Protein Lysine Acetylated/Deacetylated Enzymes and the Metabolism-Related Diseases

Lysine acetylation is a reversible posttranslational modifcation, an epigenetic phenomenon, referred to as transfer of an acetyl group from acetyl CoA to lysine ε- amino group of targeted protein, which is modulated by acetyltransferases (histone/ lysine (K) acetyltransferases, HATs/KATs) and deacetylases (histone/lysine (K) deacetylases, HDACs/KDACs). Lysine acetylation regulates various metabolic processes, such as fatty acid oxidation, Krebs cycle, oxidative phosphorylation, angiogenesis and so on. Thus disorders of lysine acetylation may be correlated with obesity, diabetes and cardiovascular disease, which are termed as the metabolic complication. With accumulating studies on proteomic acetylation, lysine acetylation also involves in cell immune status and degenerative diseases, for example, Alzheimer’s disease and Huntington’s disease. This review primarily summarizes the current studies of lysine acetylation in metabolism modulation and in metabolism-related diseases, such as cardiovascular disease and fat metabolism disorder.

PHOSPHO1 Serves as a Key Metabolism-Related Biomarker in the Tumorigenesis of Diffuse Large B-cell Lymphoma

Objective:Diffuse large B-cell lymphoma(DLBCL)is an aggressive type of non-Hodgkin lymphoma.Due to its genetic heterogeneity and abnormal metabolism,many DLBCL patients have a poor prognosis.This study investigated the key metabolism-related genes and potential mechanisms.Methods:Differentially expressed genes,differentially expressed transcription factors(TFs),and differentially expressed metabolism-related genes(DEMRGs)of glucose and lipid metabolic processes were identified using the edgeR package.Key DEMRGs were screened by Lasso regression,and a prediction model was constructed.The cell type identification by estimating relative subsets of RNA transcripts algorithm was utilized to assess the fraction of immune cells,and Gene Set Enrichment Analysis was used to determine immune-related pathways.A regulatory network was constructed with significant co-expression interactions among TFs,DEMRGs,immune cells/pathways,and hallmark pathways.Results:A total of 1551 DEMRGs were identified.A prognostic model with a high applicability(area under the curve=0.921)was constructed with 13 DEMRGs.Tumorigenesis of DLBCL was highly related to the neutrophil count.Four DEMRGs(PRXL2AB,CCN1,DECR2 and PHOSPHO1)with 32 TF-DEMRG,36 DEMRG-pathway,14 DEMRG-immune-cell,9 DEMRG-immune-gene-set,and 67 DEMRG-protein-chip interactions were used to construct the regulatory network.Conclusion:We provided a prognostic prediction model based on 13 DEMRGs for DLBCL.We found that phosphatase,orphan 1(PHOSPHO1)is positively regulated by regulatory factor X5(RFX5)and mediates MYC proto-oncogene(MYC)targeting the V2 pathway and neutrophils.

In Silico analysis and linking of metabolism-related genes with the immune landscape in head and neck squamous cell carcinoma

Metabolic reprogramming and immunologic suppression are two critical characteristics promoting the progression of head and neck squamous cell carcinoma(HNSCC).The integrative analysis of all the metabolismrelated genes(MRGs)in HNSCC is lacking and the interaction between the metabolism and the immune characteristics also requires more exploration to uncover the potential mechanisms.Therefore,this study was designed to establish a prognostic signature based on all the MRGs in HNSCC.Genes of HNSCC samples were available from the TCGA and GEO databases while the MRGs were retrieved from a previous study.Ultimately 4 prognostic MRGs were selected to construct a model possessing robust prognostic value and accuracy in TCGA cohorts.The favorable reproducibility of this model was confirmed in validation cohorts from GEO databases.The risk score calculated by this model was an independent prognostic factor that further classified these HNSCC patients into high-/low-risk groups.GSEA analyses and somatic mutations indicated the low-risk group could activate several anti-tumor pathways and possessed lower TP53 mutation.The results of ESTIMATE,single-sample GSEA,CIBERSORT,and some immune-related molecules analyses suggested the low-risk group exhibited lower metabolic activities and higher immune characteristics.The Spearman correlation test implied most metabolic pathways with tumor-promoting function were negatively correlated with the immune activity,indicating a plausible approach of combining the anti-metabolism and the immunotherapy drugs in the high-risk group to enhance therapeutic effects than applied separately.In conclusion,this prognostic signature linking MRGs with the immune landscape could promote the individualized treatment for HNSCC patients.

