Screening of Genes Associated with Immune Infiltration of Discoid Lupus Erythematosus Based on Weighted Gene Co-expression Network Analysis.

Discoid lupus erythematosus (DLE) is a disorder of the immune system commonly seen in women of childbearing age. The pathophysiology and aetiology are still poorly understood, and no cure is presently available. Therefore, there is an urgent need to explore the underlying molecular mechanisms, as well as search for new therapeutic targets. Gene expression data from skin biopsies samples of DLE patients and healthy controls were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between DLE and healthy control samples were identified by differential expression analysis. Samples were analysed using CIBERSORT to examine the proportion of immune infiltration. Weighted gene co-expression network analysis was used to screen for the module most relevant to immune infiltration. Candidate genes were uploaded to the TRRUST database to obtain the potential transcription factors regulating these genes. Protein-protein interaction (PPI) analysis was performed to obtain the hub genes most associated with immune infiltration among the candidate genes. A total of 273 DEGs were identified between the DLE and healthy control samples. The results of immunoinfiltration analysis showed that the abundances of resting memory CD4 T cells, activated memory CD4 T cells and M1 macrophages were significantly higher, while those of resting infiltration of plasma cells, regulatory T cells and dendritic cells were lower in DLE samples than in healthy control samples. Correlation analysis showed that ISG15, TRIM22, XAF1, IFIT2, OAS2, OAS3, OAS1, IFI44, IFI6, BST2, IFIT1 and MX2 were negatively correlated with the abundances of plasma cells, T-cell regulatory cells and resting dendritic cells and positively correlated with activated memory CD4 T cells and M1 macrophages. Our study shows that these hub genes may regulate DLE via immune-related pathways mediated by the infiltration of these immune cells.

Rocuronium bromide suppresses esophageal cancer via blocking the secretion of C-X-C motif chemokine ligand 12 from cancer associated fibroblasts.

BACKGROUND: Cancer associated fibroblasts (CAFs) communicate metabolically with tumor genesis and development. Rocuronium bromide (RB) is reported to exert certain inhibitory effect on tumor. Here, we investigate the role of RB in esophageal cancer (EC) malignant progression. METHODS: Tumor xenograft models with EC cells were locally and systemically administrated with RB to detect the influence of different administrations on tumor progression. Mouse CAFs PDGFRα+/F4/80- were sorted by Flow cytometry with specific antibodies. CAFs were treated with RB and co-cultured with EC cells. The proliferation, invasion and apoptosis assays of EC cells were performed to detect the influences of RB targeting CAFs on EC cell malignant progression. Human fibroblasts were employed to perform these detections to confirm RB indirect effect on EC cells. The gene expression changes of CAFs response to RB treatment were detected using RNA sequencing and verified by Western blot, immunohistochemistry and ELISA. RESULTS: Tumors in xenograft mice were observed significantly inhibited by local RB administration, but not by systemic administration. Moreover EC cells did not show obvious change in viability when direct stimulated with RB in vitro. However, when CAFs treated with RB were co-cultured with EC cells, obvious suppressions were observed in EC cell malignancy, including proliferation, invasion and apoptosis. Human fibroblasts were employed to perform these assays and similar results were obtained. RNA sequencing data of human fibroblast treated with RB, and Western blot, immunohistochemistry and ELISA results all showed that CXCL12 expression was significantly diminished in vivo and in vitro by RB. EC cells direct treated with CXCL12 showed much higher malignancy. Moreover cell autophagy and PI3K/AKT/mTOR signaling pathway in CAFs were both suppressed by RB which can be reversed by Rapamycin pretreatment. CONCLUSIONS: Our data suggest that RB could repress PI3K/AKT/mTOR signaling pathway and autophagy to block the CXCL12 expression in CAFs, thereby weakening the CXCL12-mediated EC tumor progression. Our data provide a novel insight into the underlying mechanism of RB inhibiting EC, and emphasize the importance of tumor microenvironment (cytokines from CAFs) in modulating cancer malignant progression.

Immune infiltration and diagnostic value of immune-related genes in periodontitis using bioinformatics analysis.

