Single-Center Retrospective Analysis of Prophylaxis and Treatment of Pneumocystis carinii Pneumonia in Patients with Renal Dysfunction After Renal Transplantation.

BACKGROUND Pneumocystis carinii is an opportunistic pathogen that can cause severe lung infections after renal transplantation. Trimethoprim-sulfamethoxazole (TMP-SMX) has been recognized as a first-line treatment for chemoprophylaxis of Pneumocystis carinii pneumonia (PCP). This study aimed to establish a personalized chemoprophylaxis prescription specifically for those recipients with renal insufficiency. MATERIAL AND METHODS This retrospective study included 68 patients with confirmed PCP after renal transplantation. Patients were divided into 2 groups: an abnormal renal function (ARF) group (creatinine ≥1.5 ng/dl; n=37) and a normal renal function (NRF) group (creatinine <1.5 ng/dl; n=31). Clinical characteristics and prognosis of PCP in both groups were compared and analyzed. RESULTS Patients in the ARF group had more prophylaxis after transplantation (15 [40.5%] vs. 2 [6.5%], p=0.047), had more biopsy-proven rejections (10 [27%] vs. 1 [3.2%], p=0.008), and had lower lymphocyte counts (0.6 [05-0.9] vs. 1.1 [0.7-1.6], p<0.01). Renal function after treatment was obviously improved in the ARF group, which had a significant decrease rate in creatinine (-13.2% [-22~4.8%] vs. -4.4% [-12.6~20.9%], p=0.043). CONCLUSIONS PCP prophylaxis regimens for recipients after renal transplantation are still needed regardless of whether the renal functions were normal or abnormal, especially for recipients with persistent lymphopenia or rejection after transplantation.

MiR-320a inhibits gastric carcinoma by targeting activity in the FoxM1-P27KIP1 axis.

MicroRNAs (miRNAs) regulate tumorigenesis by inhibiting gene expression. In this study, we showed that miR-320a expression is decreased in human gastric cancer tissues and correlates inversely with expression of FoxM1, a key cell cycle regulator involved in gastric carcinoma. By contrast, the expression of P27KIP1, a downstream effector of FoxM1, correlates positively with miR-320a levels. Luciferase assays indicate that miR-320a suppresses FoxM1 expression, and in vitro recovery tests using FoxM1 siRNA indicate miR-320a inhibits gastric cancer cell proliferation by suppressing activity in the FoxM1-P27KIP1 axis. In vivo, nude mice injected with BGC-823 gastric cancer cells expressing a miR-320a inhibitor exhibit faster tumor growth than mice injected with control cells. Analysis of FoxM1 and P27KIP1 expression in tumor tissues indicates that miR-320a suppression increases the tumor growth by enhancing FoxM1-P27KIP1 signaling. These results thus reveal the crucial role played by miR-320a in limiting gastric carcinoma by directly targeting FoxM1- P27KIP1 axis.

MicroRNA-200c is involved in proliferation of gastric cancer by directly repressing p27Kip1.

P27Kip1, also known as Cyclin-dependent kinase inhibitor 1B, is an important check-point protein in the cell cycle. It has been identified that although as a tumor suppressor, P27Kip1 is expressed in different cancer cell types, which shows the therapeutic potential in tumor genesis. In this study, we examined the upstream regulatory mechanism of P27Kip1 at the microRNA (miRNA) level in gastric carcinogenesis. We used bioinformatics to predict that microRNA-200c (miR-200c) might be a direct upstream regulator of P27Kip1. It was also verified in gastric epithelial-derived cell lines that overexpression of miR-200c significantly inhibited the expression levels of P27Kip1, whereas knockdown of miR-200c promoted P27Kip1 expression in AGS and BGC-823 cells. Furthermore, we identified the direct binding of miR-200c on the P27Kip1 3' -UTR sequence by luciferase assay. MiR-200c could enhance the colony formation of cells by repressing P27Kip1 expression. In addition, the negative correlation between P27Kip1 and miR-200c in human gastric cancer tissues and matched normal tissues further supported the tumor-promoting action of miR-200c in vivo. Our finding suggested that miR-200c directly regulates the expression of P27Kip1 and promotes cell growth in gastric cancer as an oncogene, which may provide new clues to treatment.