Systems biology-based analysis exploring shared biomarkers and pathogenesis of myocardial infarction combined with osteoarthritis.

Background: More and more evidence supports the association between myocardial infarction (MI) and osteoarthritis (OA). The purpose of this study is to explore the shared biomarkers and pathogenesis of MI complicated with OA by systems biology. Methods: Gene expression profiles of MI and OA were downloaded from the Gene Expression Omnibus (GEO) database. The Weighted Gene Co-Expression Network Analysis (WGCNA) and differentially expressed genes (DEGs) analysis were used to identify the common DEGs. The shared genes related to diseases were screened by three public databases, and the protein-protein interaction (PPI) network was built. GO and KEGG enrichment analyses were performed on the two parts of the genes respectively. The hub genes were intersected and verified by Least absolute shrinkage and selection operator (LASSO) analysis, receiver operating characteristic (ROC) curves, and single-cell RNA sequencing analysis. Finally, the hub genes differentially expressed in primary cardiomyocytes and chondrocytes were verified by RT-qPCR. The immune cell infiltration analysis, subtypes analysis, and transcription factors (TFs) prediction were carried out. Results: In this study, 23 common DEGs were obtained by WGCNA and DEGs analysis. In addition, 199 common genes were acquired from three public databases by PPI. Inflammation and immunity may be the common pathogenic mechanisms, and the MAPK signaling pathway may play a key role in both disorders. DUSP1, FOS, and THBS1 were identified as shared biomarkers, which is entirely consistent with the results of single-cell RNA sequencing analysis, and furher confirmed by RT-qPCR. Immune infiltration analysis illustrated that many types of immune cells were closely associated with MI and OA. Two potential subtypes were identified in both datasets. Furthermore, FOXC1 may be the crucial TF, and the relationship of TFs-hub genes-immune cells was visualized by the Sankey diagram, which could help discover the pathogenesis between MI and OA. Conclusion: In summary, this study first revealed 3 (DUSP1, FOS, and THBS1) novel shared biomarkers and signaling pathways underlying both MI and OA. Additionally, immune cells and key TFs related to 3 hub genes were examined to further clarify the regulation mechanism. Our study provides new insights into shared molecular mechanisms between MI and OA.

Fatty infiltration and morphology of cervical muscles in patients with temporomandibular disorders: A case-control study.

BACKGROUND: Changes in the fatty infiltration and/or muscle volume of neck muscles can alter cervical spine alignment and cranial load distribution, which may cause pain in the orofacial region. OBJECTIVES: The aim of the study was to examine the muscle volume and fatty infiltration of neck muscles in patients with temporomandibular disorders (TMD). MATERIAL AND METHODS: This case-control study included 18 patients with TMD and 18 ageand sex-matched controls. The muscle volume and fatty infiltration of the neck muscles of the participants were measured using magnetic resonance imaging (MRI) and ITK-SNAP software. The 3D models of the sternocleidomastoid (SCM), splenius capitis (SPLC), semispinalis cervicis (SC)-semispinalis capitis (SCP), and multifidus (M) muscles within the C3-C7 range were created using ITK-SNAP, a semi-automatic segmentation software. The models were used to determine the volumes and fatty infiltration levels. The Neck Disability Index (NDI) was used to assess neck pain-related disability. The severity of TMD was determined using the Fonseca Anamnestic Index (FAI), while jaw-related disability was measured with the Jaw Functional Limitation Scale-20 (JFLS-20). Pain levels were recorded at rest and during chewing using the numeric rating scale (NRS). RESULTS: There were no statistically significant differences in total muscle volume, fatty infiltration volume and fatty infiltration percentage of the SCM, SPLC, SCP, SC, and M muscles between the 2 groups (p > 0.05). The patient group had higher NDI scores compared to the controls (p < 0.001). The NDI scores correlated positively with the JFLS-20 (r = 0.831, p < 0.001), FAI (r = 0.815, p < 0.001) and NRS scores at rest (r = 0.753, p < 0.001) and during chewing (r = 0.686, p < 0.001). CONCLUSIONS: The present study did not identify any significant differences in the neck muscle volume or fatty infiltration between the TMD patients and controls. However, the severity of neck disability was found to correlate with jaw function, pain and TMD levels.

