Search

Remote ischemic preconditioning (RIPC) is a minimally invasive method that provides protection by reducing injury to the heart, kidneys, brain and other tissues or organs. RIPC may improve the outcome in patients undergoing surgery. Although the role of RIPC has been studied, the results remain controversial. It is difficult to confirm whether RIPC has a kidney protective effect and the understanding of the preconditioning signal pathway involved remains unclear. In the present study, the effect of RIPC in urology was evaluated. The protection against renal damage was assessed by investigating the potential mediator, hypoxia‑inducible factor‑1α (HIF‑1α), and the functional adrenomedullin (ADM) pathway. Male Sprague‑Dawley (SD) rats were used in the present study. The animal model of kidney damage induced by ischemia reperfusion (IR) was used to investigate the protective effect of the acute and delayed phase RIPC. Furthermore, the protective effects of RIPC mediated by a HIF‑1α‑ADM pathway were assessed. The indexes of renal function and oxidative damage indicators were measured by Cr, BUN, mALB, β2‑MG, MPO, MDA and SOD assays, and the expression of HIF‑1α and ADM were detected by western blot analysis, immunohistochemistry and ELISA assays. Tubular score, determined using hematoxylin and eosin staining, was used to evaluate renal tissue damage. Applying RIPC prevented IR‑induced renal dysfunction and oxidative damage by decreasing Cr, BUN, mALB, β2‑MG, MPO, MDA levels and increasing SOD activity. Findings showed that delayed RIPC had an improved effect compared with acute treatment. Delayed RIPC also upregulated the expression of HIF‑1α and ADM, indicating that the protective effect of the delayed RIPC may be associated with a HIF‑1α‑ADM‑mediated mechanism. The effect of the delayed RIPC to reduce IR‑induced renal damage and increase ADM expression was enhanced by HIF‑1α agonists DMOG and BAY 85‑3934, whereas the effect was whittled by HIF‑1α antagonists YC‑1 and 2‑MeOE2. Furthermore, receiving ADM also offered protection to the kidney in comparison with the IR+Vehicle group. These findings suggest that RIPC prevents IR‑mediated renal damage by HIF‑1α via an ADM humoral pathway. In the present study, RIPC provided an effective renal protection. ADM could also offer protection regulated by HIF‑1α in renal tissue. However, the mechanism of ADM as a protective factor in RIPC requires further research.

T-Box (TBX)-2 is a member of the T-box gene family, which is aberrantly expressed in numerous types of malignant tumors, and has previously been demonstrated to be conducive to tumor progression by acting as a transcription factor. However, specific information regarding the expression and function of TBX2 in prostate cancer cells remains to be elucidated. The present study demonstrated that silencing of TBX2 by TBX2 small interfering RNA inhibited cell proliferation and promoted cell senescence. It was demonstrated that knockdown of TBX2 inhibited cell metastatic abilities by upregulating E-cadherin and downregulating N-cadherin, Vimentin and fibronectin. In addition, the expression of TBX2 in prostate cancer tissues and tumor adjacent tissues was detected by immunohistochemistry. The results indicated that the expression rates of TBX2 were significantly increased in the cancerous tissues, compared with the healthy tumor adjacent tissue, and TBX2 increased staining was associated with the clinical stage and pathological grade. The findings of the present study therefore suggest that TBX2 expression is markedly increased in prostate cancer and TBX2 may act as a potential beneficial therapeutic target for the future treatment of prostate cancer.

Oridonin is a diterpenoid compound isolated from the medicinal herb Rabdosia rubescens, and has shown marked antitumor effects against different types of cancer. However, the definitive systematic molecular mechanism underlying the antitumor activity of oridonin in multiple myeloma remains to be elucidated. In the present study, cell viability and cytotoxicity were examined to determine the appropriate concentration for proteomic investigation. In addition, cell apoptosis was evaluated using flow cytometry and transmission electron microscopy. A proteomic investigation using a two‑dimensional electrophoresis system and mass spectrometry was performed to identify and characterize the global proteome of the apoptosis induced by oridonin. Of the proteins identified, seven were involved in the anticancer effects of oridonin. Regulation of the expression and function of target proteins, stathmin, dihydrofolate reductase and pyruvate dehydrogenase E1β, may be potential, therapeutic strategies to effectively treat multiple myeloma. These findings provide novel information on the molecular mechanisms underlying the anticancer properties of oridonin in multiple myeloma.

