[Show abstract][Hide abstract] ABSTRACT: It is generally acknowledged that drug dependence is connected with abnormal functional organization in the individual’s brain. The present study aimed to identify the anterior cingulate cortex (ACC) abnormality with the cerebral networks involved in betel quid dependence (BQD) by resting-state functional connectivity (rsFC) using functional magnetic resonance imaging (fMRI).
With fMRI data measured from 33 resting-state BQD individuals and 32 non-addicted and age-, sex-, education-matched healthy controls, we inquired into the BQD-related changes in FC between the regions of ACC with the whole brain involved in BQD individuals using a region of interest vised method, and to identify the relation of the alteration with the severity of BQD and duration.
Compared to controls, the BQD group showed increased connectivity from ACC to the regions of the reward network (brainstem including midbrain regions such as the ventral tegmental area and pons, caudate, thalamus) and cerebellum. Decreased connectivity was observed in the BQD group in regions from ACC to the default mode network (medial prefrontal cortex and precuneus) and para Hippocampal/hypothalamus. Specifically, the BQD scale was positively correlated with increased FC of right ACC to left thalamus and left ACC to pons; the durations were negatively correlated with FC of right ACC to left precuneus.
These disturbances in rsFC from ACC to the reward network and DMN revealed by fMRI may have a key function in providing insights into the neurological pathophysiology underlying BQD-associated executive dysfunction and disinhibition. These findings may contribute to our better understanding of the mechanisms underlying BQD.
Preview · Article · Dec 2016 · Journal of Translational Medicine
[Show abstract][Hide abstract] ABSTRACT: The integration of diagnosis and therapy into one nanoplatform, known as theranostics, has attracted increasing attention in the biomedical areas. Herein, we firstly present a cancer cell targeting imaging and drug delivery system based on engineered thioether-bridged periodic mesoporous organosilica nanoparticles (PMOs). The PMOs are stably and selectively conjugated with near-infrared fluorescence (NIRF) dye Cyanine 5.5 (Cy5.5) and anti-Her2 affibody on the outer surfaces to endow them with excellent NIRF imaging and cancer targeting properties. Also, taking the advantage of the thioether-group-incorporated mesopores, the release of chemotherapy drug doxorubicin (DOX) loaded in the PMOs is responsive to the tumor-related molecule glutathione (GSH). The drug release percentage reaches 84.8 % in 10 mM of GSH solution within 24 h, which is more than two-fold higher than that without GSH. In addition, the drug release also exhibits pH-responsive, which reaches 53.6 % at pH 5 and 31.7 % at pH 7.4 within 24 h. Confocal laser scanning microscopy and flow cytometry analysis demonstrate that the PMOs-based theranostic platforms can efficiently target to and enter Her2 positive tumor cells. Thus, the smart imaging and drug delivery nanoplatforms induce high tumor cell growth inhibition. Meanwhile, the Cy5.5 conjugated PMOs perform great NIRF imaging ability, which could monitor the intracellular distribution, delivery and release of the chemotherapy drug. In addition, cell viability and histological assessments show the engineered PMOs have good biocompatibility, further encouraging the following biomedical applications. Over all, the systemically engineered PMOs can serve as a novel cancer cell targeting imaging and drug delivery platform with NIRF imaging, GSH and pH dual-responsive drug release, and high tumor cell targeting ability.
No preview · Article · Jan 2016 · ACS Applied Materials & Interfaces
[Show abstract][Hide abstract] ABSTRACT: Multidrug resistance (MDR) of cancers is still a major challenge, and it is very important to develop visualized nanoprobes for the diagnosis and treatment of drug resistant cancers. In this work, we developed a multifunctional delivery system based on DOX-encapsulated NaYF4:Yb/Er@NaGdF4 yolk-shell nanostructures for simultaneous dual-modal imaging and enhanced chemotherapy in drug resistant breast cancer. Using the large pore volume of the nanostructure, the delivery system had a high loading efficiency and excellent stability. Also, an in vitro and in vivo toxicity study showed the good biocompatibility of the as-prepared yolk-shell nanomaterials. Moreover, by nanocarrier delivery, the uptake of DOX could be greatly increased in drug resistant MCF-7/ADR cells. Compared with free DOX, the as-prepared delivery system enhanced the chemotherapy efficacy against MCF-7/ADR cells, indicating the excellent capability for overcoming MDR. Furthermore, core-shell NaYF4:Yb/Er@NaGdF4 improved the upconversion luminescence (UCL) performance, and the designed delivery system could also be applied for simultaneous UCL and magnetic resonance (MR) imaging, which could be a good candidate as a dual-modal imaging nanoprobe. Therefore, we developed a multifunctional yolk-shell delivery system, which could have potential applications as a visualized theranostic nanoprobe to overcome MDR in breast cancer.
