QIGTD: identifying critical genes in the evolution of lung adenocarcinoma with tensor decomposition.

BACKGROUND: Identifying critical genes is important for understanding the pathogenesis of complex diseases. Traditional studies typically comparing the change of biomecules between normal and disease samples or detecting important vertices from a single static biomolecular network, which often overlook the dynamic changes that occur between different disease stages. However, investigating temporal changes in biomolecular networks and identifying critical genes is critical for understanding the occurrence and development of diseases. METHODS: A novel method called Quantifying Importance of Genes with Tensor Decomposition (QIGTD) was proposed in this study. It first constructs a time series network by integrating both the intra and inter temporal network information, which preserving connections between networks at adjacent stages according to the local similarities. A tensor is employed to describe the connections of this time series network, and a 3-order tensor decomposition method was proposed to capture both the topological information of each network snapshot and the time series characteristics of the whole network. QIGTD is also a learning-free and efficient method that can be applied to datasets with a small number of samples. RESULTS: The effectiveness of QIGTD was evaluated using lung adenocarcinoma (LUAD) datasets and three state-of-the-art methods: T-degree, T-closeness, and T-betweenness were employed as benchmark methods. Numerical experimental results demonstrate that QIGTD outperforms these methods in terms of the indices of both precision and mAP. Notably, out of the top 50 genes, 29 have been verified to be highly related to LUAD according to the DisGeNET Database, and 36 are significantly enriched in LUAD related Gene Ontology (GO) terms, including nuclear division, mitotic nuclear division, chromosome segregation, organelle fission, and mitotic sister chromatid segregation. CONCLUSION: In conclusion, QIGTD effectively captures the temporal changes in gene networks and identifies critical genes. It provides a valuable tool for studying temporal dynamics in biological networks and can aid in understanding the underlying mechanisms of diseases such as LUAD.

Investigating the evolution process of lung adenocarcinoma via random walk and dynamic network analysis.

Lung adenocarcinoma (LUAD) is a typical disease regarded as having multi-stage progression. However, many existing methods often ignore the critical differences among these stages, thereby limiting their effectiveness for discovering key biological molecules and biological functions as signals at each stage. In this study, we propose a method to discover the evolution between biological molecules and biological functions by investigating the multi-stage biological molecules of LUAD. The method is based on the random walk algorithm and the Monte Carlo method to generate clusters as the modules, which were used as subgraphs of the differentiated biological molecules network in each stage. The connection between modules of adjacent stages is based on the measurement of the Jaccard coefficient. The online gene set enrichment analysis tool (DAVID) was used to obtain biological functions corresponding to the individual important modules. The core evolution network was constructed by combining the aforementioned two networks. Since the networks here are all dynamic, we also propose a strategy to visualize the dynamic information together in one network. Eventually, 12 core modules and 11 core biological functions were found through such evolutionary analyses. Among the core biological functions that we obtained, six functions are related to the disease, the biological function of neutrophil chemotaxis is not directly associated with LUAD but can serve as a predictor, two functions may serve as a predictive signal, and two functions need to be verified through more biological evidence. Compared with two alternative design methods, the method proposed in this study performed more efficiently.

Several miRNAs derived from serum extracellular vesicles are potential biomarkers for early diagnosis and progression of Parkinson's disease.

BACKGROUND: Blood-based test for predicting disease progression and early diagnosis of Parkinson's disease (PD) is an unmet need in the clinic. The profiles of microRNAs (miRNAs) are regarded as potential diagnostic biomarkers for human diseases, whereas miRNAs in the periphery are susceptible to the influence of various components. MiRNAs enriched in serum extracellular vesicles (EVs) have demonstrated disease-specific advantages in diagnosis due to their high abundance, stability and resistance to degradation. This study was aimed to screen differentially expressed EV-derived miRNAs between healthy controls and PD patients to aid in diagnosis of PD. METHODS: A total of 31 healthy controls and 72 patients with a diagnosis of PD at different Hoehn and Yahr stages in Tangdu Hospital were included. In total, 185 differentially expressed miRNAs were obtained through RNA sequencing of serum EVs as well as edgeR and t-test analyses. Subsequently, the weighted gene co-expression network analysis (WGCNA) was utilized to identify the commonly expressed miRNAs in all stages of PD by constructing connections between modules, and specifically expressed miRNAs in each stage of PD by functional enrichment analysis. After aligning these miRNAs with PD-related miRNAs in Human miRNA Disease Database, the screened miRNAs were further validated by receiver operating characteristic (ROC) curves and quantitative real-time polymerase chain reaction (qRT-PCR) using peripheral blood EVs from 40 more participants. RESULTS: WGCNA showed that 4 miRNAs were commonly associated with all stages of PD and 13 miRNAs were specifically associated with different stages of PD. Of the 17 obtained miRNAs, 7 were validated by ROC curve analysis and 7 were verified in 40 more participants by qRT-PCR. Six miRNAs were verified by both methods, which included 2 miRNAs that were commonly expressed in all stages of PD and 4 miRNAs that were specifically expressed in different stages of PD. CONCLUSIONS: The 6 serum EV-derived miRNAs, hsa-miR-374a-5p, hsa-miR-374b-5p, hsa-miR-199a-3p, hsa-miR-28-5p, hsa-miR-22-5p and hsa-miR-151a-5p, may potentially be used as biomarkers for PD progression and for early diagnosis of PD in populations.

