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Cancer, characterized by uncontrolled cell division and potential tissue spread, remains a significant health problem, with breast cancer being the most common in women, accounting for 25% of all cancer cases. Natural compounds have recently gained attention as they can improve the efficacy of cancer treatment. The aim of this study is to shed light on the potential benefits of polyunsaturated fatty acids in the treatment of breast cancer. Overexpression of tyrosine kinase receptors and mutations in the breast cancer gene-1 (BRCA1) and BRCA2 genes lead to breast cancer in women. Based on the findings of papers published in various scientific search engines, n-3 polyunsaturated fatty acid (PUFA) may reduce the likelihood of developing breast cancer due to their anti-inflammatory properties. According to several studies, women who consume more n-3 polyunsaturated fatty acids have a lower risk of breast cancer. n-3 polyunsaturated fatty acids regulate breast cancer by controlling the inflammatory mediators, gene expression transcription factor and signal transducer, peroxisome proliferator-activated receptor-gamma, B-cell lymphoma-2 (Bcl-2) associated X protein or B-cell lymphoma-2, Phosphatidylinositol 3-kinase or Protein kinase B, Nuclear factor-κB, and toll-like receptor-4. Polyunsaturated fatty acids are considered a successful treatment for breast cancer patients when combined with chemotherapy drugs. Doxorubicin is a first-line drug for the treatment of triple-negative breast cancer. Giving doxorubicin and polyunsaturated fatty acids together makes chemotherapy treatments for triple-negative breast cancer work better in the MDA-MB-468 and MDA-MB-231 cell lines. This review highlights the role of PUFAs in modulating cancer-related pathways, offering valuable insights for researchers, clinicians and the pharmaceutical industry in the fight against breast cancer.
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Alzheimer's disease (AD), a catastrophic disorder that commonly affects the elderly, causes extracellular plaques to form in the hippocampus, leading to slow, progressive loss of brain function. The Blood Brain Barrier poses a significant challenge for conventional drug delivery in AD therapeutics. Therefore, introducing novel strategies such as nanotechnology-based drug delivery offers promising potential. This paper highlights the significance of nanotechnology based drug delivery in AD with respect to its pathophysiology and discusses the current situation and future prospects of the same in diagnosis and therapy. Data collection involved scientific databases such as PubMed, Science Direct, and Google Scholar. The keywords searched were AD, neurodegenerative, nanotechnology, Amyloid-beta protein, tau protein and patents. A total of 146 papers were obtained. The pathophysiology of AD with respect to the Amyloid- and tau hypotheses were found to have significant therapeutic potential. It was also found that nanotechnology systems were able to offer enhanced site-specific action, offering a low toxicity profile in areas where conventional drug delivery systems had difficulty to act on. Delivery systems that were found to have potential were nanoparticles (NPs) including inorganic NPs and magnetic NPs, Quantum Dots, liposomes, dendrimers, Micelles, etc. Thus, our work suggests that NP-based drug delivery systems are able to overcome the challenges faced by conventional systems to achieve therapeutic efficacy with substantial levels of evidence, initiating the much-needed discussions on their potential use in AD therapeutics.
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Background: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD) globally, characterized by increased albuminuria and reduced glomerular filtration rate. Recent evidence points to inflammation as a vital contributor to the development and progression of DKD, involving interactions among immune cells, cytokines, and chemokines. Our study focused on uncovering inflammation-related genes in DKD to understand its mechanisms and developed an inflammation-centric predictive model. We aimed to bridge molecular insights with immune interactions, paving the way for innovative treatments.
