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Biomedical subjects

Yi Shen

Publications and source records attributed to Yi Shen.

At least 19 recordsLinked to original sources

MicroRNA-486: a dual-function biomarker for diagnosis and tumor immune microenvironment characterization in non-small cell lung cancer.

BACKGROUND: This investigation evaluates the clinical significance and molecular mechanisms of microRNA-486 (miR-486) as a potential biomarker in non-small cell lung cancer (NSCLC) through an integrative analytical approach. METHODS: We conducted systematic search and meta-analysis of diagnostic studies from major biomedical databases from inception through April 04, 2025, followed by comprehensive bioinformatics interrogation. Protein-protein interaction (PPI) networks were constructed using STRING to identify key hub genes regulated by miR-486. Validation of hub genes employed TCGA datasets, while immune infiltration analysis utilized TIMER2.0 platform. RESULTS: The meta-analysis indicated that miR-486, both individually and in combination, could be effective biomarkers for NSCLC detection. Afterwards, functional enrichment analyses of miR-486 target genes highlighted significant ontology terms and pathways crucial to the initiation and progression of NSCLC. PPI networks revealed key proteins and modules that participate in multiple essential pathways associated with NSCLC pathogenesis. Furthermore, the identified hub genes were validated for differential expression in cancerous versus normal tissues, suggesting their potential diagnostic utility, while subsequent survival analyses confirmed their prognostic value through significant associations with overall survival. Notably, these hub genes were found to be significantly associated with immune infiltration levels, immune microenvironment scores, and immune-related proteins in NSCLC. CONCLUSIONS: This dual-modality investigation establishes miR-486 as a multi-functional biomarker in NSCLC, demonstrating both diagnostic utility and immunoregulatory potential through tumor microenvironment modulation.

Humans↗

Association of metabolic dysregulation with treatment response in rectal cancer patients undergoing chemoradiotherapy.

BACKGROUND: This study aimed to explore the metabolic changes during neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced rectal cancer (LARC) by serum metabolomics analysis, and to provide new biomarkers for individualized treatment and efficacy prediction. METHODS: Serum samples from 20 patients with LARC before, during and after NCRT were collected for metabolomic analysis. The metabolites in the serum samples were analyzed qualitatively and quantitatively using gas chromatography-mass spectrometry (GC-MS). Meanwhile, the differences in metabolic profiles at different time points were compared and significantly changed metabolites were screened. RESULTS: The metabolic profiles of patients were significantly altered at different time points of NCRT. Through metabolomic analysis, we identified metabolites that were significantly altered during NCRT and revealed alterations in the associated metabolic pathways. The predictive power of pre-radiotherapy isocitric acid and pro-radiotherapy 3-hydroxy-3-(4'-hydroxy-3'-methoxyphenyl) propionic acid in distinguishing patients sensitive and non-sensitive to NCRT was markedly high, with AUC values of 0.875 and 0.75, respectively. Additional analysis indicated that a combined panel of serum metabolites yielded even higher AUC values, thereby enhancing the accuracy of predicting the efficacy of neoadjuvant NCRT. CONCLUSION: This study revealed metabolic changes and corresponding alterations in metabolic pathways during NCRT in patients with LARC by serum metabolomic analysis. The metabolic disorders may be associated with poor outcomes in patients treated with NCRT for rectal cancer, providing new biomarkers for individualized treatment and prognostic assessment. Further studies and validation will help to gain insight into the mechanism of these metabolic changes and provide more basis for clinical application.

Humans↗

Interleukin-2 inhibits NMDA receptor-mediated currents directly and may differentially affect subtypes.

Using whole-cell patch-clamp recordings, this study investigated the effects of interleukin-2 (IL-2) on N-methyl-d-aspartate (NMDA) receptor-mediated currents (I(NMDA)) in rat cultured hippocampal neurons and human embryonic kidney (HEK) 293 cells expressing recombinant NMDA receptors. We found that IL-2 (0.01-1ng/ml) immediately and significantly decreased peak I(NMDA) in cultured neurons. Interestingly, the peak I(NMDA) induced in HEK 293 cells was also inhibited by IL-2. We also found that IL-2 differentially decreased the peak amplitudes of NR2A- and NR2B-containing NMDA receptor-mediated currents (I(NR2A) and I(NR2B)) by 54+/-5% and 30+/-4%, respectively. These results provide new evidence that IL-2 induces rapid inhibition of peak currents of NMDA receptor-mediated responses with possible NR1/NR2A and NR1/NR2B subtype-differentiation, and suggest that the inhibition is mediated by direct interaction between IL-2 and NMDA receptors.

Animals↗

Brain natriuretic peptide limits myocardial infarct size dependent of nitric oxide synthase in rats.