Insights into immune microenvironment and therapeutic targeting in androgen-associated prostate cancer subtypes.

Prostate cancer, one of the most prevalent malignancies among men worldwide, is intricately linked with androgen signaling, a key driver of its pathogenesis and progression. Understanding the diverse expression patterns of androgen-responsive genes holds paramount importance in unraveling the biological intricacies of this disease and prognosticating patient outcomes. In this study, utilizing consensus clustering analysis based on the expression profiles of androgen-responsive genes, prostate cancer patients from the TCGA database were stratified into two distinct subtypes, denoted as C1 and C2. Notably, the C1 subtype demonstrates a significant upregulation of certain genes, such as CGA and HSD17B12, along with a shorter progression-free survival duration, indicating a potentially unfavorable prognosis. Further analyses elucidated the immune infiltration disparities, mutation landscapes, and gene functional pathways characteristic of each subtype. Through integrated bioinformatics approaches and machine learning techniques, key genes such as BIRC5, CENPA, and MMP11 were identified as potential therapeutic targets, providing novel insights into tailored treatment strategies. Additionally, single-cell transcriptome analysis shed light on the heterogeneous expression patterns of these genes across different cell types within the tumor microenvironment. Furthermore, virtual screening identified candidate drugs targeting the BIRC5 receptor, offering promising avenues for drug development. Collectively, these findings deepen our understanding of prostate cancer biology, paving the way for personalized therapeutic interventions and advancing the quest for more effective treatments in prostate cancer management.

Fc receptor-like A promotes malignant behavior in renal cell carcinoma and correlates with tumor immune infiltration.

BACKGROUND: Our study aims to investigate the mechanisms through which Fc receptor-like A (FCRLA) promotes renal cell carcinoma (RCC) and to examine its significance in relation to tumor immune infiltration. MATERIALS AND METHODS: The correlation between FCRLA and data clinically related to RCC was explored using The Cancer Genome Atlas (TCGA), then validated using Gene Expression Omnibus (GEO) gene chip data. Enrichment and protein-protein interaction (PPI) network analyses were performed for FCRLA and its co-expressed genes. FCRLA was knocked down in RCC cell lines to evaluate its impact on biological behavior. Then the potential downstream regulators of FCRLA were determined by western blotting, and rescue experiments were performed for verification. The relevance between FCRLA and various immune cells was analyzed through GSEA, TIMER, and GEPIA tools. TIDE and ESTIMATE algorithms were used to predict the effect of FCRLA in immunotherapy. RESULTS: Fc receptor-like A was associated with clinical and T stages and could predict the M stage (AUC = 0.692) and 1-3- and 5-year survival rates (AUC = 0.823, 0.834, and 0.862) of RCC patients. Higher expression of FCLRA predicted an unfavorable overall survival (OS) in TCGA-RCC and GSE167573 datasets (p = 0.03, p = 0.04). FCRLA promoted the malignant biological behavior of RCC cells through the pERK1/2/-MMP2 pathway and was associated with tumor immune microenvironment in RCC. CONCLUSION: Fc receptor-like A is positively correlated with poor outcomes in RCC patients and plays an oncogenic role in RCC through the pERK1/2-MMP2 pathway. Patients with RCC might benefit from immunotherapy targeting FCRLA.

HIGD1B, as a novel prognostic biomarker, is involved in regulating the tumor microenvironment and immune cell infiltration; its overexpression leads to poor prognosis in gastric cancer patients.

