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1.
CNS Neurosci Ther ; 30(2): e14345, 2024 02.
Article in English | MEDLINE | ID: mdl-37424152

ABSTRACT

OBJECTIVE: Cognitive deficit is common in patients with temporal lobe epilepsy (TLE). Here, we aimed to investigate the modular architecture of functional networks associated with distinct cognitive states in TLE patients together with the role of the thalamus in modular networks. METHODS: Resting-state functional magnetic resonance imaging scans were acquired from 53 TLE patients and 37 matched healthy controls. All patients received the Montreal Cognitive Assessment test and accordingly were divided into TLE patients with normal cognition (TLE-CN, n = 35) and TLE patients with cognitive impairment (TLE-CI, n = 18) groups. The modular properties of functional networks were calculated and compared including global modularity Q, modular segregation index, intramodular connections, and intermodular connections. Thalamic subdivisions corresponding to the modular networks were generated by applying a 'winner-take-all' strategy before analyzing the modular properties (participation coefficient and within-module degree z-score) of each thalamic subdivision to assess the contribution of the thalamus to modular functional networks. Relationships between network properties and cognitive performance were then further explored. RESULTS: Both TLE-CN and TLE-CI patients showed lower global modularity, as well as lower modular segregation index values for the ventral attention network and the default mode network. However, different patterns of intramodular and intermodular connections existed for different cognitive states. In addition, both TLE-CN and TLE-CI patients exhibited anomalous modular properties of functional thalamic subdivisions, with TLE-CI patients presenting a broader range of abnormalities. Cognitive performance in TLE-CI patients was not related to the modular properties of functional network but rather to the modular properties of functional thalamic subdivisions. CONCLUSIONS: The thalamus plays a prominent role in modular networks and potentially represents a key neural mechanism underlying cognitive impairment in TLE.


Subject(s)
Cognition Disorders , Cognitive Dysfunction , Epilepsy, Temporal Lobe , Humans , Epilepsy, Temporal Lobe/complications , Epilepsy, Temporal Lobe/diagnostic imaging , Epilepsy, Temporal Lobe/pathology , Thalamus/diagnostic imaging , Magnetic Resonance Imaging/methods , Cognitive Dysfunction/pathology , Cognition Disorders/pathology
2.
Front Neurosci ; 17: 1277690, 2023.
Article in English | MEDLINE | ID: mdl-38027476

ABSTRACT

Background: Individuals suffering from short-term insomnia disorder (SID) experience difficulties in falling or staying asleep, often leading to daytime fatigue and impaired concentration. However, the underlying mechanisms of SID remain unclear. This study aims to investigate the alterations in brain activation patterns and functional connectivity in patients with SID. Methods: The study enrolled a total of 31 adults diagnosed with SID and 31 healthy controls (HC). Functional near-infrared spectroscopy (fNIRS) was utilized to assess the concentrations of oxyhemoglobin (Oxy-Hb) and functional connectivity in the prefrontal cortex of each participant while performing the verbal fluency test (VFT) task. Results: In the VFT task, no significant difference was found between the SID group and the HC group in terms of integral values, centroid values, and mean Oxy-Hb variations. These findings suggest that both groups exhibit similar hemodynamic responses. However, the functional connectivity analysis revealed significant differences in inter-channel connectivity strength between the two groups. The SID group showed significantly lower average inter-channel connectivity strength compared to the HC group. Moreover, six channel pairs (right frontopolar cortex - left frontopolar cortex, left orbitofrontal cortex - left temporopolar cortex, left temporopolar cortex - left frontopolar cortex, left frontopolar cortex-Ch38, left frontopolar cortex - right pre-motor and supplementary motor cortex, and left frontopolar cortex - right dorsolateral prefrontal cortex) exhibited significantly higher connectivity strength in the HC group compared to the SID group (FDR corrected, p < 0.05). Specifically, channel 27 exhibited the highest frequency of significant connectivity across different channel pairs, occurring five times in total. The channel pair Ch27-Ch39, representing left frontopolar cortex and right dorsolateral prefrontal cortex, exhibited a negative correlation with PSQI scores (r = -0.422, p = 0.018). Conclusion: Our findings suggest that patients with SID may exhibit altered brain connectivity during the VFT task, as measured by fNIRS. These results provide valuable insights into the functional brain differences associated with SID. Further research is needed to validate and expand upon these findings.

