Search Results (4,160)

Hydroperoxides (ROOHs) are known as damaging agents capable of mediating mutation, while a role as signaling agents through oxidation of protein sulfhydryls that can alter cancer-related pathways has gained traction. Glutathione peroxidase 2 (GPX2) is an antioxidant enzyme that reduces ROOHs at the expense of glutathione (GSH). GPX2 is noted for a tendency of large increases or decreases in expression levels during tumorigenesis that leads to investigators focusing on its role in cancer. However, GPX2 is only one component of multiple enzyme families that metabolize ROOH, and GPX2 levels are often very low in the context of these other ROOH-reducing activities. Colorectal cancer (CRC) was selected as a case study for examining GPX2 function, as colorectal tissues and cancers are sites where GPX2 is highly expressed. A case can be made for a significant impact of changes in expression levels. There is also a link between GPX2 and NADPH oxidase 1 (NOX1) from earlier studies that is seldom addressed and is discussed, presenting data on a unique association in colon and CRC. Tumor-derived cell lines are quite commonly used for pre-clinical studies involving the role of GPX2 in CRC. Generally, selection for this type of work is limited to identifying cell lines based on high and low GPX2 expression with the standard research scheme of overexpression in low-expressing lines and suppression in high-expressing lines to identify impacted pathways. This overlooks CRC subtypes among cell lines involving a wide range of gene expression profiles and a variety of driver mutation differences, along with a large difference in GPX2 expression levels. A trend for low and high GPX2 expressing cell lines to segregate into different CRC subclasses, indicated in this report, suggests that choices based solely on GPX2 levels may provide misleading and conflicting results by disregarding other properties of cell lines and failing to factor in differences in potential protein targets of ROOHs. CRC and cell line classification schemes are presented here that were intended to assist workers in performing pre-clinical studies but are largely unnoted in studies on GPX2 and CRC. Studies are often initiated on the premise that the transition from normal to CRC is associated with upregulation of GPX2. This is probably correct. However, the source normal cells for CRC could be almost any colon cell type, some with very high GPX2 levels. These factors are addressed in this study. Full article

Colorectal cancer (CRC) is one of the top 10 most common cancers worldwide and caused approximately 10 million deaths in 2022. CRC mortality has increased by 10% since 2020 and 52.000 deaths will occur in 2024, highlighting the limitations of current treatments due to ineffectiveness, toxicity, or non-adherence. The widely used chemotherapeutic agent, 5-fluorouracil (5-FU), is associated with several adverse effects, including renal, cardiac, and hepatic toxicity; mucositis; and resistance. Taurine (TAU), an essential β-amino acid with potent antioxidant, antimutagenic, and anti-inflammatory properties, has demonstrated protective effects against tissue toxicity from chemotherapeutic agents like doxorubicin and cisplatin. Taurine deficiency is linked to aging and cancers such as breast and colon cancer. This study hypothesized that TAU may mitigate the adverse effects of 5-fluorouracil (5-FU). Carcinogenesis was chemically induced in rats using 1,2-dimethylhydrazine (DMH). Following five months of cancer progression, taurine (100 mg/kg) was administered orally for 8 days, and colon tissues were analyzed. The results showed 80% of adenocarcinoma (AC) in DMH-induced control animals. Notably, the efficacy of 5-FU showed 70% AC and TAU 50% while, in the 5-FU + TAU group, no adenocarcinoma was observed. No differences were observed in the inflammatory infiltrate or the expression of genes such as K-ras, p53, and Ki-67 among the cancer-induced groups whereas APC/β-catenin expression was increased in the 5FU + TAU-treated group. The mitotic index and dysplasia were increased in the induced 5-FU group and when associated with TAU, the levels returned to normal. These data suggest that 5-FU exhibits a synergic anticancer effect when combined with taurine. Full article

Metabolic reprogramming is a critical pathogenesis of colorectal cancer (CRC), referring to metabolic disorders that cancer cells make in response to the stimulating pressure. Metabolic reprogramming induces changes in genetic material and promotes CRC progression and has been proven to be an efficient target of CRC. As natural products have garnered interest due to notable pharmacological effects and potential in counteracting chemoresistance, an increasing body of research is delving into the impact of these natural products on the metabolic reprogramming associated with CRC. In this review, we collected published data from the Web of Science and PubMed, covering the period from January 1980 to October 2023. This article focuses on five central facets of metabolic alterations in cancer cells, glucose metabolism, mitochondrial oxidative phosphorylation (OXPHOS), amino acid metabolism, fatty acid synthesis, and nucleotide metabolism, to provide an overview of recent advancements in natural product interventions targeting metabolic reprogramming in CRC. Our analysis underscores the potential of natural products in disrupting the metabolic pathways of CRC, suggesting promising therapeutic targets for CRC and expanding treatment options for metabolic-associated ailments. Full article

