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W C Liu

Publications and source records attributed to W C Liu.

At least 19 recordsLinked to original sources

[Laryngeal squamous cell carcinoma-derived exosomes promote neuronal axonal growth by remodeling the neural microenvironment].

Objective: Perineural invasion (PNI) is a critical determinant of poor prognosis in laryngeal squamous cell carcinoma (LSCC), but its underlying mechanisms remain unclear. This study aimed to investigate whether LSCC-derived exosomes induce axonal growth by delivering neuroactive molecules, thereby contributing to tumor perineural invasion. Methods: Clinical data from the laryngeal cancer cohort of The Cancer Genome Atlas Head and Neck Squamous Cell Carcinoma (TCGA-HNSC) dataset were analyzed. Propensity score matching (PSM) and Cox regression were used to evaluate the prognostic value of nerve density, and these findings were validated using 35 pairs of laryngeal cancer and adjacent normal tissue specimens collected at Yantai Yuhuangding Hospital between 2022 and 2026 to assess neural morphological changes. Exosomes were isolated from the human LSCC cell line AMC-HN-8, characterized by quality-control assays, and co-cultured with PC12 cells. A rescue experiment using GW4869, a specific inhibitor of neutral sphingomyelinase, was performed to confirm the exosome-dependent effect. Neurite outgrowth was evaluated by immunofluorescence, and the expression of axonal growth-related genes was measured by RT-qPCR. Targeted metabolomics was employed for the absolute quantification of neuroactive metabolites within the vesicles and for pathway enrichment analysis. Results: After PSM adjustment, high nerve density was identified as an independent poor prognostic factor in LSCC patients (HR=2.10, P=0.035), with particularly pronounced prognostic value in the early-stage node-negative (N0) subgroup (HR=4.07, P=0.001). Pathological sections showed high expression of the neural markers &#x3b2;III-tubulin and PGP9.5 in LSCC tissues (&#x3b2;III-tubulin: t=2.234, P<0.05; PGP9.5: t=2.575, P<0.05). Exosomes were successfully isolated from AMC-HN-8 cells and passed quality control. In vitro assays showed that LSCC-derived exosomes significantly promoted neurite extension and branching in PC12 cells (t=4.147, P<0.000 1) and upregulated core axonal growth genes, including GAP-43, NEFL, and NEFM (GAP-43: t=3.698, P<0.05; NEFL: t=5.113, P<0.01; NEFM: t=5.263, P<0.01); this effect was completely reversed by the exosome-release inhibitor GW4869 (t=3.535, P<0.001). Targeted metabolomics revealed a specific enrichment of 12 neurotransmitters and metabolites within LSCC exosomes, centered on glutamine (83.411 &#x3bc;mol/L, FC=1.88) and glutamate (18.461 &#x3bc;mol/L, FC=1.21), which were significantly enriched in signaling pathways such as "central carbon metabolism in cancer" and "glutamatergic synapse". Conclusion: Nerve density is a potential adverse prognostic factor in patients with LSCC. LSCC-derived exosomes can directly induce axonal growth in neuron-like cells, suggesting that tumor cells actively remodel the neural microenvironment and drive axonal growth through exosome-mediated long-range signaling.

Exosomes↗

Testosterone regulates alpha-synuclein mRNA in the avian song system.

Alpha-synuclein is a small, highly conserved protein in vertebrates that has been linked to several neurodegenerative diseases. The avian song control system is one of the model systems in which the protein was independently discovered. Alpha-synuclein is dynamically regulated in the song system during song learning, a process in which sex steroids play a central role. We compared alpha-synuclein mRNA expression in the brains of 12 adult male chipping sparrows (Spizella passerina) treated with either testosterone or blank s.c. implants. We saw pronounced upregulation of alpha-synuclein mRNA in, as well as an increase in the volume of, the song control nucleus area X in response to exogenous testosterone. To our knowledge this is the first report of steroid regulation of synuclein gene expression in any model system.

Animals↗

Different mechanisms of radiation-induced loss of heterozygosity in two human lymphoid cell lines from a single donor.