[Show abstract][Hide abstract] ABSTRACT: Personality dimension extraversion describes individual differences in social behaviour and socio-emotional functioning. The intrinsic functional connectivity patterns of the brain are reportedly associated with extraversion. However, whether or not extraversion is associated with functional hubs warrants clarification. Functional hubs are involved in the rapid integration of neural processing, and their dysfunction contributes to the development of neuropsychiatric disorders. In this study, we employed the functional connectivity density (FCD) method for the first time to distinguish the energy-efficient hubs associated with extraversion. The resting-state functional magnetic resonance imaging data of 71 healthy subjects were used in the analysis. Short-range FCD was positively correlated with extraversion in the left cuneus, revealing a link between the local functional activity of this region and extraversion in risk-taking. Long-range FCD was negatively correlated with extraversion in the right superior frontal gyrus and the inferior frontal gyrus. Seed-based resting-state functional connectivity (RSFC) analyses revealed that a decreased long-range FCD in individuals with high extraversion scores showed a low long-range functional connectivity pattern between the medial and dorsolateral prefrontal cortex, middle temporal gyrus, and anterior cingulate cortex. This result suggests that decreased RSFC patterns are responsible for self-esteem, self-evaluation, and inhibitory behaviour system that account for the modulation and shaping of extraversion. Overall, our results emphasize specific brain hubs, and reveal long-range functional connections in relation to extraversion, thereby providing a neurobiological basis of extraversion.
No preview · Article · Nov 2015 · Journal of Neuropsychology
[Show abstract][Hide abstract] ABSTRACT: Background:
Early neurological deterioration (END) is an important factor associated with worse clinical outcome in minor strokes. Early magnetic resonance imaging (MRI) findings can provide better sensitivity to delineate stroke pathophysiology and have diagnostic value associated with causative mechanisms. The aim of this study was to investigate the relationship between early MRI finding and the presence of END in minor stroke patients with lesions in the middle cerebral artery (MCA) territory.
Consecutive MCA minor stroke patients who were admitted to our center within 24 hours of symptom onset were included in this study. All patients underwent MRI within 24 hours of admission. We analyzed baseline characteristics, infarction patterns, and treatment algorithms. The correlation between early MRI findings and END, defined as National Institutes of Health Stroke Scale score increasing more than 2 points during 72 hours after admission, was also determined.
Across 211 patients meeting entry criteria between January 2010 and December 2013, internal border-zone (IBZ) infarcts on early MRI scan were observed in 23 of 65 patients with END (35.4%) and in 18 of 146 patients without END (12.3%, P < .001). Patients with IBZ infarcts were found to have more hyperlipidemia, less perforating artery infarcts, more pial artery infarcts, more cortical border-zone infarcts and more ipsilateral large arterial stenosis. Logistic regression analysis revealed that IBZ infarct was independently associated with END after adjustment for other factors (odds ratio, 2.50; 95% confidence interval, 1.09-5.74; P = .031).
Early MRI patterns of IBZ infarction are associated with END in minor stroke patients with acute infarcts of the MCA territory.
No preview · Article · Nov 2015 · Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association
[Show abstract][Hide abstract] ABSTRACT: Drug resistance is a major barrier that limits the effectiveness of chemotherapies against breast cancer. Here, gold nanoparticles (GNPs) characterized by good dispersivity, high stability, low cytotoxicity, and simple synthesis were developed to deliver small interfering RNA (siRNA) against PLK1 (PLK1-siRNA) and overcome the drug resistance of breast cancer cells. Compared with the commonly used Lipofectamine 2000, GNPs showed higher PLK1-siRNA delivery efficiency and resulted in the remarkable gene silencing of
in drug resistance breast cancer cells MCF-7/MDR1 with low cytotoxicity
. Moreover, delivery of PLK1-siRNA by GNPs could cause 14.23% apoptosis of MCF-7/MDR1 cells, which was apparently higher than 11.01% apoptosis conducted by Lipofectamine 2000. In addition, GNPs showed strong X-ray attenuation coefficient, indicating the potential theranostic application of this system. Therefore, this study disclosed an important step in the use of GNPs as transfection vector of siRNA that will be of great benefit to gene therapy against drug resistant cancer.
