Biomedical subjects

Kun Guo

Publications and source records attributed to Kun Guo.

9 recordsLinked to original sources

PubMed2024

ST3GAL1 Promotes Malignant Phenotypes in Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) has a poor prognosis, and elucidation of the molecular mechanisms underlying iCCA malignancy is of great significance. Glycosylation, an important post-translational modification, is closely associated with tumor progression. Altered glycosylation, including aberrant sialylation resulting from abnormal expression of sialyltransferases (STs) and neuraminidases (NEUs), is a significant feature of cancer cells. However, there is limited information on the roles of STs and NEUs in iCCA malignancy. Here, utilizing our proteogenomic resources from a cohort of 262 patients with iCCA, we identified ST3GAL1 as a prognostically relevant molecule in iCCA. Moreover, overexpression of ST3GAL1 promoted proliferation, migration, and invasion and inhibited apoptosis of iCCA cells in vitro. Through proteomic analyses, we identified the downstream pathway potentially regulated by ST3GAL1, which was the NF-κB signaling pathway, and further demonstrated that this pathway was positively correlated with malignancy in iCCA cells. Notably, glycoproteomics showed that O-glycosylation was changed in iCCA cells with high ST3GAL1 expression. Importantly, the altered O-glycopeptides underscored the potential utility of O-glycosylation profiling as a discriminatory marker for iCCA cells with ST3GAL1 overexpression. Additionally, miR-320b was identified as a post-transcriptional regulator of ST3GAL1, capable of suppressing ST3GAL1 expression and then reducing the proliferation, migration, and invasion abilities of iCCA cell lines. Taken together, these results suggest ST3GAL1 could serve as a promising therapeutic target for iCCA.

Female↗

PubMed2007

A glycoproteome database of normal human liver tissue.

PURPOSE: To extensively investigate the glycoproteins of normal human liver tissue, constructing the glycoprotein profile and database of the normal human liver tissue. METHODS: The total proteins were extracted from the normal human liver tissue and then subjected to two-dimensional electrophoresis (2-DE). Finally, 2-DE gels were stained according to the methods of multiplexed proteomics (MP) technology. Glycoprotein spots were excised from 2-DE gel and then characterized by matrix assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS). RESULTS: The PDQuest software detected 1,011 glycoprotein spots and 1,923 total protein spots in the 2-DE gels of sample from the normal human liver tissue. Furthermore, 116 species of glycoproteins were successfully identified via peptide mass profiling using MALDI-TOF-MS/MS and annotated to our databases. In addition, we also applied bioinformatics softwares to predict N- or O-glycosylation sites of identified glycoproteins. CONCLUSION: This study demonstrates the feasibility of a novel technological platform to contruct glycoprotein databases. These results lay the foundation for future physiological and pathological studies of the human liver.

Databases, Protein↗

PubMed2006

Investigation on glycosylation patterns of proteins from human liver cancer cell lines based on the multiplexed proteomics technology.

Glycosylation, a very important post-translational modification of proteins, is increasingly coming into notice. However, large-scale, throughput investigations on glycosylated proteins are few. We applied a sensitive and fast fluorescence-based multiplexed proteomics (MP) technology which included two-dimensional gel electrophoresis (2-DE) followed by the fluorescence staining of glycoprotein and mass spectrometry identification for the purpose of constructing glycoprotein databases of the typical human hepatocellular carcinoma cell lines including Hep3B cell line without metastasis and MHCC97H with highly metastatic potential as well as the control non-tumor Chang liver cell. 74+/-2 (n=3), 78+/-3 (n=3) and 72+/-5 (n=3) glycoprotein spots were detected on 2-DE gels from Chang liver, Hep3B and MHCC97H cell sample using this MP technique, respectively. In all, 80 glycoproteins from three cell lines were successfully identified via peptide mass profiling using MALDI-TOF-MS/MS and the identified glycoproteins were annotated to our databases. In addition, we also found the glycosylation pattern differences among these three cell lines. The protein glycosylation alteration would be have great significance for the diagnosis of HCC and prediction of its metastasis. This study described the construction of glycosylation patterns of proteins and glycoproteome databases of human liver cells by the novel technological platform. The glycoproteome databases also provide essential basis for following study.

Animals↗

PubMed2005

Longer fixation duration while viewing face images.

The spatio-temporal properties of saccadic eye movements can be influenced by the cognitive demand and the characteristics of the observed scene. Probably due to its crucial role in social communication, it is argued that face perception may involve different cognitive processes compared with non-face object or scene perception. In this study, we investigated whether and how face and natural scene images can influence the patterns of visuomotor activity. We recorded monkeys' saccadic eye movements as they freely viewed monkey face and natural scene images. The face and natural scene images attracted similar number of fixations, but viewing of faces was accompanied by longer fixations compared with natural scenes. These longer fixations were dependent on the context of facial features. The duration of fixations directed at facial contours decreased when the face images were scrambled, and increased at the later stage of normal face viewing. The results suggest that face and natural scene images can generate different patterns of visuomotor activity. The extra fixation duration on faces may be correlated with the detailed analysis of facial features.

Analysis of Variance↗

PubMed2005

Centre-surround interactions in response to natural scene stimulation in the primary visual cortex.

Centre-surround interaction in the primary visual cortex (area V1) has been studied extensively using artificial, abstract stimulus patterns, such as bars, gratings and simple texture patterns. In this experiment, we extend the study of centre-surround interaction by using natural scene images. We systematically varied the contrast of natural image surrounds presented outside the classical receptive field (CRF), and recorded neuronal response to a natural image patch presented within the CRF in area V1 of awake, fixating macaques. For the majority of neurons (67 out of 111), the natural image surrounds profoundly modulated, mainly by suppressing, neuronal responses to CRF images. These modulatory effects started at the earliest stage of neuronal responses, and often depended on the contrast and higher-order structures of the surrounds. For 47 out of 67 neurons, randomising the phases of the Fourier spectrum of the natural image surround diminished the centre-surround interaction. Our results suggest that the centre-surround interaction in area V1 can be extended to natural vision, and is sensitive to the higher-order structures of natural scene images, such as image contours.