Allelic loss is an important mutational mechanism in human carcinogenesis. Loss of heterozygosity (LOH) at an autosomal locus is one outcome of the repair of DNA double-strand breaks (DSBs) and can occur by deletion or by mitotic recombination. We report that mitotic recombination between homologous chromosomes occurred in human lymphoid cells exposed to densely ionizing radiation. We used cells derived from the same donor that express either normal TP53 (TK6 cells) or homozygous mutant TP53 (WTK1 cells) to assess the influence of TP53 on radiation-induced mutagenesis. Expression of mutant TP53 (Met 237 Ile) was associated with a small increase in mutation frequencies at the hemizygous HPRT (hypoxanthine phosphoribosyl transferase) locus, but the mutation spectra were unaffected at this locus. In contrast, WTK1 cells (mutant TP53) were 30-fold more susceptible than TK6 cells (wild-type TP53) to radiation-induced mutagenesis at the TK1 (thymidine kinase) locus. Gene dosage analysis combined with microsatellite marker analysis showed that the increase in TK1 mutagenesis in WTK1 cells could be attributed, in part, to mitotic recombination. The microsatellite marker analysis over a 64-cM region on chromosome 17q indicated that the recombinational events could initiate at different positions between the TK1 locus and the centromere. Virtually all of the recombinational LOH events extended beyond the TK1 locus to the most telomeric marker. In general, longer LOH tracts were observed in mutants from WTK1 cells than in mutants from TK6 cells. Taken together, the results demonstrate that the incidence of radi-ation-induced mutations is dependent on the genetic background of the cell at risk, on the locus examined, and on the mechanisms for mutation available at the locus of interest.

Alleles↗

A modeling study of water quality in main channel and estuarine wetland.

A simple computation framework is applied to include estuarine wetland and their interaction with main channels in estuarine modeling. The concept and the model implementation of the scheme are explained using a vertical two-dimensional model of estuarine hydrodynamics and water quality. The model was applied to the Tanshui River estuary and Kuan-Du wetland. The model is calibrated and verified by the available measured data. Simulations are also conducted for various upstream freshwater discharges to predict water quality in the main channel and estuarine wetland. The results show that the inclusion of estuarine wetland in a water-quality model not only provides a framework for computing water-quality conditions but also accounts for the interaction between wetland and main channel. The model provides a useful tool for environmental planning, protection and proposed wetland restoration works.

Conservation of Natural Resources↗

Therapeutic effect of pirenzepine for clozapine-induced hypersalivation: a randomized, double-blind, placebo-controlled, cross-over study.

The objective of this study was to investigate the efficacy of pirenzepine in the treatment of clozapine-induced hypersalivation. Pirenzepine is reported to counteract hypersalivation by its selective antagonistic activity on the M4-muscarinic receptor, which is stimulated by clozapine. Twenty patients with clozapine-induced hypersalivation underwent a random-order, double-blind, placebo-controlled, cross-over trial which lasted 8 weeks each for the pirenzepine and placebo investigations, with a 4-week washout period in between. The severity of hypersalivation was assessed using an objective measure: saliva production monitored through the diameter of wetted surface on tissue paper placed over the patient's pillow. Our study showed that pirenzepine had no significant therapeutic effect on hypersalivation compared with placebo, suggesting that hypersalivation induced by clozapine might have a neurobiological basis other than the M4-muscarinic receptor.

Adult↗

Detection of circulating CEA molecules in human sera and leukopheresis of peripheral blood stem cells with E. coli expressed bispecific CEAScFv-streptavidin fusion protein-based immuno-PCR technique.

In this study, a method called bispecific CEAScFv-streptavidin fusion protein-based immuno-PCR technique will be tested experimentally. The application of the bispecific fusion protein-based immuno-PCR technique has the significant advantage that it can be readily applied in the clinical setting, as well as tested as a potential screening tool in high-risk populations of certain types of cancer.

Carcinoembryonic Antigen↗

Functional magnetic resonance imaging of working memory impairment after traumatic brain injury.