BACKGROUND AND OBJECTIVES: Periodontitis, which is a chronic inflammatory periodontal disease resulting in destroyed periodontal tissue, is the leading cause of tooth loss in adults. Many studies have found that inflammatory immune responses are involved in the risk of periodontal tissue damage. Therefore, we analyzed the association between immunity and periodontitis using bioinformatics methods to further understand this disease. MATERIALS AND METHODS: First, the expression profiles of periodontitis and healthy samples were downloaded from the GEO database, including a training dataset GSE16134 and an external validation dataset GSE10334. Then, differentially expressed genes were identified using the limma package. Subsequently, immune cell infiltration was calculated by using the CIBERSORT algorithm. We further identified genes linking periodontitis and immunity from the ImmPort and DisGeNet databases. In addition, some of them were selected to construct a diagnostic model via a logistic stepwise regression analysis. RESULTS AND CONCLUSIONS: Two hundred sixty differentially expressed genes were identified and found to be involved in responses to bacterial and immune-related processes. Subsequently, immune cell infiltration analysis demonstrates significant differences in the abundance of most immune cells between periodontitis and healthy samples, especially in plasma cells. These results suggested that immunity doses play a non-negligible role in periodontitis. Twenty-one genes linking periodontitis and immunity were further identified. And nine hub genes of them were identified that may be key genes involved in the development of periodontitis. Gene ontology analyses showed that these genes are involved in response to molecules of bacterial origin, cell chemotaxis, and response to chemokines. In addition, three genes of them were selected to construct a diagnostic model. And its good diagnostic performance was demonstrated by the receiver operating characteristic curves, with an area under the curve of 0.9424 for the training dataset and 0.9244 for the external validation dataset.

Gene expression changes reveal the impact of the space environment on the skin of International Space Station astronauts.

BACKGROUND: The various types of ionizing radiation and altered gravity in the space environment present a risk to humans during space missions. Changes in the space environment lead to skin diseases, affecting the status of the aviators to fly. Therefore, it is important to explore the molecular-level changes in the skin during space missions. OBJECTIVES: Bioinformatics analysis of gene arrays from hair follicle tissue of 10 astronauts was performed to explore changes in gene expression before, during and after space missions. METHODS: First, STEM (Short Time-series Expression Miner) software was used to identify the expression patterns of hair follicle genes of astronauts pre-, in- and postflight. Gene Ontology Enrichment Analysis was then performed to explore the gene functions within the module. Protein-protein interaction network analysis was performed on skin-related genes. The transcriptional regulatory network within the module was constructed using the TRRUST database. The circadian rhythm-related genes within the module were screened using the MSigDB (Molecular Signatures Database). RESULTS: Based on differential expression analysis between the two groups, there were 327 differentially expressed genes after the astronauts entered space compared with preflight, and only 54 differentially expressed genes after returning to Earth. This outcome suggests that the expression of most genes can be recovered on return to the ground, but there are a small number of genes whose expression cannot be recovered in a short period of time. Based on time series analysis, 311 genes showed increased expression on entry into space and decreased expression on return to Earth. The genes of this expression pattern were associated with skin development, keratinocyte differentiation and cornification. Ten hub genes were identified as skin-related genes within the module, as well as nine transcription factors and three circadian genes. One hundred and seventy-nine genes decreased in expression after entry into space and increased on return to Earth. By reviewing the literature, we found that four of the genes, CSCD2, HP, CXCR1 and SSTR4, are associated with skin diseases. CONCLUSIONS: Through bioinformatics analysis, we found that the space environment affects skin keratinocyte differentiation, leading to skin barrier damage and inflammatory responses, and that this effect was decreased after return to Earth.

FGF21 promotes angiotensin II-induced abdominal aortic aneurysm via PI3K/AKT/mTOR pathway.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a potentially fatal vascular disorder with a high mortality rate. It was previously reported that fibroblast growth factor 21 (FGF21) was highly expressed in AAA patients. Nonetheless, its underlying mechanism in AAA progression is unclarified. METHODS: Angiotensin II (Ang-II) was used to induce AAA in human aortic vascular smooth muscle cells (HASMCs) and mouse models. Western blotting and RT-qPCR were utilized for measuring protein and RNA levels. Immunofluorescence staining was utilized for detecting LC3B expression in HASMCs. Elastica van Gieson staining was conducted for histological analysis of the abdominal aortas of mice. RESULTS: FGF21 displayed a high level in Ang-II-stimulated HASMCs and AAA mice. FGF21 depletion ameliorated abdominal aorta dilation and Ang-II-triggered pathological changes in mice. FGF21 silencing hindered autophagy and PI3K/AKT/mTOR pathway. CONCLUSIONS: FGF21 contributes to AAA progression by enhancing autophagy and activating PI3K/AKT/mTOR pathway.