Action Potentials↗

PubMed2004

Effects on orientation perception of manipulating the spatio-temporal prior probability of stimuli.

Spatial and temporal regularities commonly exist in natural visual scenes. The knowledge of the probability structure of these regularities is likely to be informative for an efficient visual system. Here we explored how manipulating the spatio-temporal prior probability of stimuli affects human orientation perception. Stimulus sequences comprised four collinear bars (predictors) which appeared successively towards the foveal region, followed by a target bar with the same or different orientation. Subjects' orientation perception of the foveal target was biased towards the orientation of the predictors when presented in a highly ordered and predictable sequence. The discrimination thresholds were significantly elevated in proportion to increasing prior probabilities of the predictors. Breaking this sequence, by randomising presentation order or presentation duration, decreased the thresholds. These psychophysical observations are consistent with a Bayesian model, suggesting that a predictable spatio-temporal stimulus structure and an increased probability of collinear trials are associated with the increasing prior expectation of collinear events. Our results suggest that statistical spatio-temporal stimulus regularities are effectively integrated by human visual cortex over a range of spatial and temporal positions, thereby systematically affecting perception.

Bayes Theorem↗

PubMed2004

Pattern motion is present in V1 of awake but not anaesthetized monkeys.

We compared responses of neurons, recorded in striate cortex (area V1) of awake, fixating monkeys, to a single drifting grating with those to a 'plaid' pattern comprised of two superimposed drifting gratings separated in orientation by 90 degrees. Five out of 54 (9%) of V1 direction selective neurons responded to the direction of motion of the whole pattern [pattern motion (PM) selectivity]. Tuning curves for plaid stimuli were similar in both optimum direction and width of tuning to those for single gratings. Twenty nine out of 54 (54%) responded simply to the motion of individual orientated gratings within the pattern [component motion (CM) selectivity]. The remaining 37% (20/54) neurons were unclassified. In control experiments, 39 direction selective neurons were recorded in area V1 of anaesthetized monkey and cats. Unlike area V1 in behaving monkeys, none of these neurons exhibited PM selectivity to the drifting plaids. Twenty eight out of 39 (72%) of them responded to the direction of the component gratings and were classified as CM selectivity. Our results indicate that although most V1 neurons are CM selective, as described in anaesthetized animals, a subpopulation is clearly PM selective in behaving monkeys, reflecting integration of locally derived motion signals. Neurons in V1 therefore carry signals that may contribute to pattern motion processing and perception. This perceptual interpretation in V1 might depend much more critically on information integration mechanisms that only function properly in awake, perceiving animals.

Anesthesia↗

PubMed2003

How do monkeys view faces?--A study of eye movements.

Face perception plays a crucial role in primate social communication. We have investigated the pattern of eye movements produced by rhesus monkeys (Macaca mulatta) as they viewed images of faces. Eye positions were recorded accurately using implanted eye coils, while neutral upright, inverted and scrambled images of monkey and human faces were presented on a computer screen. The monkeys exhibited a similar eye scan pattern while viewing familiar and unfamiliar monkey face images, or while viewing monkey and human face images. No differences were observed in the distribution of viewing times, number of fixations, time into the trial of first saccade to local facial features, and the temporal and spatial characteristics of viewing patterns across the facial images. However, there was a greater probability of re-fixation of the eye region of unfamiliar faces during the first few seconds of the trial suggesting that the eyes are important for the initial encoding of identity. Indeed, the highest fixation density was found in the eye region of all the face images. The viewing duration and the number of fixations per image decreased when inverted or scrambled faces were presented. The eye region in these modified images remained the primary area of fixation. However, the number of fixations directed to the eyes decreased monotonically from the upright images through the inverted versions to the scrambled face images. Nonetheless, the eyes remain the most salient facial substructure regardless of the arrangement of other features, although the extent of salience which they attain may depend both on the low level properties of the eyes and on the global arrangement of facial features.

Animals↗

PubMed2002

Myogenic Akt signaling regulates blood vessel recruitment during myofiber growth.

Blood vessel recruitment is an important feature of normal tissue growth. Here, we examined the role of Akt signaling in coordinating angiogenesis with skeletal muscle hypertrophy. Hypertrophy of C2C12 myotubes in response to insulin-like growth factor 1 or insulin and dexamethasone resulted in a marked increase in the secretion of vascular endothelial growth factor (VEGF). Myofiber hypertrophy and hypertrophy-associated VEGF synthesis were specifically inhibited by the transduction of a dominant-negative mutant of the Akt1 serine-threonine protein kinase. Conversely, transduction of constitutively active Akt1 increased myofiber size and led to a robust induction of VEGF protein production. Akt-mediated control of VEGF expression occurred at the level of transcription, and the hypoxia-inducible factor 1 regulatory element was dispensable for this regulation. The activation of Akt1 signaling in normal mouse gastrocnemius muscle was sufficient to promote myofiber hypertrophy, which was accompanied by an increase in circulating and tissue-resident VEGF levels and high capillary vessel densities at focal regions of high Akt transgene expression. In a rabbit hind limb model of vascular insufficiency, intramuscular activation of Akt1 signaling promoted collateral and capillary vessel formation and an accompanying increase in limb perfusion. These data suggest that myogenic Akt signaling controls both fiber hypertrophy and angiogenic growth factor synthesis, illustrating a mechanism through which blood vessel recruitment can be coupled to normal tissue growth.

Animals↗