Methods: This study involves comprehensive data collection from gene expression omnibus (GEO) datasets (GSE1009 and GSE30528) to identify differentially expressed genes (DEGs) between patients with DKD and healthy controls (HC). Using the ComBat method for batch effect removal, R package Limma for DEGs identification, and Metascape for enrichment analysis, we focused on the interplay between inflammation-associated genes and immune cell infiltration. We developed a predictive model for DKD using the least absolute shrinkage and selection operator (LASSO) regression, centered on six potential candidate genes: chitinase-3-like protein 1 (CHI3L1), coagulation factor V (F5), decay-accelerating factor (CD55), insulin-like growth factor 1 (IGF1), vascular endothelial growth factor A (VEGFA), and 15-hydroxyprostaglandin dehydrogenase (HPGD), within a training cohort. This model was subsequently validated in a test cohort utilizing data extracted from the GEO dataset GSE96804. Immune cell infiltration was determined using CIBERSORT, followed by Pearson correlation analysis to elucidate the interactions between hub genes, immune cells, and chemokines.
Results: We identified 349 DEGs, including 99 upregulated and 250 downregulated genes, highlighting the significant role of inflammation in DKD. Through weighted gene co-expression network analysis (WGCNA), a module consisting of 784 genes strongly associated with DKD was identified. Within this module, six inflammatory-related genes were identified as crucial for the predictive model, achieving an area under the receiver operating characteristic curve (AUC) of 1 in training and 0.76 in validation. Analysis of immune cells revealed significant differences between DKD patients and controls, while Pearson correlation analysis highlighted key associations with immune infiltration and regulation.
Conclusions: Our study provides novel insights into the genetic and inflammatory landscape of DKD, establishing a predictive model with high accuracy compared to existing models. We pinpoint significant correlations between hub genes and immune cell dynamics, potentially opening avenues for new therapeutic strategies. Our findings underscore the promise of precision medicine in diagnosing and treating DKD.
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Background: Intrahepatic cholangiocarcinoma (ICC) is a prevalent type of cancer originating from epithelial cells of the bile duct within the liver. The molecular mechanisms underlying ICC proliferation, invasion, and metastasis remain unclear. Recently, N6-methyladenosine (m6A) RNA methylation has been associated with tumor progression. Methyltransferase 3 (METTL3) is a crucial methyltransferase for m6A. However, its biological significance and the regulatory mechanisms underlying ICC invasion and metastasis remain poorly understood. Therefore, we aimed to explore the role of METTL3 in ICC progression and its potential mechanisms.
Methods: We analyzed the expression of METTL3 in ICC using bioinformatics, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and immunohistochemistry analysis. Furthermore, we evaluated the impact of METTL3 on ICC cell proliferation and metastasis in vivo and in vitro. For mechanistic studies, we used RNA-Seq to screen the crucial downstream targets of METTL3 in ICC cells. Furthermore, we examined the regulatory impact of METTL3 on the phenotype of ICC cells through S100 calcium-binding protein A4 (S100A4) using qRT-PCR, Western blot, and rescue experiments. Finally, we assessed the effect of METTL3 on S100A4 stability by mediating m6A modification using the methylated RNA immunoprecipitation qPCR (MeRIP-qPCR) and messenger RNA (mRNA) degradation experiments.
Results: The expression of METTL3 was upregulated in patients with ICC (p < 0.05). Moreover, METTL3 knockdown inhibited the proliferation, migration, and invasion ability of ICC cells (p < 0.05). Mechanistically, METTL3 mediated m6A modification of S100 calcium-binding protein A4 (S100A4) mRNA and inhibited S100A4 mRNA decay in an m6A-dependent manner (p < 0.05), thus promoting the proliferation and metastasis of ICC.
Conclusions: METTL3 promotes ICC proliferation and metastasis by mediating S100A4 mRNA degradation, suggesting that METTL3 may be a potential target for treating ICC.
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Background: Colorectal cancer, an invasive tumor originating in the mucosal lining of the large intestine and rectum, represents a prevalent form of gastrointestinal malignancy. Although extensive investigations have been conducted on colorectal cancer, the precise molecular mechanisms underlying this neoplasm remain uncharacterized. Alterations in the genetic material have been linked to colorectal cancer progression. To analyze the prognosis of individuals with colorectal cancer, it is crucial to identify new biomarkers. Using integrated bioinformatics analysis, this study successfully identified and confirmed the fundamental gene linked to colorectal cancer.