Effects of melatonin on blood pressure in stress-induced hypertension in rats.

Melatonin, acting through its receptors, is involved in numerous physiological processes, including blood pressure (BP) regulation. In present study, the effect of melatonin inhibition on stress-induced hypertension was investigated. The hypertensive model consisted of male Sprague-Dawley rats subjected to electrical foot-shock combined with noise. Microinjection of melatonin (0.1 and 1.0 mmol/L) into the anterior hypothalamic area (AHA) produced a fall in BP in nomortensive rats and stress-induced hypertensive rats (SIHR). Luzindole (10 mmol/L), a competitive antagonist of melatonin MT1 and MT2 receptors, almost completely abolished the depressor effect of melatonin, the MT2 receptor-specific antagonist 4-phenyl-2-propionamidotetralin (10 mmol/L) partially blocked (by approximately 60%) the depressor effect of melatonin, whereas the MT3 receptor-selective antagonist prazosin (10 mmol/L) failed to antagonize the effects of melatonin. Brain microdialysis was performed in the AHA and the rostral ventrolateral medulla (RVLM). Melatonin and amino acids in the dialysate samples collected were detected by high-performance liquid chromatography combined with fluorescence detection. The results indicated that melatonin concentrations in the AHA were reduced in SIHR. Microinjection of melatonin into the AHA decreased glutamate release and increased GABA and taurine release in the RVLM, which were paralleled by a decrease in arterial pressure. The mRNA expression of MT2 in the AHA of SIHR was higher than that in normotensive control rats, whereas there was no significant difference in MT1 mRNA expressin between the two groups. The results of the present study suggest that both a decrease of melatonin and an increase in the MT2 receptor in the AHA are involved in the manifestation of stress-induced hypertension. Both MT1 and MT2 receptors participated in the antihypertensive effect of melatonin in the AHA. The antihypertensive effect of melatonin was related to the decreases in the excitatory amino acid glutamate and increases in the inhibitory amino acids taurine and GABA in the RVLM.

Prefrontal modulation of tactile responses in the ventrobasal thalamus of rats.

Prefrontal cortex (PFC) has been implicated in modulation of sensory information processing in somatosensory cortex. However, it remains unclear whether or not PFC regulates sensory information in thalamus. In the present study, the effect of PFC stimulation on tactile responses of neurons in the ventrobasal thalamus (VB) of the rat was investigated by single-unit recording. PFC stimulation significantly enhanced the signal-noise ratio (tactile responses/background activities) in 16 out of 66 VB neurons (24.2%) that had receptive fields in fore or hind limbs. Such changes can be classified into three different categories: (1) PFC stimulation not only increased the tactile responses, but also suppressed the background activities of neurons (six neurons, 9.1%); (2) PFC stimulation only increased the tactile responses of neurons (five neurons, 7.6%); (3) PFC stimulation only suppressed the background activities of neurons (five neurons, 7.6%). Our results suggest that PFC also modulates somatosensory information at the thalamic level.

Properties of tactile responses of neurons in rat thalamic ventroposterolateral nucleus.