Selenium (Se), zinc (Zn), and copper (Cu) are known to be involved in carcinogenesis and participate in the defence against reactive oxygen species (ROS). This study aimed to evaluate the clinical utility of serum Se, Zn, and Cu concentrations and plasma total antioxidant status (TAS) in the diagnosis of colorectal cancer (CRC) and colorectal adenoma (CRA) in a population of low Se and borderline Zn status. Based on clinical examination and colonoscopy/histopathology, the patients (n = 79) were divided into three groups: colorectal cancer (n = 30), colorectal adenoma (n = 19), and controls (CONTROL, n = 30). The serum Se concentration was lower in the CRC group than in the CRA group (by 9.1%, p < 0.0001) and the CONTROL group (by 7.9%, p < 0.0001). In turn, the serum Zn concentration was decreased in the CRA group (by 17.9%, p = 0.019) when compared to the CONTROL group. Plasma TAS was lower in the CRC group (by 27.8%, p = 0.017) than in the CONTROL group. In turn, the serum Zn concentration was decreased in the CRA group when compared to the CONTROL group. Plasma TAS was lower in the CRC group than in the CONTROL group. ROC (receiver operating characteristic) curve analysis revealed that the Se level was of the highest diagnostic utility for the discrimination of the CRC group from both the CRA group (area under ROC curve (AUC) 0.958, sensitivity 84.21%, specificity 100%) and the CONTROL group (AUC 0.873, sensitivity 100%, specificity 66.67%). The Zn and TAS levels were significantly accurate in the differentiation between the groups. An individualised risk of colorectal adenoma and cancer approach could comprise Se, Zn, and TAS assays in the population. Full article

Infection by the mustard clubroot disease pathogen Plasmodiophora brassicae has a significant negative impact on the quality and yield of Chinese mustard (Brassica juncea). At present, screening resistant resources for breeding programs is the most economical and effective method available to control this disease. In this study, we isolated P. brassicae physiological race 4 from Chinese cabbage and examined 483 mustard germplasm resources (193 leaf mustard, 96 stem mustard, and 194 root mustard) from China and abroad to identify resistance to clubroot disease at the seedling stage through irrigation inoculation with the isolated pathogen. The results showed that there were no immune varieties among the tested mustard germplasm, but that there were differences in resistance to clubroot disease among the three mustard types. More than 90% of leaf and stem mustard resources were susceptible to clubroot disease, whereas 38.66% of root mustard resources showed resistance. In total, we detected 4 highly resistant, 9 resistant, and 83 moderately resistant varieties, of which 4 highly resistant, 8 resistant, and 63 moderately resistant varieties were root mustard resources, whereas only 1 resistant and 5 moderately resistant varieties were stem mustard resources, and 15 moderately resistant varieties were leaf mustard resources. In addition, we used seven molecular markers for clubroot disease resistance in Chinese cabbage to detect stem and root mustard resources. The results showed that the marker CRk was detected in 97.87% of stem mustard and 92.49% of root mustard resources. Six markers (Crr1, Crr2, Crr3, CRa, CRb, and CRc) were detected in 18.09%, 7.45%, 2.13%, 6.38%, 12.77%, and 12.77% of stem mustard germplasms, and four markers (Crr1, Crr2, Crr3, and CRc) were detected in 8.09%, 8.67%, 10.40%, and 8.67% of root mustard germplasms, respectively, suggesting that these markers are not suitable for detecting mustard germplasm resistance to clubroot disease. This study provides a technical reference and material support for the breeding of mustard varieties resistant to clubroot disease. Full article

