Updates in the Treatment of Knee Osteoarthritis.

Knee osteoarthritis (OA) is an inflammatory and degenerative condition resulting in articular cartilage destruction and functional loss. Its prevalence has grown considerably due to increased life expectancy and obesity, and its diagnosis relies on evaluation, medical examination, and confirmation by supplementary radiographic images. Knee OA is multifactorial and influenced by several local, systemic, and external aspects. In addition, its progress and therapeutic responses highly depend on the characteristics of each subject. The initial recommendation is drug treatment and alternative therapies to improve quality of life. However, if these treatments are unsuccessful, one must consider surgical treatment. Surgical options include arthroscopies, osteotomies, and partial and total arthroplasties, while non-surgical treatments include medications and alternative therapies such as infiltrations, acupuncture, and physical exercise. It is worth highlighting that biomarkers can be a significant strategy for early disease detection, assessment of disease activity, prediction of prognosis, and monitoring a better response to therapy. Nevertheless, this topic must be the focus of further research to confirm its findings.

Transcriptome analysis revealed SMURF2 as a prognostic biomarker for oral cancer.

BACKGROUND: The activation of TGF-ß pathway can facilitate tumorigenesis. Understanding the TGF-related genes (TRGs) in oral cancer and determining their prognostic value is of utmost importance. METHODS: The TRGs were selected to develop a prognostic model based on lasso regression. Oral cancer patients were classified into high-risk and low-risk groups based on the risk model. Subsequently, multivariate COX regression was employed to identify the prognostic marker. Additionally, the expression of SMURF2 was validated using quantitative real-time polymerase chain reaction (qRT-PCR) and the Human Protein Atlas (HPA) database. To investigate the relationship between SMURF2 expression and immune cell infiltrations, we conducted single-sample Gene Set Enrichment Analysis (ssGSEA) analyses. RESULTS: We identified 16 differentially expressed TRGs in oral cancer, all of which showed upregulation. From these, we selected eight TRGs as prognostic signatures. Furthermore, the high-risk group demonstrated lower infiltration levels of immune cells, immune score, and higher tumor purity. Interestingly, we also found that SMURF2 serves as an independent prognostic biomarker. SMURF2 was upregulated in oral cancer, as confirmed by public databases and qRT-PCR analysis. Importantly, our results indicate a close association between SMURF2 expression and the immune microenvironment. CONCLUSION: The 8-TRG signature prognosis model that we constructed has the ability to predict the survival rate and immune activity of oral cancer patients. SMURF2 could be effective in recognizing prognosis and evaluating immune efficacy for oral cancer.

Transforming growth factor-induced gene TGFBI is correlated with the prognosis and immune infiltrations of breast cancer.

BACKGROUND: Transforming growth factor ß (TGFß) is a critical regulator of lung metastasis of breast cancer and is correlated with the prognosis of breast cancer. However, not all TGFß stimulated genes were functional and prognostic in breast cancer lung metastatic progress. In this study, we tried to determine the prognosis of TGFß stimulated genes in breast cancer. METHODS: TGFß stimulated genes in MDA-MB-231 cells and lung metastasis-associated genes in LM2-4175 cells were identified through gene expression microarray. The prognosis of the induced gene (TGFBI) in breast cancer was determined through bioinformatics analysis and validated using tissue microarray. The immune infiltrations of breast cancer were determined through "ESTIMATE" and "TIMER". RESULTS: TGFBI was up-regulated by TGFß treatment and over-expressed in LM2-4175 cells. Through bioinformatics analysis, we found that higher expression of TGFBI was associated with shorted lung metastasis-free survival, relapse-free survival, disease-free survival, and overall survival of breast cancer. Moreover, the prognosis of TGFBI was validated in 139 Chinese breast cancer patients. Chinese breast cancer patients with higher TGFBI expression had lower overall survival. Correspondingly, breast cancer patients with higher TGFBI methylation had higher overall survival. TGFBI was correlated with the score of the TGFß signaling pathway and multiple immune-related signaling pathways in breast cancer. The stromal score, immune score, and the infiltrations of immune cells were also correlated with TGFBI expression in breast cancer. CONCLUSIONS: TGFß-induced gene TGFBI was correlated with the prognosis and immune infiltrations of breast cancer.