Preview · Article · Oct 2015 · Journal of Nanomaterials
[Show abstract][Hide abstract] ABSTRACT: Magnetic hyperthermia ablation is a new and minimally invasive modality for localized tumor removal. However, an inadequate ablation dosage can leave a residual tumor or cause a variety of complications. In addition, commonly used magnetic nanoparticles can easily escape from the tumor tissue, which presents potential safety problems. In this study, a smart phase transitional and injectable implant based on biocompatible poly lactic-co-glycolic acid (PLGA) implant incorporating magnetic material (Fe powder) and anti-cancer drug [doxorubicin (DOX)] was developed. The magnetic-induced hyperthermia and release efficiency of DOX was evaluated in vitro. Drug release can be controlled under external alternating current magnetic field (AMF). The results of the in vivo tumor therapeutic efficacy showed that when exposed to external AMF, this smart injectable DOX/PLGA-Fe implant could converse magnetic energy into heat and accelerate the release of DOX, which leads to increasing the temperature to achieve tumor coagulative necrosis and accelerating the release of DOX to enhance residual tumor apoptosis. Furthermore, there was no leakage of magnetic material, as demonstrated using real-time ultrasound (US) and computerized tomography (CT) imaging, realizing the guidance and monitoring of tumor therapy. In conclusion, this smart phase transitional and injectable implant DOX/PLGA-Fe has the ability to improve the efficiency of this newly developed minimally invasive magnetic ablation of tumor treatment technique, and will provide a new avenue of developing minimally invasive synergistic tumor therapy.
No preview · Article · Oct 2015 · Acta biomaterialia
[Show abstract][Hide abstract] ABSTRACT: To identify the distinct pattern of anatomical network reorganization in surgically refractory mesial temporal lobe epilepsy (MTLE) patients using a longitudinal design. We collected longitudinal diffusion-weighted images of 19 MTLE patients before and after anterior temporal lobectomy. Patients were classified as seizure-free (SF) or nonseizure-free (NSF) at least 1 year after surgery. We constructed whole-brain anatomical networks derived from white matter tractography and evaluated network connectivity measures by graph theoretical analysis. The reorganization trajectories of network measures in SF and NSF patients were investigated by two-way mixed analysis of variance, with factors “group” (SF vs NSF) and “treatment” (presurgery vs postsurgery). Widespread brain structures showed opposite reorganization trajectories in FS and NSF groups (interaction effect). Most of them showed group difference before surgery and then converge after surgery, suggesting that surgery remodeled these structures into a similar status. Conversly, contralateral amygdala-planum-temporale and thalamic-parietal tracts showed higher connectivity strength in NSF than in SF patients after surgery, indicating maladaptive neuroplastic responses to surgery in NSF patients. Our findings suggest that surgical outcomes are associated not only with the preoperative pattern of anatomical connectivity, but also with connectome reconfiguration following surgery. The reorganization of contralateral temporal lobe and corticothalamic tracts may be particularly important for seizure control in MTLE.
[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: Background:
Recent research suggests that variability in brain signal provides important information about brain function in health and disease. However, it is unknown whether blood oxygen level-dependent (BOLD) signal variability is altered in post-traumatic stress disorder (PTSD). We aimed to identify the BOLD signal variability changes of PTSD patients during symptom provocation and compare the brain patterns of BOLD signal variability with those of brain activation.
Twelve PTSD patients and 14 age-matched controls, who all experienced a mining accident, underwent clinical assessment as well as fMRI scanning while viewing trauma-related and neutral pictures. BOLD signal variability and brain activation were respectively examined with standard deviation (SD) and general linear model analysis, and compared between the PTSD and control groups. Multiple regression analyses were conducted to explore the association between PTSD symptom severity and these two brain measures across all subjects as well as in the PTSD group.