Predictive biomarkers for immune checkpoint inhibitors (ICIs) in solid tumors such as melanoma, hepatocellular carcinoma (HCC), colorectal cancer (CRC), non-small cell lung cancer (NSCLC), endometrial carcinoma, renal cell carcinoma (RCC), or urothelial carcinoma (UC) include programmed cell death ligand 1 (PD-L1) expression, tumor mutational burden (TMB), defective deoxyribonucleic acid (DNA) mismatch repair (dMMR), microsatellite instability (MSI), and the tumor microenvironment (TME). Over the past decade, several types of ICIs, including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, anti-programmed cell death 1 (PD-1) antibodies, anti-programmed cell death ligand 1 (PD-L1) antibodies, and anti-lymphocyte activation gene-3 (LAG-3) antibodies have been studied and approved by the Food and Drug Administration (FDA), with ongoing research on others. Recent studies highlight the critical role of the gut microbiome in influencing a positive therapeutic response to ICIs, emphasizing the importance of modeling factors that can maintain a healthy microbiome. However, resistance mechanisms can emerge, such as increased expression of alternative immune checkpoints, T-cell immunoglobulin (Ig), mucin domain-containing protein 3 (TIM-3), LAG-3, impaired antigen presentation, and alterations in the TME. This review aims to synthesize the data regarding the interactions between microbiota and immunotherapy (IT). Understanding these mechanisms is essential for optimizing ICI therapy and developing effective combination strategies. Full article

This study delves deeper into the impact of environmental temperature variations on the nervous system in teleost fish. Previous research has demonstrated that exposing adult zebrafish (Danio rerio) to 18 °C and 34 °C for 4 or 21 days induces behavioural changes compared to fish kept at a control temperature of 26 °C, suggesting alterations in the nervous system. Subsequent studies revealed that these temperature conditions also modify brain protein expression, indicating potential neurotoxic effects. The primary aim of this work was to investigate the effects of prolonged exposure (21 days) to 18 °C or 34 °C on the brain lipidomes of adult zebrafish compared to a control temperature. Analysis of the brain lipidome highlighted significant alteration in the relative abundances of specific lipid molecules at 18 °C and 34 °C, confirming distinct effects induced by both tested temperatures. Exposure to 18 °C resulted in an increase in levels of phospholipids, such as phosphatidylethanolamine, alongside a general reduction in levels of sphingolipids, including sphingomyelin. Conversely, exposure to 34 °C produced more pronounced effects, with increases in levels of phosphatidylethanolamine and those of various sphingolipids such as ceramide, gangliosides, and sphingomyelin, alongside a reduction in levels of ether phospholipids, including lysophosphatidylethanolamine ether, phosphatidylethanolamine ether, and phosphatidylglycerol ether, as well as levels of glycolipids like monogalactosyldiacylglycerol. These results, when integrated with existing proteomic and behavioural data, offer new insights into the effects of thermal variations on the nervous system in teleost fish. Specifically, our proteomic and lipidomic findings suggest that elevated temperatures may disrupt mitochondrial function, increase neuronal susceptibility to oxidative stress and cytotoxicity, alter axonal myelination, impair nerve impulse transmission, hinder synapse function and neurotransmitter release, and potentially lead to increased neuronal death. These findings are particularly relevant in the fields of cell biology, neurobiology, and ecotoxicology, especially in the context of global warming. Full article

Micro- and nano-plastics (MNPLs) can move along the food chain to higher-level organisms including humans. Three significant routes for MNPLs have been reported: ingestion, inhalation, and dermal contact. Accumulating evidence supports the intestinal toxicity of ingested MNPLs and their role as drivers for increased incidence of colorectal cancer (CRC) in high-risk populations such as inflammatory bowel disease (IBD) patients. However, the mechanisms are largely unknown. In this review, by using the leading scientific publication databases (Web of Science, Google Scholar, Scopus, PubMed, and ScienceDirect), we explored the possible effects and related mechanisms of MNPL exposure on the gut epithelium in healthy conditions and IBD patients. The summarized evidence supports the idea that oral MNPL exposure may contribute to intestinal epithelial damage, thus promoting and sustaining the chronic development of intestinal inflammation, mainly in high-risk populations such as IBD patients. Colonic mucus layer disruption may further facilitate MNPL passage into the bloodstream, thus contributing to the toxic effects of MNPLs on different organ systems and platelet activation, which may, in turn, contribute to the chronic development of inflammation and CRC development. Further exploration of this threat to human health is warranted to reduce potential adverse effects and CRC risk. Full article

