Jianming Tan

To investigate the long-term effects of combining bone marrow mesenchymal stem cells (MSCs) with mononuclear cells (MCs) in the treatment of type 2 diabetes mellitus (T2DM). T2DM patients were divided into the combination group (Dual MSC + MC, n = 33), the mononuclear cell group (MC-Only, n = 32) and the control group (Control, n = 31). All groups were treated with insulin and metformin. The Dual MSC + MC group additionally received MSC and MC infusion and the MC-Only group additionally received MC infusion. The patients were followed up for 8 years. The primary endpoint was the C-peptide area under the curve (C-p AUC) at 1 year. This study was registered with clinicaltrial.gov (NCT01719640). A total of 97 patients were included and 89 completed the follow-up. The area under the curve of C-peptide of the Dual MSC + MC group and the MC-Only group was significantly increased (50.6% and 32.8%, respectively) at 1 year. After eight years of follow-up, the incidence of macrovascular complications was 13.8% (p = 0.009) in the Dual MSC + MC group and 21.4% (p = 0.061) in the MC-Only group, while it was 44.8% in the Control group. The incidence of diabetic peripheral neuropathy (DPN) was 10.3% (p = 0.0015) in the Dual MSC + MC group, 17.9% (p = 0.015) in the MC-Only group, and 48.3% in the Control group. The combination of MSC and MC therapy can reduce the incidence of chronic diabetes complications and improves metabolic control with mild side effects in T2DM patients.

Circular RNAs (circRNAs) are a class of noncoding RNAs closely related to the development and progression of various human cancers. However, it is unclear whether circRNAs play an important role in the development of bladder cancer. We utilized human circRNA array V2 microarrays to screen circRNA expression profiles in bladder cancer tissues. Bioinformatic tools including circBank, dbDEMC 2.0, miRCancer, TarBase v7.0, miRtarbase, TCGA–BLCA, Cytoscape-MCODE, String, ENCORI, and Venny 2.1 were then employed to construct the circRNA–miRNA–mRNA regulatory networks. In total, 105 upregulated circRNAs and 167 downregulated circRNAs (fold change >2 and p < 0.001) were filtered out. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of filtered dysregulated circRNAs disclosed that the circRNAs regulatory network was closely related with mRNA processing and cell cycle, etc. Further excavation analysis showed that seven differentially overexpressed circRNAs including hsa_circ_0000133, hsa_circ_0023610, hsa_circ_0005615, hsa_circ_0030162, hsa_circ_0077007, hsa_circ_0001140, and hsa_circ_0107031 were associated with bladder cancer invasiveness, and the cell cycle signal axis. has_circTPT1_003–has-miR-218-5p–CCNE2/SMC4 was finally clarified as a possible mechanism for bladder cancer progression. Based on results derived from multiple approaches, we identified that has_circTPT1_003–has-miR-218-5p–CCNE2/SMC4 signal axis may be involved in the invasion process of bladder cancer.