Methods: Bioinformatics software tools were employed to assess the mRNA expression level of Erythroferrone (ERFE) by analyzing the Cancer Genome Atlas (TCGA) dataset, which included 647 tumor samples and 51 control samples. In order to verify the findings, a comparison was conducted with data available on the Gene Expression Omnibus (GEO). In order to determine the clinical significance and expression level of ERFE, a bioinformatics investigation was carried out using logistic regression analysis. To assess survival rates in both high- and low-expression ERFE groups, univariate and multivariate Cox proportional hazards model (Cox) regression analyses were conducted. To validate the expression of ERFE at both the gene and protein levels in colorectal cancer (CRC) cells (HCT116 and Lovo) and normal epithelial cells, reverse transcription quantitative polymerase chain reaction and western blot experiments were performed. The knock-down efficiency of ERFE in HCT116 and LoVo cell lines was assessed using western blot experiments. The effect of ERFE gene function was compared and analyzed through various assays such as cell counting kit-8 (CCK-8), Transwell, and scratch tests before and after ERFE knock-down in HCT116 and LoVo cell lines.
Results: An analysis of data obtained from TCGA and GEO databases unveiled a remarkable increase in the expression of ERFE mRNA in CRC tissue compared to both normal and paracancerous tissues (p < 0.001). Furthermore, it was discovered that the overexpression of ERFE was linked to an unfavorable prognosis and had the potential to act as an independent prognostic indicator for predicting overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS) among colorectal cancer patients. Additionally, a positive correlation was found between heightened ERFE expression, infiltration of numerous immune cells, and levels of immune checkpoint molecules. Experimental evaluations, including the CCK-8 assay, scratch assay, and transwell assay, provided compelling evidence demonstrating a significant reduction in the proliferative, migratory, and invasive capabilities of colorectal cancer cells upon knocking down ERFE.
Conclusions: In summary, ERFE, functioning as a pro-oncogene in CRC, is linked to the initiation and advancement of cancer, and can serve as a standalone marker for unfavorable prognosis among CRC patients.
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Background: Esophageal squamous cell carcinoma (ESCC) represents a prevalent malignancy within the digestive tract, often diagnosed at advanced stages, leading to treatment challenges and poor prognosis. Despite its essential roles in biosynthesis, antioxidation, and energy metabolism, the involvement of lysine in cancer pathogenesis remains poorly understood. This study aimed to elucidate the significance of lysine-associated genes in ESCC, potentially enhancing treatment outcomes.
Methods: mRNA expression data for ESCC were retrieved from The Cancer Genome Atlas (TCGA) for limma differential expression analysis. Lysine-related genes were extracted from the GeneCards database and overlapped with differentially expressed genes. Lysine levels were quantified using single-sample Gene Set Enrichment Analysis (ssGSEA), followed by metabolic pathway analysis comparing high and low lysine levels. The random survival forest (RSF) algorithm identified lysine-related genetic signatures associated with poor prognosis of ESCC. Further analysis encompassed drug susceptibility profiling and assessment of immune cell infiltration. Subsequently, single-cell analysis was conducted using data from the Gene Expression Omnibus (GEO) database (GSE196756) to validate key lysine-related genes.