3.
Neuroradiology ; 64(10): 2021-2030, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35618843

ABSTRACT

PURPOSE: Previous studies have discovered different neuroimaging features in anti-NMDAR encephalitis associated with cognitive dysfunction. However, it is unknown whether there is a correlation between abnormal homotopic connectivity and cognitive impairment in anti-NMDAR encephalitis. We aim to explore the homotopic connectivity patterns of patients with anti-NMDAR encephalitis and their associations with clinical characteristics. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) was performed on 29 patients with anti-NMDAR encephalitis and 26 healthy controls (HCs). Voxel-mirrored homotopic connectivity (VMHC) and multivariate pattern analysis (MVPA) were applied to analyze the imaging data. A correlation was also performed between aberrant brain regions and clinical parameters. RESULTS: Compared to HCs, the performance of alertness in the patient group was typically worse (p < 0.05). A significant decrease in VMHC was observed in many regions of the patients in comparison to HCs, including the cerebellar 6, para-hippocampal gyrus, insula, precuneus, and middle frontal gyrus (p < 0.001). The insula and middle frontal gyrus were found to show positive correlations with alertness. The MVPA method achieved a classification accuracy of 74.55% with a sensitivity of 82.76% and a specificity of 65.38% in discriminating patients from HCs. CONCLUSION: Our findings indicate that interhemispheric functional imbalance may play a significant role in the pathophysiology of cognitive dysfunction in anti-NMDAR encephalitis. The MVPA results suggest that abnormal VMHC may play a crucial role in the identification of patients with anti-NMDAR encephalitis from HCs.


Subject(s)
Anti-N-Methyl-D-Aspartate Receptor Encephalitis , Cognitive Dysfunction , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/diagnostic imaging , Brain/diagnostic imaging , Humans , Magnetic Resonance Imaging/methods , Neuroimaging
4.
Eur J Neurol ; 29(1): 277-285, 2022 01.
Article in English | MEDLINE | ID: mdl-34546615

ABSTRACT

BACKGROUND AND PURPOSE: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is characterized by a range of cognitive impairments, especially in executive function. Our study aims to identify the abnormal regional homogeneity (ReHo) in anti-NMDAR encephalitis patients and its relationship with the executive function. METHODS: Forty patients and 42 healthy volunteers undertook an Attention Network Test and a resting-state functional magnetic resonance imaging scan. ReHo analysis was performed to investigate the neuronal activity synchronization in all subjects. Based on ReHo analysis, a multivariate pattern analysis (MVPA) was carried out to identify the brain regions that differed the most between the two groups. RESULTS: Compared to controls, the patients had higher executive control scores (p < 0.05). The patients presented reduced ReHo values in the bilateral posterior cerebellar lobe, anterior cerebellar lobe, midbrain, bilateral caudate nucleus, right superior frontal gyrus, right middle temporal gyrus, bilateral inferior parietal lobule and the left middle frontal gyrus. The ReHo values of the bilateral inferior parietal lobule in patients were found to be negatively associated with executive control scores. The classification of patients and controls using MVPA had an accuracy of 76.83%, a sensitivity of 82.50%, a specificity of 71.43% and the area under the curve was 0.83. CONCLUSIONS: Our study provides evidence of abnormal cerebral function in anti-NMDAR encephalitis patients, which may contribute to unveiling the neuropathological mechanisms of anti-NMDAR encephalitis and their influences on executive dysfunction. The MVPA classifier, based on ReHo, is helpful in identifying anti-NMDAR encephalitis patients from healthy controls.


Subject(s)
Anti-N-Methyl-D-Aspartate Receptor Encephalitis , Cognitive Dysfunction , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/complications , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/diagnostic imaging , Brain/pathology , Brain Mapping/methods , Cognitive Dysfunction/complications , Cognitive Dysfunction/etiology , Humans , Magnetic Resonance Imaging/methods
5.
J Neurosci Res ; 99(10): 2688-2705, 2021 10.
Article in English | MEDLINE | ID: mdl-34269468