Background: HIGD1B (HIG1 Hypoxia Inducible Domain Family Member 1B) is a protein-coding gene linked to the occurrence and progression of various illnesses. However, its precise function in gastric cancer (GC) remains unclear. Methods: The expression of HIGD1B is determined through the TCGA and GEO databases and verified using experiments. The association between HIGD1B and GC patients' prognosis was analyzed via the Kaplan-Meier (K-M) curve. Subsequently, the researchers utilized ROC curves to assess the diagnostic capacity of HIGD1B and employed COX analysis to investigate risk factors for GC. The differentially expressed genes (DEGs) were then subjected to functional enrichment analysis, and a nomogram was generated to forecast the survival outcome and probability of GC patients. Additionally, we evaluated the interaction between HIGD1B and the immune cell infiltration and predicted the susceptibility of GC patients to therapy. Results: HIGD1B is markedly elevated in GC tissue and cell lines, and patients with high HIGD1B expression have a poorer outcome. In addition, HIGD1B is related to distinct grades, stages, and T stages. The survival ROC curves of HIGD1B and nomogram for five years were 0.741 and 0.735, suggesting appropriate levels of diagnostic efficacy. According to Cox regression analysis, HIGD1B represents a separate risk factor for the prognosis of gastric cancer (p<0.01). GSEA analysis demonstrated that the HIGD1B is closely related to cancer formation and advanced pathways. Moreover, patients with high HIGD1B expression exhibited a higher level of Tumor-infiltration immune cells (TIICs) and were more likely to experience immune escape and drug resistance after chemotherapy and immunotherapy. Conclusion: This study explored the potential mechanisms and diagnostic and prognostic utility of HIGD1B in GC, as well as identified HIGD1B as a valuable biomarker and possible therapeutic target for GC.

Analysis of machine learning based integration to identify the crosslink between inflammation and immune response in non-alcoholic fatty liver disease through bioinformatic analysis.

Background: The prevalence of nonalcoholic fatty liver disease (NAFLD) is a major form of chronic liver disease. This study aimed to scrutinize the diagnostic biomarkers of NAFLD and their correlation with the immune microenvironment through bioinformatic analysis. Methods: To identify genes associated with nonalcoholic fatty liver disease (NAFLD), we obtained microarray datasets (GSE63067 and GSE89632) from the Gene Expression Omnibus (GEO) database. Machine learning techniques such as Support Vector Machine (SVM), Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest (RF) were used to identify key genes. We performed gene ontology analysis to identify the driver pathways of NAFLD. External datasets (merging GSE48452, GSE66676 and GSE135251) were used to validate the identified genes and confirm protein levels by Western blotting. The CIBERSORT algorithm and immune-related techniques, such as ssGSEA, were used to assess the level of infiltration of different immune cell types and their functions. Finally, Spearman's analysis confirmed the relationship between pivotal genes and immune cells. Results: Hub genes (BBOX1, FOSB, NR4A2, RAB26 and SOCS2) were identified as potential biomarkers. This study demonstrates that these hub genes are significantly dysregulated in NAFLD, suggesting that they may be useful as diagnostic indicators and possible targets for treatment. Also covered are their possible effects on inflammation, immune cell activation, and liver damage in NAFLD. A better understanding of the intricate relationship between metabolic inefficiency, immunological response, and liver pathology in NAFLD may be gained from this work, which can lead to the development of new diagnostic tools and clinical treatments. Conclusion: The current study identified BBOX1, FOSB, NR4A2, RAB26 and SOCS2 as important diagnostic biomarkers for NAFLD. The study highlights the important function of immune cell infiltration in developing NAFLD. Their findings provide valuable molecular biological insights into the development of NAFLD and may lead to novel therapeutic strategies for treating this disease.

Weighted gene coexpression network analysis and machine learning for the determination of tfh cell and B cell infiltrating biomarkers in thymoma-associated myasthenia gravis.

Patients with thymoma (THYM)-associated myasthenia gravis (MG) typically have a poor prognosis and recurring illness. This study aimed to discover important biomarkers associated with immune cell infiltration and THYM-associated MG (THYM-MG) development. Gene expression microarray data were downloaded from The Cancer Genome Atlas website (TCGA) and Gene Expression Omnibus (GEO). A total of 102 differentially expressed genes were investigated. According to the immune infiltration data, the distribution of Tfh cells, B cells, and CD4 T cells differed significantly between the THYM-MG and THYM-NMG groups. WGCNA derived 25 coexpression modules; one hub module (the blue module) strongly correlated with Tfh cells. Combining differential genes revealed 21 intersecting genes. LASSO analysis subsequently revealed 16 hub genes as potential THYM-MG biomarkers. ROC curve analysis of the predictive model revealed moderate diagnostic value. The association between the 16 hub genes and infiltrating immune cells was further evaluated in TIMER2.0 and the validation dataset. Draggability analysis identified the therapeutic target genes PTGS2 and ALB, along with significant drugs including Firocoxib, Alclofenac, Pyridostigmine, and Stavudine. This was validated through MD simulation, PCA, and MM-GBSA analyses. The interaction between numerous activated B cells and follicular helper T cells is closely associated with THYM-MG pathogenesis from a bioinformatics perspective. Hub genes (including SP6, SCUBE3, B3GNT7, and MAGEL2) may be downregulated in immune cells in THYM-MG and associated with progression.