Activating transcription factor 4 aggravates angiotensin II-induced cell dysfunction in human vascular aortic smooth muscle cells via transcriptionally activating fibroblast growth factor 21.

Abdominal aortic aneurysm (AAA) is a life-threatening disorder worldwide. Fibroblast growth factor 21 (FGF21) was shown to display a high level in the plasma of patients with AAA; however, its detailed functions underlying AAA pathogenesis are unclear. An in vitro AAA model was established in human aortic vascular smooth muscle cells (HASMCs) by angiotensin II (Ang-II) stimulation. Cell counting kit-8, wound healing, and Transwell assays were utilized for measuring cell proliferation and migration. RT-qPCR was used for detecting mRNA expression of FGF21 and activating transcription factor 4 (ATF4). Western blotting was utilized for assessing protein levels of FGF21, ATF4, and markers for the contractile phenotype of HASMCs. ChIP and luciferase reporter assays were implemented for identifying the binding relation between AFT4 and FGF21 promoters. FGF21 and ATF4 were both upregulated in Ang-II-treated HASMCs. Knocking down FGF21 attenuated Ang-II-induced proliferation, migration, and phenotype switch of HASMCs. ATF4 activated FGF21 transcription by binding to its promoter. FGF21 overexpression reversed AFT4 silencing-mediated inhibition of cell proliferation, migration, and phenotype switch. ATF4 transcriptionally upregulates FGF21 to promote the proliferation, migration, and phenotype switch of Ang-II-treated HASMCs.

Human Schlafen 5 regulates reversible epithelial and mesenchymal transitions in breast cancer by suppression of ZEB1 transcription.

BACKGROUND: Human Schlafen 5 (SLFN5) has been reported to inhibit or promote cell invasion in tumours depending on their origin. However, its role in breast cancer (BRCA) is undetermined. METHODS: Differential expression analyses using The Cancer Genome Atlas (TCGA) data, clinical samples and cell lines were performed. Lentiviral knockdown and overexpression experiments were performed to detect changes in cell morphology, molecular markers and invasion. Chromatin immunoprecipitation-sequencing (ChIP-Seq) and luciferase reporter assays were performed to detect the SLFN5-binding motif. RESULTS: TCGA, clinical samples and cell lines showed that SLFN5 expression was negatively correlated with BRCA metastasis. SLFN5 knockdown induced epithelial-mesenchymal transition (EMT) and enhanced invasion in BRCA cell lines. However, overexpression triggered mesenchymal-epithelial transition (MET). SLFN5 inhibited the expression of ZEB1 but not ZEB2, SNAI1, SNAI2, TWIST1 or TWIST2. Knockdown and overexpression of ZEB1 indicated that it was a mediator of the SLFN5-governed phenotype and invasion changes. Moreover, SLFN5 inhibited ZEB1 transcription by directly binding to the SLFN5-binding motif on the ZEB1 promoter, but a SLFN5 C-terminal deletion mutant did not. CONCLUSION: SLFN5 regulates reversible epithelial and mesenchymal transitions, and inhibits BRCA metastasis by suppression of ZEB1 transcription, suggesting that SLFN5 could be a potential target for BRCA therapy.

MTNR1B gene on susceptibility to gestational diabetes mellitus: a two-stage hospital-based study in Southern China.

Large-scale studies on genetic risk loci for melatonin receptor 1B (MTNR1B) gene and GDM risk have not been well generalized to the Chinese population. In this study, we performed two-stage case-control study: 1.429 pregnant women: 753 GDM/676 controls in the Southern Chinese population by genotyping 5 SNPs (rs10830963, rs1387153, rs2166706, rs1447352, and rs4753426) in MTNR1B. Genotypes were determined using the Sequenom MassARRAY platform and TaqMan allelic discrimination assay. Interactions between genetic variants and age/BMI as predictors of GDM risk were evaluated under the logistic regression model. In the first stage, the SNP rs10830963 was discovered to be potentially related to GDM risk (additive model: OR = 1.27, 95%CI = 1.05-1.55, P = 0.025), which was further confirmed in the second stage with a similar effect (additive model: OR = 1.53, 95%CI = 1.19-1.98, P = 0.005). In the combined stage, the G allele of rs10830963 was potentially associated with GDM risk (additive model: OR = 1.36, 95%CI = 1.17-1.59, P < 0.001; dominant model: OR = 1.45, 95%CI = 1.15-1.83, P = 0.005). The rs10830963 interacted with age and BMI to contribute to GDM risk in the combined participants. And, the similar interactive effects for the other four SNPs also exist. These findings offer the potential to improve our understanding of the etiology of GDM, and particularly of biological mechanisms.