PTSD patients showed increased activation in the middle occipital gyrus compared with controls, and an inverse correlation was found between PTSD symptom severity and brain activation in the hippocampus and anterior cingulate cortex/medial prefrontal cortex. Brain variability analysis revealed increased SD in the insula, anterior cingulate cortex/medial prefrontal cortex, and vermis, and decreased SD in the parahippocapal gyrus, dorsolateral prefrontal cortex, somatosensory cortex, and striatum. Importantly, SD alterations in several regions were found in both traumatic and neutral conditions and were stratified by PTSD symptom severity.
BOLD signal variability may be a reliable and sensitive biomarker of PTSD, and combining brain activation and brain variability analysis may provide complementary insight into the neural basis of this disorder.
Preview · Article · Aug 2015 · Neuropsychiatric Disease and Treatment
[Show abstract][Hide abstract] ABSTRACT: Recurrently and abnormally hypersynchronous discharge is a striking feature of idiopathic generalized epilepsy (IGE). Resting-state functional magnetic resonance imaging has revealed aberrant spontaneous brain synchronization, predominately in low-frequency range (<0.1 Hz), in individuals with IGE. Little is known, however, about these changes in local synchronization across different frequency bands. We examined alterations to frequency-specific local synchronization in terms of spontaneous blood oxygen level-dependent (BOLD) fluctuations across 5 bands, spanning 0 to 0.25 Hz. Specifically, we compared brain activity in a large cohort of IGE patients (n = 86) to age- and sex-matched normal controls (n = 86). IGE patients showed decreased local synchronization in low frequency (<0.073 Hz), primarily in the default mode network (DMN). IGE patients also exhibited increased local synchronization in high-frequency (>0.073 Hz) in a "conscious perception network," which is anchored by the pregenual and dorsal anterior cingulate cortex, as well as the bilateral insular cortices, possibly contributing to impaired consciousness. Furthermore, we found frequency-specific alternating local synchronization in the posterior portion of the DMN relative to the anterior part, suggesting an interaction between the disease and frequency bands. Importantly, the aberrant high-frequency local synchronization in the middle cingulate cortex was associated with disease duration, thus linking BOLD frequency changes to disease severity. These findings provide an overview of frequency-specific local synchronization of BOLD fluctuations, and may be helpful in uncovering abnormal synchronous neuronal activity in patients with IGE at specific frequency bands.
[Show abstract][Hide abstract] ABSTRACT: Noble-metal nanomaterials were widely investigated as theranostic systems for surface enhanced Raman scattering (SERS) imaging, and also for photothermal therapy (PTT) of cancers. However, it was still a major challenge to explore multifunctional nanoprobes with high performance, high stability, and low toxicity. In this work, Raman reporter (DTTC)-coupled Agcore@Aushell nanostars (Ag@Au-DTTC) were synthesized and investigated for in vivo improved SERS imaging and near-infrared (NIR)-triggered PTT of breast cancers. By the two-step coupling of DTTC, the SERS signal was improved obviously, and the cytotoxicity of nanoparticles was also decreased by coating Au nanostars onto Ag nanoparticles. The as-prepared Ag@Au-DTTC nanostars showed high photostability and excellent photothermal performance, in which the photothermal conversion efficiency was up to 79.01% under the irradiation of an 808 nm laser. The in vitro and in vivo SERS measurements of Ag@Au-DTTC nanostars showed that the many sharp and narrow Raman peaks located at 508, 782, 844, 1135, 1242, 1331, 1464, 1510, and 1580 cm(-1) could be obviously observed in MCF-7 cells and in MCF-7 tumor-bearing nude mice, compared with that in pure DTTC. In 14-day treatments, the tumor volume of MCF-7 tumor-bearing nude mice injected with Ag@Au-DTTC nanostars and irradiated by an 808 nm laser almost disappeared. This study demonstrated that the as-prepared Ag@Au-DTTC nanostars could be excellent multifunctional agents for improved SERS imaging and NIR-triggered PTT of breast cancers with low risk.
