Anemoside B4 regulates fatty acid metabolism reprogramming in mice with colitis-associated cancer / 中国中药杂志

The study aimed to investigate the effect of anemoside B4(B4) on fatty acid metabolism in mice with colitis-associated cancer(CAC). The CAC model was established by azoxymethane(AOM)/dextran sodium sulfate(DSS) in mice. Mice were randomly divided into a normal group, a model group, and low-, medium-, and high-dose anemoside B4 groups. After the experiment, the length of the mouse colon and the size of the tumor were measured, and the pathological alterations in the mouse colon were observed using hematoxylin-eosin(HE) staining. The slices of the colon tumor were obtained for spatial metabolome analysis to analyze the distribution of fatty acid metabolism-related substances in the tumor. The mRNA levels of SREBP-1, FAS, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 were determined by real-time quantitative PCR(RT-qPCR). The results revealed that the model group showed decreased body weight(P<0.05) and colon length(P<0.001), increased number of tumors, and increased pathological score(P<0.01). Spatial metabolome analysis revealed that the content of fatty acids and their derivatives, carnitine, and phospholipid in the colon tumor was increased. RT-qPCR results indicated that fatty acid de novo synthesis and β-oxidation-related genes, such as SREBP-1, FASN, ACCα, SCD-1, ACOX, UCP-2, and CPT-1 mRNA expression levels increased considerably(P<0.05, P<0.001). After anemoside B4 administration, the colon length increased(P<0.01), and the number of tumors decreased in the high-dose anemoside B4 group(P<0.05). Additionally, spatial metabolome analysis showed that anemoside B4 could decrease the content of fatty acids and their derivatives, carnitine, and phospholipids in colon tumors. Meanwhile, anemoside B4 could also down-regulate the expression of FASN, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 in the colon(P<0.05, P<0.01, P<0.001). The findings of this study show that anemoside B4 may inhibit CAC via regulating fatty acid metabolism reprogramming.

The role of lipids and fatty acid metabolism in the development of prostate cancer

The reprogramming of lipid metabolism and signaling pathways is the central aspect of cancer biology. It is hypothesized that tumor cells can alter the lipid spectrum in order to fulfill their metabolic requirements. Furthermore, they can alter potential tumors and suppressive mechanisms in which lipids' involvement is essential. Recently, more attentions have been given on the alteration of lipid metabolism during prostate cancer development, and investigations have shown unique regulation of "de novo" lipid synthesis in cancer cells. Cancer cells often use newer pathways and enzymes to simplify the synthesis of fatty acids, and the newly synthesized lipids affect cellular processes, which impacts cancer cell proliferation and survival outcomes. Herein, we aimed to study the influence of lipid profile alterations on the development of prostate cancer. We found that the total amounts of lipids and phospholipids were increased within tissues from men with the malignant prostate tumor as compared with the benign prostate tissue. Significant changes were also observed in the composition of saturated and unsaturated fatty acids within the malignant tumor tissues. Intensification of lipid peroxidation has also been observed in malignant prostate tumors compared to benign prostate tumors. Collectively, these findings further highlights the fact that lipid and fatty acids play unique regulatory roles in the cellular development of prostate malignant transformation.

Endogenous HMGB1 Modulates Fatty Acid Metabolism of Hypoxic and Nutrient-poor Pancreatic Cancer Cells and Related Mechanism / 肿瘤防治研究

Objective To explore the role and mechanism of HMGB1 in the fatty acid metabolism reprogramming and mitochondrial fusion/fission of hypoxic and nutrient-poor pancreatic cancer cells. Methods The correlation between the expression level of HMGB1 in pancreatic cancer tissue and the survival rate of pancreatic cancer patients were analyzed by GEPIA database. CCK-8 assay was used to measure cell proliferation rate, and scratch test and Transwell chamber method were carried out to detect the effects of endogenous HMGB1 on the invasion and migration abilities of human pancreatic cancer cell line Patu8988 after hypoxic and nutrient-poor treatment. Laser confocal microscope was used to observe the changes of mitochondrial morphology of Patu8988 cells. Western blot was used to detect the expression levels of mitochondrial fusion/fission and de novo fatty acid synthesis-related proteins. Results GEPIA database analysis results showed that HMGB1 was highly expressed in pancreatic cancer tissues (P < 0.01), and the expression level was negatively correlated with the survival time of pancreatic cancer patients (P=0.00097). Knockdown of HMGB1 expression could inhibit the proliferation, invasion and migration abilities of Patu8988 cells under hypoxic and nutrient-poor conditions. However, mitochondrial fission in patu8988 cells was increased. Knockdown of HMGB1 in Patu8988 cells increased the expression of fission-related protein FIS1 while decreased the expression of p-DRP1(Ser637) and fusion-related protein MFN1 and MFN2 in hypoxic and nutrient-poor environment; ACLY, p-ACLY and FASN protein expression levels were down-regulated. Conclusion Endogenous HMGB1 can promote the fusion and inhibit the fission of mitochondria in hypoxic and nutrient-poor Patu8988 cells, maintain mitochondrial morphology and function, and thereby up-regulate ACLY protein expression and phosphorylation level, promote FA synthesis, and maintain the proliferation, invasion and migration abilities of pancreatic cancer cells.