Bioinformatics analysis reveals the potential common genes and immune characteristics between atrial fibrillation and periodontitis.

BACKGROUND AND OBJECTIVE: Atrial fibrillation (AF) and periodontitis, both classified under chronic inflammatory diseases, share common etiologies, including genetic factors and immune pathways. However, the exact mechanisms are still poorly understood. This study aimed to explore the potential common genes and immune characteristics between AF and periodontitis. METHODS: Gene expression datasets for AF and periodontitis were downloaded from the Gene Expression Omnibus (GEO) database. Differential expression analysis was used to identify common genes in the training set. Functional analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, were conducted to elucidate the underlying mechanisms. Hub genes were further screened based on expression levels, receiver operating characteristic (ROC) curves, and least absolute shrinkage and selection operator (LASSO) regression. Then, based on the expression levels and ROC values of the hub genes in the validation set, the target genes were identified. Finally, immune cell infiltration analysis was performed on the AF and periodontitis datasets in the training set using the "CIBERSORT" R package. The relationships between target genes, infiltrating immune cells, and inflammatory factors were also investigated. In addition, AF susceptibility, atrial fibrosis, inflammatory infiltration, and RGS1 protein expression in rat models of periodontitis were assessed through in vivo electrophysiology experiments, Masson's trichrome staining, hematoxylin-eosin staining, immunohistochemistry, and western blotting, respectively. RESULTS: A total of 21 common genes were identified between AF and periodontitis among the differentially expressed genes. After evaluating gene expression levels, ROC curves, and LASSO analysis, four significant genes between AF and periodontitis were identified, namely regulator of G-protein signaling 1 (RGS1), annexin A6 (ANXA6), solute carrier family 27 member 6 (SLC27A6), and ficolin 1 (FCN1). Further validation confirmed that RGS1 was the optimal shared target gene for AF and periodontitis. Immune cell infiltration analysis revealed that neutrophils and T cells play an important role in the pathogenesis of both diseases. RGS1 showed a significant positive correlation with activated memory CD4 T cells and gamma-delta T cells and a negative correlation with CD8 T cells and regulatory T cells in both training sets. Moreover, RGS1 was positively correlated with classical pro-inflammatory cytokines IL1ß and IL6. In periodontitis rat models, AF susceptibility, atrial fibrosis, and inflammatory infiltration were significantly increased, and RGS1 expression in the atrial tissue was upregulated. CONCLUSION: A common gene between AF and periodontitis, RGS1 appears central in linking the two conditions. Immune and inflammatory responses may underlie the interaction between AF and periodontitis.

Heme Metabolism-Related Gene TENT5C is a Prognostic Marker and Investigating Its Immunological Role in Colon Cancer.

Background: There is a strong correlation between consuming high amounts of heme and an elevated risk of developing various types of cancer, including colorectal cancer. However, the role of heme metabolism-related genes (HRGs) in colorectal cancer remains unclear. Our study aimed to identify prognostic markers for colorectal cancer patients based on these genes. Methods: The heme metabolism score was assessed using gene set variation analysis (GSVA). Potential prognostic HRGs were identified from the TCGA-COAD dataset using LASSO and COX regression analyses. The expression level of TENT5C was validated in the GEO database and clinical samples. To explore the association between TENT5C expression and immune cell infiltrations, we performed ESTIMATE and single-sample gene set enrichment analysis (ssGSEA). Results: The low level of heme metabolism score was associated with a poor prognosis in colorectal cancer patients. TENT5C is a prognostic gene and an independent prognostic biomarker for overall survival. Its expression was confirmed in multiple datasets and clinical samples, showing a positive correlation with immune cells and immune score. GSEA results suggested TENT5C's significant role in regulating immune and inflammatory responses in colorectal cancer. Conclusion: TENT5C can be used as a biomarker in colorectal cancer. Additionally, TENT5C is associated with both prognosis and immune infiltration. These findings lay a strong groundwork for future research to delve into the specific role of TENT5C in the development and advancement of colorectal cancer.

Hierarchical clustering identifies oxidative stress-related subgroups for the prediction of prognosis and immune microenvironment in gastric cancer.

