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Liver cirrhosis is a chronic condition of the liver and is the 14th most common cause of death around the world; yet it remains an incurable disease. Probiotics have gained significant popularity as a potential treatment option for liver cirrhosis. METHODS: A systematic review and meta-analysis was conducted to assess the effects of probiotics on liver cirrhosis. PubMed, Scopus, Cochrane Central Register for Controlled Trials (CENTRAL) and ProQuest Dissertation and Thesis were searched from 2000 to January 2024 for studies that evaluated the effects of probiotics on a variety of outcomes of liver disease. RESULTS: A total of 22 randomised controlled trial studies were included in the meta-analysis. Probiotics significantly decreased Gamma-glutamyl transferase (effect size: 0.307, p = 0.024, 95% CI [-0.572, -0.040]) and Aspartate aminotransferase (p = 0.013, 95% CI [-17.927, -2.128]). Significant reduction in serum ammonia levels (effect size = -1.093, p = 0.000, 95% CI [-1.764, -0.423]) and endotoxin levels (effect size = -0.961, p = 0.000, 95% CI [-1.537, -0.385]) were also found. SUMMARY: Overall probiotics could be recommended as a potential adjunct therapy for patients with cirrhosis, as they appear to have some benefit in improving liver function, and are well tolerated with minimal adverse effects. More comprehensive research with larger sample sizes is recommended to understand more about the widespread effects of probiotic use.
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Cellobiose 2-epimerase (CE) catalyzes the conversion of the lactose into its high-value derivatives, epilactose and lactulose, which has great prospects in food applications. In this study, CE sequences from the Qinghai-Tibet Plateau gene catalogue, we screened these for structural flexibility through molecular dynamics simulation to identify potential psychrophilic CE candidates. One such psychrophilic CE we termed psyCE demonstrated exceptional epimerization activity, achieving an optimum activity of 122.2 ± 1.6 U/mg. Its kinetic parameters (Kcat and Km) for epimerization activity were 219.9 ± 5.6 s-1 and 261.9 ± 18.1 mM, respectively, representing the highest Kcat recorded among known cold-active CEs. Notably, this is the first report of a psychrophilic CE. The psyCE can effectively produce epilactose at 8 °C, converting 20.3 % of 200 mM lactose into epilactose within four hours. These findings suggest that psyCE is highly suitable for cryogenic food processing, and glaciers may serve as a valuable repository of psychrophilic enzymes.
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BACKGROUND: Osteosarcoma (OS), the most common primary malignant bone tumor, predominantly affects children and young adults and is characterized by high invasiveness and poor prognosis. Despite therapeutic advancements, the survival rate remains suboptimal, indicating an urgent need for novel biomarkers and therapeutic targets. This study aimed to investigate the prognostic significance of LGMN expression and immune cell infiltration in the tumor microenvironment of OS. METHODS: We performed an integrative bioinformatics analysis utilizing the GEO and TARGET-OS databases to identify differentially expressed genes (DEGs) associated with LGMN in OS. We conducted Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) to explore the biological pathways and functions. Additionally, we constructed protein-protein interaction (PPI) networks, a competing endogenous RNA (ceRNA) network, and applied the CIBERSORT algorithm to quantify immune cell infiltration. The diagnostic and prognostic values of LGMN were evaluated using the area under the receiver operating characteristic (ROC) curve and Cox regression analysis. Furthermore, we employed Consensus Clustering Analysis to explore the heterogeneity within OS samples based on LGMN expression. RESULTS: The analysis revealed significant upregulation of LGMN in OS tissues. DEGs were enriched in immune response and antigen processing pathways, suggesting LGMN's role in immune modulation within the TME. The PPI and ceRNA network analyses provided insights into the regulatory mechanisms involving LGMN. Immune cell infiltration analysis indicated a correlation between high LGMN expression and increased abundance of M2 macrophages, implicating an immunosuppressive role. The diagnostic AUC for LGMN was 0.799, demonstrating its potential as a diagnostic biomarker. High LGMN expression correlated with reduced overall survival (OS) and progression-free survival (PFS). Importantly, Consensus Clustering Analysis identified two distinct subtypes of OS, highlighting the heterogeneity and potential for personalized medicine approaches. CONCLUSIONS: Our study underscores the prognostic value of LGMN in osteosarcoma and its potential as a therapeutic target. The identification of LGMN-associated immune cell subsets and the discovery of distinct OS subtypes through Consensus Clustering Analysis provide new avenues for understanding the immunosuppressive TME of OS and may aid in the development of personalized treatment strategies. Further validation in larger cohorts is warranted to confirm these findings.