SPARC correlates with unfavorable outcome and promotes tumor growth in lung squamous cell carcinoma.

Secreted protein acidic and rich in cysteine (SPARC) plays a crucial role in the malignant progression of a number of human cancers. However, the roles of SPARC in lung squamous cell carcinoma (LSCC) remain elusive. In this present study, we first detected SPARC expression and investigated the relationship between SPARC expression and the clinicopathological attributes of LSCC patients. Then we constructed SPARC-overexpression model in LSCC cell line to explore the characteristics of SPARC in LSCC development both in vitro and in vivo. The data demonstrated a remarkably higher level of SPARC in LSCC tissues than in corresponding non-cancerous tissues and elevated SPARC expression was significantly correlated with poor outcome in LSCC patients. Moreover, a serial of phenotypic experiments indicated that SPARC overexpression substantially facilitated the growth and inhibited the apoptosis in LSCC cells and xenografts. Taken together, our results suggest that SPARC is a novel prognostic marker for LSCC prognosis and SPARC significantly promotes LSCC tumorigenesis. Targeting SPARC may provide a novel therapeutic strategy for LSCC management.

Association of Polymorphisms of the Matrix Metalloproteinase 9 Gene with Ischaemic Stroke in a Southern Chinese Population.

BACKGROUND/AIMS: Matrix metalloproteinase 9 (MMP9), a potent endopeptidase degrading extracellular matrix, plays a pivotal role in the pathogenesis of ischaemic stroke (IS). The present study was undertaken to determine the association of MMP9 gene polymorphisms and the risk of IS in a southern Chinese population. METHODS: A cohort of 1274 patients and 1258 age-matched healthy controls were genotyped to detect the four MMP9 polymorphisms (rs17156, rs3787268, rs3918241 and rs3918242) using SNaPshot. RESULTS: Our study demonstrated a significant difference in the genotype and allele frequencies of the MMP9 rs3918242 polymorphism between the IS patients and the controls (P = 0.012 for the genotype and P = 0.0092 for the allele). Stratification by smoking status showed statistically significant differences in the frequency and allele of the rs3918242 polymorphism between IS patients and the controls (P = 0.0052 for the genotype and P = 0.0019 for the allele). Further stratification by IS subtypes revealed that the presence of the T allele of the MMP9 rs3918242 polymorphism confers a higher risk of the large artery atherosclerosis subtype of IS (P = 0.017). Moreover, IS patients with the rs3918242 T allele of MMP9 presented with increased serum MMP9 production, and this increase was more significant in smokers with IS (P = 0.022). Patients carrying the variant T allele of the MMP9 rs3918242 polymorphism exhibited significantly higher infarct volumes than those with the major CC genotype (P = 0.036). CONCLUSION: Our study provides preliminary evidence that the MMP9 rs3918242 polymorphism is linked to a higher risk of IS, confirming the role of MMP9 in the pathophysiology of IS, with potentially important therapeutic implications.

Analysis of ADAM17 polymorphisms and susceptibility to sporadic abdominal aortic aneurysm.

BACKGROUND: Accumulating evidence suggests that the principal TNF-α converting enzyme, a disintegrin and metalloproteinase 17 (ADAM17), is involved in the development of human abdominal aortic aneurysm (AAA). However, the association between ADAM17 gene polymorphisms and AAA has not been explored. The present study was aimed to determine the association between ADAM17 promoter polymorphisms and AAA. METHODS: A total of 316 patients with AAA and 306 age-matched healthy controls were enrolled in this study. Two ADAM17 promoter polymorphisms (rs12692386 and rs1524668) were determind. Real-time PCR was employed to detect the expression of ADAM17. RESULTS: Overall, there was a significant difference in the frequency of the genotype rs12692386 between the AAA and control subjects (P=0.0096). Furthermore, men with the rs12692386 AG genotype conferred a higher risk of developing AAA (P=0.0058). Additionally, the rs12692386 mutated AG genotype of ADAM17 was significantly associated with increased ADAM17 expression (P=0.035) and TNF-α production (P=0.042) in AAA patients. In contrast, the allele frequency of rs1524668 was not statistically associated with AAA. CONCLUSIONS: Our findings indicate a positive association between the rs12692386 polymorphism of ADAM17 and AAA. This new knowledge about ADAM17 identifies a role for ADAM17 in the pathophysiology of AAA and has important clinical implications with regard to potential therapeutics.