Background: Gastric cancer (GC) is a prevalent malignancy of the digestive tract globally, demonstrating a substantial occurrence of relapse and metastasis, alongside the absence of efficacious treatment. Tumor progression and the development of cancer are linked to oxidative stress. Our objective was twofold: first, to determine distinct subcategories based on oxidative stress in GC patients, and second, to establish oxidative stress-related genes that would aid in stratifying the risk for GC patients. Methods: TCGA-STAD and GSE84437 datasets were utilized to obtain the mRNA expression profiles and corresponding clinical information of GC patients. Through consensus clustering analysis, distinct subgroups related to oxidative stress were identified. To uncover the underlying mechanisms, GSEA and GSVA were performed. xCell, CIBERSORT, MCPCounter, and TIMER algorithms were employed to evaluate the immune microenvironment and immune status of the different GC subtypes. A prognostic risk model was developed using the TCGA-STAD dataset and substantiated using the GSE84437 dataset. Furthermore, qRT-PCR was employed to validate the expression of genes associated with prognosis. Results: Two distinct subtypes of oxidative stress were discovered, with markedly different survival rates. The C1 subtype demonstrated an activated immune signal pathway, a significant presence of immune cell infiltration, high immune score, and a high microenvironment score, indicating a poor prognosis. Moreover, a prognostic signature related to oxidative stress (IMPACT and PXDN) was able to accurately estimate the likelihood of survival for patients with gastric cancer. A nomogram incorporating the patients' gender, age, and risk score was able to predict survival in gastric cancer patients. Additionally, the expression of IMPACT and PXDN showed a strong correlation with overall survival and the infiltration of immune cells. Conclusion: Based on signatures related to oxidative stress, we developed an innovative system for categorizing patients with GC. This stratification enables accurate prognostication of individuals with GC.

Identification of key claudin genes associated with survival prognosis and diagnosis in colon cancer through integrated bioinformatic analysis.

The claudin multigene family is associated with various aberrant physiological and cellular signaling pathways. However, the association of claudins with survival prognosis, signaling pathways, and diagnostic efficacy in colon cancer remains poorly understood. Methods: Through the effective utilization of various bioinformatics methods, including differential gene expression analysis, gene set enrichment analysis protein-protein interaction (PPI) network analysis, survival analysis, single sample gene set enrichment analysis (ssGSEA), mutational variance analysis, and identifying receiver operating characteristic curve of claudins in The Cancer Genome Atlas colon adenocarcinoma (COAD). Results: We found that: CLDN2, CLDN1, CLDN14, CLDN16, CLDN18, CLDN9, CLDN12, and CLDN6 are elevated in COAD. In contrast, the CLDN8, CLDN23, CLDN5, CLDN11, CLDN7, and CLDN15 are downregulated in COAD. By analyzing the public datasets GSE15781 and GSE50760 from NCBI-GEO (https://www.ncbi.nlm.nih.gov/geo/), we have confirmed that CLDN1, CLDN2, and CLDN14 are significantly upregulated and CLDN8 and CLDN23 are significantly downregulated in normal colon, colon adenocarcinoma tumor, and liver metastasis of colon adenocarcinoma tissues from human samples. Various claudins are mutated and found to be associated with diagnostic efficacy in COAD. Conclusion: The claudin gene family is associated with prognosis, immune regulation, signaling pathway regulations, and diagnosis of COAD. These findings may provide new molecular insight into claudins in the treatment of colon cancer.

PROS1, a clinical prognostic biomarker and tumor suppressor, is associated with immune cell infiltration in breast cancer: A bioinformatics analysis combined with experimental verification.