ABSTRACT

The brain network alterations associated with temporal lobe epilepsy (TLE) progression are still unclear. The purpose of this study was to investigate altered patterns of static and dynamic functional network connectivity (sFNC and dFNC) in TLE with different durations of disease. In this study, 19 TLE patients with a disease duration of ≤5 years (TLE-SD), 24 TLE patients with a disease duration of >5 years (TLE-LD), and 21 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging and attention network test. We used group independent component analysis to determine the target resting-state networks. Sliding window correlation and k-means clustering analysis methods were used to obtain different dFNC states, temporal properties, and temporal variability. We then compared sFNC and dFNC between groups and found that compared with HCs, TLE-SD patients had increased sFNC between the dorsal attention network and sensorimotor network/visual network (VN), but decreased sFNC between the inferior-posterior default mode network and VN. In the strongly connected dFNC state, TLE-SD patients spent more time, had greater mean dwell time, and showed greater inconsistent abnormal network connectivity. There was a significant negative correlation between the temporal variability of auditory network- left fronto-parietal network connectivity and orienting effect. No significant differences in sFNC and dFNC were detected between TLE-LD and HC groups. These findings suggest that the damage and functional brain network abnormalities gradually occur in TLE patients after the onset of epilepsy, which might lead to functional network reorganization and compensatory remodeling as the disease progresses.


Subject(s)
Attention/physiology , Brain/diagnostic imaging , Epilepsy, Temporal Lobe/diagnostic imaging , Magnetic Resonance Imaging/methods , Nerve Net/diagnostic imaging , Adult , Brain/physiopathology , Cross-Sectional Studies , Epilepsy, Temporal Lobe/physiopathology , Female , Humans , Male , Nerve Net/physiopathology , Time Factors , Young Adult
6.
Front Neurosci ; 15: 820641, 2021.
Article in English | MEDLINE | ID: mdl-35126048

ABSTRACT

OBJECTIVE: Temporal lobe epilepsy (TLE) can be conceptualized as a network disease. However, the network characteristics in lateralization remain controversial. METHODS: In this study, resting-state functional MRI scans were acquired from 53 TLE patients [22 with left-side TLE (LTLE) and 31 with right-side TLE (RTLE)] and 37 matched healthy controls. We focused on the characteristics of static and dynamic functional connectivity, including static connectivity patterns and topological properties, as well as temporal properties of the dynamic connectivity state and the variability of the dynamic connectivity and network topological organization. Correlation analyses were conducted between abnormal static and dynamic properties and cognitive performances. RESULTS: The static functional connectivity analysis presented a significantly decreased cortical-cortical connectivity pattern and increased subcortical-cortical connectivity pattern in RTLE. The global-level network in RTLE showed a significant decrease in global efficiency. The dynamic functional connectivity analysis revealed that RTLE patients exhibited aberrant connectivity states, as well as increased variability in the subcortical-cortical connectivity. The global-level network in RTLE revealed increased variance in global efficiency and local efficiency. The static or dynamic functional connectivity in LTLE did not show any significant abnormalities. The altered dynamic properties were associated with worsening cognitive performance in language and conceptual thinking by the TLE patients. CONCLUSION: Our findings demonstrated the presence of abnormalities in the static and dynamic functional connectivity of TLE patients. RTLE patients exhibited more pronounced aberrant connectivity patterns and topological properties, which might represent a mechanism for reconfiguration of brain networks in RTLE patients. These observations extended our understanding of the pathophysiological network mechanisms of TLE.

7.
Stud Health Technol Inform ; 264: 1712-1713, 2019 Aug 21.
Article in English | MEDLINE | ID: mdl-31438306

ABSTRACT

We developed a HeartGuardian app and explored its effects supporting people with CVD on lipid control and medication adherence. Fifty-seven patients were enrolled, 29 in the intervention group and 28 in the control group. The 12-week intervention resulted in a moderate improvement in lipid level and greater improvement in medication adherence (82.14% vs 37.93%, P = 0.001). These outcomes translate into significant differences in occurrence of major adverse cardiac events (28.75% vs 72.43%, P = 0.001).


Subject(s)
Cardiovascular Diseases , Secondary Prevention , Smartphone , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/prevention & control , Humans , Medication Adherence
8.
ACS Omega ; 4(6): 9823-9827, 2019 Jun 30.
Article in English | MEDLINE | ID: mdl-31460072

ABSTRACT

A facile approach was developed to produce MoS2 nanosheets by ultrasound-assisted reflux exfoliation, which was highly efficient for large-scale production and sustainable for environment. The interlayer force of bulk MoS2 was first exhausted in employing LiOH/NaOH solution by reflux and thereafter quickly exfoliated by ultrasound. The lateral size of the as-prepared MoS2 nanosheets with about 2-9 layers became smaller. Definitely, the average friction coefficient and wear scar diameter of 0.08 wt % MoS2-based oil decreased by about 21.87 and 38.09% relative to the base oil, which displayed better antifriction and antiwear performances.