OBJECTIVES: To examine patterns of brain activation while performing a working memory task in persons with moderate to severe traumatic brain injury (TBI) and healthy controls. It is well established that working memory is an area of cognition that is especially vulnerable to disruption after TBI. Although much has been learned about the system of cerebral representation of working memory in healthy people, little is known about how this system is disrupted by TBI. METHODS: Functional magnetic resonance imaging (fMRI) was used to assess brain activation during a working memory task (a modified version of the paced auditory serial addition test) in nine patients with TBI and seven healthy controls. RESULTS: Patients with TBI were able to perform the task, but made significantly more errors than healthy controls. Cerebral activation in both groups was found in similar regions of the frontal, parietal, and temporal lobes, and resembled patterns of activation found in previous neuroimaging studies of working memory in healthy persons. However, compared with the healthy controls, the TBI group displayed a pattern of cerebral activation that was more regionally dispersed and more lateralised to the right hemisphere. Differences in lateralisation were particularly evident in the frontal lobes. CONCLUSIONS: Impairment of working memory in TBI seems to be associated with alterations in functional cerebral activity.

Adult↗

Serotonin 6 receptor polymorphism in schizophrenia: frequency, age at onset and cognitive function.

The relative abundance of serotonin 6 receptor (5HT6) in some limbic regions and the high affinity of some antipsychotics for 5HT6 suggest that the 5HT6 gene might play a role in the pathogenesis of schizophrenic disorders. A recent study reported an association between a C267T polymorphism of the 5HT6 gene and schizophrenia. In order to test whether the 5HT6 gene plays a role in the pathogenesis of schizophrenic disorders, patients (n = 148) and control subjects (n = 160) were genotyped for 5HT6. We also investigated the relationship between genotypes and patients' age at onset and cognitive function in schizophrenic patients. Cognitive function in the patients was evaluated by the Mini-Mental State Examination (MMSE). The results demonstrated no significant differences in genotype or allele frequencies between controls and patients. In the patient group, age at onset and MMSE score did not differ significantly among the three 5HT6 genotpyes. The results of this study suggest that the 5HT6 C267T polymorphism plays no major role in susceptibility to the development of schizophrenia and is not related to cognitive impairment or age at onset in schizophrenic patients. Further studies of the relation between 5HT6 polymorphism and the symptoms and the therapeutic response in schizophrenic patients may help to elucidate the role of 5HT6 in the pathogenesis of schizophrenia.

Adult↗

Identification of the corticospinal tracts achieved using blood-oxygen-level-dependent and diffusion functional MR imaging in patients with brain tumors.

Diffusion-weighted MR imaging was used to delineate the corticospinal tract (CST) successfully and to depict its relationship to adjacent brain tumors. The CST was defined by a method by which it seems possible to delimit the distance from the CST to the main tumor mass and to show displacement and infiltration of the tract by the neoplasia. This information cannot be gathered from routine anatomic MR imaging.

Adolescent↗

Invasion sequence affects predator-prey dynamics in a multi-species interaction.

Ecologists seek to understand the rules that govern the assembly, coexistence and persistence of communities of interacting species. There is, however, a variety of sequences in which a multi-species community can be assembled--unlike more familiar one- and two-species systems. Ecological systems can exhibit contrasting dynamics depending on initial conditions, but studies have been focused on simple communities initiated at different densities, not on multi-species communities constructed in different sequences. Investigations of permanence and convergence in ecological communities have been concerned with the flux of whole species (presence or absence) but have not addressed the central issues concerning the dynamics exhibited by individual species in particular interactions. Here we examine data for replicated three-species systems and demonstrate that the dynamic trajectories of both a predator and its prey within the system are determined by the sequence in which it is constructed, and that for one construction-sequence alternative dynamic patterns are possible.

Animals↗

Does a herniated nucleus pulposus contribute significantly to a decrease in height of the intervertebral disc? Quantitative volumetric MRI.