P21-activated kinase 5 plays essential roles in the proliferation and tumorigenicity of human hepatocellular carcinoma.

AIM: To investigate the roles of P21-activated kinase 5 (PAK5) in proliferation and tumorigenicity of human hepatocellular carcinoma (HCC). METHODS: HCC and matched paraneoplastictis tissue samples were obtained from 30 patients. Human HCC cell lines SMMC7721, HepG2, Hep3B, SK-HEP-1, Huh-7, and liver cell line HL-7702 were examined. The expression of PAK5 gene was studied using real-time qPCR and Western blotting. Cell proliferation was quantified with the MTT assay. Cell cycle was analyzed with flow cytometry. The tumorigenicity of Lv-shRNA-transfected HepG2 cells was evaluated in BALB/cA nude mice. RESULTS: The mRNA level of PAK5 was significantly higher in 25 out of 30 HCC samples compared to the matched paraneoplastic tissues. The HCC cell lines showed varying expression of PAK5 protein, and the highest level was found in the HepG2 cells. PAK5 gene silencing in HepG2 cells markedly reduced the cell proliferation and colony formation, and induced cell cycle arrest in the G1 phase. Furthermore, PAK5 gene silencing suppressed the tumor formation in nude mice, and significantly decreased the expression of HCC-related genes Cyclin D1 and beta-catenin. CONCLUSION: PAK5 may play essential roles in the initiation and progression of human HCC. Thus, it may be an effective therapeutic target or perhaps serve as a clinical diagnostic or prognostic marker in human HCC.

Single Cell Sequencing Technology and Its Application in Alzheimer's Disease.

Alzheimer's disease (AD) involves degeneration of cells in the brain. Due to insidious onset and slow progression, AD is often not diagnosed until it gets progressed to a more severe stage. The diagnosis and treatment of AD has been a challenge. In recent years, high-throughput sequencing technologies have exhibited advantages in exploring the pathogenesis of diseases. However, the types of cells of the central nervous system are complex and traditional bulk sequencing cannot reflect their heterogeneity. Single-cell sequencing technology enables study at the individual cell level and has an irreplaceable advantage in the study of complex diseases. In recent years, this field has expanded rapidly and several types of single-cell sequencing technologies have emerged, including transcriptomics, epigenomics, genomics and proteomics. This review article provides an overview of these single-cell sequencing technologies and their application in AD.

Visible-Light-Induced Difunctionalization of 3-Butenoic Acid with Bromodifluoromethyl Heteroarylsulfones.

Herein, we report a visible-light-induced iridium-promoted direct bifunctionalization of 3-butenoic acid with bromodifluoromethyl heteroarylsulfones. This methodology enables the concurrent introduction of difluoromethyl heteroarylsulfone and bromine groups into 3-butenoic acid under mild reaction conditions. Various α-substituted 3-butenoic acids and bromodifluoromethyl heteroarylsulfones were found to be compatible, yielding the corresponding products in moderate to good yields. This method opens a new route for the synthesis of fluorocarboxylic acid derivatives.

Transcriptomic analysis identifies the shared diagnostic biomarkers and immune relationship between Atherosclerosis and abdominal aortic aneurysm based on fatty acid metabolism gene set.