Natural killer cell-associated prognosis model characterizes immune landscape and treatment efficacy of diffuse large B cell lymphoma.

PURPOSE: NK cells are essential for the detection, identification and prediction of cancer. However, so far, there is no prognostic risk model based on NK cell-related genes to predict the prognosis and treatment outcome of DLBCL patients. This study aimed to explore a risk assessment model that could accurately predict the prognosis and treatment efficacy of DLBCL. METHODS: Bioinformatics analysis of the expression profiles of DLBCL samples in the GEO database was performed. Cox regression and LASSO regression analysis were used to determine NK cell-related genes associated with patient's prognosis. Based on these genes, a risk assessment model was constructed to predict the prognosis of patients and the effectiveness of treatment. Finally, qRT-PCR was used to verify the expression of gene tags in clinical samples. RESULTS: We identified seven prognosis-related NK cell-related genes (MAP2K1, PRKCB, TNFRSF10B, IL18, LAMP1, RASGRP1, and SP110), and DLBCL patients were divided into low- and high-risk groups based on these genes. Survival analysis showed that the prognosis of patients with low-risk group was better. Pathway enrichment analysis showed that the differentially expressed genes between the two risk groups were related to immune response pathways. Compared with the high-risk group, the low-risk group had higher infiltration of immune cells in tumor tissues. Besides, compared with high-risk group, low-risk patients by immunotherapy or other commonly used anti-tumor drugs might have better efficacy after treatment. In addition, qRT-PCR showed that the expression of risk genes including TNFRSF10B, IL18 and LAMP1 were significantly increased in most DLBCL samples compared to control samples, while the expression of protective genes including MAP2K1, PRKCB, RASGRP1 and SP110 were significantly decreased. CONCLUSION: The NK cell-related gene signatures were proved to be a reliable indicator of the success of immunotherapy in patients with DLBCL, thus providing a unique evaluation method.

Esculetin facilitates post-stroke rehabilitation by inhibiting CKLF1-mediated neutrophil infiltration.

Esculetin (ESC) is a coumarin-derived phytochemical prevalent in traditional Chinese medicine that exhibits anti-acute ischemic stroke activities. Our previous studies demonstrate that CKLF1 is a potential anti-stroke target for coumarin-derived compound. In this study we investigated whether CKLF1 was involved in the neuroprotective effects of ESC against photothrombotic stroke in mice. The mice were treated with ESC (20, 40 or 80 mg·kg-1·d-1, i.g.) for two weeks. The therapeutic effect of ESC was assessed using MRI, neurological function evaluation, and a range of behavioral tests on D1, 3, 7 and 14 of ESC administration. We showed that oral administration of ESC dose-dependently reduced the cerebral infarction volume within one week after stroke, improved behavioral performance, and alleviated neuropathological damage within two weeks. Functional MRI revealed that ESC significantly enhanced the abnormal low-frequency fluctuation (ALFF) value of the motor cortex and promoted functional connectivity between the supplementary motor area (SMA) and multiple brain regions. We demonstrated that ESC significantly reduced the protein levels of CKLF1 and CCR5, as well as the CKLF1/CCR5 protein complex in the peri-infarcted area. We showed that ESC (0.1-10 µM) dose-dependently blocked CKLF1-induced chemotactic movement of neutrophils in the Transwell assay, reducing the interaction of CKLF1/CCR5 on the surface of neutrophils, thereby reducing neutrophil infiltration, and decreasing the expression of ICAM-1, VCAM-1 and MMP-9 in the peri-infarct tissue. Knockout of CKLF1 reduced brain infarction volume and motor dysfunction after stroke but also negated the anti-stroke efficacy and neutrophil infiltration of ESC. These results suggest that the efficacy of ESC in promoting post-stroke neural repair depends on its inhibition on CKLF1-mediated neutrophil infiltration, which offering novel perspectives for elucidating the therapeutic properties of coumarins.