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This mini-review addresses lipoxygenases and receptors for leukotrienes in hematological malignancies. Potential novel biomarkers and drug targets in leukemia and B-cell lymphoma are discussed.
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Heart failure (HF) is a clinical syndrome resulting from left ventricular systolic and diastolic dysfunction, leading to significant morbidity and mortality worldwide. Despite improvements in medical treatment, the prognosis of HF patients remains unsatisfactory, with high rehospitalization rates and substantial economic burdens. The heart, a high-energy-consuming organ, relies heavily on ATP production through oxidative phosphorylation in mitochondria. Mitochondrial dysfunction, characterized by impaired energy production, oxidative stress, and disrupted calcium homeostasis, plays a crucial role in HF pathogenesis. Additionally, inflammation contributes significantly to HF progression, with elevated levels of circulating inflammatory cytokines observed in patients. The interplay between mitochondrial dysfunction and inflammation involves shared risk factors, signaling pathways, and potential therapeutic targets. This review comprehensively explores the mechanisms linking mitochondrial dysfunction and inflammation in HF, including the roles of mitochondrial reactive oxygen species (ROS), calcium dysregulation, and mitochondrial DNA (mtDNA) release in triggering inflammatory responses. Understanding these complex interactions offers insights into novel therapeutic approaches for improving mitochondrial function and relieving oxidative stress and inflammation. Targeted interventions that address the mitochondria-inflammation axis hold promise for enhancing cardiac function and outcomes in HF patients.
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Insuficiência Cardíaca , Inflamação , Estresse Oxidativo , Humanos , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/imunologia , Inflamação/imunologia , Animais , Espécies Reativas de Oxigênio/metabolismo , Mitocôndrias/metabolismo , DNA Mitocondrial , Cálcio/metabolismo , Mitocôndrias Cardíacas/metabolismoRESUMO
The aggregation of graphene oxide (GO) during the hydration process limits its wide application. Polymer superplasticizers have been used to improve the dispersion state of GO due to their adsorption and site-blocking effects, though the formation of a large amount of foam during the mixing process weakens the mechanical properties of cement. A highly dispersed amphoteric polycarboxylate superplasticizer-stabilized graphene oxide (APC/GO) toughening agent was prepared by electrostatic self-assembly. Results demonstrate that the APC/GO composite dispersed well in a cement pore solution due to the steric effect offered by the APC. Additionally, the well-dispersed GO acted as an antifoaming agent in the cement since GO nanosheets can be absorbed at the air-liquid interface of APC foam via electrostatic interactions and eliminate the air-entraining effect. The well-dispersed APC/GO sheets promoted cement hydration and further refined its pore structure owing to the nucleation effect. The flexural and compressive strength of the cement containing the APC/GO composite were enhanced by 21.51% and 18.58%, respectively, after a 7-day hydration process compared with a blank sample. The improved hydration degree, highly polymerized C-S-H gel, and refined pore structure provided enhanced mechanical properties.
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We report the combination of organo-photocatalysis with transition metal (TM) catalysis for directed ortho-hydroxylation of substituted anilides for the synthesis of α-aminophenol derivatives under mild conditions. The developed metallaphotocatalysis utilizes N-pivaloyl as a directing group and phenyl iodine(III) bis(trifluoroacetate) (PIFA) in the combination of the 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN) photocatalyst and [RuCl2(p-cymene)]2 TM catalyst under visible-light irradiation at room temperature. The hydroxylation reaction works well for a wide range of substrates containing electron-withdrawing substituents and could be applied to late-stage functionalization and ortho-hydroxyl metabolite generation for drug compounds-containing anilides with electron-withdrawing substituents in a single mild reaction.