9.
RSC Adv ; 9(30): 17016-17024, 2019 May 29.
Article in English | MEDLINE | ID: mdl-35519880

ABSTRACT

The exfoliation of bulk MoS2 into few layers has attracted considerable attention as 2D nanomaterials in the past decade. We developed a facile approach for producing MoS2 nanosheets by hydrothermal-assisted shearing exfoliation based on organic-free strategy. This original exfoliation was highly efficient for large-scale production and sustainable for the environment. The thickness of the as-exfoliated MoS2 nanosheets was about 4-6 layers, and the lateral size became smaller from hydrothermal processing to shearing. The hydrothermal processing with the participation of ammonium carbonate played an important role in hydrothermal-assisted shearing exfoliation. As a prospective application, the antifriction performance of the as-exfoliated MoS2 nanosheets in oil was evaluated using a ball-on-ball mode. Evidently, the average friction coefficient and wear scar diameter of 0.08 wt% MoS2-based oil dropped to about 20.66% and 47.27% relative to those of the base oil, which exhibited an excellent antifriction and antiwear ability.

10.
Oncotarget ; 9(9): 8629-8641, 2018 Feb 02.
Article in English | MEDLINE | ID: mdl-29492222

ABSTRACT

Caspase-3 is a vital executioner molecule during the apoptotic process. Numerous studies have revealed the close association of caspase-3 expression and breast cancer. Nevertheless, the prognostic value of caspase-3 expression for patients with breast cancer remains uncertain. To thoroughly analyze the prognostic effect of caspase-3 expression on the clinicopathological features and survival of breast cancer, we conducted this meta-analysis. With various search strategies, electronic databases were comprehensively searched. A total of 3091 patients from 21 studies were ultimately obtained. The analysis results indicated that increased expression of caspase-3 had a negative influence on the overall survival (OS) of breast cancer (HR = 1.73, 95%CI 1.12-2.67, P = 0.014). Subgroup analyses based on race revealed that the value of caspase-3 for evaluating patients' OS was more useful in Asian patients (HR = 3.16, 95%CI 1.20-8.15, P = 0.020), and subgroup analyses based on study analytical methods revealed that caspase-3 was a risk factor for breast cancer patients in multivariate overall survival analyses (HR = 1.67, 95%CI 1.02-2.75, P = 0.044). As for the relationship between caspase-3 expression and breast cancer subtype as well as progression, caspase-3 might serve as a risk factor for the progestogen receptor (PR) and human epidermal growth factor receptor-2 (HER-2) subtypes (OR = 1.44, 95%CI 1.09-1.89, P = 0.010; OR = 1.76, 95%CI 1.18-2.62, P = 0.050, respectively) of breast cancer. However, no evidence showed that increased expression of caspase-3 was statistically correlated with tumor differentiation state (low/moderate or high), tumor TNM stage (I-II/III-IV) or lymph node metastasis (-/+). In conclusion, this meta-analysis revealed that increased caspase-3 expression was significantly associated with worse prognosis and two subtypes of breast cancer. More prospective studies are urgently needed to define the prognostic value of caspase-3 expression in patients with breast cancer.