Transcriptomic observations of Intra and extracellular immunotherapy targets for pediatric brain tumors.

OBJECTIVES: Despite surgical resection, chemoradiation and targeted therapy, brain tumors remain a leading cause of cancer related death in children. Immunotherapy has shown some promise and is actively being investigated for treating childhood brain tumors. However, a critical step in advancing immunotherapy for these patients is to uncover targets that can be effectively translated into therapeutic interventions. METHODS: In this study, our team performed a transcriptomic analysis across pediatric brain tumor types to identify potential targets for immunotherapy. Additionally, we assessed components that may impact patient response to immunotherapy, including the expression of genes essential for antigen processing and presentation, inhibitory ligands and receptors, interferon signature, and overall predicted T cell infiltration. RESULTS: We observed distinct expression patterns across tumor types. These included elevated expression of antigen genes and antigen processing machinery in some tumor types while other tumors had elevated inhibitory checkpoint receptors, known to be associated with response to checkpoint inhibitor immunotherapy. CONCLUSION: These findings suggest that pediatric brain tumors exhibit distinct potential for specific immunotherapies. We believe our findings can guide investigators in their assessment of appropriate immunotherapy classes and targets in pediatric brain tumors.

Comprehensive proteomic characterization of urethral stricture disease in the Chinese population.

Background: Male urethral stricture disease (USD) is predominantly characterized by scar formation. There are few effective therapeutic drugs, and comprehensive molecular characterizations of USD formation remain undefined. Methods: The proteomic profiling of twelve scar tissues and five matched normal adjacent tissues (NATs). Proteomic analysis methods were applied to explore the molecular characterizations of USD formation, including uncovering mechanistic pathways and providing novel biomarkers for scar formation. Results: Comparative proteomic analysis showed that the extracellular matrix (ECM) and complement cascade signaling were predominant in scar tissues. COL11A1 and CD248 significantly contributed to the accumulation of ECM components. Our study presented diverse molecular mechanisms of scar formation across different ages and suggested the potential effects of PXK in Age 1 (<45) patients. Furthermore, immune infiltration studies indicated the therapeutic potential of inhibiting the complement system (C4A, C4B) in Age 2 (≥45) patients, providing a potential clinical strategy for USD. Conclusion: This study illustrated the pathogenesis of USD formation and the diverse characteristics of USD patients with different ages, enhancing our understanding of the disease's pathogenesis and providing a valuable resource for USD treatment.

Identification of macrophage differentiation related genes and subtypes linking atherosclerosis plaque processing and metabolic syndrome via integrated bulk and single-cell sequence analysis.

Metabolic syndrome(MS) is a separate risk factor for the advancement of atherosclerosis(AS) plaque but mechanism behind this remains unclear. There may be a significant role for the immune system in this process. This study aims to identify potential diagnostic genes in MS patients at a higher risk of developing and progressing to AS. Datasets were retrevied from gene expression omnibus(GEO) database and differentially expressed genes were identified. Hub genes, immune cell dysregulation and AS subtypes were identified using a conbination of muliple bioinformatic analysis, machine learning and consensus clustering. Diagnostic value of hub genes was estimated using a nomogram and ROC analysis. Finally, enrichment analysis, competing endogenous RNA(ceRNA) network, single-cell RNA(scRNA) sequencing analysis and drug-protein interaction prediction was constructed to identify the functional roles, potential regulators and distribution for hub genes. Four hub genes and two macrophage-related subtypes were identified. Their strong diagnostic value was validated and functional process were identified. ScRNA analysis identified the macrophage differentiation regulation function of F13A1. CeRNA network and drug-protein binding modes revealed the potential therapeutic method. Four immune-correlated hub genes(F13A1, MMRN1, SLCO2A1 and ZNF521) were identified with their diagnostic value being assesed, which F13A1 was found strong correlated with macrophage differentiation and could be potential diagnostic and therapeutic marker for AS progression in MS patients.