OBJECTIVE: To determine whether the convergences of tactile information also occur at thalamic ventroposterolateral nucleus in rats, we investigated the properties of tactile responses of the thalamic ventroposterolateral nucleus in rats. METHODS: Unit responses were recorded extracellularly from thalamic ventroposterolateral nucleus in anesthetized rats. RESULTS: Among 156 neurons examined, 140 neurons (89.7%) had the single, continual and small receptive fields, and 16 neurons (10.3%) had two discrete receptive fields. Some neurons?exhibited different responses to the same intensity stimulation which delivered to different points in their receptive fields. In addition, 4.5% neurons (n = 7) responded only to locomotive stimulation but?not to a punctiform tactile stimulation. CONCLUSION: The majority of neurons in ventroposterolateral nucleus of rats have the spatial, temporal and submodal characteristics of cutaneous receptors, while the minority of neurons exhibit the responses of interaction of different peripheral receptors. Therefore, it is concluded that there are convergences of tactile information at the ventroposterolateral nucleus of rats.

Properties of tactile responses of neurons in rat thalamic ventroposterolateral nucleus / 神经科学通报·英文版

<p><b>OBJECTIVE</b>To determine whether the convergences of tactile information also occur at thalamic ventroposterolateral nucleus in rats, we investigated the properties of tactile responses of the thalamic ventroposterolateral nucleus in rats.</p><p><b>METHODS</b>Unit responses were recorded extracellularly from thalamic ventroposterolateral nucleus in anesthetized rats.</p><p><b>RESULTS</b>Among 156 neurons examined, 140 neurons (89.7%) had the single, continual and small receptive fields, and 16 neurons (10.3%) had two discrete receptive fields. Some neurons?exhibited different responses to the same intensity stimulation which delivered to different points in their receptive fields. In addition, 4.5% neurons (n = 7) responded only to locomotive stimulation but?not to a punctiform tactile stimulation.</p><p><b>CONCLUSION</b>The majority of neurons in ventroposterolateral nucleus of rats have the spatial, temporal and submodal characteristics of cutaneous receptors, while the minority of neurons exhibit the responses of interaction of different peripheral receptors. Therefore, it is concluded that there are convergences of tactile information at the ventroposterolateral nucleus of rats.</p>

GABA mediaties the inhibitory effect of lateral amygdaloid nucleus stimulation on the acoustic response of neurons in A I cortex: An in vivo microiontophoretic study.

Experiments were performed on Sprague Dawley rats with multibarrel microelectrode technique. The effects of acoustic response of A I cortex neurons produced by electrical stimulation of lateral amygdaloid nucleus (LA) and the influence of GABA were observed. Experimental results showed that iontophoretic administration of GABA caused a pronounced inhibition of the electrical activity of A-I neurons. Blockade of GABA(A) with bicuculline (BIC) facilitated the acoustic response. The acoustic response of A-I neurons was inhibited when the LA was stimulated. Iontophoretic application of GABA resulted in a similar inhibitory effect as that of LA stimulation. Blockade of GABA(A) with bicuculline reversed the inhibitory effect of LA stimulation on the acoustic response of A-I neurons. In contrast, application of strychnine, a glycine receptor antagonist, could not reverse the inhibitory effect of LA. Baclofen, a GABA(B) agonist, did not affect the acoustic response of the auditory neurons. These results indicate that GABA is the ultimate transmitter which mediates the LA stimulation-induced inhibition of the acoustic response of A-I neurons in rats, possibly via the GABA(A) receptor.

GABA mediaties the inhibitory effect of lateral amygdaloid nucleus stimulation on the acoustic response of neurons in A I cortex: An in vivo microiontophoretic study / 生理学报

Experiments were performed on Sprague Dawley rats with multibarrel microelectrode technique. The effects of acoustic response of A I cortex neurons produced by electrical stimulation of lateral amygdaloid nucleus (LA) and the influence of GABA were observed. Experimental results showed that iontophoretic administration of GABA caused a pronounced inhibition of the electrical activity of A-I neurons. Blockade of GABA(A) with bicuculline (BIC) facilitated the acoustic response. The acoustic response of A-I neurons was inhibited when the LA was stimulated. Iontophoretic application of GABA resulted in a similar inhibitory effect as that of LA stimulation. Blockade of GABA(A) with bicuculline reversed the inhibitory effect of LA stimulation on the acoustic response of A-I neurons. In contrast, application of strychnine, a glycine receptor antagonist, could not reverse the inhibitory effect of LA. Baclofen, a GABA(B) agonist, did not affect the acoustic response of the auditory neurons. These results indicate that GABA is the ultimate transmitter which mediates the LA stimulation-induced inhibition of the acoustic response of A-I neurons in rats, possibly via the GABA(A) receptor.