11.
Int J Mol Med ; 41(5): 2813-2831, 2018 May.
Article in English | MEDLINE | ID: mdl-29484429

ABSTRACT

Mounting evidence has shown that miR-23b-3p, which is associated with cell proliferation, invasion, and apoptosis, acts as a biomarker for diagnosis and outcomes in numerous cancers. However, the clinicopathological implication of miR-23b-3p in hepatocellular carcinoma (HCC) remains unclear. Our study evaluated the role of miR-23b-3p in HCC and investigated its potential application as a marker for preliminary diagnosis and therapy in HCC. High-throughput data from the NCBI Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were collected and analyzed. One hundred and one tissue sections of HCC were paired with adjacent non-cancerous HCC as further supplements. miR-23b-3p expression was detected using quantitative real-time PCR. Additionally, the relationship between miR-23b-3p expression and HCC progression and Time-to-recurrence (months) was explored. Ten algorithms were applied to predict the prospective target genes of miR-23b-3p. Next, we conducted bioinformatics analysis for further study. miR-23b-3p expression was pronouncedly decreased in HCC tissues in contrast with their paired adjacent non-cancerous HCC (P<0.001) with RT-qPCR. In total, 405 targets, acquired with consistent prediction from at least five databases, were used for the bioinformatics analysis. According to the Gene Ontology (GO) analysis, all targets were classified into biological processes, cellular components and molecular functions. In the pathway analysis, targets of miR-23b-3p were primarily enriched in the signaling pathways of renal cell carcinoma, hepatitis B and pancreatic cancer (corrected P-value <0.05). In the protein-protein interaction (PPI) network for miR-23b-3p, a total of 8 targets, including SRC, AKT1, EGFR, CTNNB1, BCL2, SMAD3, PTEN and KDM6A, were located in the key nodes with high degree (>35). In conclusion, this study provides impressive illumination of the potential role of miR-23b-3p in HCC tumorigenesis and progression. Furthermore, miR-23b-3p may act as a predictor of HCC and could be a new treatment target.


Subject(s)
Carcinoma, Hepatocellular/genetics , Down-Regulation , Gene Expression Regulation, Neoplastic , Liver Neoplasms/genetics , MicroRNAs/genetics , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/pathology , Disease Progression , Female , Gene Regulatory Networks , Humans , Liver/metabolism , Liver/pathology , Liver Neoplasms/diagnosis , Liver Neoplasms/pathology , Male , Middle Aged , Real-Time Polymerase Chain Reaction , Transcriptome
12.
ACS Omega ; 3(11): 15002-15008, 2018 Nov 30.
Article in English | MEDLINE | ID: mdl-31458166

ABSTRACT

One-dimensional MoS2 nanotubes with the specific surface area of 89.34 m2/g and the average pore size of 2.52 nm were successfully synthesized by the thermolytical approach assisted by halloysite nanotubes. The tribological properties of MoS2 nanotubes with good dispersion in oil were tested with a four-ball wear tester. The tribological testing results indicated that the average friction coefficient and the average wear scar diameter of the 0.08 wt % MoS2-based oil at 25 °C decreased about 39.2 and 35.0%, respectively, compared to those of the 150 SN base oil, indicating that the as-prepared MoS2 nanotubes as a lubricating additive can enhance the tribological performances. Finally, the lubrication mechanism of MoS2 nanotubes was put forward.

13.
Oncotarget ; 8(62): 104960-104980, 2017 Dec 01.
Article in English | MEDLINE | ID: mdl-29285225

ABSTRACT

PURPOSE: The prognostic role of miR-204-5p (previous ID: miR-204) is varied and inconclusive in diverse types of malignant neoplasm. Therefore, the purposes of the study comprehensively explore the overall prognostic role of miR-204-5p based on high-throughput microRNA sequencing data, and to investigate the potential role of miR-204-5p via bioinformatics approaches. MATERIALS AND METHODS: The data of microRNA sequencing and survival were downloaded from The Cancer Genome Atlas (TCGA), and the prognostic value of miR-204-5p was analyzed by using Kaplan-Meier and univariate cox regressions. Then a meta-analysis was conducted with all TCGA data and relevant studies collected from literature. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. The prospective molecular mechanism of miR-204-5p was also assessed at a functional level with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-to-protein interactions (PPI) network. RESULTS: From TCGA data, the prognostic value of miR-204-5p obviously varied among 20 types of cancers. The pooled HR was 0.928 (95% CI: 0.774-1.113, P = 0.386, 6203 cases of malignancies). For the meta-analysis based on 15 studies from literature, the pooled HR was 0.420 (95% CI: 0.306-0.576, P < 0.001, 1783 cases of malignancies) for overall survival (OS). Furthermore, the combined HR from both TCGA and literature was 0.708 (95% CI: 0.600-0.834, P < 0.001, 7986 cases of malignancies). Subgroup analyses revealed that miR-204-5p could act as a prognostic marker in cancers of respiratory system and digestive system. Functional analysis was conducted on genes predicted as targets (n = 2057) after the overlay genes from six out of twelve software were extracted. Two significant KEGG pathways were enriched (hsa04360: Axon guidance and hsa04722: Neurotrophin signaling pathway). PPI network revealed some hub genes/proteins (CDC42, SOS1, PIK3R1, MAPK1, PLCG1, ESR1, MAPK11, and AR). CONCLUSIONS: The current study demonstrates that over-expression of miR-204-5p could be a protective factor for a certain group of cancers. Clinically, the low miR-204-5p level could gain a predictive value for a poor survival in cancers of respiratory system and digestive system. The detailed molecular mechanisms of miR-204-5p remain to be verified.