5-Fluorouracil resistance-based immune-related gene signature for COAD prognosis.

Background: Drug resistance is the primary obstacle to advanced tumor therapy and the key risk factor for tumor recurrence and death. 5-Fluorouracil (5-FU) chemotherapy is the most common chemotherapy for individuals with colorectal cancer, despite numerous options. Methods: The Gene Expression Omnibus database was utilized to extract expression profile data of HCT-8 human colorectal cancer wild-type cells and their 5-FU-induced drug resistance cell line. These data were used to identify 5-FU resistance-related differentially expressed genes (5FRRDEGs), which intersected with the colorectal adenocarcinoma (COAD) transcriptome data provided by the Cancer Genome Atlas Program database. A prognostic signature containing five 5FRRDEGs (GOLGA8A, KLC3, TIGD1, NBPF1, and SERPINE1) was established after conducting a Cox regression analysis. We conducted nomogram development, drug sensitivity analysis, tumor immune microenvironment analysis, and mutation analysis to assess the therapeutic value of the prognostic qualities. Results: We identified 166 5FRRDEGs in patients with COAD. Subsequently, we created a prognostic model consisting of five 5FRRDEGs using Cox regression analysis. The patients with COAD were divided into different risk groups by risk score; the high-risk group demonstrated a worse prognosis than the low-risk group. Conclusion: In summary, the 5FRRDEG-based prognostic model is an effective tool for targeted therapy and chemotherapy in patients with COAD. It can accurately predict the survival prognosis of these patients as well as to provide the direction for exploring the resistance mechanism underlying COAD.

Ferroptosis-related gene transferrin receptor protein 1 expression correlates with the prognosis and tumor immune microenvironment in cervical cancer.

Background: Ferroptosis is a non-apoptotic iron-dependent form of cell death implicated in various cancer pathologies. However, its precise role in tumor growth and progression of cervical cancer (CC) remains unclear. Transferrin receptor protein 1 (TFRC), a key molecule associated with ferroptosis, has been identified as influencing a broad range of pathological processes in different cancers. However, the prognostic significance of TFRC in CC remains unclear. The present study utilized bioinformatics to explore the significance of the ferroptosis-related gene TFRC in the progression and prognosis of CC. Methods: We obtained RNA sequencing data and corresponding clinical information on patients with CC from The Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx) and Gene Expression Omnibus (GEO) databases. Using least absolute shrinkage and selection operator (LASSO) Cox regression, we then generated a multigene signature of five ferroptosis-related genes (FRGs) for the prognostic prediction of CC. We investigated the relationship between TFRC gene expression and immune cell infiltration by employing single-sample GSEA (ssGSEA) analysis. The potential functional role of the TFRC gene was evaluated through gene set enrichment analysis (GSEA). Immunohistochemistry and qPCR was employed to assess TFRC mRNA and protein expression in 33 cases of cervical cancer. Furthermore, the relationship between TFRC mRNA expression and overall survival (OS) was investigated in patients. Results: CC samples had significantly higher TFRC gene expression levels than normal tissue samples. Higher TFRC gene expression levels were strongly associated with higher cancer T stages and OS events. The findings of multivariate analyses illustrated that the OS in CC patients with high TFRC expression is shorter than in patients with low TFRC expression. Significant increases were observed in the levels of TFRC mRNA and protein expression in patients diagnosed with CC. Conclusion: Increased TFRC expression in CC was associated with disease progression, an unfavorable prognosis, and dysregulated immune cell infiltration. In addition, it highlights ferroptosis as a promising therapeutic target for CC.

Postoperative Intimal Hyperplasia: Review from My Research.