Background: Epidemiological research has demonstrated that there is a connection between lipid metabolism disorder and an increased risk of developing arteriosclerosis (AS) and abdominal aortic aneurysm (AAA). However, the precise relationship between lipid metabolism, AS, and AAA is still not fully understood. The objective of this study was to examine the pathways and potential fatty acid metabolism-related genes (FRGs) that are shared between AS and AAA. Methods: AS- and AAA-associated datasets were retrieved from the Gene Expression Omnibus (GEO) database, and the limma package was utilized to identify differentially expressed FRGs (DFRGs) common to both AS and AAA patients. Functional enrichment analysis was conducted on the (DFRGs), and a protein-protein interaction (PPI) network was established. The selection of signature genes was performed through the utilization of least absolute shrinkage and selection operator (LASSO) regression and random forest (RF). Subsequently, a nomogram was developed using the results of the screening process, and the crucial genes were validated in two separate external datasets (GSE28829 and GSE17901) as well as clinical samples. In the end, single-sample gene set enrichment analysis (ssGSEA) was utilized to assess the immune cell patterns in both AS and AAA. Additionally, the correlation between key crosstalk genes and immune cell was evaluated. Results: In comparison to control group, both AS and AAA patients exhibited a decrease in fatty acid metabolism score. We found 40 DFRGs overlapping in AS and AAA, with lipid and amino acid metabolism critical in their pathogenesis. PCBD1, ACADL, MGLL, BCKDHB, and IDH3G were identified as signature genes connecting AS and AAA. Their expression levels were confirmed in validation datasets and clinical samples. The analysis of immune infiltration showed that neutrophils, NK CD56dim cells, and Tem cells are important in AS and AAA development. Correlation analysis suggested that these signature genes may be involved in immune cell infiltration. Conclusion: The fatty acid metabolism pathway appears to be linked to the development of both AS and AAA. Furthermore, PCBD1, ACADL, MGLL, BCKDHB, and IDH3G have the potential to serve as diagnostic markers for patients with AS complicated by AAA.

Krüppel-like factor 8 is a novel androgen receptor co-activator in human prostate cancer.

AIM: Krüppel-like factor 8 (KLF8) plays important roles in cell cycle and oncogenic transformation. On other hand, androgen receptor (AR) is crucial in development of both androgen-dependent and independent prostatic malignancies. The aim of this study is to investigate the role of KLF8 in prostate cancer (PCa) and the relationship between KLF8 and AR. METHODS: Eight human PCa cell lines, including androgen-dependent LNCap cells and androgen-independent 22Rv1 cells, as well as human PCa samples were studied. LNCap cells and 22Rv1 cells were transfected with plasmids encoding full-length wild-type KLF8 or KLF8 shRNA. The expression of KLF8 protein was detected using Western blotting or immunohistochemical staining. Cell proliferation in vitro was measured with MTT assay, and in vivo in a xenograft nude mouse model. Yeast two-hybrid screening, co-immunoprecipitation and pull down assays were used to examine the binding of KLF8 to AR. Luciferase reporter gene assay was used to measure the transcriptional activity of the genes targeted by AR. RESULTS: In 133 human PCa samples, KLF8 protein staining was observed in 92.65% (63/68) of high-grade PCa, 66.15% (43/65) of low-grade PCa, and 6.82% (3/44) of adjacent normal tissues. The expression of KLF8 was significantly associated with poorer overall survival. Overexpression of KLF8 enhanced the proliferation of both LNCap and 22Rv1 cells, while knockdown of endogenous KLF8 suppressed the proliferation. These manipulations exerted similar effects on the tumor volumes in the xenograft nude mouse model. Yeast two-hybrid screening revealed that KLF8 was a novel AR-interacting protein. With pull down assay and co-immunoprecipitation assay, we demonstrated that KLF8 bound directly to AR, and KLF8 enhanced AR target gene transcription. CONCLUSION: The results demonstrate that KLF8 is a novel AR transcriptional co-activator that is overexpressed in PCa and may play a role in progression of hormone-refractory PCa.

Effects of spaceflight on the spleen and thymus of mice: Gene pathway analysis and immune infiltration analysis.

During space flight, the immune system function of the body is disrupted due to continuous weightlessness, radiation and other factors, resulting in an increased incidence of infectious diseases in astronauts. However, the effect of space flight on the immune system at the molecular level is unknown. The aim of this study was to identify key genes and pathways of spatial environmental effects on the spleen and thymus using bioinformatics analysis of the GEO dataset. Differentially expressed genes (DEGs) in the spleen and thymus of mice preflight and postflight were screened by comprehensive analysis of gene expression profile data. Then, GO enrichment analysis of DEGs was performed to determine the biological role of DEGs. A protein-protein interaction network was used to identify hub genes. In addition, transcription factors in DEGs were screened, and a TF-target regulatory network was constructed. Finally, immune infiltration analysis was performed on spleen and thymus samples from mice. The results showed that DEGs in the spleen and thymus are mainly involved in immune responses and in biological processes related to platelets. Six hub genes were identified in the spleen and 13 in the thymus, of which Ttr, Aldob, Gc and Fabp1 were common to both tissues. In addition, 5 transcription factors were present in the DEGs of the spleen, and 9 transcription factors were present in the DEGs of the thymus. The spatial environment can influence the degree of immune cell infiltration in the spleen and thymus. Our study bioinformatically analyzed the GEO dataset of spacefaring mice to identify the effects of the space environment on the immune system and the genes that play key roles, providing insights for the treatment of spaceflight-induced immune system disorders.