This work aimed to discover new therapeutic targets in renal clear cell carcinoma by bioinformatics and detect the effect of candidate gene TRIP13 in renal cell carcinoma (RCC) cell proliferation, migration, and invasion. Differentially expressed mRNAs were screened based on The Cancer Genome Atlas (TCGA)-Kidney Renal Clear Cell Carcinoma (KIRC) databases, and functional enrichments, survival analysis, receiver operating characteristic curve (ROC), and Protein–Protein Interaction (PPI) protein interaction analysis were performed by R software to screen the candidate gene TRIP13. Then, the expression of candidate gene TRIP13 in 92 pairs of cancer and adjacent normal tissues of renal clear cell carcinoma patients were detected by qRT-PCR, western blotting, and immunochemical analysis. The TRIP13 level and clinicopathological characteristics of patients with renal clear cell carcinoma were analyzed. Using 186-O and ACHN RCC cell lines with TRIP13 overexpressing or downregulating, the effect of TRIP13 on cell viability and proliferation were detected by CCK8 and EdU staining, respectively. The migration and invasion were detected by Transwell assays. A total of 19858 differentially expressed genes, 5823 differentially expressed genes, 3657 up-regulated genes, and 2166 down-regulated genes were identified. TRIP13 was closed associated with cell cycle regulation, and survival and prognosis of renal clear cell carcinoma were selected as a candidate gene. The mRNA and protein levels of TRIP13 in cancer tissues were higher than that in adjacent normal tissues. TRIP13 level was significantly associated with tumor size, tumor stage, Fuhrman grade, and lymph node metastasis. TRIP13 overexpression significantly increased cell viability, proliferation, migration, and invasion, while downregulating of TRIP13 had opposite effects in both 186-O and ACHN cells. Therefore, TRIP13 promotes RCC proliferation and metastasis, which should be a novel biomarker for early diagnosis, treatment, and prognosis of RCC.

Tet methylcytosine dioxygenase 2 (TET2) acts as an antioncogene that is investigated in different cancers. But the effects of TET2 in renal cell cancer (RCC) is still known little. Here, quantitative real-time PCR (qRT-PCR), Western blot, and immunofluorescence were performed to exam gene and protein expression. Cell proliferation was measured using Cell Counting Kit-8 (CCK-8). Transwell assay was performed to detect cell metastasis viability. Flow cytometry was performed to analyze the cell cycle and cell apoptosis. The effects of TET2 on RCC growth in vivo was analyzed using a mouse xenograft model.We found that TET2 and miR-200c were decreased in RCC tissues, and hypermethylation of miR-200c promoter was found. Overexpression of TET2 promoted miR-200c expression by reducing miR-200c promoter methylation. Additionally, overexpression of TET2 or miR-200c suppressed cell growth and metastasis. Also, knockdown of miR-200c could moderate TET2 mediated cell growth inhibition. Furthermore, we found miR-200c directly regulates Stearoyl-CoA desaturase (SCD) gene expression. Moreover, in vivo experiment results confirmed that TET2 inhibited tumor growth. In conclusion, TET2 acts as an antioncogene in RCC by regulating the miR-200c-SCD axis and providing a potential target for RCC diagnosis and treatment.

Early outcomes following solid organ transplantation have markedly improved in recent years. Antibody-mediated rejection caused by donor specific anti-human leukocyte antigen antibodies (HLA-DSA) is widely recognized to be a risk factor for rejection episode, graft loss and decreased graft survival. The presence of HLA-DSA before transplantation and the appearance of these antibodies after transplantation can induce a wide spectrum of allograft injuries, ranging from the absence of allograft lesions with normal biopsy histopathologies to indolent subclinical processes to acute rejection with early allograft loss. However, the interpretation of the current DSA results is not easy and has led to many discussions and controversies. Current challenges exist in identification of pathologic DSA, monitoring and diagnostic algorithms, appropriate risk stratification, minimization for preformed or de novo DSA by proper use of immunosuppression. This article summarizes recent advances concerning the impact of preformed and de novo DSA in solid organ transplantation, with a focus on the clinical significance of DSA and available treatment modalities. Areas requiring further investigation are also identified.

MicroRNAs (miRNAs) have vastly expanded our view of RNA world in intracellular signal regulating networks. Here, we functionally characterized a normally highly expressed miRNA, miR-30a-5p (MIMAT0000087), which exhibits downregulated expression profiles in prostate cancer samples. MiR-30a-5p knockdown and overexpression in PC-3 cell line alters cell proliferation supporting a tumour suppressor role. We also discovered that PCLAF is the direct target of miR-30a-5p. Notably, PC-3 cell proliferation is inhibited by miR-30a-5p/PCLAF axis. miR-30a-5p represents a novel molecule of functionally important miRNAs which may shed light on the novel therapeutic targets for prostate cancer.