Postoperative intimal hyperplasia is the major cause of the vein graft occlusion. It is very important to establish an animal model for the start of research. After my vascular surgery residency in Japan, I started my research work on postoperative intimal hyperplasia at the University of Wisconsin-Madison. My research showed that endothelial injury and monocyte infiltration is the key for postoperative intimal hyperplasia, which is very similar to Ross' pathogenesis of atherosclerosis as an inflammatory disease. Focusing on postoperative intimal hyperplasia as an inflammatory disease, especially on tumor necrosis factor-α, FR-167653 (tumor necrosis factor-α suppressive agent, inhibitor of p 38 mitogen-activated protein kinase; Fujisawa Pharmaceutical Co., Ltd., Japan) is found to suppress postoperative intimal hyperplasia in a rat model by reducing serum monocyte chemoattractant protein-1 levels. However, FR-167653 is not commercially available today. Because endothelial injury is the first step of postoperative intimal hyperplasia, I investigated whether the free radical scavenger, edaravone (Radicut, Mitsubishi Tanabe Pharma Co., Japan), which alleviates the endothelial injury in vitro , can also suppress postoperative intimal hyperplasia. Moreover, the free radical scavenger edaravone (Radicut®, Mitsubishi Tanabe Pharma Co.) is also found to suppress postoperative intimal hyperplasia, by alleviating endothelial injury. In clinical settings, it is very important to detect postoperative intimal hyperplasia before its establishment. Hepatocyte growth factor is not only a hepatic growth factor but also a vascular endothelial growth factor. Recently, serum hepatocyte growth factor level was found to be a candidate biomarker for postoperative intimal hyperplasia in our rat model.

Integrated bioinformatics analysis and experimental validation to understand tryptophan metabolism-related genes in hepatocellular carcinoma.

Background: Tryptophan (Trp) metabolism is closely related to tumor immunity, and its disorder can cause an immunosuppressive microenvironment, promoting the occurrence and development of hepatocellular carcinoma (HCC). The aim of this study is to explore and validate the independent prognostic genes in patients suffered from HCC. Methods: The transcriptome data of GSE87630 from GEO database were downloaded to analyze differentially expressed genes (DECs) which were intersected with the gene sets of Trp metabolism from MsigDB database. Univariate/multivariate COX regression was performed to identify the genes with independent prognostic significance. TCGA, GTEx, UALCAN, and GEPIA2 databases were applied to analyze DEGs for prognosis. RNA seq data of HCC from TCGA database were collected for Lasso regression analysis. The ssGSEA algorithm was used to perform the analysis of TCGA data. The effects of the candidate differential gene on HCC cells proliferation and migration were evaluated using EdU immunofluorescence and transwell assays. Results: Trp metabolism-related DECs for HCCs were obtained, including MAOB, CYP1A2, KYNU, CYP2E1, ALDH2, CYP2C18, TDO2, AOX1, CYP3A4 and INMT. Moreover, multivariate COX regression results showed that ALDH2 can serve as an independent prognostic molecule and its transcriptional and translational levels were significantly reduced in the tumor tissues. The low expression of ALDH2 was associated with poor prognosis. Overexpression of ALDH2 dramatically reduced the HCC cells proliferation and migration. Conclusion: ALDH2 is associated with Trp metabolism and its downregulation in HCC has a potential value on prognosis. Overexpression of ALDH2 can reduce the proliferation and migration of HCC cells.

Corrigendum: Correlation between degeneration of cervical intervertebral disc degeneration of paravertebral muscle.

[This corrects the article DOI: 10.3389/fendo.2024.1391970.].

Nc-RNA-mediated low expression of AZIN1 correlated with unfavorable prognosis in kidney renal clear cell carcinoma.

OBJECTIVE: Kidney renal clear cell carcinoma (KIRC, ccRCC) is the most common type of renal cancer with high recurrence and mortality. It has long been recognized that Antizyme inhibitor 1 (AZIN1) serves as a pro-oncogenic molecule in multiple cancers. However, the clinicopathological features of AZIN1 in KIRC remain unexplored. MATERIALS AND METHODS: The Cancer Genome Atlas (TCGA, TIMER, and GEPIA) were employed for pan-cancer expression and survival analysis of AZIN1, indicating the unique anti-tumor role of AZIN1 in KIRC. The expression and clinical characteristics of AZIN1 in KIRC were further proven via Human Protein Atlas and TCGA. single-sample GSEA was employed to investigate the immune infiltration of AZIN1. Then the downstream pathways were illustrated via the LinkedOmics, Metascape, and Cytoscape databases. The possible upper regulating noncoding RNAs (ncRNAs) were analyzed from five programs-TargetScan, StarBase, miRanda, PITA, and miRmap. RESULTS: AZIN1 is downregulated in KIRC patients. Lower levels of AZIN1 were linked with unfavorable outcomes in KIRC patients. The AZIN1 expression was positively related to immune cell infiltration in KIRC. We also elucidated a possible upstream regulatory ncRNA of AZIN1 in KIRC namely STK4-AS1/AC068338.2-miR-106b-5p-AZIN1 axis as well as the downstream signaling pathways. CONCLUSION: This study illustrated the unique anti-tumor role of AZIN1 in KIRC and provided potential value for guiding immunotherapy and targeted therapy.

