Identification of Novel Hub Genes Associated with Inflammation and Autophagy in Astragaloside Membranaceus ameliorates Lupus Nephritis by Bioinformatics Analysis and Molecular Dynamics Simulation.

BACKGROUND: Lupus nephritis is an autoimmune disease, and its pathogenesis involves inflammation and autophagy disorders. Studies have demonstrated that Astragalus membranaceus can effectively suppress the progression of LN, but the underlying therapeutic target is still unclear. OBJECTION: This study aimed to investigate the therapeutic target whereby AM ameliorates LN. METHOD: We downloaded AM and LN-related chips from the TCMSP and GEO databases, respectively. We selected the two compound targets for the subsequent analysis via WGCNA, and constructed protein interaction networks of compound targets and determined the core targets. GO, KEGG analyses were conducted on compound targets to identify enriched functional and genomic pathways. The core genes were further validated in clinical and external datasets. Molecular docking of AS with the core targets was performed using the AutoDock software, and molecular dynamics simulation was conducted for the optimal core protein ligand obtained by molecular docking by Gromacs 2020.6 software. RESULT: We obtained 10 core targets, namely IL-1ß, EGF, CCND1, CASP3, STAT1, PTGS2, PPARγ, AR, CXCL10, and KDR, from the 24 compound targets identified. The results of the GO enrichment analysis mainly included cell growth regulation. The results of the KEGG enrichment analysis showed that 7 out of 23 valid targets were significantly enriched in the mitogen-activated protein kinase pathway (p < 0.01). Combined with the clinical datasets, we found that IL-1ß, EGF, CCND1, CASP3, STAT1, PTGS2, and PPARγ have high diagnostic values for LN. In the validation dataset, all the core targets were significantly differentially expressed, except for EGF deletion. The molecular docking and molecular dynamics simulation results showed that AM and IL- 1ß, CASP3, STAT1, and PPARγ all had binding energies < -5 kJ·mol-1 and good binding properties. CONCLUSION: IL-1ß, CASP3, STAT1, and PPARγ could be potential biomarkers and therapeutic targets in AM ameliorates LN.

CD163 as a Potential Biomarker-associated Immune Inflammation in Diabetes Mellitus: A Systematic Review and Bioinformatics Analysis.

BACKGROUND: Several studies have identified CD163 as a potential mediator of diabetes mellitus through an immune-inflammation. Further study is necessary to identify its specific mechanism. OBJECTIVES: In this study, we aimed to investigate CD163 as a potential biomarker associated with immune inflammation in diabetes mellitus through a systematic review and bioinformatics analysis. METHODS: We searched PubMed, Web of Science, the Cochrane Library, and Embase databases with a time limit of September 2, 2022. Furthermore, we conducted a systematic search and review based on PRISMA guidelines. Additionally, diabetic gene expression microarray datasets GSE29221, GSE30528, GSE30529, and GSE20966 were downloaded from the GEO database (http://www.ncbi.nlm.nih.gov/geo) for bioinformatics analysis. The PROSPERO number for this study is CRD420222347160. RESULTS: Following the inclusion and exclusion criteria, seven articles included 1607 patients, comprising 912 diabetic patients and 695 non-diabetic patients. This systematic review found significantly higher levels of CD163 in diabetic patients compared to non-diabetic patients. People with diabetes had higher levels of CRP expression compared to the control group. Similarly, two of the three papers that used TNF- α as an outcome indicator showed higher expression levels in diabetic patients. Furthermore, IL-6 expression levels were higher in diabetic patients than in the control group. A total of 62 samples were analyzed by bioinformatics (33 case controls and 29 experimental groups), and 85 differential genes were identified containing CD163. According to the immune cell correlation analysis, CD163 was associated with macrophage M2, γδ T lymphocytes, macrophage M1, and other immune cells. Furthermore, to evaluate the diagnostic performance of CD163, we validated it using the GSE20966 dataset. In the validation set, CD163 showed high diagnostic accuracy. CONCLUSION: This study suggests CD163 participates in the inflammatory immune response associated with diabetes mellitus and its complications by involving several immune cells. Furthermore, the results suggest CD163 may be a potential biomarker reflecting immune inflammation in diabetic mellitus.

Gut-Skin Axis: Unravelling the Link Between Gut Microbiome and Chronic Kidney Disease-Related Skin Lesions.

