DEPDC1 as a metabolic target regulates glycolysis in renal cell carcinoma through AKT/mTOR/HIF1α pathway.

Renal cell carcinoma (RCC) is considered a "metabolic disease" characterized by elevated glycolysis in patients with advanced RCC. Tyrosine kinase inhibitor (TKI) therapy is currently an important treatment option for advanced RCC, but drug resistance may develop in some patients. Combining TKI with targeted metabolic therapy may provide a more effective approach for patients with advanced RCC. An analysis of 14 RCC patients (including three needle biopsy samples with TKI resistance) revealed by sing-cell RNA sequencing (scRNA-seq) that glycolysis played a crucial role in poor prognosis and drug resistance in RCC. TCGA-KIRC and glycolysis gene set analysis identified DEPDC1 as a target associated with malignant progression and drug resistance in KIRC. Subsequent experiments demonstrated that DEPDC1 promoted malignant progression and glycolysis of RCC, and knockdown DEPDC1 could reverse TKI resistance in RCC cell lines. Bulk RNA sequencing (RNA-seq) and non-targeted metabolomics sequencing suggested that DEPDC1 may regulate RCC glycolysis via AKT/mTOR/HIF1α pathway, a finding supported by protein-level analysis. Clinical tissue samples from 98 RCC patients demonstrated that DEPDC1 was associated with poor prognosis and predicted RCC metastasis. In conclusion, this multi-omics analysis suggests that DEPDC1 could serve as a novel target for TKI combined with targeted metabolic therapy in advanced RCC patients with TKI resistance.

Protective effects of gut microbiota and gut microbiota-derived acetate on chicken colibacillosis induced by avian pathogenic Escherichia coli.

Chicken colibacillosis is caused by avian pathogenic Escherichia coli (APEC), and results in huge economic losses to the poultry industry. With the investigation of the gut-lung axis, more studies have demonstrated the important role of gut microbiota in lung inflammation. The precise role of the gut microbiota in chickens-associated colibacillosis, however, is unknown. Thus, this study assessed the function of the gut microbiota in the chicken defense against APEC infection. Chicken gut microbiota was depleted by drinking water with a mixture of antibiotics (Abx), and subsequently, a model of colibacillosis was established by the intranasal perfusion of APEC. The results showed that gut microbiota protects the chicken challenge by APEC from aggravated lung histopathologic injury, up-regulated pro-inflammatory cytokine production, and increased bacterial load in lung tissues compared with controls. In addition, the air-blood barrier permeability was significantly increased in gut microbiota-depleted chickens compared to the control chickens after challenge with APEC. Furthermore, feeding acetate significantly inhibited the lung inflammatory response and the reduced air-blood permeability induced by APEC infection. The expression of free fatty acid receptor 2 (FFAR2), a receptor for acetate, was also increased in the lung after treatment with acetate. In conclusion, depletion of the gut microbiota resulted in increased susceptibility of chickens to APEC challenge, and gut microbiota derived acetate acted as a protective mediator during the APEC challenge. Novel therapeutic targets that focus on the gut microbiota may be effective in controlling colibacillosis in poultry.