Expression Analysis of Proline Metabolism-related Genes From Halophyte Arabis stelleri under Osmotic Stress Conditions

Arabis stelleri var. japonica evidenced stronger osmotic stress tolerance than Arabidopsis thaliana. Using an A. thaliana microarray chip, we determined changes in the expression of approximately 2 800 genes between A. stelleri plants treated with 0.2 M mannitol versus mock-treated plants. The most significant changes in the gene expression patterns were in genes defining cellular components or in genes associated with the endomembrane system, stimulus response, stress response, chemical stimulus response, and defense response. The expression patterns of three de novo proline biosynthesis enzymes were evaluated in A. stelleri var. japonica seedlings treated with 0.2 M mannitol, 0.2 M sorbitol, and 0.2 M NaCI. The expression of At-pyrroline-5-carboxylate synthetase was not affected by NaCI stress but was similarly induced by mannitol and sorbitol. The proline dehydrogenase gene, which is known to be repressed by dehydration stress and induced by free L-proline, was induced at an early stage by mannitol treatment, but the level of proline dehydrogenase was increased later by treatment with both mannitol and NaCI. The level of free L-proline accumulation increased progressively in response to treatments with mannitol, sorbitol, and NaCI. Mannitol induced L-proline accumulation more rapidly than NaCI or sorbitol. These findings demonstrate that the osmotic tolerance of the novel halophyte, Arabis stelleri, is associated with the accumulation of L-proline.

Treatment for non-alcoholic steatohepatitis with type 2 diabetes by traditional Chinese medicine:a case report and experience

Non-alcoholic fatty liver disease and type 2 diabetes are common comorbidities or target organ damage,which can lead to adverse metabolism and increased risk of cardiovascular and cerebrovascular diseases.In the management plan of non-alcoholic fatty liver disease and type 2 diabetes,there is no drug with significant efficacy or both.The dialectical idea of traditional Chinese medicine has a good curative effect and significant advantages in treating metabolic disorders.The author now reviewed a case of non-alcoholic steatohepatitis combined with type 2 diabetes.In this case,the method of invigorating the spleen and eliminating turbidity was effective,which effectively prevented the progression of liver disease in the patient,and T2DM was alleviated by maintaining within the standard range after the use of insulin was stopped.It can be said that“killing two birds with one stone”,more fully reflects the advantages of traditional Chinese medicine in the integrated treatment of metabolic-related diseases.

Azotobacter inoculation can enhance the resistance of Bt cotton to cotton bollworm, Helicoverpa armigera

The rising trend in the cultivation of Bacillus thuringiensis (Bt) transgenic crops may cause a destabilization of agroecosystems, thus increasing concerns about the sustainability of Bt crops as a valid pest management method. Azotobacter can be used as a biological regulator to increase environmental suitability and improve the soil nitrogen utilization efficiency of crops, especially Bt cotton. A laboratory test investigated effects on the development and food utilization of Helicoverpa armigera fed with different Cry1Ab/Cry1Ac proteins and nitrogen metabolism-related compounds from cotton (transgenic variety SCRC 37 vs non-Bt cotton cv. Yu 2067) inoculated with Azospirillum brasilense (Ab) and Azotobacter chroococcum (Ac). The findings indicate that inoculation with Azotobacter significantly decreased the partial development and food utilization indexes (pupal weight;pupation rate;adult longevity;fecundity;relative growth rate, RGR;efficiency of conversion of digested food, ECD;and efficiency of conversion of ingested food, ECI) of H. armigera fed on Bt cotton, but contrasting trends were found among these indexes in H. armigera fed on non-Bt cotton inoculated with Azotobacter, as a result of differences in Bt toxin production. Overall, the results showed that inoculation with Azotobacter had negative effects on the development and food utilization of H. armigera fed on Bt cotton, leading to enhanced target insect resistance. Presumably, Azotobacter inoculation can be used to stimulate plant soil nitrogen uptake to increase nitrogen metabolism-related compounds and promote plant growth for Bt and non-Bt cotton, simultaneously raising Bt protein expression and enhancing resistance efficacy against cotton bollworm in Bt cotton.