Prognostic Value of Insulin Growth Factor-Like Receptor 1 (IGFLR1) in Stage II and III Colorectal Cancer and Its Association with Immune Cell Infiltration.

IGFLR1 is a novel biomarker, and some evidences suggested that is involved in the immune microenvironment of CRC. Here, we explored the expression of IGFLR1 and its association with the prognosis as well as immune cell infiltration in CRC, with the aim to provide a basis for further studies on IGFLR1. Immunohistochemical staining for IGFLR1, TIM-3, FOXP3, CD4, CD8, and PD-1 was performed in eligible tissues to analyze the expression of IGFLR1 and its association with prognosis and immune cell infiltration. Then, we screened colon cancer samples from TCGA and grouped patients according to IGFLR1-related genes. We also evaluated the co-expression and immune-related pathways of IGFLR1 to identify the potential mechanism of it in CRC. When P < 0.05, the results were considered statistically significant. IGFLR1 and IGFLR1-related genes were associated with the prognosis and immune cell infiltration (P < 0.05). In stage II and III CRC tissue and normal tissue, we found (1) IGFLR1 was expressed in both the cell membrane and cytoplasm and which was differentially expressed between cancer tissue and normal tissue. IGFLR1 expression was associated with the expression of FOXP3, CD8, and gender but was not associated with microsatellite instability. (2) IGFLR1 was an independent prognostic factor and patients with high IGFLR1 had a better prognosis. (3) A model including IGFLR1, FOXP3, PD-1, and CD4 showed good prognostic stratification ability. (4) There was a significant interaction between IGFLR1 and GATA3, and IGFLR1 had a significant co-expression with related factors in the INFR pathway. IGFLR1 has emerged as a new molecule related to disease prognosis and immune cell infiltration in CRC patients and showed a good ability to predict the prognosis of patients.

Response of soil moisture to rainfall following deep soil drying in China's hilly loess lands.

Deep soil drying is a physical soil phenomenon that has become increasingly characteristic to artificial afforestation on China's Loess Plateau. Current research is largely short of conclusive reports on soil moisture recovery following deep soil drying in afforested lands. In this study, a 10-m deep underground column was constructed at Pengyang Experimental Station in Ningxia. The CS650-CR1000 automatic soil moisture monitoring system and BLJW-4 small meteorological observation stations were used to respectively monitor soil moisture and meteorological conditions in the study area for the period 2014-2019. The local rainfall was classified and the characteristics of soil infiltration analyzed at both monthly and annual scales. The results showed that: i) Deep soil moisture recovery in the semi-arid Loess Plateau region depended mainly on 25-49.9 mm and >50 mm types of rainfall; together accounting for 35.44 % of the precipitation. ii) Deep soil moisture replenishment occurred mainly for the period from April to October. While this accounted for 30.13 % of the precipitation, evaporation loss accounted for 69.87 % of it. With increasing monthly rainfall (Pm), the variation in monthly infiltration depth (Zm) was quadratic in shape - where Zm = -0.0094 Pm2 + 3.7702 Pm (R2 = 0.9577). iii) At the annual scale, deep soil moisture replenishment was mainly driven by year-on-year infiltration water accumulation. This is because a single year precipitation infiltration was not enough to replenish deep soil moisture. The cumulative infiltration depth for 2014-2019 was 180, 260, 400, 700, 1000 > 1000 cm. It suggested that soil water infiltration and deep dry soil recovery occurred at different times under rainfed conditions in the semi-arid loess hills in China. This is key for in-depth studies of the hydrological process in dry soil regions.