14.
J Back Musculoskelet Rehabil ; 30(4): 725-733, 2017.
Article in English | MEDLINE | ID: mdl-28282792

ABSTRACT

BACKGROUND: Little is known about the effects of Kinesio taping and therapeutic exercise on correcting forward head posture. OBJECTIVE: To compare Kinesio taping versus therapeutic exercise for forward head posture on static posture, dynamic mobility and functional outcomes. METHODS: Sixty subjects (31 women, 29 men) with forward head postures participated in this study. They were randomly assigned to either one of the three groups: (1) exercise group (n = 20), (2) taping group (n = 20), and (3) control groups (n = 20). The horizontal forward displacement (HFD) between ear lobe and acromion process, upper cervical and lower cervical angle (UCA, LCA), active range of motion (AROM) of cervical spine, and neck disability index (NDI) were measured before and after a 5-week intervention, and a 2-week follow-up. Data were analyzed by means of a mixed design repeated-measures ANOVA. RESULTS: Both taping and exercise groups showed significant improvements in HFD compared with the control group at post-treatment and follow-up. Compared with the control group, the exercise group exhibited significant improvements in the LCA and the side bending AROM at post-treatment. CONCLUSIONS: Both Kinesio taping and therapeutic exercise improve forward head posture after intervention and a 2-week follow-up. The effectiveness of therapeutic exercise is better than taping.


Subject(s)
Athletic Tape , Cervical Vertebrae/physiology , Exercise Therapy , Posture , Adult , Exercise , Female , Humans , Male , Prospective Studies , Range of Motion, Articular , Young Adult
15.
Stud Health Technol Inform ; 245: 268-272, 2017.
Article in English | MEDLINE | ID: mdl-29295096

ABSTRACT

Obstructive Sleep Apnea (OSA) has been proven to increase the risk of high blood pressure, heart attack, stroke, obesity, and diabetes. If people would like to know whether they are suffering from this sleep disorder, they need to go to particular hospital with which a sleep center that could perform polysomnography (PSG); however, for most people, this is not convenient. Consequently, the goal of this study is to develop a convenient, lower priced, and easy-to-use home-based sleep monitoring system. The researchers have developed the "Sleep Healthcare Management System" for OSA patients and healthcare providers. It combines smartphone and wearable devices that can perform real-time sleep monitoring. Healthcare providers could apply their professional knowledge to provide customized feedback via a web application. When the patient is diagnosed with an abnormal sleep health condition, healthcare providers may be able to provide appropriate and timely care.


Subject(s)
Polysomnography , Sleep Apnea, Obstructive , Humans , Obesity , Sleep , Smartphone
16.
J Photochem Photobiol B ; 162: 611-618, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27484966

ABSTRACT

For the first time, the effects of picoplatin on the structure and esterase-like catalytic activity of human serum albumin (HSA) have been investigated by spectroscopic approaches and molecular modeling. The circular dichroism (CD) spectral examinations indicated that the binding of picoplatin with HSA induced a slight decrease of a-helix content of protein and unfolded the constituent polypeptides of the protein. The synchronous fluorescence and three-dimensional fluorescence spectral methods were used to estimate the effect of picoplatin on the micro-environmental changes of the Trp and Tyr residues of HSA, indicating that the micro-environment around the Tyr and Trp residue is partly disturbed by picoplatin. UV-vis absorption spectral result indicated the formation of the ground state complex between picoplatin with HSA. The ANS binding assay indicated the existence of competitive combination of picoplatin and ANS with HSA. The studies on the effects of picoplatin on the binding of HSA with bilirubin and heme showed that picoplatin binding caused a change of angle between two chromophores of bound bilirubin and the binding site of picoplatin does not locate in subdomain IB in HSA that bound with heme. The molecular modeling results showed that picoplatin binds to the connection between domain I and domain II by hydrophobic, hydrogen bonds, and van der Waals forces. In addition, HSA maintains most of its esterase activity in the presence of picoplatin. The investigations on how picoplatin interacts with HSA are important for the understanding of the anticancer mechanism and toxicity of platinum-based anticancer drug.