[Show abstract][Hide abstract] ABSTRACT: The synthesis of well-defined and complex hollow structures through a simple method is still a major challenge. In this work, a facile and controllable "multi-interface transformation" approach for preparation of monodisperse multi-shelled periodic mesoporous organosilica (PMO) hollow spheres has been established by a one-step hydrothermal treatment of successively-grown organosilica particles. The multi-shelled PMO hollow spheres have inorganic-organic hybrid frameworks, controllable number (1-4) of shells, high surface area (~ 805 m2/g), accessible ordered mesochannels (~ 3.2 nm), large pore volume (1.0 cm3/g), uniform and tunable diameter (300-550 nm), chamber size (4-54 nm), and shell thickness (10-30 nm). In addition, various organic groups (alkyl, aromatic, or/and heteroelement fragments) are successfully incorporated into the multi-shelled PMO hollow spheres by successively adding different bridged organosilica precursors. Notably, the distribution of different kind of organic groups in the multi-shelled PMO hollow spheres can be precisely controlled, showing great potential for future applications. We propose that the formation of the multi-shelled PMO hollow structures is ascribed to the creation of multiple high cross-linking organosilica interfaces, providing a new and interesting fundamental principle for PMO materials. Due to their unique structure and frameworks, the triple-shelled ethane-bridged PMO hollow spheres were successfully loaded with anti-cancer drug doxorubicin and perﬂuoropentane (PFP) gas, which present excellent effects in killing of cancer cells and ultrasound imaging. It is expected that the multi-interface transformation strategy provides a simple, controllable, versatile, and template-free method for preparation of various multifunctional PMOs for different applications.
Full-text · Article · Jun 2015 · Journal of the American Chemical Society
[Show abstract][Hide abstract] ABSTRACT: Betel quid dependence (BQD) patients have a cluster of cognitive, behavioral, and physiological symptoms which are associated with structural abnormalities in brain gray matter. However, so far there have neither been brain structural studies investigating the alterations related to BQD, nor studies assessing the brain structural changes with clinical indexes.
65 subjects were recruited including 33 'pure' BQD patients and another 32 gender and age matched in the control group. T1 structural voxel-based morphometry (VBM) was performed to investigate the gray matter (GM) volume alterations. In BQD patients, Pearson correlation analysis was performed to investigate the association between GM segmentations and clinical indexes, including BQD scores, illness duration, SAS and SDS.
Compared with that of the control group, the VBM of GM in BQD patients exhibited a significant decrease in volume (All P values > 0.05, AlphaSim correction) in the midbrain, right anterior cingulate cortex (rACC), bilateral dorsolateral prefrontal cortex (dlPFC) and right superior temporal gyrus (STG), and also there was an increased volume in right hippocampal and right precuneus. GM volumes of the left DLPFC and right rACC showed negative correlation with the duration of BQD, meanwhile, midbrain volumes were negative correlating with BQD scores (All P values > 0.05).
Our findings suggested that brain structural changes were present in BQD patients, and those may be a neurobiological basis for BQD patients. These findings may provide a new insight into the pathogenesis of BQD. Also, VBM is an effective tool for in vivo investigation of gray matter alterations in patients with BQD.
No preview · Article · Apr 2015 · American Journal of Translational Research
[Show abstract][Hide abstract] ABSTRACT: Multifunctional gold nanostructures possessing the abilities of photothermal therapy (PTT) effect and high-quality X-ray/computed tomography (CT) imaging have drawn much attention in recent research. In particular, the developing of more effective PTT to cancer is always an attractive focus for further clinical need. Since the intracellular concentration is critical for the photothermal therapeutic efficacy of gold nanostructures, we dedicatedly decorated gold nanostructures with positively charged polyethylene glycol (PEG) to boost their degree of cell uptake. Herein gold nanostars (GNSs) were designed and decorated with amine-terminated PEG (GNS-PEG-NH2) and methoxy-terminated PEG (GNS-mPEG). PEGylated GNSs showed good dispersivity, high stability and low cytotoxicity. Moreover, compared with GNS-mPEG, GNS-PEG-NH2 exhibited superior thermal therapeutic efficacy to breast tumor cells due to their higher cellular uptake. Measurement of the X-ray absorption coefficient revealed that the attenuation of GNS-PEG-NH2 was about 3.6 fold higher than commercial CT contrast agent iodixanol at the concentration of 25 mg/L. Importantly, GNS-PEG-NH2 also exhibited effective tumor therapeutic efficacy in vivo, and the tumor sites injected with GNS-PEG-NH2 showed high contrast X-ray/CT imaging. And most of the injected GNS-PEG-NH2 was cleared from tumors 15 days post-injection, indicating the rapid clearance and minimal toxicity of GNS-PEG-NH2. Such PEGylated GNSs integrating high distinguishable contrast imaging-guided enhanced PTT therapy might bring opportunities for future cancer theranostic development.