BACKGROUND: Brain natriuretic peptide (BNP) has recently been shown to have a cardioprotective effect in animal models of myocardial ischemia-reperfusion (I-R) injury. We hypothesized that exogenous BNP limits myocardial infarction on nitric oxide synthase pathway. METHODS: A rat model of myocardial I-R injury was established by ligating the left descending coronary artery for 30 min and then reperfusing for 2 h. BNP was injected with different dose 5 min after the ligation and lasting for 145 min. The myocardial infarct size and the area at risk of ischemia were measured by staining with triphenyltetrazolium chloride (TTC) and Evans blue dye. To examine the role of nitric oxide synthase (NOS), expression of eNOS in the left ventricle was analyzed by western blotting. Nomega-nitro-L-arginine methyl ester (L-NAME; 30 ug/kg), or S-methylisothiourea (SMT; 3 ug/kg) was administrated before I-R with or without BNP. RESULTS: The control infarct-to-risk ratio was 45.1+/-1.72% (means+/-SE). BNP infused 5 min after ischemia limited infarct size in a dosage-dependent manner, with maximal protection observed at 0.01 ug/(kg min) (infarct-to-risk: 24.7+/-1.69%, P<0.01 vs. control), associated with a 10-fold increase of myocardial endothelial nitric oxide synthase above the control value. Protection afforded by BNP was abolished by L-NAME but not by SMT, suggesting the involvement of putative endothelial but not inducible nitric oxide synthase activation. CONCLUSIONS: We conclude that natriuretic peptide/NOS/NO signaling may constitute an important injury-limiting mechanism in myocardium.

Animals↗

A method on calculating high-dimensional mutual information and its application to registration of multiple ultrasound images.

Using mutual information as a criterion for medical image registration, which requires no prior segmentation or preprocessing, has been both theoretically and practically proved to be an effective method in these years. However, this technique is confined in registering two images and hard to apply to multiple ones. The reason is that unlike mutual information between two variables, high-dimensional mutual information is ill defined. In textbooks and theoretical essays, three-dimensional mutual information is proposed based on Venn diagram. Unfortunately, mutual information defined in this way is not necessarily nonnegative. In order to overcome the problem, in this paper, we introduce the mutual information matrix. By calculating its eigenvalues, high-dimensional mutual information is defined. This definition is nonnegative, bounded, and could be extended to higher dimensions, thus enables us to register more than three images. In the end, this definition is tested and proved to be effective on registration of multiple US images through simulation.

Algorithms↗

A novel clutter rejection scheme in color flow imaging.

In ultrasound color flow imaging systems, it is important to suppress the clutter signals originated from stationary and slowly moving tissue sufficiently. Without sufficient clutter rejection, the estimation of the blood flow velocity will be inaccurate, and the imaging quality will be poor. In this paper we present a new clutter rejection scheme involving first down-mixing the clutter signals to zero frequency and then cancelling the stationary echo by subtracting the signals from two consecutive pulses. This stationary echo cancelling scheme is easy to be realized with small computational power, and is adaptive to the clutter signals. Theoretical analysis and simulation using RF data prove that it's an efficient and practical clutter rejection scheme for color flow imaging.

Algorithms↗

Growth and motility inhibition of breast cancer cells by epidermal growth factor receptor degradation is correlated with inactivation of Cdc42.

Overexpression of epidermal growth factor receptor (EGFR) contributes to increased cell proliferation and migration in breast cancer. However, mechanisms of EGFR overexpression remain elusive and often cannot be attributed to gene amplification. In NIH3T3 fibroblasts, active Cdc42 inhibits c-Cbl-regulated EGFR degradation to induce cellular transformation. Here, we use two EGFR-overexpressing breast cancer cell lines, MDA-MB-231 and BT20, as models to test the hypothesis that up-regulated Cdc42 activity impairs c-Cbl-mediated EGFR degradation and contributes to EGFR overexpression. We show that silencing Cdc42 significantly reduces protein levels of EGFR, leading to a marked reduction in cell proliferation and migration, and c-Cbl knockdown increases the levels of EGFR. Expression of c-Cbl-N480, a c-Cbl mutant that is not regulated by Cdc42 and blocks Cdc42-induced transformation but still binds and ubiquitinates EGFR, enhances the rate of EGFR degradation and subsequently inhibits cell proliferation. Moreover, down-regulated EGFR signaling induced by c-Cbl-N480 decreased activity of Cdc42 and Rac1, resulting in inhibition of cell migration. These findings indicate that Cdc42 and c-Cbl are critical components involved in the regulation of EGFR protein levels and that restoration of proper EGFR degradation by disrupting Cdc42 regulation of c-Cbl can reduce cell proliferation and migration in MDA-MB-231 and BT20 cells.