Results: Ubiquitination Factor E4A (UBE4A) and Apolipoprotein C1 (APOC1) were identified as key lysine-associated genes in ESCC. Functional enrichment analysis revealed that the lysine-related genes remarkably enriched lysine-regulated pathways, including histone modification, histone lysine methylation, and lysine degradation pathways. Moreover, these lysine-related differentially expressed genes (DEGs) served as independent prognostic factors, and a nomogram incorporating these genes and clinical factors accurately predicted 1- and 2-year survival rates in ESCC patients. Drug databases highlighted AICAR, BI.D1870, MS.275, and lapatinib as potential therapeutic agents. Immunemicroenvironment infiltration analysis indicated that UBE4A was actively connected with T cells CD4 memory resting and passively connected with B cells memory. APOC1 was actively linked to macrophages M2, T cells CD4 memory activated, T cells CD8, and was passively linked to the activated Dendritic cells, T cells CD4 memory resting and Eosinophils. We further performed single-cell analysis, and 21 subtypes were obtained by t-Distributed Stochastic Neighbor Embedding (tSNE) algorithm. The total clusters were labeled to tissue stem cells, neurons, epithelial cells, B cells, neutrophils, monocytes, T cells, smooth muscle cells, NK cells, and endothelial cells.
Conclusions: Our findings underscore the pivotal role of lysine-related gene regulation in ESCC. The identified lysine-related genes hold promise as prognostic indicators for ESCC patients, shedding light on potential mechanisms underlying poor prognosis and facilitating the search for targeted therapeutics to enhance the success rate of ESCC treatment.
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Background & Objective: Colchicine improves cardiovascular outcomes in patients with coronary heart disease, but the underlying mechanisms remain incompletely elucidated. The aim of this study was to evaluate the effects of colchicine on systemic inflammation, peripheral blood CD4+ T cell subsets, and oxidative stress after percutaneous coronary intervention in patients with coronary heart disease combined with gout from the perspective of population study.
Methods: From January 2019 to June 2022, a total of 128 patients with coronary heart disease combined with gout who underwent percutaneous coronary intervention (PCI) at our hospital were retrospectively collected and divided into colchicine group (n = 64) and control group (n = 64) according to whether colchicine was routinely used or not. Systemic inflammation (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and hypersensitivity C-reactive protein (hs-CRP)), peripheral blood CD4+ T cell subsets (Th1 cells, Th17 cells, and regulatory T cells), and oxidative stress indicators (serum superoxide dismutase (SOD) and malondialdehyde (MDA)) were compared between the two groups after PCI. hs-CRP ≥2 mg/L was defined as a patient at risk of residual inflammatory. Logistic regression was used to analyze the association between colchicine treatment and the risk of residual inflammation.
Results: There was no significant difference between the two groups in terms of age, gender, smoking history, disease history, body mass index (BMI), time from symptom onset to PCI, blood pressure, hypersensitivity troponin I (hs-TnI), neutrophils, triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), serum creatinine, and the equilibrium was comparable (p > 0.05). After PCI treatment, TNF-α and IL-6 levels were significantly decreased in both groups, and the levels of TNF-α and IL-6 in the colchicine group were significantly lower than control group (TNF-α: 22.5 ± 4.9 vs 41.6 ± 4.1 μg/L; IL-6: 21.3 ± 12.8 vs 40.9 ± 17.5 ng/L; both p < 0.001). Patients in the colchicine group had a significantly proportion of risk of residual inflammation compared with controls (37.5% vs 62.5%, p = 0.005). Logistic regression showed that, using the control group as a reference, we still found that colchicine use was independently associated with a reduced risk of residual inflammation when corrected for other confounders (odds ratio [OR], 0.372; 95% confidence interval [CI], 0.156–0.889; p = 0.026). Regarding peripheral blood CD4+ T cell subsets, Th1 cell, Th17 cell, and regulatory T cell counts were significantly higher in the colchicine group than control group after PCI treatment (p < 0.01). As for oxidative stress indicators, SOD levels were significantly higher and MDA levels were significantly lower in the colchicine group after PCI treatment compared with the control group (p < 0.001).
Conclusions: Colchicine administration was associated with reduced systemic inflammatory indexed, promoted proliferation of peripheral blood CD4+ T cells, and improved oxidative stress levels in patients with coronary heart disease combined with gout after PCI.
