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Theranostics 2023Metabolic reprogramming is one of the most important hallmarks of malignant tumors. Specifically, lipid metabolic reprogramming has marked impacts on cancer progression... (Review)
Review
Metabolic reprogramming is one of the most important hallmarks of malignant tumors. Specifically, lipid metabolic reprogramming has marked impacts on cancer progression and therapeutic response by remodeling the tumor microenvironment (TME). In the past few decades, immunotherapy has revolutionized the treatment landscape for advanced cancers. Lipid metabolic reprogramming plays pivotal role in regulating the immune microenvironment and response to cancer immunotherapy. Here, we systematically reviewed the characteristics, mechanism, and role of lipid metabolic reprogramming in tumor and immune cells in the TME, appraised the effects of various cell death modes (specifically ferroptosis) on lipid metabolism, and summarized the antitumor therapies targeting lipid metabolism. Overall, lipid metabolic reprogramming has profound effects on cancer immunotherapy by regulating the immune microenvironment; therefore, targeting lipid metabolic reprogramming may lead to the development of innovative clinical applications including sensitizing immunotherapy.
Topics: Humans; Tumor Microenvironment; Lipid Metabolism; Immunotherapy; Cell Death; Lipids; Neoplasms
PubMed: 37064872
DOI: 10.7150/thno.82920 -
Cell Death & Disease Feb 2023Sepsis is a life-threatening disorder disease defined as infection-induced dysregulated immune responses and multiple organ dysfunction. The imbalance between... (Review)
Review
Sepsis is a life-threatening disorder disease defined as infection-induced dysregulated immune responses and multiple organ dysfunction. The imbalance between hyperinflammation and immunosuppression is a crucial feature of sepsis immunity. Epigenetic modifications, including histone modifications, DNA methylation, chromatin remodeling, and non-coding RNA, play essential roles in regulating sepsis immunity through epi-information independent of the DNA sequence. In recent years, the mechanisms of histone modification in sepsis have received increasing attention, with ongoing discoveries of novel types of histone modifications. Due to the capacity for prolonged effects on immune cells, histone modifications can induce immune cell reprogramming and participate in the long-term immunosuppressed state of sepsis. Herein, we systematically review current mechanisms of histone modifications involved in the regulation of sepsis, summarize their role in sepsis from an immune perspective and provide potential therapeutic opportunities targeting histone modifications in sepsis treatment.
Topics: Humans; Histones; Histone Code; Epigenesis, Genetic; Sepsis; DNA Methylation
PubMed: 36774341
DOI: 10.1038/s41419-023-05656-9 -
Metabolites Dec 2022Gliomas are highly lethal tumours characterised by heterogeneous molecular features, producing various metabolic phenotypes leading to therapeutic resistance. Lipid... (Review)
Review
Gliomas are highly lethal tumours characterised by heterogeneous molecular features, producing various metabolic phenotypes leading to therapeutic resistance. Lipid metabolism reprogramming is predominant and has contributed to the metabolic plasticity in glioma. This systematic review aims to discover lipids alteration and their biological roles in glioma and the identification of potential lipids biomarker. This systematic review was conducted using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Extensive research articles search for the last 10 years, from 2011 to 2021, were conducted using four electronic databases, including PubMed, Web of Science, CINAHL and ScienceDirect. A total of 158 research articles were included in this study. All studies reported significant lipid alteration between glioma and control groups, impacting glioma cell growth, proliferation, drug resistance, patients' survival and metastasis. Different lipids demonstrated different biological roles, either beneficial or detrimental effects on glioma. Notably, prostaglandin (PGE2), triacylglycerol (TG), phosphatidylcholine (PC), and sphingosine-1-phosphate play significant roles in glioma development. Conversely, the most prominent anti-carcinogenic lipids include docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and vitamin D3 have been reported to have detrimental effects on glioma cells. Furthermore, high lipid signals were detected at 0.9 and 1.3 ppm in high-grade glioma relative to low-grade glioma. This evidence shows that lipid metabolisms were significantly dysregulated in glioma. Concurrent with this knowledge, the discovery of specific lipid classes altered in glioma will accelerate the development of potential lipid biomarkers and enhance future glioma therapeutics.
PubMed: 36557318
DOI: 10.3390/metabo12121280 -
Biomedicine & Pharmacotherapy =... Sep 2022In multicellular organisms, nutrient uptake and its metabolism are subject to stringent regulation to maintain cellular integrity and prevent aberrant cell... (Review)
Review
In multicellular organisms, nutrient uptake and its metabolism are subject to stringent regulation to maintain cellular integrity and prevent aberrant cell proliferation. However, the altered signaling pathways and gene expression disorders in hepatocellular carcinoma (HCC) induce the transformation of metabolic patterns. The reprogrammed metabolic pattern not only conferred HCC cells viability in nutrient-deficient environments, but also contributed to the formation of a unique immune surveillance barrier. Furthermore, in this metabolic pattern, the accumulation of a large number of oxidation products in cells also activates tumor-related signaling pathways. Therefore, the exploration of underlying molecular mechanisms of the metabolic switch will help to improve therapeutic strategies for HCC. We systematically reviewed the landmark events and current research breakthroughs in the study of glucometabolic reprogramming in HCC. Focusing on the central carbon metabolism, the internal energy conversion in HCC and its cancerous mechanisms were fully explained. Furthermore, we also discussed the HCC-specific acellular regulation, metabolic switch of cancer stem cells, oxidative stress adaptation and the formation of immunosuppressive microenvironment, hoping to provide insights for future basic and clinical research.
