Kaempferol (Kae), a natural flavonoid, is widely distributed in fruits and vegetables. Previous studies have identified Kae as a possible cancer preventive and therapeutic agent. We found Kae to exhibit potent antiproliferation and anti-migration effects in human bladder cancer EJ cells. Kaempferol robustly induced apoptosis in EJ cells in a dose-dependent manner, as evidenced by increased cleavage of caspase-3. Furthermore, we found Kae-induced apoptosis in EJ cells to be associated with phosphatase and the tensin homolog deleted on the chromosome 10 (PTEN)/PI3K/Akt pathway. Kae significantly increased PTEN and decreased Akt phosphorylation. Kae-induced apoptosis was partially attenuated in PTEN-knockdown cells. Our findings indicate that Kae could be an alternative medicine for bladder cancer, based on a PTEN activation mechanism.

Due to the increasing number of DCD transplantations since 2015, the transmission of rabies through solid organ transplantation has become a notable problem in China and has attracted the attention of the public. From 2015 to 2017, four solid organ recipients in our centre were successively diagnosed with rabies that was considered to have been transmitted from two donors who died due to viral encephalitis of unknown cause and acute disseminated encephalomyelitis. The incubation periods were 44, 48, 158 and 303 days. The four patients had neurological symptoms associated with rabies and died. The survival times were 44, 34, 8 and 6 days. Another kidney transplant recipient received timely post-exposure prophylaxis and has remained asymptomatic. Organs should be discarded whenever rabies is confirmed or suspected, especially in cases diagnosed as encephalitis of unknown cause. It is important to establish a supervisory system to manage donor-derived infectious diseases. When rabies-infected donor organs are inadvertently transplanted, the recipients must receive post-exposure prophylaxis in a timely manner, which may be the only possible effective method to prevent the transmission of rabies.

Vascular remodeling is a key process leading to arterial stenosis. Ufmylation, a novel ubiquitin-like modification, was observed to be associated with many biological processes. However, whether ufmylation is involved in the regulation of vascular remodeling remains unclear. Therefore, the present study focused on the role of ufmylation in vascular remodeling. Mouse femoral artery guidewire injury models were used for inducing vascular remodeling. We found that the expression of Ufm1 was upregulated in hyperplastic neointima. By treating vascular smooth muscle cells (VSMCs) with platelet-derived growth factor BB (PDGF-BB) for 3, 6, 12, and 24 h, respectively, we observed that ufmylation was significantly activated in a time-dependent manner. Consistently, the expression levels of Ufc1, Ufl1, and Ufbp1, as key components of the ufmylation system, were all upregulated by PDGF-BB. In contrast, knockdown of Ufm1 expression attenuated PDGF-BB-induced VSMC proliferation. In addition, we observed that ufmylation was activated by lipopolysaccharide (LPS) in endothelial cells, whereas knockdown of Ufm1 was synergized with LPS-induced endothelial cell injury. These findings indicate that ufmylation may participate in regulation of the VSMC phenotypic switch and endothelial cell injury, which may help in the understanding of vascular remodeling.

Renal ischemia/reperfusion injury (IRI) is a main risk factor for the occurrence of delayed graft function or primary graft nonfunction of kidney transplantation. However, it lacks ideal molecular markers for indicating IRI in kidney transplantation. The present study is to explore novel candidate genes involved in renal IRI. Experimental renal IRI mouse models were constructed, and the differentially expressed genes were screened using a microarray assay. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed. The expression of genes was detected using real-time qPCR assay. Western blotting and immunohistochemistry staining assays were performed for protein determination. We identified that renal IRI induced the upregulation of SPRR2F , SPRR1A , MMP-10 , and long noncoding RNA (lncRNA) Malat1 in kidney tissues for 479.3-, 4.98-, 238.1-, and 3.79-fold, respectively. The expression of miR-139-5p in kidney tissues of IRI-treated mice was decreased to 40.4% compared with the sham-operated mice. These genes are associated with keratinocyte differentiation, regeneration and repair of kidney tissues, extracellular matrix degradation and remodeling, inflammation, and cell proliferation in renal IRI. Identification of novel biomarkers involved in renal IRI may provide evidences for the diagnosis and treatment of renal IRI.

Renal ischemia/reperfusion (IR) injury is one of the most important risk factors for the occurrence of delayed graft function (DGF) after kidney transplantation; however, its mechanism remains not fully understood. In the present study, we screened differentially expressed genes in a murine model of renal IR injury by using high-throughput assays. We identified Corin as one of the most significantly downregulated genes among 2218 differentially expressed genes (≥2-fold, P<0.05). By using a real-time qPCR assay, we observed that the expression of renal Corin in IR-injured mice was reduced to 11.5% of the sham-operated mice and that the protein level of renal Corin in IR-injured mice was also downregulated. Interestingly, renal IR injury in mice induced the downregulation of Corin in heart tissues, suggesting that the overall synthesis of Corin may be suppressed. We recruited 11 recipients complicated with DGF and 16 without DGF, and plasma Corin concentrations were determined by ELISA. We observed that the plasma Corin levels were indeed reduced in recipients complicated with DGF (0.98 vs. 1.95 ng/ml, P<0.05). These findings demonstrate that Corin may be a potential biomarker of DGF after kidney transplantation and may participate in the regulation of renal IR injury.

Renal cancer is one of the most common malignant urological tumors; however, its diagnosis and treatment are not well established. In the present study, we identified that CDK5 regulatory subunit-associated protein 3 (CDK5RAP3), a putative tumor suppressor in many cancers, was downregulated in renal cancer tissues. Through loss- and gain-of-function experiments, we observed that the action of CDK5RAP3 in renal cancer cells was different in Caki-1 and 769-P cell lines. Knockdown of endogenous CDK5RAP3 in Caki-1 slightly increased cell viability, whereas overexpression of CDK5RAP3 in 769-P cells inhibited cell viability. In addition, we observed that CDK5RAP3 participated in the regulation of autophagy in renal cancer. Knockdown of CDK5RAP3 induced significant inhibition of autophagy in Caki-1 cells but not in 769-P cells. In contrast, overexpression of CDK5RAP3 significantly activated autophagy in 769-P cells, as evidenced by increased LC3-II levels. However, the LC3-II could not be altered by CDK5RAP3 overexpression in Caki-1 cells. These findings demonstrated that CDK5RAP3 is downregulated in renal cancer and may be associated with autophagy.