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Protein S-nitrosylation, which is defined by the covalent attachment of nitric oxide (NO) to the thiol group of cysteine residues, is known to play critical roles in plant development and stress responses. NO promotes seedling photomorphogenesis and NO emission is enhanced by light. However, the function of protein S-nitrosylation in plant photomorphogenesis is largely unknown. E3 ligase CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) and transcription factor ELONGATED HYPOCOTYL 5 (HY5) antagonistically regulate seedling photomorphogenesis. COP1 inhibits plant photomorphogenesis by targeting photomorphogenic promoters like HY5 for 26S proteasome degradation. Here, we report that COP1 is S-nitrosylated in vitro. Mass spectrometry analyses revealed that two evolutionarily well conserved residues, cysteine 425 and cysteine 607, in the WD40 domain of COP1 are S-nitrosylated. S-nitrosylated glutathione (GSNO) is an important physiological NO donor for protein S-nitrosylation. The Arabidopsis (Arabidopsis thaliana) gsnor1-3 mutant, which accumulates higher level of GSNO, accumulated higher HY5 levels than wildtype (WT), indicating that COP1 activity is inhibited. Protein S-nitrosylation can be reversed by Thioredoxin-h5 (TRXh5) in plants. Indeed, COP1 interacts directly with TRXh5 and its close homolog TRXh3. Moreover, catalase 3 (CAT3) acts as a transnitrosylase that transfers NO to its target proteins like GSNO reductase (GSNOR). We found that CAT3 interacts with COP1 in plants. Taken together, our data indicate that the activity of COP1 is likely inhibited by NO via S-nitrosylation to promote the accumulation of HY5 and photomorphogenesis.
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Proteínas de Arabidopsis , Arabidopsis , Fatores de Transcrição de Zíper de Leucina Básica , Óxido Nítrico , Ubiquitina-Proteína Ligases , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Óxido Nítrico/metabolismo , Luz , Cisteína/metabolismo , Plântula/metabolismo , Plântula/crescimento & desenvolvimento , Plântula/genética , Aldeído Oxirredutases/metabolismo , Aldeído Oxirredutases/genética , Regulação da Expressão Gênica de PlantasRESUMO
BACKGROUND: Cancer-associated fibroblasts (CAFs) drive cancer progression and treatment failure on one hand, while their tumor-restraining functions are also observed on the other. Recent single cell RNA sequencing (scRNA-seq) analyses demonstrates heterogeneity of CAFs and defines molecular subtypes of CAFs, which help explain their different functions. However, it remains unclear whether these CAF subtypes have the same or different biological/clinical implications in prostate cancer (PCa) or other malignancies. METHODS: PCa cells were incubated with supernatant from normal fibroblasts and CAFs to assess their effects on cell behaviors. Sequencing, genomic, and clinical data were collected from TCGA, MSKCC, CPGEA and GEO databases. CAF molecular subtypes and total CAF scores were constructed and grouped into low and high groups based on CAF-specific gene expression. Progression free interval (PFI), clinicopathological features, telomere length, immune cell infiltration, drug treatment and somatic mutations were compared among CAF molecular subtypes and low/high score groups. RESULTS: The PCa CAF-derived supernatant promoted PCa cell proliferation and invasion. Based on differentially expressed genes identified by scRNA-seq analyses, we classified CAFs into 6 molecular subtypes in PCa tumors, and each subtype was then categorized into score-high and low groups according to the subtype-specific gene expression level. Such score models in 6 CAF subtypes all predicted PFI. Telomeres were significantly shorter in high-score tumors. The total CAF score from 6 CAF subtypes was also associated with PFI in PCa patients inversely, which was consistent with results from cellular experiments. Immunosuppressive microenvironment occurred more frequently in tumors with a high CAF score, which was characterized by increased CTLA4 expression and indicated better responses to CTLA4 inhibitors. Moreover, this model can also serve as a useful PFI predictor in pan-cancers. CONCLUSION: By combining scRNA-seq and bulk RNA-seq data analyses, we develop a CAF subtype score system as a prognostic factor for PCa and other cancer types. This model system also helps distinguish different immune-suppressive mechanisms in PCa, suggesting its implications in predicting response to immunotherapy. Thus, the present findings should contribute to personalized PCa intervention.