Topics: Carbon; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Proliferation; Gene Expression Regulation, Neoplastic; Glycolysis; Humans; Liver Neoplasms; Tumor Microenvironment
PubMed: 36076503
DOI: 10.1016/j.biopha.2022.113485 -
Frontiers in Endocrinology 2023Reprogramming of cellular metabolism is now a hallmark of tumorigenesis. In recent years, research on pancreatic neuroendocrine tumors (pNETs) has focused on genetic and... (Review)
Review
INTRODUCTION
Reprogramming of cellular metabolism is now a hallmark of tumorigenesis. In recent years, research on pancreatic neuroendocrine tumors (pNETs) has focused on genetic and epigenetic modifications and related signaling pathways, but few studies have been devoted to characterizing the metabolic profile of these tumors. In this review, we thoroughly investigate the metabolic pathways in pNETs by analyzing the transcriptomic and metabolomic data available in the literature.
METHODOLOGY
We retrieved and downloaded gene expression profiles from all publicly available gene set enrichments (GSE43797, GSE73338, and GSE117851) to compare the differences in expressed genes based on both the stage and MEN1 mutational status. In addition, we conducted a systematic review of metabolomic data in NETs.
RESULTS
By combining transcriptomic and metabolomic approaches, we have identified a distinctive metabolism in pNETs compared with controls without pNETs. Our analysis showed dysregulations in the one-carbon, glutathione, and polyamine metabolisms, fatty acid biosynthesis, and branched-chain amino acid catabolism, which supply the tricarboxylic acid cycle. These targets are implicated in pNET cell proliferation and metastasis and could also have a prognostic impact. When analyzing the profiles of patients with or without metastasis, or with or without MEN1 mutation, we observed only a few differences due to the scarcity of published clinical data in the existing research. Consequently, further studies are now necessary to validate our data and investigate these potential targets as biomarkers or therapeutic solutions, with a specific focus on pNETs.
Topics: Humans; Pancreatic Neoplasms; Neuroendocrine Tumors; Prognosis; Epigenesis, Genetic; Neuroectodermal Tumors, Primitive
PubMed: 37908747
DOI: 10.3389/fendo.2023.1248575 -
International Journal of Molecular... Sep 2023Aging is a complex process influenced by genetics and the environment, leading to physiological decline and increased susceptibility to diseases. Cognitive decline is a... (Review)
Review
Aging is a complex process influenced by genetics and the environment, leading to physiological decline and increased susceptibility to diseases. Cognitive decline is a prominent feature of aging, with implications for different neurodegenerative disorders. The gut microbiome has gained attention for its potential impact on health and disease, including cognitive function. This systematic review and meta-analysis aimed to investigate the relationship between the gut microbiome and cognitive function in the context of aging. Following PRISMA guidelines, a comprehensive search strategy was employed in PubMed, Scopus, and Web of Science databases. Studies exploring the role of the microbiome in cognition and neurodegenerative disorders, published between 2013 and 2023, were included. Data extraction and quality assessment were performed. Quantitative synthesis using statistical analyses was performed to examine microbial diversity and relative abundance in various cognitive conditions. Sixteen studies involving a total of 1303 participants were included in the analysis. The gut microbiota's relative abundance was different in individuals with cognitive impairments such as Alzheimer's disease, Parkinson's disease, and dementia, compared to the healthy controls. The most prevalent phyla affected were Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria. Meta-analyses indicated substantial heterogeneity among studies focusing on Alzheimer's disease. The overall quality of evidence related to microbial analysis was moderate. The gut microbiome's role in cognitive decline and neurodegenerative disorders warrants investigation. Altered microbial abundance, particularly in specific phyla, is associated with cognitive impairments. However, variations in study findings and methodologies highlight the complexity of the relationship between the gut microbiome and cognitive function. Further studies are needed to better understand the mechanisms underlying this connection and its potential implications for aging and cognitive health.
