The multilineage differentiation potential of human umbilical cord mesenchymal stem cells (HUCMSCs) holds therapeutic promise for non-healing ulcers and tissue regeneration. The present study evaluated the effects of HUCMSC transplantation after angioplasty for treatment of diabetic foot. Included in the study were 53 patients (72 limbs) with severe symptoms of Fontaine II-IV diabetic foot accompanied by varying degrees of lower extremity arterial disease. The patients were randomly apportioned to a control group (25 patients; 38 limbs) or an experimental group (28 patients; 34 limbs). Patients of both groups received interventional treatment with angioplasty; those in the experimental group also received HUCMSCs by endovascular infusion and injection around the foot ulcer. Within the 3-month follow-up, relative to patients in the control group, those in the experimental group experienced significantly greater and more stable improvements in skin temperature, ankle-brachial pressure index, transcutaneous oxygen tension, and claudication distance. Notably, 3 months after treatment a significant increase in neovessels, accompanied by complete or gradual ulcer healing, was shown in the experimental group. In addition, no serious complications or adverse reactions were associated with the treatment. Therefore, our results indicate that HUCMSC transplantation after angioplasty is a safe and effective clinical therapy for severe diabetic foot.

Castration resistance is a serious problem facing clinical treatment of prostate cancer (PCa). The underlying molecular mechanisms of acquired proliferation ability of tumor cells upon androgen deprivation are largely undetermined. In the present study, we identified that ubiquitin specific peptidase 39 (USP39) was significantly upregulated in PCa samples and cell lines. Elevated USP39 expression was positively correlated with Gleason score, predicted a poor outcome, and functioned as an independent risk factor for biochemical recurrence (BCR) especially in patients with a Gleason score ≤7. Our cell-based study showed that the expression level of USP39 was the highest in AR-negative PCa cell lines. Knockdown of USP39 in PCa cells inhibited cancer colony formation and tumor cell growth, and induced G2/M arrest and cell apoptosis. Microarray analysis suggested that knockdown of USP39 caused a reduced expression of EGFR. Silencing of USP39 inhibited the expression of EGFR 3′-end, and presented a remarkable block to the maturation of EGFR mRNA, suggesting that silencing of USP39 decreased the transcriptional elongation and maturation of EGFR mRNA. Oncomine datasets analysis showed that USP39 expression was positively correlated with EGFR level. The above findings suggest that USP39 plays a vital oncogenic role in the tumorigenesis of PCa and may prove to be a potential biomarker for predicting the prognosis of PCa patients.

Significant enhancement of the glycolysis pathway is a major feature of tumor cells, even in the presence of abundant oxygen; this enhancement is known as the Warburg effect, and also called aerobic glycolysis. The Warburg effect was discovered nearly a hundred years ago, but its specific mechanism remains difficult to explain. DNA methylation is considered to be a potential trigger for the Warburg effect, as the two processes have many overlapping links during tumorigenesis. Based on a widely recognized potential mechanism of the Warburg effect, we here summarized the relationship between DNA methylation and the Warburg effect with regard to cellular energy metabolism factors, such as glycolysis related enzymes, mitochondrial function, glycolysis bypass pathways, the tumor oxygen sensing pathway and abnormal methylation conditions. We believe that clarifying the relationship between these different mechanisms may further help us understand how DNA methylation works on tumorigenesis and provide new opportunities for cancer therapy.

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