RESUMO
Backgrounds: Alcoholic hepatitis (AH) is a major health problem worldwide. There is increasing evidence that immune cells, iron metabolism and copper metabolism play important roles in the development of AH. We aimed to explore biomarkers that are co-associated with M1 macrophages, ferroptosis and cuproptosis in AH patients. Methods: GSE28619 and GSE103580 datasets were integrated, CIBERSORT algorithm was used to analyze the infiltration of 22 types of immune cells and GSVA algorithm was used to calculate ferroptosis and cuproptosis scores. Using the "WGCNA" R package, we established a gene co-expression network and analyzed the correlation between M1 macrophages, ferroptosis and cuproptosis scores and module characteristic genes. Subsequently, candidate genes were screened by WGCNA and differential expression gene analysis. The LASSO-SVM analysis was used to identify biomarkers co-associated with M1 macrophages, ferroptosis and cuproptosis. Finally, we validated these potential biomarkers using GEO datasets (GSE155907, GSE142530 and GSE97234) and a mouse model of AH. Results: The infiltration level of M1 macrophages was significantly increased in AH patients. Ferroptosis and cuproptosis scores were also increased in AH patients. In addition, M1 macrophages, ferroptosis and cuproptosis were positively correlated with each other. Combining bioinformatics analysis with a mouse model of AH, we found that ALDOA, COL3A1, LUM, THBS2 and TIMP1 may be potential biomarkers co-associated with M1 macrophages, ferroptosis and cuproptosis in AH patients. Conclusion: We identified 5 potential biomarkers that are promising new targets for the treatment and diagnosis of AH patients.
Assuntos
Apoptose , Ferroptose , Hepatite Alcoólica , Animais , Camundongos , Biomarcadores , Biologia Computacional , Modelos Animais de Doenças , Ferroptose/genética , Hepatite Alcoólica/diagnóstico , Hepatite Alcoólica/genética , Macrófagos , CobreRESUMO
Alpinetin (ALP) has been reported to act as an anticancer agent. This study was carried out to elucidate the effect of ALP on high-fat diet (HFD)-induced aggressive cancer progression. C57BL/6 mice were fed with a control diet (CD) or HFD and administered with ALP. Following 6 weeks of feeding, mice were inoculated subcutaneously with Lewis lung carcinoma cells (LLC) to develop transplanted lung tumour. ALP suppressed cell proliferation which drives HFD-induced lung cancer progression. ALP inhibited lipid accumulation in tumour and tumour cells cultured in vitro. qPCR and ELISA analysis of tumour tissues revealed ALP restrained macrophages accumulation, M2s polarization and chemokine secretion. Further, in macrophages cultured in tumour cells conditioned medium (CM), ALP was confirmed to decrease M2s markers expression and chemokine production under high fat. These results demonstrate that ALP suppresses HFD-promoted harmful changes in tumour microenvironments which are crucial in curbing pulmonary tumour aggravation.
Assuntos
Dieta Hiperlipídica/efeitos adversos , Flavanonas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Metabolismo dos Lipídeos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Macrófagos/fisiologia , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Cardamonin (CAD) is a member of the aromatic ketones family that is closely related to anti-bacterial, anti-inflammatory and anti-cancer effects. Nevertheless, the physiological function of cardamonin in chronic colitis and colon cancer has not been well verified. We found that cardamonin treatment alleviates intestinal disease, including recurring colitis and colitis-associated tumorigenesis, along with the reduced secretion of IL-1ß and TNF-α. Further, cardamonin inhibits cell viability and inflammation factors of colorectal cancer cells in vitro. In tumor cells, the inhibitory effect of cardamonin on cell proliferation is closely related to decreased phosphorylation of signal transducers and activators of transcription (STAT) signals. This study reveals the crucial role of cardamonin in sustaining gastrointestinal homeostasis and offers a new strategy for colon cancer therapy.