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The recent global pandemic of coronavirus disease 2019 (COVID-19) has enormously promoted the development of diagnostic technology. To control the spread of pandemic diseases and achieve rapid screening of the population, ensuring that patients receive timely treatment, rapid diagnosis has become the top priority in the development of clinical technology. This review article aims to summarize the current rapid nucleic acid diagnostic technologies applied to pandemic disease diagnosis, from rapid extraction and rapid amplification to rapid detection. We also discuss future prospects in the development of rapid nucleic acid diagnostic technologies.
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COVID-19 , Ácidos Nucleicos , Humanos , Pandemias , COVID-19/diagnóstico , COVID-19/epidemiologia , Tecnologia , Teste para COVID-19RESUMO
Electronically conductive protein-based materials can enable the creation of bioelectronic components and devices from sustainable and nontoxic materials, while also being well-suited to interface with biological systems, such as living cells, for biosensor applications. However, as proteins are generally electrical insulators, the ability to render protein assemblies electroactive in a tailorable manner can usher in a plethora of useful materials. Here, an approach to fabricate electronically conductive protein nanowires is presented by aligning heme molecules in proximity along protein filaments, with these nanowires also possessing charge transfer abilities that enable energy harvesting from ambient humidity. The heme-incorporated protein nanowires demonstrate electron transfer over micrometer distances, with conductive atomic force microscopy showing individual nanowires having comparable conductance to other previously characterized heme-based bacterial nanowires. Exposure of multilayer nanowire films to humidity produces an electrical current, presumably through water molecules ionizing carboxyl groups in the filament and creating an unbalanced total charge distribution that is enhanced by the heme. Incorporation of heme and potentially other metal-center porphyrin molecules into protein nanostructures could pave the way for structurally- and electrically-defined protein-based bioelectronic devices.
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Condutividade Elétrica , Heme , Nanofios , Nanofios/química , Heme/química , Microscopia de Força Atômica , Proteínas/químicaRESUMO
Strong light-matter coupling between molecules and electromagnetic field lead to the formation of hybrid polaritonic states for surface enhanced Raman scattering (SERS) detection. However, owing to the inefficient interaction between zero-point fluctuations of photons/plasmons and molecular electronic transitions, the Raman enhancement is limited in relative low levels. Here, we propose and fabricate a TiOx/Cu2-xSe/R6G nanocavity based photonic-plasmonic-polaritonic resonator for single molecular SERS detection. Through precisely matching the energy levels of illuminated photon, generated plasmon, and molecular polariton, an extremely high Raman enhancement factor of 2.6 × 109 is implemented. The rationally designed SERS substrate allows sensitive detection of miRNA-21 in single molecular level with a detection limit of 1.58 aM. The hybrid SERS mechanism both from electromagnetic and chemical perspectives in this photonic-plasmonic-polaritonic resonance strategy provides insight into polaritonic semiconductor systems, thus paving the way for new experimental possibilities in light-matter hybrids.
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Técnicas Biossensoriais , MicroRNAs , Nanotecnologia , Óptica e Fotônica , Análise Espectral RamanRESUMO
Wetlands have long been recognized as efficient nitrogen (N) processing systems. While widespread interest is in constructing wetlands to mitigate N pollution, there is a dearth of information about the environmental consequences following wetland dismantlement. This study elucidated the changing trajectories of water quality and N removal capacity in a headwater river that initially contained a series of constructed wetlands but later underwent wetland destruction. An estimated 17% surge in total N concentration has been reported since the wetlands' destruction. This adverse trend is primarily attributed to a weakened in-stream N removal capacity, which was reduced to a mere 25% of the levels observed when the wetlands were operational. Further analysis confirms that the presence of wetlands actively shapes desirable environmental settings for N processing. In stark contrast, wetland destruction leads to unfavorable environmental conditions, which not only restrain in-stream anaerobic metabolisms but also trigger algal proliferation and biological N fixation. Collectively, this research provides compelling evidence of the detrimental consequences associated with wetland destruction, emphasizing the need for remedial strategies to mitigate these negative effects.