Animals↗

GABA(A) receptor beta isoform protein expression in human alcoholic brain: interaction with genotype.

Chronic alcohol misuse by human subjects leads to neuronal loss in regions such as the superior frontal cortex. Reduced GABA transmission may mediate this. The expression of GABA(A) receptor beta(1), beta(2), and beta(3) isoform proteins was analyzed by western blotting in vulnerable (superior frontal cortex) and spared (primary motor cortex) cortical tissue obtained at autopsy from Caucasian subjects, and the effect of genotypes of candidate genes for alcoholism assessed. There was a significant regional difference in global isoform expression, but no significant overall group difference in beta(2) or beta(3)expression between controls and alcoholics undifferentiated by genotype in either cortical region. There were significant, regionally selective, interactions of DRD2B, SLC1A2 and APOE genotypes with beta protein expression when alcoholics were compared with controls. In each instance possession of the alcoholism-associated allele increased the beta(2):beta(3) ratio in the pathologically vulnerable region, by two distinct mechanisms. The SFC beta(2):beta(3) ratio in DRD2B-B2,B2 alcoholics was 22% higher than that in DRD2B-B1,B1 alcoholics, and 17% higher than that in DRD2B-B2,B2 controls. The SFC beta(2):beta(3) ratio in SLC1A2A603 homozygote alcoholics was 25% higher than that in alcoholics with at least one 603G allele, and 75% higher than that in SLC1A2A603 homozygote controls. The SFC beta(2):beta(3) ratio in alcoholics lacking an APOE epsilon3 allele was 73% higher than that in alcoholics with at least one epsilon3 allele, and 70% higher than that in controls without an epsilon3 allele. ADH1C genotype also differentiated cases and controls, but the effect was not localized. GABRB2 and GRIN2B genotypes were associated with significant regional differences in the pattern of beta subunit expression, but this was not influenced by alcoholism status. DRD2A and SLC6A4 genotypes were without significant effect. A restricted set of genotypes may influence subunit expression in this group of high-consumption alcoholics.

Aging↗

Suppression of human hepatoma growth in vivo by a monoclonal antibody against a Mr 45,000 protein.

The monoclonal antibody T2-2 was originally raised against the colorectal carcinoma cell line LS174T and was found to bind to several other human carcinomas, including hepatoma and ovarian cancer. The goal of this study was to investigate the antitumor activity of mAb T2-2 in human tumor models and further characterize the antigen. mAb T2-2 inhibited the growth of human hepatocellular cell line SMMC 7721 in vivo and in vitro. Western blot analysis revealed that this mAb recognizes an unique Mr 45,000 band from tissue extracts of human hepatocellular carcinoma (HCC), which localizes to the cell periphery. In vitro cell assays indicate that T2-2 decreases cell adhesion to laminin, implying the functional role of T2-2 antigen in cell-matrix interaction and cell migration.

Animals↗

[Study on the method of testing the wall filter performance].

In order to test the performance of wall filters, we propose a method for simulation of Hybrid Doppler testing signal, which adopts a rectangular power spectrum. In the method, the parameters of clutter, blood flow and system noise can be adjusted with flexibility. The problem about choosing model parameters is discussed as an emphasis. Several reasonable and typical parameter combination patterns are presented. Furthermore, an example is given to explain the process of choosing the parameters and testing the wall filter performance.

Blood Flow Velocity↗

Noise reduction for doppler ultrasound signal based on the adapted local cosine transform and the garrote thresholding method.

In this paper, a novel approach, using the adapted local cosine transform combined with the non-negative garrote thresholding, is proposed to remove noise from the Doppler ultrasound signal. In the proposed approach, the local cosine transform is first performed on the signal of interest followed by a search algorithm to select the best basis. Then the coefficients of the obtained best basis are thresholded based on the non-negative garrote thresholding method. By means of the thresholded coefficients of the best basis, the signal is reconstructed. In the simulation study, the estimation precisions of the mean frequency waveform and the spectral width waveform are studied for the signal after denoising. The simulation and clinical results have shown that the proposed approach is superior to ones based on the wavelet transform, especially under low signal-to-noise ratio (SNR) circumstances.

Algorithms↗

[A new MTI scheme in ultrasonic color flow mapping systems].

In color flow imaging systems, the ultrasound Doppler signal scattered from blood is heavily corrupted by the strong clutter signal reflected from the slow-moving muscular tissue. Moving target indicator (MTI) is a key technique of rejecting the clutter signal and detecting blood flow. To improve the performance of detecting blood flow, a new MTI scheme is proposed in this paper. It consists of a pre-filter, a clutter weak-rejector and a 2-order AR estimator. After the processing of pre-filtering and clutter weak-rejection, the strong clutter signal is effectively eliminated and its strength is comparable with blood flow. Under such condition, the optimal performance can be attained by the 2-order AR estimator. It is illustrated in the simulation that, compared with the data from traditional methods, the blood flow parameters are estimated with smaller deviation and the lower speed flow is detected.