Irritable bowel syndrome (IBS) is a gastrointestinal (GI) disease accompanied by changes in bowel habits without any specific cause. Gintonin is a newly isolated glycoprotein from ginseng that is a lysophosphatidic acid (LPA) receptor ligand. To investigate the efficacy and mechanisms of action of gintonin in IBS, we developed a zymosan-induced IBS murine model. In addition, electrophysiological experiments were conducted to confirm the relevance of various ion channels. In mice, gintonin restored colon length and weight to normal and decreased stool scores, whilst food intake remained constant. Colon mucosal thickness and inflammation-related tumor necrosis factor-α levels were decreased by gintonin, along with a reduction in pain-related behaviors. In addition, the fecal microbiota from gintonin-treated mice had relatively more Lactobacillaceae and Lachnospiraceae and less Bacteroidaceae than microbiota from the control mice. Moreover, gintonin inhibited transient receptor potential vanilloid (TRPV) 1 and TRPV4 associated with visceral hypersensitivity and voltage-gated Na⁺ 1.5 channels associated with GI function. These results suggest that gintonin may be one of the effective components in the treatment of IBS. Full article

The rising incidence and mortality of early-onset colorectal cancer (EOCRC) emphasize the urgent need for effective non-invasive screening. Circulating microRNAs (miRNAs) have emerged as promising biomarkers for cancer detection. This systematic review aims to evaluate the diagnostic performance of circulating miRNAs in detecting colorectal cancer (CRC). A literature search was conducted in PubMed and Scopus. Studies that report sensitivity, specificity, or area under the curve (AUC) for CRC detection by miRNA were included. The miRNA miR-21 was the most frequently studied biomarker, with a varying range of AUC from 0.55 to 0.973 attributed to differences in study populations and methodologies. The miRNAs miR-210 and miR-1246 showed potential diagnostic capacity with miR-1246 achieving an AUC of 0.924, 100% sensitivity, and 80% specificity. The miRNA panels offer improved diagnostic performance compared to individual miRNA. The best performing panel for CRC patients below 50 is miR-211 + miR-25 + TGF-β1 with AUC 0.99 and 100 specificity and 97 sensitivity. Circulating miRNAs hold significant promise as non-invasive biomarkers for CRC screening. However, the variability in diagnostic performance highlights the need for a standardized method and robust validation studies. Future research should focus on large-scale, ethnically diverse cohorts to establish clinically relevant miRNA biomarkers for CRC, particularly in younger populations. Full article

Colorectal cancer (CRC) is a heterogeneous disease and classified into various subtypes, among which transcriptional alterations result in CRC progression, metastasis, and drug resistance. Forkhead-box M1 (FOXM1) is a proliferation-associated transcription factor which is overexpressed in CRC and the mechanisms of FOXM1 regulation have been under investigation. Previously, we showed that FOXM1 binds to promoters of certain microRNAs. Database mining led to several microRNAs that might interact with FOXM1 3’UTR. The interactions between shortlisted microRNAs and FOXM1 3’UTR were quantitated by a dual-luciferase reporter assay. MicroRNA-532-3p interacted with the 3’UTR of the FOXM1 mRNA transcript most efficiently. MicroRNA-532-3p was ectopically overexpressed in colorectal cancer (CRC) cell lines, leading to reduced transcript and protein levels of FOXM1 and cyclin B1, a direct transcriptional target of FOXM1. Further, a clonogenic assay was conducted in overexpressed miR-532-3p CRC cells that revealed a decline in the ability of cells to form colonies and a reduction in migratory and invading potential. These alterations were reinforced at molecular levels by the altered transcript and protein levels of the conventional EMT markers E-cadherin and vimentin. Overall, this study identifies the regulation of FOXM1 by microRNA-532-3p via its interaction with FOXM1 3’UTR, resulting in the suppression of proliferation, migration, and invasion, suggesting its role as a tumor suppressor in CRC. Full article