Subject(s)
Organoplatinum Compounds/metabolism , Serum Albumin/metabolism , Bilirubin/chemistry , Bilirubin/metabolism , Binding Sites , Circular Dichroism , Heme/chemistry , Heme/metabolism , Humans , Hydrogen Bonding , Hydrophobic and Hydrophilic Interactions , Molecular Docking Simulation , Organoplatinum Compounds/chemistry , Protein Binding , Protein Structure, Tertiary , Serum Albumin/chemistry , Spectrometry, Fluorescence , Spectrophotometry, Ultraviolet
17.
Int J Biol Macromol ; 92: 593-599, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27456118

ABSTRACT

In this report, circular dichroism (CD) along with steady-state fluorescence spectroscopy and molecular modeling investigations were carried out to better understand the interaction of miriplatin with human serum albumin (HSA). The presence of miriplatin in solution is found to destabilize the native structure of HSA: The tertiary structure of HSA was changed and the microenvironment of Trp residue became more hydrophobic; the binding affinity of HSA with miriplatin indicating by 8-Anilino-1-naphthalenesulfonic acid (ANS) fluorescence study was 1.74×106L/mol; miriplatin induced the denaturation and unfolding of HSA and disrupted the polar contacts and decreasing the reversibility of the unfolding process of protein. In addition, molecular modeling studies indicated miriplatin bound to domain II of HSA by hydrophobic force, hydrogen bonds, and electrostatic force interactions. HSA retained most of its esterase activity even after its binding with miriplatin. These results provide valuable insight into the binding mechanism between miriplatin and a plasma protein that is known to play an important role in the drug delivery of medicinal drugs to target organs.


Subject(s)
Organoplatinum Compounds/metabolism , Serum Albumin/chemistry , Serum Albumin/metabolism , Anilino Naphthalenesulfonates/chemistry , Binding Sites , Circular Dichroism , Esterases/metabolism , Humans , Molecular Docking Simulation , Organoplatinum Compounds/chemistry , Organoplatinum Compounds/pharmacology , Protein Denaturation/drug effects , Protein Stability/drug effects , Protein Structure, Secondary , Spectrometry, Fluorescence , Temperature , Tryptophan/metabolism
18.
Tumour Biol ; 37(9): 12555-12569, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27350368

ABSTRACT

There has been accumulative evidence that microRNAs (miRNAs) play essential roles in the tumorigenesis and progression of bladder cancer. However, individual studies and small sample size caused discrepant outcomes. Thus, the current study focused on a comprehensive profiling of all differentially expressed miRNAs in a total of 519 bladder cancer tissue samples, based on miRNA microarray data. Altogether, 11 prioritized miRNAs stated by 21 published microarray datasets, including five down-regulated (miR-133a-3p, miR-1-3p, miR-99a-5p, miR-490-5p, and miR-133b) and six up-regulated candidate miRNAs (miR-182-5p, miR-935, miR-518e-3p, miR-573, miR-100-3p, and miR-3171) were analyzed with vote-counting strategy and a Robust Rank Aggregation method. Subsequently, miRNA in silico target prediction and potential pathway enrichment analysis were performed to investigate the prospective molecular mechanism of miRNAs in the tumorigenesis of bladder cancer. We found that most of the relative pathways of the aberrantly expressed miRNAs found in the current study were closely correlated with different biological processes, cellular components, molecular functions, cancer pathogeneses, and some cell signalings, such as Wnt signaling, insulin/IGF, PI3 kinase, and FGF signaling pathways. Hence, a comprehensive overview on the miRNA expression pattern in bladder cancer tissues was gained by the current study. These miRNAs might be involved in the tumorigenesis and deterioration of bladder cancer.


Subject(s)
MicroRNAs/analysis , Urinary Bladder Neoplasms/genetics , Humans , Oligonucleotide Array Sequence Analysis , Urinary Bladder Neoplasms/etiology
19.
PLoS One ; 10(12): e0145659, 2015.
Article in English | MEDLINE | ID: mdl-26710214