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Desnitrificação , Áreas Alagadas , Rios , Nitrogênio/análise , Nitrogênio/metabolismo , Qualidade da ÁguaRESUMO
This article comments on: Wu Y, Sexton WK, Zhang Q, Bloodgood D, Wu Y, Hooks C, Coker F, Vasquez A, Wei C-I, Xiao S. 2024. Leaf abaxial immunity to powdery mildew in Arabidopsis is conferred by multiple defense mechanisms. Journal of Experimental Botany 75, 1465-1478.
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Arabidopsis , Botânica , Arabidopsis/genética , Folhas de PlantaRESUMO
The sensitivity of grassland above- (AGB, gC m-2) and below-ground biomass (BGB, gC m-2) to climate has been shown to be significant on the Tibetan Plateau, however, the spatial patterns and sensitivity of biomass with altitudinal change needs to be quantitated. In this study, large data sets of AGB and BGB during the peak growth season, and the corresponding geographical and climate conditions in the grasslands of the Tibetan Plateau between 2001 and 2020 were analyzed, and modelled using a Cubist regression trees algorithm. The mean values for AGB and BGB were 61.3 and 1304.3 gC m-2, respectively, for the whole region over the two decades. There was a significant change in spatial AGB of 64.8 % on the Plateau (P < 0.05, with areas where AGB increased being twice as large as areas where AGB decreased), while BGB did not change significantly in majority the of the region (≥ 90.1 %, P > 0.05). In general, the areas where AGB showed positive partial correlations with precipitation were larger than the areas where AGB had positive correlations with temperature (P < 0.05). However, these trends varied depending on the climatic conditions: in the wetter regions, temperature had a greater effect on the size of the areas with positive AGB responses than precipitation (P < 0.05), while precipitation had a greater effect on the size of areas with positive BGB changes than temperature (P < 0.05). In the drier areas, however, precipitation affected the AGB response significantly compared to temperature (P < 0.05), while temperature influenced the BGB response greater than precipitation (P < 0.05). The response and sensitivity of grassland biomass to temperature and precipitation varied according to the altitude of the Plateau: the response and sensitivity were stronger and more sensitive at medium altitudes, and weak at the higher or lower altitudes. Likely, this phenomenon was resulted from the natural selection of plants to maintain the efficient use of resources during un-favourable and stressed conditions for maximum plant development and growth. These findings will help assess the ecological consequences of global climate change for the grasslands of the Tibetan Plateau, particularly in those regions with highly variable altitudes.
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Mudança Climática , Pradaria , Biomassa , Tibet , Plantas , EcossistemaRESUMO
Solar-driven photocatalytic CO2 reduction is an energy-efficient and sustainable strategy to mitigate CO2 levels in the atmosphere. However, efficient and selective conversion of CO2 into multi-carbon products, like C2H4, remains a great challenge due to slow multi-electron-proton transfer and sluggish C-C coupling. Herein, a two-dimensional thin-layered hybrid perovskite is fabricated through filling of oxygen into iodine vacancy in pristine DMASnI3 (DMA = dimethylammonium). The rational-designed DMASnI3(O) induces shrinkage of active sites distance and facilitates dimerization of C-C coupling of intermediates. Upon simulated solar irradiation, the DMASnI3(O) photocatalyst achieves a high selectivity of 74.5%, corresponding to an impressive electron selectivity of 94.6%, for CO2 to C2H4 conversion and an effective C2H4 yield of 11.2 µmol g-1 h-1. In addition, the DMASnI3(O) inherits excellent water stability and implements long-term photocatalytic CO2 reduction to C2H4 in a water medium. This work establishes a unique paradigm to convert CO2 to C2+ hydrocarbons in a perovskite-based photocatalytic system.