Introduction: Colorectal cancer (CRC) is the third most common cancer globally and a leading cause of cancer-related deaths. While liver metastasis is common, brain metastasis (BM) is rare, occurring in 0.1% to 14% of cases. Risk factors for BM include lung metastasis at diagnosis, rectal cancer, and mutations in RAS and KRAS genes. Due to its rarity, guidelines for BM screening and treatment are limited. The aim of this study is to identify the clinical characteristics and predictors of BM at the time of the initial diagnosis of CRC. Methods: We evaluated patients ≥18 years old with metastatic colorectal cancer and brain metastases at diagnosis from the SEER database (2010–2021). A retrospective cohort study was conducted to analyze overall survival and predictive factors for brain metastasis, utilizing multivariate logistic regression, Kaplan–Meier survival analysis, and the Cox proportional hazards models, with p-values < 0.05 considered significant. Results: Out of 24,703 patients with metastatic colorectal cancer (mCRC), 228 (0.92%) had brain metastasis (BM) at diagnosis. BM was more prevalent in average-onset mCRC (≥50 years) compared to early-onset (<50 years) (1% vs. 0.55%, p = 0.004). Certain factors, such as older age and adenocarcinoma subtype, were associated with BM. Additionally, Asians/Pacific-Islanders (HR 1.83 CI: 1.01-3-33, p = 0.045) and American Indians/Alaska Natives (HR 4.79 CI 1.15–19.97, p = 0.032) had higher mortality rates, while surgical treatment and chemotherapy were linked to decreased mortality. Patients with BM had significantly worse overall survival (6 months vs. 21 months, p < 0.001). Conclusion: BM in mCRC is uncommon, but it is associated with significantly worse outcomes, including markedly reduced overall survival. Our study highlights several critical factors associated with the presence of BM, such as older age and specific racial/ethnic groups, which may inform risk stratification and early-detection strategies. Our findings emphasize the need for heightened awareness and screening for BM in high-risk mCRC patients, as well as the inclusion of these patients in clinical trials to explore tailored therapeutic approaches aimed at improving survival and quality of life. Full article

Background/Objectives: The objective of this study was to investigate the metabolomic profiles of patients with colorectal cancer (CRC) across various stages of the disease. Methods: The plasma samples were obtained from 255 subjects, including patients with CRC in stages I-IV, polyps, and controls. We employed capillary electrophoresis time-of-flight mass spectrometry and liquid chromatography triple quadrupole mass spectrometry to analyze hydrophilic metabolites comprehensively. The data were randomly divided into two groups, and consistent differences observed in both groups were analyzed. Results: Acetylated polyamines, such as N¹-acetylspermine and N¹, N¹²-diacetylspermine, consistently showed elevated concentrations in stage IV compared to stages I-III. Non-acetylated polyamines, including spermine and spermidine, exhibited increasing trends from polyp to stage IV. Other metabolites, such as histidine and o-acetylcarnitine, showed decreasing trends across stages. While acetylated polyamines have been reported as CRC detection markers, our findings suggest that they also possess diagnostic potential for distinguishing stage IV from other stages. Conclusions: This study showed stage-specific changes in metabolic profiles, including polyamines, of colorectal cancer. Full article

Colorectal cancer (CRC) represents a significant global health burden, with high incidence and mortality rates worldwide. Recent progress in research highlights the distinct clinical and molecular characteristics of colon versus rectal cancers, underscoring tumor location’s importance in treatment approaches. This article provides a comprehensive review of our current understanding of CRC epidemiology, risk factors, molecular pathogenesis, and management strategies. We also present the intricate cellular architecture of colonic crypts and their roles in intestinal homeostasis. Colorectal carcinogenesis multistep processes are also described, covering the conventional adenoma–carcinoma sequence, alternative serrated pathways, and the influential Vogelstein model, which proposes sequential APC, KRAS, and TP53 alterations as drivers. The consensus molecular CRC subtypes (CMS1-CMS4) are examined, shedding light on disease heterogeneity and personalized therapy implications. Full article

Per- and polyfluoroalkyl substance (PFAS) contamination has emerged as a significant environmental concern, necessitating the development of effective degradation technologies. Among these technologies, ultrasonication has gained increasing attention. However, there is still limited knowledge of its scale-up or on-site applications due to the complexity of real-world conditions and its high energy consumption. Herein, we provide an overview of recent advancements in the ultrasonic degradation of PFAS toward hybrid technologies. This review contains information regarding the physical and chemical properties of PFAS, followed by an exploration of degradation challenges, the mechanisms of ultrasonication, and recent experimental findings in this field. The key factor affecting ultrasonication is cavitation intensity, which depends on ultrasonic frequency, power density, and PFAS structure. Its main advantages include the generation of reactive species without chemicals and the compatibility with other degradation technologies, while its main disadvantages are high energy consumption and limited applications to liquid-based media. We also highlight the integration of ultrasonication with other advanced oxidation processes (AOPs) to create hybrid systems for enhanced degradation of PFAS in order to significantly improve PFAS degradation efficiency, with enhancement factors ranging between 2 and 12. Finally, we discuss prospects for scaling up the ultrasonic degradation of PFAS and address the associated limitations. This review aims to deepen the understanding of ultrasonication technology in addressing PFAS contamination and to guide future research and development efforts. Full article