PubMed: 37761988
DOI: 10.3390/ijms241813680 -
Biomedicines Feb 2023MicroRNAs (miRNAs) are involved in the regulation of mitochondrial function and homeostasis, and in the modulation of cell metabolism, by targeting known oncogenes and... (Review)
Review
MicroRNAs (miRNAs) are involved in the regulation of mitochondrial function and homeostasis, and in the modulation of cell metabolism, by targeting known oncogenes and tumor suppressor genes of metabolic-related signaling pathways involved in the hallmarks of cancer. This systematic review focuses on articles describing the role, association, and/or involvement of miRNAs in regulating the mitochondrial function and metabolic reprogramming of cancer cells. Following the PRISMA guidelines, the articles reviewed were published from January 2010 to September 2022, with the search terms "mitochondrial microRNA" and its synonyms (mitochondrial microRNA, mitochondrial miRNA, mito microRNA, or mitomiR), "reprogramming metabolism," and "cancer" in the title or abstract). Thirty-six original research articles were selected, revealing 51 miRNAs with altered expression in 12 cancers: bladder, breast, cervical, colon, colorectal, liver, lung, melanoma, osteosarcoma, pancreatic, prostate, and tongue. The actions of miRNAs and their corresponding target genes have been reported mainly in cell metabolic processes, mitochondrial dynamics, mitophagy, apoptosis, redox signaling, and resistance to chemotherapeutic agents. Altogether, these studies support the role of miRNAs in the metabolic reprogramming hallmark of cancer cells and highlight their potential as predictive molecular markers of treatment response and/or targets that can be used for therapeutic intervention.
PubMed: 36979672
DOI: 10.3390/biomedicines11030693 -
Medicine Jul 2021Accumulating studies have focused on the clinicopathological and prognostic roles of large intergenic noncoding RNA regulator of reprogramming (lincRNA-ROR) in cancer... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Accumulating studies have focused on the clinicopathological and prognostic roles of large intergenic noncoding RNA regulator of reprogramming (lincRNA-ROR) in cancer patients. However, the results were controversial and unconvincing. Thus, we performed a meta-analysis to assess the associations between lincRNA-ROR expression and survival and clinicopathological characteristics of cancer patients.
METHODS
Hazard ratios for overall survival and disease-free survival with their 95% confidence intervals were used to evaluate the role of lincRNA-ROR expression in the prognosis of cancer patients. Risk ratios with their 95% confidence intervals were applied to assess the relationship between lincRNA-ROR expression and clinicopathological parameters.
RESULTS
A total of 18 articles with 1441 patients were enrolled. Our results indicated that high lincRNA-ROR expression was significant associated with tumor size, TNM stage, clinical stage, lymph metastasis, metastasis and vessel invasion of cancer patients. There were no correlations between high lincRNA-ROR expression and age, gender, infiltration depth, differentiation, serum CA19-9 and serum CEA of cancer patients. In addition, high lincRNA-ROR expression was associated with shorter Overall survival and disease-free survival on both univariate and multivariate analyses. Meanwhile, there were no obvious publication bias in our meta-analysis.
CONCLUSIONS
LincRNA-ROR expression was associated with the clinicopathological features and outcome of cancer patients, which suggested that lincRNA-ROR might serve as a potential biomarker for cancer prognosis.
ETHICAL APPROVAL
Since this study is on the basis of published articles, ethical approval and informed consent of patients are not required.
Topics: Biomarkers, Tumor; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; Prognosis; RNA, Long Noncoding
PubMed: 34232190
DOI: 10.1097/MD.0000000000026535 -
Fertility and Sterility Mar 2013In this systematic review of ovulation induction and epigenetic control, studies mainly done in the mouse model highlight how hormone treatments may be prejudicial to... (Review)
Review
In this systematic review of ovulation induction and epigenetic control, studies mainly done in the mouse model highlight how hormone treatments may be prejudicial to the epigenetic reprogramming of gametes as well as early embryos. Moreover, the hormone protocols used in assisted reproduction may also modify the physiologic environment of the uterus, a potential link to endometrial epigenetic disturbances. At present, the few available data in humans are insufficient to allow us to independently determine the impact of a woman's age and infertility problems and treatment protocols and hormone doses on such processes as genomic imprinting.
Topics: Animals; Epigenesis, Genetic; Female; Genetic Diseases, Inborn; Humans; Mice; Models, Animal; Ovulation Induction; Reproductive Techniques, Assisted
PubMed: 23714436
DOI: 10.1016/j.fertnstert.2012.12.047 -
Mitochondrion Jul 2021Metabolic reprogramming and mitochondrial dysfunction are central elements in a broad variety of physiological and pathological processes. While cell culture established... (Review)
Review
Metabolic reprogramming and mitochondrial dysfunction are central elements in a broad variety of physiological and pathological processes. While cell culture established itself as a versatile technique for the elaboration of physiology and disease, studying metabolism using standard cell culture protocols is profoundly interfered by the Crabtree effect. This phenomenon refers to the adaptation of cultured cells to a glycolytic phenotype, away from oxidative phosphorylation in glucose-containing medium, and questions the applicability of cell culture in certain fields of research. In this systematic review we aim to provide a comprehensive overview and critical appraisal of strategies reported to circumvent the Crabtree effect.
Topics: Cell Culture Techniques; Culture Media; Glucose; Glycolysis; Humans; Mitochondria; Mitochondrial Dynamics; Oxidative Phosphorylation
PubMed: 33812964
DOI: 10.1016/j.mito.2021.03.014