BACKGROUND: PROS1 is an encoding gene that can generate protein S. This protein is a glycoprotein found in plasma that conducts physiological functions with vitamin K. However, the impact of its expression remains absent in the progression and prognosis of breast cancer (BC). METHODS: In this study, we comprehensively explored the expression of PROS1 in BC and its relationship with BC patient survival, prognosis, and other clinicopathological features. We investigated how PROS1 influenced the malignant biological behavior of BC cells. A series of enrichment analyses were conducted, and the immune landscape was explored in BC affected by PROS1. We also determined correlations between PROS1 and common drug sensitivities used for BC treatments. RESULTS: PROS1 had low expression in BC, which tended to result in poor survival of BC patients. Overexpressed PROS1 inhibited the migration and invasion of BC cells as well as the epithelial-mesenchymal transition process by downregulating SNAIL. Functional enrichment analyses revealed that PROS1 was more active in extracellular matrix (ECM) organization and structural constituent, ECM-receptor interaction, and other pathways with its related genes. PROS1 was also found to affect immune activity, including various immune cells infiltrating BC. BC patients with high PROS1 expression tended to have lower IC50 values of three common medications and obtained better efficacy. CONCLUSIONS: PROS1 can become a promising prognostic factor and a possible therapeutic target in BC patients and suppress BC cell metastatic potential. In addition, PROS1 is a crucial factor in immune infiltration in BC.

Articaine Infiltrations of the Mandibular Lateral Incisor-Is It Volume or Location of the Infiltrations That Affect Success? A Prospective, Randomized Crossover Study.

INTRODUCTION: A combination labial infiltration (1.8 mL) plus lingual infiltration (1.8 mL) of 4% articaine with 1:100,000 epinephrine in the mandibular lateral incisor was found superior to a labial infiltration of 1.8 mL of the same solution. However, it is not known whether the volume or the location had the greatest effect. Therefore, the purpose of this prospective, randomized crossover study was to determine the anesthetic efficacy of a labial infiltration of a 3.6 mL volume of 4% articaine with 1:100,000 epinephrine compared with labial infiltration (1.8 mL) plus lingual infiltration (1.8 mL) of 4% articaine with 1:100,000 epinephrine in the mandibular lateral incisor. METHODS: One hundred subjects randomly received 2 sets of injections, using 4% articaine with 1:100,000 epinephrine, consisting of labial and lingual infiltrations of 1.8 mL (3.6 mL total) and 2 labial infiltrations of 1.8 mL (3.6 mL total) of the mandibular lateral incisor in 2 separate appointments. Electric pulp testing was used to determine anesthetic success (highest 80/80 reading). The data were analyzed statistically. RESULTS: The labial and lingual combination exhibited a significantly higher anesthetic success rate (97%) when compared with the 2 labial infiltrations (74%) and had significantly higher 80/80s readings from 1 minute to 58 minutes. CONCLUSIONS: Within the limitations of this clinical study, a combination labial plus lingual infiltration using a 3.6-mL volume of 4% articaine with 1:100,000 epinephrine significantly increased pulpal anesthetic success for the mandibular lateral incisor when compared with a labial infiltration using a 3.6-mL volume of articaine. Therefore, location of the infiltrations was more important than volume.

Identification of Novel Targets for Treatment of Dilated Cardiomyopathy Based on the Ferroptosis and Immune Heterogeneity.

Purpose: This study aimed to investigate the role of ferroptosis in dilated cardiomyopathy (DCM) and to identify new targets for treatment and diagnosis of DCM. Methods: GSE116250 and GSE145154 were downloaded from the Gene Expression Omnibus database. Unsupervised consensus clustering of DCM patients was used to confirm the impact of ferroptosis. Ferroptosis-related hub genes were identified by WGCNA and single cell sequencing analyses. Finally, we established a DCM mouse model via injection of Doxorubicin to verify the expression level of OTUD1 and colocalization between cell markers and OTUD1 in DCM mouse heart. Results: A total of 13 ferroptosis-related differentially expressed genes (DEGs) were identified. The DCM patients were divided into two clusters according to the expression of 13 DEGs. The DCM patients in different clusters showed discrepancies in immune infiltration. Four hub genes were further identified by WGCNA analysis. Single cell data analysis revealed that OTUD1 may regulate B cells and DC cells and then participate in immune infiltration discrepancy. The upregulation of OTUD1 and the colocalization of OTUD1 with CD19 (B cell maker) and CD11c (DCs markers) markers were confirmed in DCM mouse hearts. Conclusion: Ferroptosis and the immune microenvironment are closely associated with DCM, and OTUD1 may play an important role through B cells and DCs.

Decapping enzyme 2 is a novel immune-related biomarker that predicts poor prognosis in glioma.