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Psychrophilic enzymes are primarily produced by microorganisms from extremely low-temperature environments which are known as psychrophiles. Their high efficiency at low temperatures and easy heat inactivation property have attracted extensive attention from various food and industrial bioprocesses. However, the application of these enzymes in molecular biology is still limited. In a previous review, the applications of psychrophilic enzymes in industries such as the detergent additives, the food additives, the bioremediation, and the pharmaceutical medicine, and cosmetics have been discussed. In this review, we discuss the main cold adaptation characteristics of psychrophiles and psychrophilic enzymes, as well as the relevant information on different psychrophilic enzymes in molecular biology. We summarize the mining and screening methods of psychrophilic enzymes. We finally recap the expression of psychrophilic enzymes. We aim to provide a reference process for the exploration and expression of new generation of psychrophilic enzymes.
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Sepsis-induced acute lung injury has been deemed to be an life-threatening pulmonary dysfunction caused by a dysregulated host response to infection. The modification of N6-Methyladenosine (m6A) is implicated in several biological processes, including mitochondrial transcription and ferroptosis. Ferroptosis is an iron-dependent type of programed cell death, which plays a role in sepsis-induced acute lung injury (ALI). Nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial regulator of intracellular oxidative homeostasis, linked to ferroptosis resistance. This research aims to explore the effect of m6A in ferroptosis in sepsis-induced ALI. First, we found a time-dependent dynamic alteration on pulmonary methylation level during sepsis-induced ALI. We identified METTL4 as a differentially expressed gene in ALI mice using m6A sequencing and RNA-sequencing, and revealed the methylation of several ferroptosis related genes (Nrf2). Thus, we generated METTL4 deficiency mice and found that METTL4 knockdown alleviated ferroptosis, as evidenced by lipid ROS, MDA, Fe2+, as well as alterations in GPX4 and SLC7A11 protein expression. Consistently, we found that METTL4 silencing could decrease ferroptosis sensitivity in LPS-induced TC-1 cells. Furthermore, both the dual-luciferase reporter assay and rescue experiments indicated that METTL4 mediated the N6-methyladenosine of Nrf2 3'UTR, then YTHDF2 binded with the m6A site, promoting the degradation of Nrf2. In conclusion, we revealed that METTL4 promoted alveolar epithelial cells ferroptosis in sepsis-induced lung injury via N6-methyladenosine of Nrf2, which might provide a novel approach to therapeutic strategies for sepsis-induced ALI.
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Lesão Pulmonar Aguda , Ferroptose , Sepse , Animais , Camundongos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/genética , Células Epiteliais Alveolares , Ferroptose/genética , Fator 2 Relacionado a NF-E2/genética , Sepse/complicações , Sepse/genética , Metiltransferases/metabolismoRESUMO
AIMS: Dysregulated copper metabolism has been noticed in many types of cancer including hepatocellular carcinoma (HCC); however, a comprehensive understanding about this dysregulation still remains unclear in HCC. METHODS: A set of bioinformatic tools was integrated to analyze the expression and prognostic significance of copper metabolism-related genes. A related risk score, termed as CMscore, was developed via univariate Cox regression, least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression. Pathway enrichment analyses and tumor immune cell infiltration were further investigated in CMscore stratified HCC patients. Weighted correlation network analysis (WGCNA) was used to identify potential regulator of cuproptosis. RESULTS: Copper metabolism was dysregulated in HCC. HCC patients in the high-CMscore group showed a significantly lower overall survival (OS) and enriched in most cancer-related pathways. Besides, HCC patients with high CMscore had higher expression of pro-tumor immune infiltrates and immune checkpoints. Moreover, cancer patients with high CMscore from two large cohorts exhibited significantly prolonged survival time after immunotherapy. WGCNA and subsequently correlation analysis revealed that SLC27A5 might be a potential regulator of cuproptosis in HCC. In vitro experiments revealed that SLC27A5 inhibited cell proliferation and migration of HCC cells and could upregulate FDX1, the key regulator of cuproptosis. SIGNIFICANCE: The CMscore is helpful in clustering HCC patients with distinct prognosis, gene mutation signatures, and sensitivity to immunotherapy. SLC27A5 might serve as a potential target in the induction of cuproptosis in HCC.