in individual differences in dispositional mindfulness during the resting state and its relation with hedonic and eudaimonic well-being. To investigate this issue, the present study employed resting-state functional magnetic resonance imaging (rs-fMRI) to evaluate the regional homogeneity (ReHo) that measures the local synchronization of spontaneous brain activity in a large sample. We found that dispositional mindfulness was positively associated with the ReHo in the left orbitofrontal cortex (OFC), left parahippocampal gyrus (PHG) and right insula implicated in emotion processing, body awareness and self-referential processing, and negatively associated with the ReHo in right inferior frontal gyrus (IFG) implicated in response inhibition and attentional control. Furthermore, we found different neural associations with hedonic (i.e., positive and negative affect) and eudaimonic well-being (i.e., the meaningful and purposeful life). Specifically, the ReHo in the IFG predicted eudaimonic well-being whereas the OFC predicted positive affect, both of which were mediated by dispositional mindfulness. Taken together, our study provides the first evidence for linking individual differences in dispositional mindfulness to spontaneous brain activity and demonstrates that dispositional mindfulness engages multiple brain mechanisms that differentially influence hedonic and eudaimonic well-being.
Social neuroscience 09/2015; DOI:10.1080/17470919.2015.1092469 · 2.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Deficits in social communication are one of the behavioral signatures of autism spectrum disorder (ASD). Because faces are arguably the most important social stimuli that we encounter in everyday life, investigating the ability of individuals with ASD to process faces is thought to be important for understanding the nature of ASD. However, although a considerable body of evidence suggests that ASD individuals show specific impairments in face processing, a significant number of studies argue otherwise. Through a literature review, we found that this controversy is largely attributable to the different face tests used across different studies. Therefore, a more reliable and valid face test is needed. To this end, we performed a meta-analysis on data gleaned from a variety of face tests conducted on individuals with developmental prosopagnosia (DP) who suffer a selective deficit in face processing. Based on this meta-analysis, we selected an old/new face recognition test that relies on face memory as a standard diagnostic test for measuring specific face processing deficits. This test not only reliably reflects DP individuals' subjective experiences with faces in their daily lives, but also effectively differentiates deficits in face processing from deficits caused by other general problems. In addition, DP individuals' performance in this test predicts their performance in a variety of face tests that examine specific components of face processing (e.g., holistic processing of faces). Finally, this test can be easily administrated and is not overly sensitive to prior knowledge. In summary, this test can be used to evaluate face-processing ability, and it helped to resolve the controversy whether individuals with ASD exhibit face-processing deficits.
Science China. Life sciences 09/2015; DOI:10.1007/s11427-012-4337-4 · 1.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Resveratrol exerts inhibitory effects on ovarian cancer cells, while its underlying mechanism and critical molecular target(s) have been lesser known. Activations of Wnt, Notch and STAT3 signaling are frequent in ovarian cancers/OCs and supposed to be important for OC formation and progression, while the impacts of resveratrol on these signaling pathways in OC cells remain obscure.
In this study, two human ovarian cancer cell lines, OVCAR-3 and CAOV-3, were treated by 120 μM resveratrol and their responses to the treatment and the statuses of Wnt, Notch and STAT3 signaling in them were analyzed by multiple experimental approaches. Selective inhibitors of Wnt, Notch or STAT3 signaling were employed to treat OVCAR-3 and CAOV-3 cells to elucidate the significance of individual signaling pathways for ovarian cancers.
The results demonstrated distinct inhibitory effects of resveratrol on human ovarian cancer cells in terms of remarkable G1 phase accumulation, increased apoptosis fraction and concurrent suppression of Wnt, Notch and STAT3 signaling as well as their downstream cancer-related gene expression. Treatments with Wnt, Notch or STAT3 selective inhibitor revealed that only AG490, a JAK-specific inhibitor, inhibits OVCAR-3 and CAOV-3 cells in the extent as similar as that of resveratrol.
Our results suggest the significance of STAT3 activation in the maintenance and survival of ovarian cancer cells. The activated STAT3 signaling is the critical molecular target of resveratrol. Resveratrol would be a promising candidate in the management of ovarian cancers, especially the ones with resistance to conventional therapeutic agents.
Journal of Ovarian Research 04/2015; 8(1):25. DOI:10.1186/s13048-015-0152-4 · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Glioblastomas respond differently to all-trans retinoic acid (RA) for unknown reasons. Because CRABP-II and FABP5 mediate RA intracellular signaling respectively and lead to distinct biological consequences, their expression patterns in different grades of astrocytomas and the glioblastoma cells lines LN18, LN428 and U251 were examined to identify potential correlations with RA sensitivities. The response of glioblastoma cells to RA, decitabine or the FABP5 competitive inhibitor, BMS309403, was analyzed. CRABP-II and FABP5 were expressed to varying degrees by the 84-astrocytoma cases examined. Treatment of LN428, U251 and LN18 cells with RA failed to suppress their growth; however, U251 proliferation was inhibited by decitabine. The combination of decitabine and RA suppressed the growth of all three cell lines and induced significant apoptosis of LN428 and U251 cells. Both CRABP-II and FABP5 were transcribed in the three cell lines but FABP5 proteins were undetectable in U251 cells. The ratio of CRABP-II to FABP5 was not altered after RA, decitabine or RA and decitabine treatment and the resistance of cells to RA was not reversed by BMS309403 treatment. In conclusion, CRABP-II and FABP5 expression patterns are neither related to the tumor grades nor correlated with RA sensitivity. Additional molecular factors may be present that determines the sensitivity of glioblastoma cells to RA. Dicitabine may improve the sensitivity of glioblastoma cells to RA, however, its underlying mechanism and its in vivo feasibility need to be investigated.
[Show abstract][Hide abstract] ABSTRACT: Resveratrol possesses anti-tumor activities against central nervous system (CNS) tumors in vitro but has not yet been used clinically due to its low bioavailability, particularly in the CNS. This study thus aimed to elucidate brain bioavailability of trans-resveratrol by monitoring brain concentrations and dwell times following administration of resveratrol through intragastric, intraperitoneal, external carotid artery/ECA and intrathecal routes. In parallel, we evaluated the biological responses of rat RG2 glioblastoma cells as well as RG2-formed rat intracranial glioblastomas treated with resveratrol via intrathecal administration. The results revealed that resveratrol was detected in rat brains except when administered systemically. Intrathecal administration of reseveratrol led to abundant apoptotic foci and increased staining of the autophagy proteins, LC-3 and Beclin-1 and shrinkage of the intracranial tumors. In conclusion, the BBB penetrability of resveratrol is remarkably increased by intracthecal administration. Regular short-term resveratrol treatments suppress growth and enhance autophagic and apoptotic activities of rat RG2 glioblastoma cells in vitro and in vivo. Therefore, intrathecal administration of resveratrol could be an optimal intervention approach in the adjuvant management of brain malignancies.
Journal of the American Society for Experimental NeuroTherapeutics 01/2015; 12(2). DOI:10.1007/s13311-014-0334-6 · 5.05 Impact Factor
[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.
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.
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.
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 this 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. 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 precuneus volume
and global life satisfaction. Taken together, we provide the first evidence for the structural neural basis of life satisfaction,
and highlight that self-esteem might play a crucial role in cultivating an individual’s life satisfaction.
Social Cognitive and Affective Neuroscience 11/2014; 10(7). DOI:10.1093/scan/nsu144 · 7.37 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.