This study analyzed sequencing and clinical data from the Cancer Genome Atlas (TCGA) and gene expression synthesis, and used Chinese glioma Genome Atlas (CGGA) data for external validation. The expression of DCP2 in normal brain and tumor tissue was compared. We analyzed the clinical and molecular characteristics and prognostic value of DCP2 in glioma. In addition, DCP2 expression levels were evaluated in 30 glioma tissue samples and upregulated in glioma samples compared to normal brain tissue (p < 0.001). Multivariate data analysis from TCGA showed that increased DCP2 expression was an independent risk factor for overall survival and prognosis of glioma patients. As indicated by the analysis of the TCGA data set. The expression level of DCP2 is closely related to tumor immunity, including tumor immune cell infiltration, immune score, and co-expression of multiple immune-related genes. In addition, DCP2 was positively correlated with IL-6 and IL-7. Glioma cell proliferation and invasion were evaluated using cell viability, colony formation, wound healing, and transwell assays.Apoptosis and cell cycle were detected by flow cytometry. DCP2 promoted the proliferation, invasion and migration of glioma cells T98G and U251, inhibited apoptosis and blocked the S phase of the cell cycle. As a result of the altered expression of DCP2, a new prognostic biomarker may be identified that can improve patient survival.These findings suggest DCP2 as a potential biomarker for the prognosis of glioma and a candidate immunotherapy target.

WGCNA-based identification of potential targets and pathways in response to treatment in locally advanced breast cancer patients.

Locally advanced breast cancer patients have a poor prognosis; however, the relationship between potential targets and the response to treatment is still unclear. The gene expression profiles of breast cancer patients with stages from IIB to IIIC were downloaded from The Cancer Genome Atlas. We applied weighted gene co-expression network analysis and differentially expressed gene analysis to identify the primary genes involved in treatment response. The disease-free survival between low- and high-expression groups was analyzed using Kaplan-Meier analysis. Gene set enrichment analysis was applied to identify hub genes-related pathways. Additionally, the CIBERSORT algorithm was employed to evaluate the correlation between the hub gene expression and immune cell types. A total of 16 genes were identified to be related to radiotherapy response, and low expression of SVOPL, EDAR, GSTA1, and ABCA13 was associated with poor overall survival and progression-free survival in breast cancer cases. Correlation analysis revealed that the four genes negatively related to some specific immune cell types. The four genes were downregulated in H group compared with the L group. Four hub genes associated with the immune cell infiltration of breast cancer were identified; these genes might be used as a promising biomarker to test the treatment in breast cancer patients.

Co-amplified with PDGFRA, IGFBP7 is a prognostic biomarker correlated with the immune infiltrations of glioma.

BACKGROUND: A subgroup of glioma carry genetic 4q12 amplification including platelet derived growth factor receptor α (PDGFRA) and insulin like growth factor binding protein 7 (IGFBP7). However, the prognosis of PDGFRA and IGFBP7 in glioma is unclear. METHODS: The prognosis of PDGFRA and IGFBP7 was determined using cox regression and Kaplan-Meier survival analysis. Pathways associated with IGFBP7 were analyzed through gene set enrichment analysis (GSEA). Immune profiling of glioma was determined using "ESTIMATE" and "TIMER" database. RESULTS: PDGFRA amplification or expression was not correlated with the outcomes of glioblastoma (GBM). IGFBP7 but not PDGFRA was over-expressed in GBM. IGFBP7 over-expression was correlated with the unfavorable outcomes of GBM. In lower grade glioma (LGG), PDGFRA over-expression was not correlated with the unfavorable prognosis of LGG, while, IGFBP7 was a prognostic biomarker of LGG. LGG patients with IGFBP7 lower expressions had prolonged clinical overall survival. Combination of IDH mutation, LGG grade and IGFBP7 achieved even better prognostic effects in LGG. Moreover, IGFBP7 was over-expressed in glioma patients with wild type IDH or with high grades. IGFBP7 over-expression was correlated with the unfavorable outcomes of glioma. Furthermore, IGFBP7 was hypo-methylated in GBM or LGG patients without IDH mutations. IGFBP7 hyper-methylation was correlated with the lower overall survival of GBM or LGG. LGG patients with wild type IDH and with IGFBP7 hypo-methylation demonstrated even worse prognosis. IGFBP7 was associated with multiple immune-related signaling pathways in GBM or LGG. The stromal score, immune score and the infiltrations of immune cells were also correlated with IGFBP7 and the prognosis of LGG. CONCLUSIONS: IGFBP7 but not PDGFRA served an ideal prognostic marker and therapeutic target of glioma.