It is well known that skin lesions are among the most common complications of chronic kidney disease (CKD), which significantly impact the patient's quality of life. Research has demonstrated that gut and skin lesions are closely interconnected and affect each other. This interaction is referred to as the "gut-skin axis" and the intestinal microbiota plays a critical role in this interaction. Changes in gut microbiota composition and function are associated with the development of skin diseases, which are part of the "gut-skin axis". Presently, preliminary results have been demonstrated in basic and clinical research on CKD skin lesions. With further research, the "gut-skin axis" theory can provide new ideas for treating CKD skin lesions and may become a potential treatment target.

Is the L2 lexicon different from the L1 lexicon? Evidence from novel word lexicalization.

Studies on the representation of newly learned words in the native language show that after repeated sessions of learning, novel words produce less form priming than nonwords when they are used as primes in a masked priming experiment. This suggests that the newly learned words have established lexical representations, and therefore start to behave more like real words than nonwords (Qiao & Forster, 2013). Since adult language learning normally happens in a foreign language context rather than in the native language context, it is important to see whether similar results could be obtained if bilingual subjects were taught novel words in their second language (L2) rather than their first language (L1). The current experiment explores this issue using the same procedure and materials as used in the L1 experiment. Results show that in contrast to the nonsignificant priming observed with the L1 speakers, L2 speakers show enhanced facilitatory priming after the same training process. In addition, a significant facilitatory priming effect is also obtained with real words as primes, suggesting that the L1 and L2 lexicons might work in rather different ways. One possibility is that the L2 lexicon is not represented in the same type of memory system as the L1 lexicon, rather it is represented in a system where competitive effects are not observed.

Novel word lexicalization and the prime lexicality effect.

This study investigates how newly learned words are integrated into the first-language lexicon using masked priming. Two lexical decision experiments are reported, with the aim of establishing whether newly learned words behave like real words in a masked form priming experiment. If they do, they should show a prime lexicality effect (PLE), in which less priming is obtained due to form similarity when the prime is a word. In the first experiment, subjects were taught the meanings of novel words that were neighbors of real words, but no PLE was observed; that is, equally strong form priming was obtained for both trained and untrained novel primes. In the second experiment, 4 training sessions were spread over 4 weeks, and under these conditions, a clear PLE was obtained in the final session. It is concluded that lexicalization requires multiple training sessions. Possible explanations of the PLE are discussed.

Transposed letter priming with horizontal and vertical text in Japanese and English readers.

It is well established that in masked priming, a target word (e.g., JUDGE) is primed more effectively by a transposed letter (TL) prime (e.g., jugde) than by an orthographic control prime (e.g., junpe). This is inconsistent with the slot coding schemes used in many models of visual word recognition. Several alternative coding schemes have been proposed in which special bigram detectors for frequently occurring nonadjacent letter combinations are developed as a product of perceptual learning. In order to examine this perceptual learning hypothesis, we asked whether bigram detectors are defined in terms of visuospatial coordinates. Japanese-English bilinguals who were equally familiar with horizontal and vertical text in Japanese demonstrated strong TL priming in both orientations when reading Japanese words, but, when reading English words, the evidence for vertical TL priming was not as strong. However, native English speakers showed a clear TL priming effect with vertically presented English words despite minimal exposure to vertical text, which is not consistent with a perceptual learning account. It is proposed instead that the initial letter array is transformed into an abstract ordinal code (first to last) regardless of orientation and that the speed with which this transformation is carried out depends on the familiarity of the script.

Is banara really a word?

Bowers, Davis, and Hanley (Bowers, J. S., Davis, C. J., & Hanley, D. A. (2005). Interfering neighbours: The impact of novel word learning on the identification of visually similar words. Cognition, 97(3), B45-B54) reported that if participants were trained to type nonwords such as banara, subsequent semantic categorization responses to similar words such as banana were delayed. This was taken as direct experimental support for a process of lexical competition during word recognition. This interpretation assumes that banara has been lexicalized, which predicts that masked form priming for items such as banara-banana should be reduced or eliminated. An experiment is reported showing that the trained novel words produced the same amount of priming as untrained nonwords on both the first and the second day of training, suggesting that the interference observed by Bowers et al was not due to word-on-word competition.