Metabolic reprogramming of the de novo fatty acid synthesis pathway in cancer devel-opment and progression / 中国肿瘤临床

Cancer cell metabolic reprogramming is a highly significant feature in tumor development and progression.This process is an extension of aerobic glycolysis(i.e.,Warburg effect).The metabolic pattern,such as that of glycolysis,oxidative phosphorylation, amino acid metabolism,fatty acid metabolism,and nucleic acid metabolism,is altered significantly during cell carcinogenesis.Fatty ac-id metabolism is required for energy storage,membrane proliferation,and signaling molecule generation.Thus,studying the mecha-nism of de novo fatty acid synthesis and its relationship with the development and progression of tumor,as well as the use and target-ing of the key enzyme in this metabolic pathway,is vital for the diagnosis,prevention,and treatment of cancer.Herein,we provide a brief review of metabolic reprogramming in cancer cells.We focus on the pathways of de novo fatty acid synthesis during the develop-ment and progression of tumor.

Metabolic reprogramming of the de novo fatty acid synthesis pathway in cancer devel-opment and progression / 中国肿瘤临床

Cancer cell metabolic reprogramming is a highly significant feature in tumor development and progression.This process is an extension of aerobic glycolysis(i.e.,Warburg effect).The metabolic pattern,such as that of glycolysis,oxidative phosphorylation, amino acid metabolism,fatty acid metabolism,and nucleic acid metabolism,is altered significantly during cell carcinogenesis.Fatty ac-id metabolism is required for energy storage,membrane proliferation,and signaling molecule generation.Thus,studying the mecha-nism of de novo fatty acid synthesis and its relationship with the development and progression of tumor,as well as the use and target-ing of the key enzyme in this metabolic pathway,is vital for the diagnosis,prevention,and treatment of cancer.Herein,we provide a brief review of metabolic reprogramming in cancer cells.We focus on the pathways of de novo fatty acid synthesis during the develop-ment and progression of tumor.

Draft Genome of Toxocara canis, a Pathogen Responsible for Visceral Larva Migrans

This study aimed at constructing a draft genome of the adult female worm Toxocara canis using next-generation sequencing (NGS) and de novo assembly, as well as to find new genes after annotation using functional genomics tools. Using an NGS machine, we produced DNA read data of T. canis. The de novo assembly of the read data was performed using SOAPdenovo. RNA read data were assembled using Trinity. Structural annotation, homology search, functional annotation, classification of protein domains, and KEGG pathway analysis were carried out. Besides them, recently developed tools such as MAKER, PASA, Evidence Modeler, and Blast2GO were used. The scaffold DNA was obtained, the N50 was 108,950 bp, and the overall length was 341,776,187 bp. The N50 of the transcriptome was 940 bp, and its length was 53,046,952 bp. The GC content of the entire genome was 39.3%. The total number of genes was 20,178, and the total number of protein sequences was 22,358. Of the 22,358 protein sequences, 4,992 were newly observed in T. canis. Following proteins previously unknown were found: E3 ubiquitin-protein ligase cbl-b and antigen T-cell receptor, zeta chain for T-cell and B-cell regulation; endoprotease bli-4 for cuticle metabolism; mucin 12Ea and polymorphic mucin variant C6/1/40r2.1 for mucin production; tropomodulin-family protein and ryanodine receptor calcium release channels for muscle movement. We were able to find new hypothetical polypeptides sequences unique to T. canis, and the findings of this study are capable of serving as a basis for extending our biological understanding of T. canis.

Effect of epinephrine on the in vitro biosynthesis of fibrinogen.

In an in vitro rat liver slice incubation system, the synthesis of fibrinogen, when measured by immunoprecipitation technique was stimulated in the presence of epinephrine. An increase in poly (A)+ RNA content of the liver slice was also observed after epinephrine treatment. This in vitro experiment demonstrated that epinephrine stimulated de novo synthesis of fibrinogen by acting directly on the liver.