A Comparison for Type 2 Cytokines and Lesional Inflammatory Infiltrations in Bullous Pemphigoid and Atopic Dermatitis.

Background: Bullous pemphigoid (BP) and atopic dermatitis (AD) are both type 2 inflammatory skin diseases with similar clinical features. Thymic stromal lymphopoietin (TSLP) is an epithelial-derived cytokine which is upregulated in AD. However, the expression of TSLP in BP and the correlation between TSLP and inflammatory infiltrations have not been fully studied. Objective: To characterize the serum Th2 cytokines level and Th2 inflammatory cell infiltrations in BP and AD. To study TSLP levels in serum, blister fluids and expression in lesional skin in patients with BP and AD. Methods: TSLP level in serum and blister fluids was measured by enzyme-linked immunosorbent assay (ELISA). Inflammatory cells (CD4+ T cells, CD8+ T cells, CD1a+ cells, eosinophils and mast cells) were stained immunohistochemically and quantified by image analysis. Results: TSLP level was significantly increased in blister fluids of BP and was highly expressed in lesional skin of BP and AD. Serum levels of IL-6, IL-4, IL-22, IFN-γ and thymic activation regulates chemokines (TARC) were significantly higher in patients with BP and AD than in healthy controls. CD4+ T cells, CD8+ T cells and CD1a+ cells were significantly more in upper dermis of BP and AD lesions. Eosinophils were found more in BP lesions while mast cells were found more in AD lesions than in healthy controls. A distinct correlation was found between TSLP levels and the intensities of CD4+ T cells, CD1a+ cells infiltrations. Conclusion: TSLP was significantly higher in blister fluids and skin lesions of BP, suggesting that it might contribute to the pathogenesis of BP. BP exhibited a similar type 2 immune response and a slight difference in cells infiltrations with AD.

Transient and Recurrent Pulmonary Infiltrations Associated with Familial Mediterranean Fever.

Chest symptoms and pleural effusion due to serositis in familial Mediterranean fever (FMF) are occasionally misdiagnosed as acute pneumonia. However, the actual pulmonary involvement of FMF is extremely rare. A 67-year-old man was referred to our hospital due to repeated and transient anterior chest pain. Chest images revealed a moderate amount of pericardial fluid, slight bilateral pleural effusion, and infiltrations in both lower lung lobes. Colchicine treatment without antibiotics rapidly improved these symptoms and findings. Pericarditis, pleurisy and the response to colchicine indicated FMF. FMF should be considered as a causative disease of pulmonary infiltrations, especially if it occurs repeatedly.

Identification and validation of a fatty acid metabolism-related lncRNA signature as a predictor for prognosis and immunotherapy in patients with liver cancer.

BACKGROUND: Fatty acid (FA) metabolism is considered the emerging cause of tumor development and metastasis, driving poor prognosis. Long non-coding RNAs (lncRNAs) are closely related to cancer progression and play important roles in FA metabolism. Thus, the discovery of FA metabolism-related lncRNA signatures to predict outcome and immunotherapy response is critical in improving the survival of patients with hepatocellular carcinoma (HCC). METHODS: FA metabolism scores and a FA metabolism-related lncRNA signature were constructed using a single-sample gene set enrichment analysis based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. "ConsensusClusterPlus" was used to screen molecular subtypes. Chi-squared test and Fisher's exact test were applied to explore the relationship between clinical, genomic mutation characteristics and subtypes. Transcription factor (TF) activity scores, cellular distributions, immune cell infiltration, and immunotherapy response were employed to investigate the functions of FA metabolism-related lncRNA signatures. FA metabolism microarray and western blot were performed to detect the biological function of candidate lncRNAs. RESULTS: A total of 70 lncRNAs that highly correlated with FA metabolism scores in two cohorts were used to construct two distinct clusters. Patients in cluster 2 had lower FA metabolism scores and worse survival than those in cluster 1. Patients in cluster 2 exhibited a high frequency of DNA damage, gene mutations, oncogenic signaling such as epithelial-to-mesenchymal transition, and a high degree of immune cell infiltration. Moreover, the lncRNA signature could predict the effects of immunotherapy in patients with HCC. Furthermore, three lncRNAs (SNHG1, LINC00261, and SNHG7) were identified that were highly correlated with FA metabolism. Additionally, SNHG1 and SNHG7 were found to regulate various FA metabolism-related genes and ferroptosis-related genes in vitro experiments. GSEA analysis revealed that SNHG1 and SNHG7 promote fatty acid beta-oxidation. SNHG1 and SNHG7 silencing dramatically reduced lipid droplets in HCC cells. Many immune-infiltration genes and TFs were overexpressed in HCC tissues with SNHG1 and SNHG7 high expression. CONCLUSIONS: A novel molecular model of FA metabolism-related lncRNAs was developed, which has significantly prognostic potential in HCC diagnosis and aids in clinical decision making.