A lumbar intervertebral disc with a herniated nucleus pulposus (HNP) often exhibits a decrease in the height of the intervertebral space. Our purpose was to ascertain whether the loss of volume of an HNP is sufficient to cause a perceptible decrease in the height of the intervertebral space. MRI of 44 patients with 51 HNPs were reviewed. The volumes of the herniated material and of the intervertebral discs were calculated for every level from L1-2 to L5-S1. The average volume of the HNP was 503 +/- 301 mm3. The average volumes of all 220 intervertebral discs and of the 127 normal-appearing discs were 14,442 +/- 4200 mm3 and 17,476 +/- 2885 mm3 respectively. The average volume of the HNP represented 3.5% of the parent disc. An average HNP caused a decrease in intervertebral space height of 0.35 mm (0.56 pixels). Therefore, the loss of the volume of the HNP does not cause a significant decrease in the intervertebral space height. The average calculated decrease in the disc height is less than that reported in normal diurnal variation.

Adult↗

Positioning of vagal nerve stimulators: technical note.

BACKGROUND: Vagal nerve stimulation has become an important treatment for patients with intractable seizure disorders. Many of these patients will require magnetic resonance imaging (MRIs) of the brain after the stimulator has been implanted to monitor underlying neurologic conditions. Functional MRI (fMRI) is also being used in the evaluation of epilepsy. With the current recommended implant techniques the magnetic field of the MRI will deactivate the pulse generator while the patient is in the supine position for the scan. A simple change in positioning of the pulse generator will help to avoid deactivating the device during an MRI. This will avoid exposing the patient to lengthy time periods with a deactivated stimulator and also allow for the performance of fMRIs and any other MRI scans needed to monitor underlying neurologic conditions. METHODS: A working model of the NeuroCybernetic Prosthesis (NCP) pulse generator was assessed with an oscilloscope and LED light connected to it that related activation of the generator while in the MRI. This simulation was performed with the device alone, in multiple positions. Then patients with implanted devices who could personally confirm the activation of their stimulators were also studied. RESULTS: A pulse generator placed with the electrode inputs parallel to the long axis of the body was not deactivated by the magnetic field of the MRI when the patient was in the supine position. CONCLUSION: Changing the implant position of a vagal nerve stimulator pulse generator will help to prevent deactivation of the device while in the MRI, allowing for the performance of fMRIs while not exposing the patient to lengthy time periods with a deactivated vagal nerve stimulator.

Electric Stimulation Therapy↗

Functional magnetic resonance imaging aided radiation treatment planning.

Functional MRI (magnetic resonance imaging) allows one to noninvasively identify various eloquent cortices in the brain. The integration of cortical activation information into radiosurgical treatment planning may provide an alternative to prevent or minimize radiation damage to eloquent cortex. A novel approach of directly integrating the fMRI (functional magnetic resonance imaging) brain map into treatment planning is proposed. Three brain tumor patients have been studied using this method with motor and/or visual paradigms. Brain activation was demonstrated in eloquent cortex at the precentral gyrus (motor area) and medial occipital lobe (visual area). The activation maps were transferred to a treatment planning workstation, (XKnife), and 3D (three-dimensional) activation maps were generated and co-registered to a 3D CT (computed tomography) anatomical data set, which provided the calibration localizer, for treatment planning. Radiosurgery was designed based on both functional and structural information by the medical team consisting of a radiation oncologist, a neurosurgeon and a physicist. The average maximum dose for the tumor was 2113 cGy. The average maximum dose for tissue surrounding the tumor was 1600 cGy. The average dose with fMRI information to the eloquent cortex was 163.4 cGy over three patients, while without fMRI information it was 240.5 cGy. The average percentage dose reduction over three patients is 32%. The results suggest that using this method can reduce the dose to the eloquent cortex. This approach provides the physician with additional information for treatment planning and may spare the patient unnecessary radiation exposure to adjacent eloquent cortices.

Adult↗

The effect of brain tumors on BOLD functional MR imaging activation in the adjacent motor cortex: implications for image-guided neurosurgery.