The effects of esketamine on the intestinal microenvironment and intestinal microbiota in mice.

OBJECTIVE: This study aimed to investigate the impact of esketamine on the intestinal flora and microenvironment in mice using mRNA transcriptome sequencing and 16S rRNA sequencing. METHODS: Ten female mice were randomly assigned to two groups. One group received daily intramuscular injections of sterile water, while the other group received esketamine. After 24 days, the mice were sacrificed, and their intestinal tissues and contents were collected for 16S rRNA sequencing and mRNA transcriptome sequencing. The intergroup differences in the mouse intestinal flora were analyzed. Differentially expressed genes were utilized to construct ceRNA networks and transcription factor regulatory networks to assess the effects of esketamine on the intestinal flora and intestinal tissue genes. RESULTS: Esketamine significantly altered the abundance of intestinal microbiota, including Adlercreutzia equolifaciens and Akkermansia muciniphila. Differential expression analysis revealed 301 significantly upregulated genes and 106 significantly downregulated genes. The ceRNA regulatory network consisted of 6 lncRNAs, 44 miRNAs, and 113 mRNAs, while the regulatory factor network included 13 transcription factors and 53 target genes. Gene Ontology enrichment analysis indicated that the differentially expressed genes were primarily associated with immunity, including B-cell activation and humoral immune response mediation. The biological processes in the ceRNA regulatory network primarily involved transport, such as organic anion transport and monocarboxylic acid transport. The functional annotation of target genes in the TF network was mainly related to epithelial cells, including epithelial cell proliferation and regulation. CONCLUSION: Esketamine induces changes in gut microbiota and the intestinal microenvironment, impacting the immune environment and transport modes.

Identification of mitochondrial-related genes as potential biomarkers for the subtyping and prediction of Alzheimer's disease.

Introduction: Alzheimer's disease (AD) is a progressive and debilitating neurodegenerative disorder prevalent among older adults. Although AD symptoms can be managed through certain treatments, advancing the understanding of underlying disease mechanisms and developing effective therapies is critical. Methods: In this study, we systematically analyzed transcriptome data from temporal lobes of healthy individuals and patients with AD to investigate the relationship between AD and mitochondrial autophagy. Machine learning algorithms were used to identify six genes-FUNDC1, MAP1LC3A, CSNK2A1, VDAC1, CSNK2B, and ATG5-for the construction of an AD prediction model. Furthermore, AD was categorized into three subtypes through consensus clustering analysis. Results: The identified genes are closely linked to the onset and progression of AD and can serve as reliable biomarkers. The differences in gene expression, clinical features, immune infiltration, and pathway enrichment were examined among the three AD subtypes. Potential drugs for the treatment of each subtype were also identified. Discussion: The findings observed in the present study can help to deepen the understanding of the underlying disease mechanisms of AD and enable the development of precision medicine and personalized treatment approaches.

Migfilin: Cell Adhesion Effect and Comorbidities.

Cell adhesion manifests as cell linkages to neighboring cells and/or the extracellular matrix (ECM). Migfilin is a widely expressed adhesion protein. It comprises three LIM domains in the C-terminal region and one proline-rich sequence in the N-terminal region. Through interplay with its various binding partners, such as Kindlin-2, Filamin, vasodilator-stimulated phosphoprotein (VASP) protein and the transcription factor CSX, Migfilin facilitates the dynamic association of connecting actomyosin fibers, orchestrating cell morphogenetic movement and cell adhesion, proliferation, migration, invasion, differentiation and signal transduction. In this review, to further elucidate the functional contributions of and pathogenesis induced by Migfilin, we focused on the structure of Migfilin and the targets which it directly binds with. We also summarized the role of Migfilin and its binding partners in the progression of different diseases and malignancies. As a possible candidate for coordinating various cellular processes and because of its association with both the pathogenesis and progression of certain tumors, Migfilin likely has utility as a therapeutic target against multiple diseases in the clinic.