Development of skeletal muscle atrophy and intermuscular adipose tissue in patients with early breast cancer treated with chemotherapy.

Chemotherapy is a common therapy to treat patients with breast cancer but also leads to skeletal muscle deconditioning. Skeletal muscle deconditioning is multifactorial and intermuscular adipose tissue (IMAT) accumulation is closely linked to muscle dysfunction. To date, there is no clinical study available investigating IMAT development through a longitudinal protocol and the underlying mechanisms remain unknown. Our study was dedicated to investigating IMAT content in patients with early breast cancer who were treated with chemotherapy and exploring the subsequent cellular mechanisms involved in its development. We included 13 women undergoing chemotherapy. Muscle biopsies and ultrasonography assessment were performed before and after chemotherapy completion. Histological and Western blotting analyses were conducted. We found a substantial increase in protein levels of three mature adipocyte markers (perilipin, +901%; adiponectin, +135%; FABP4, +321%; P < 0.05). These results were supported by an increase in oil red O-positive staining (+358%; P < 0.05). A substantial increase in PDGFRα protein levels was observed (+476%; P < 0.05) highlighting an increase in fibro-adipogenic progenitors (FAPs) content. The cross-sectional area of the vastus lateralis muscle fibers substantially decreased (-21%; P < 0.01), and muscle architecture was altered, as shown by a decrease in fascicle length (-15%; P < 0.05) and a decreasing trend in muscle thickness (-8%; P = 0.08). We demonstrated both IMAT development and muscle atrophy in patients with breast cancer who were treated with chemotherapy. FAPs, critical stem cells inducing both IMAT development and skeletal muscle atrophy, also increased, suggesting that FAPs likely play a critical role in the skeletal muscle deconditioning observed in patients with breast cancer who were treated with chemotherapy.

Novel insight into ferroptosis-related genes, molecular subtypes, and immune characteristics in intracranial aneurysms.

OBJECTIVES: This study aimed to identify the role of ferroptosis in intracranial aneurysm (IA). METHODS: GSE122897, GSE75436, GSE15629, and GSE75434 datasets were downloaded from the Gene Expression Omnibus database. The differentially expressed ferroptosis-related genes (DEFRGs) were selected to construct a diagnostic model integrating with machine learning. Then, a consensus clustering algorithm was performed to classify IA patients into distinct ferroptosis-related clusters. Functional analyses, including GO, KEGG, GSVA, and GSEA analyses, were conducted to elucidate the underlying mechanisms. ssGSEA and xCell algorithms were performed to uncover the immune characteristics. RESULTS: We identified 28 DEFRGs between IAs and controls from the GSE122897 dataset. GO and KEGG results showed that these genes were enriched in cytokine activity, ferroptosis, and the IL-17 signaling pathway. Immune analysis showed that the IAs had higher levels of immune infiltration. A four FRGs model (MT3, CDKN1A, ZEP69B, and ABCC1) was established and validated with great IA diagnostic ability. We divided the IA samples into two clusters and found that cluster 2 had a higher proportion of rupture and immune infiltration. We identified 10 ferroptosis phenotypes-related markers in IAs. CONCLUSION: Ferroptosis and the immune microenvironment are closely associated with IAs, providing a basis for understanding the IA development.