Blood Flow Velocity↗

[Effects of nuclear factor-kappaB on ventilator induced lung biotrauma by higher tidal volume and its interaction with pro-inflammatory cytokines].

OBJECTIVES: To investigate the changes of nuclear factor (NF)-kappaB activation in lung tissues and expression of cytokines in homogenate from lung tissues in infant rabbits with mechanical ventilation (MV) caused lung injury. METHODS: Forty-five general grade healthy infant rabbits were randomly divided into 3 groups: (1) CONTROL: with no MV (NMV, n = 9); (2): Conventional MV (CMV, n = 9): V(T) = 8 ml/kg; (3): MV with large tidal volume (V(T)) (LMV, n = 9), V(T) = 24 ml/kg. NF-kappaB activity in nuclear protein from lung tissues was measured with electrophoretic mobility shift assay (EMSA); quantity of IkappaBalpha in cellular plasma from lung tissues was analyzed with Western blotting method; TNF-alpha and IL-8 mRNA and their concentrations in homogenate were measured from lung tissues with RT-PCR and ELISA, respectively. RESULTS: At all time points NF-kappaB activity was higher in LMV than that in CMV and NMV groups (P < 0.01). Quantity of IkappaBalpha decreased progressively in LMV with time (P < 0.01) as compared to CMV and NMV. The expressions of TNF-alpha and IL-8 and their protein quantity in lung tissues significantly increased in LMV after ventilation compared to that in CMV and NMV (P < 0.01). The expression level of TNF-alpha reached its peak at 4 hrs and IL-8 at 6 hrs after ventilation then TNF-alpha decreased significantly at 6 hrs after ventilation. Pathological examination of the lung tissues showed that as MV extended over the time in LMV, alveolar structures were severely destroyed and large number of WBC infiltrated in both alveolar sacs and pulmonary interstitia with RBC leakage. However, there was less lung injury in CMV and no obvious injury in NMV. CONCLUSIONS: IkappaBalpha degradation and NF-kappaB activation were involved in modulating the expression of pro-inflammatory cytokines in lung tissues during the occurrence of lung injury caused by injuring MV.

Animals↗

[Determination of water-soluble glucose, fructose and sucrose in flue-cured tobacco by high performance anion exchange chromatography coupled with pulsed amperometric detection].

The quantitative determination of water-soluble sugars such as glucose, fructose and sucrose in flue-cured tobacco by high performance anion exchange chromatography coupled with pulsed amperometric detection (HPAEC-PAD) was developed. The method was used to determine flue-cured tobacco samples containing large amounts of carbohydrates after pretreatment by water-leaching and membrane filtration. The separation was performed on a Dionex CarboPac PA-1 anion exchange column with 0.2 mol/L NaOH solution as the eluent at a flow rate of 1.0 mL/min. The injection volume was 20 microL. Good linearities were obtained for glucose, fructose and sucrose within the range of 0.5-100 mg/L (r2 > 0.997). The detection limits (S/N = 3) were 0.1 mg/L, 0.1 mg/L and 0.2 mg/L, and the average recoveries were 97.3%, 101.4% and 98.9% with good reproducibility for glucose, fructose and sucrose, respectively.

English Abstract↗

[Quadrature Doppler ultrasound signal denoising based on adapted local cosine transform].

The spectrogram of Doppler ultrasound signal has been widely used in clinical diagnosis. The additional frequency components arising from internal or external noise to the system will produce adverse effects on its subjective and quantitative analysis. A novel approach based on the adapted local cosine transform and the non-negative Garrote thresholding method was proposed to remove noise from quadrature Doppler signal. At first, the directional information was extracted from the quadrature signal. And then the denoising method based on the adapted local cosine transform is performed on the forward and backward flow signals, respectively. At last, the estimated signal was reconstructed from the denoised signals using Hilbert transform. In the simulation study, both the mean frequency and spectral width waveform were studied for the denoised signal. The simulation results had shown that this approach was superior to that based on the wavelet transform, especially under low SNR conditions.

Algorithms↗

[Designing and realization of the dynamic filter in B mode ultrasonic scanning].

This paper introduces the design and realization of the FIR dynamic filter by EP1C6Q240 of Cyclone of Altera Corporation, showing the hardware diagram of the filter and the process of calculating parameters, and compares and analyzes the B mode ultrasound images created by using the dynamic filter and by using the constant filter.

Algorithms↗