BACKGROUND AND PURPOSE: Functional MR (fMR) imaging data coregistered to a neurosurgical navigation system have been proposed as guides for the resection of brain tumor in or adjacent to eloquent cortices. The purpose of this study was to compare data obtained from the side of the brain affected by tumor with the contralateral side and to determine if there are physiological limitations of fMR imaging in accurately determining the location of the primary motor cortex. METHODS: Ten patients with tumors in or directly adjacent to the motor cortex were studied with fMR imaging (finger-tapping paradigm). fMR imaging data were analyzed using multiple R values. These data were coregistered to a real-time intraoperative neurosurgical navigation system. RESULTS: Significant variability of motor cortex activation patterns was noted among individual patients. The activation volumes on the side of the tumor were significantly smaller compared with the contralateral side for all tumors not previously resected (0.66+/-0.47). This was most pronounced in glioblastomas (0.27+/-0.21). We propose that these differences were caused by a loss of autoregulation in the tumor vasculature of glioblastomas and venous effects. CONCLUSION: Notwithstanding the differences noted, the motor cortex was identified successfully in all patients. This was confirmed by intraoperative physiological identification of the motor cortex and a lack of postoperative neurologic deficit.

Brain Neoplasms↗

Single-shot echo-planar imaging of multiple sclerosis: effects of varying echo time.

Our aim was to determine the relative merits of short and long echo times (TE) with single-shot echo-planar imaging for imaging cerebral lesions such as multiple sclerosis. We examined seven patients with clinically definite multiple sclerosis were imaged at 1.5 T. Patients were scanned with spinecho, single-shot echo-planar imaging, using TEs of 45, 75, 105, and 135 ms. Region of interest (ROI) measurements were performed on 36 lesions at or above the level of the corona radiata. The mean image contrast (IC) was highest (231.1) for a TE of 45 ms, followed by 75 ms (218.9), 105 ms (217.9), and 135 ms (191.6). When mean contrast-to-noise ratios (C/N) were compared, the value was again highest (29.7) for TE 45 ms, followed by 75 ms (28.9), 105 ms (28.5), and 135 ms (26.3). In a lesion-by-lesion comparison, TE 45 ms had the highest IC and C/N in the largest number of cases (50 % and 47.2 %, respectively). IC and C/N for TE 45 ms were superior to those of 75 ms in 64% and 58%, respectively. These results support the use of relatively short TEs for single-shot echo-planar imaging in the setting of cerebral lesions such as multiple sclerosis.

Cerebral Cortex↗

Cortical representation of swallowing in normal adults: functional implications.

OBJECTIVE: Dysphagia of neurogenic or postsurgical origin presents management and therapeutic challenges to the otolaryngologist. Improvements in management and therapeutic approaches may be facilitated by understanding how the central nervous system controls swallowing. The purpose of this investigation was to utilize functional magnetic resonance imaging to determine patterns of cortical activity during swallowing in normal, healthy adult subjects. STUDY DESIGN: Functional magnetic resonance imaging (fMRI) was performed on eight healthy adult subjects using conventional BOLD (blood oxygenation level dependent) techniques. METHODS: Subjects performed three different swallowing tasks including dry and bolus swallows, and performed a control finger movement task. Statistical maps of cortical activation were generated using a cross-correlation analysis. One-way and two-way ANOVA statistical analyses were performed to compare activated areas among the different tasks and to determine the effects of task sequence. RESULTS: Activation during the three swallowing tasks occurred in the primary motor cortex, primary somatosensory cortex, and other cortical and subcortical sites. Cortical representation of swallowing and finger movement followed somatotopic maps. Differential distribution of cortical activation was observed for the different swallowing tasks. CONCLUSIONS: Activation of the primary motor and somatosensory cortices, as well as other sensory-motor areas, occurs with swallowing in normal adults. Differential distribution of cortical activity with different swallowing tasks suggests differential functional organization for different swallowing tasks. Understanding these mechanisms may facilitate improved management and therapeutic intervention for neurogenic and postsurgical dysphagia.

Adult↗