ABSTRACT

BACKGROUND: There have been numerous articles as to whether the staining index (SI) of astrocyte elevated gene-1 (AEG-1) adversely affects clinical progression and prognosis of gastrointestinal cancers. Nevertheless, controversy still exists in terms of correlations between AEG-1 SI and clinicopathological parameters including survival data. Consequently, we conducted a comprehensive meta-analysis to confirm the role of AEG-1 in clinical outcomes of gastrointestinal carcinoma patients. METHODS: We performed a comprehensive search in PubMed, ISI Web of Science, Cochrane Central Register of Controlled Trials, EMBASE, Science Direct, Wiley Online Library, China National Knowledge Infrastructure (CNKI), WanFang and Chinese VIP databases. STATA 12.0 (STATA Corp., College, TX) was used to analyze the data extracted from suitable studies and Newcastle-Ottawa Scale was applied to assess the quality of included articles. RESULTS: The current meta-analysis included 2999 patients and our results suggested that strong associations emerged between AEG-1 SI and histological differentiation (OR = 2.129, 95%CI: 1.377-3.290, P = 0.001), tumor (T) classification (OR = 2.272, 95%CI: 1.147-4.502, P = 0.019), lymph node (N) classification (OR = 2.696, 95%CI: 2.178-3.337, P<0.001) and metastasis (M) classification (OR = 3.731, 95%CI: 2.167-6.426, P<0.001). Furthermore, high AEG-1 SI was significantly associated with poor overall survival (OS) (HR = 2.369, 95%CI: 2.005-2.800, P<0.001) and deteriorated disease-free survival (DFS) (HR = 1.538, 95%CI: 1.171-2.020, P = 0.002). For disease-specific survival (DSS) and relapse-free survival (RFS), no statistically significant results were observed (HR = 1.573, 95%CI: 0.761-3.250, P = 0.222; HR = 1.432, 95%CI: 0.108-19.085, P = 0.786). Subgroup analysis demonstrated that high AEG-1 SI was significantly related to poor prognosis in esophageal squamous cell carcinoma (ESCC) (HR = 1.715, 95%CI: 1.211-2.410, P = 0.002), gastric carcinoma (GC) (HR = 2.255, 95%CI: 1.547-3.288, P<0.001), colorectal carcinoma (CRC) (HR = 2.922, 95%CI: 1.921-4.444, P<0.001), gallbladder carcinoma (GBC) (HR = 3.047, 95%CI: 1.685-5.509, P<0.001), hepatocellular carcinoma (HCC) (HR = 2.245, 95%CI: 1.620-3.113, P<0.001), pancreatic adenocarcinoma (PAC) (HR = 2.408, 95%CI: 1.625-3.568, P<0.001). CONCLUSIONS: The current meta-analysis indicated that high AEG-1 SI might be associated with tumor progression and poor survival status in patients with gastrointestinal cancer. AEG-1 might play a vital role in promoting tumor aggression and could serve as a potential target for molecular treatments. Further clinical trials are needed to validate whether AEG-1 SI provides valuable insights into improving treatment decisions.


Subject(s)
Biomarkers, Tumor/metabolism , Cell Adhesion Molecules/metabolism , Gastrointestinal Neoplasms/metabolism , Female , Gastrointestinal Neoplasms/mortality , Gastrointestinal Neoplasms/pathology , Humans , Male , Membrane Proteins , Observational Studies as Topic , Odds Ratio , Prognosis , RNA-Binding Proteins , Survival Analysis
20.
Article in English | MEDLINE | ID: mdl-26123604

ABSTRACT

In this article, an attempt is made to analysis the binding mechanism of γ-Fe2O3 nanoparticles with fibrinogen by using a combination of circular dichroism, UV-vis, fluorescence spectroscopic and computational methods. The multi-spectroscopic data revealed that the complex easily formed between γ-Fe2O3 nanoparticles and fibrinogen by mainly hydrogen bonding forces. The binding constants of fibrinogen with γ-Fe2O3 nanoparticles were 2.24×10(7), 1.15×10(7) and 0.72×10(7)Lmol(-1) at 298, 304, and 310K, respectively. Furthermore, the results from circular dichroism, UV-vis, synchronous fluorescence, and three-dimensional fluorescence studies showed that the strong binding interaction of γ-Fe2O3 nanoparticles with fibrinogen induced an obvious perturbation in the protein secondary and tertiary structure. Moreover, the results of molecular modeling indicated the existence of the preferable binding site on fibrinogen for γ-Fe2O3 NPs model.


Subject(s)
Ferric Compounds/chemistry , Fibrinogen/chemistry , Nanoparticles/chemistry , Binding Sites , Circular Dichroism , Ferric Compounds/metabolism , Fibrinogen/metabolism , Humans , Hydrogen Bonding , Models, Molecular , Protein Binding , Spectrometry, Fluorescence
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