The expression of SET nuclear proto‑oncogene (SET) is commonly associated with cell proliferation and tumorigenesis. In the present study, a eukaryotic SET expression plasmid (pEGFP‑N1‑SET) was constructed and transiently transfected into 293T human embryonic kidney cells. Transfection led to expression of the SET oncoprotein at high levels, as indicated by polymerase chain reaction and western blot analysis. In addition, the relative mRNA and protein expression of protein phosphatase 2A in pEGFP‑N1‑SET‑transfected 293T cells was downregulated compared with that in empty vector‑transfected cells. Furthermore, overexpression of SET increased the percentage of 293T cells in S and G2/M phases compared with the control transfectants. An increase in B‑cell lymphoma 2 (Bcl‑2) and a decrease in Bcl‑2‑associated X (Bax) protein expression was observed in the pEGFP‑N1‑SET‑transfected cells compared with that in the controls, and their susceptibility to As4S4‑induced apoptosis was decreased. The protein SET is involved in a number of cellular processes, including DNA replication, chromatin remodeling, gene transcription, differentiation, migration and cell cycle regulation. SET is overexpressed in several neoplasms, particularly in acute myeloid leukemia. The findings of the present study suggested that the SET gene may contribute to tumorigenesis and may be a potential novel effective therapeutic target for leukemia and other cancer types.

Chitosan is a linear polysaccharide that is made by treating the chitin shells of shrimp and crustaceans with an alkaline substance, for example sodium hydroxide. Due to its unique physical and chemical properties, chitosan has a wide range of applications in the medical field. Currently, there are no effective treatments for liver fibrosis; therefore, the aim of the present study was to investigate the therapeutic effect of chitosan in a CCl4‑induced hepatic fibrosis (HF) rat model. The serum levels of aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were measured by ELISA. Collagen (COL) 3 and α‑smooth muscle actin (SMA) expression levels in the rat liver were detected by reverse transcription‑semiquantitative polymerase chain reaction and western blotting, respectively. The results demonstrated that treatment with chitosan significantly improved HF, by decreasing the serum levels of AST, ALT, and ALP; improving liver histology; and decreasing the expression levels of COL3 and α‑SMA. Chitosan may offer an alternative approach for the clinical treatment of HF.

The renal allograft survival rates of patients with immunoglobulin A nephropathy (IgAN), and patients with or without other glomerular diseases, have yet to be fully elucidated. In this study, the clinicopathological factors associated with long-term allograft survival for the prognosis of renal allograft recipients with IgAN were examined. All patients enrolled in this study were diagnosed with IgAN following clinical and pathological examinations. Patients underwent renal graft biopsy and were hospitalized at the Fuzhou General Hospital between June, 2004 and December, 2010. Common demographic and clinical indicators were recorded in patients who had graft loss and in those who had functional renal grafts. Forty-two of the 202 biopsy specimens (20.8%) met the diagnostic criteria for IgAN and were divided into two groups, the graft loss group (n=17) and the functional graft group (n=25). Patients were followed up for 1-257 months after kidney transplantation. The mean patient age was 40.6 ± 9.3 years at the time of renal graft biopsy. Examination results indicated concomitant proteinuria and hematuria in 25 patients (59.5%) and proteinuria alone in six patients (14.3%). Graft loss occurred in 17 patients during the follow-up period. Comparison of the graft loss and the functional graft groups indicated that patients in the graft loss group were more likely to have proteinuria (P=0.047), high creatinine levels at the time of biopsy (P=0.009), low glomerular filtration rates (P=0.013), low serum total protein (P=0.01), a high Banff score (P=0.001), extensive glomerulosclerosis (P=0.002), a greater likelihood of crescent formation (P=0.01), severe tubular atrophy (P=0.013) and more extensive interstitial fibrosis (P=0.033). However, the two groups showed no significant differences in blood pressure, hematuria, BUN, UA, Hb, TG and CHO levels. The allograft survival rate of patients with IgAN was identified to be similar to that of patients with and without other glomerular diseases.

To investigate the effects of pirfenidone (PFD) on the attenuation of bladder remodeling, and the associated functional changes caused by partial bladder outlet obstruction (pBOO), the present study performed surgery on adult male Sprague‑Dawley rats produce a model of pBOO. The rats in the pBOO group were administered a placebo and, in the CMC group, PFD mixed with the placebo was administered orally at 500 mg/kg body weight each day for 5 weeks, from 1 week after surgery. The rat bladders were harvested for biochemical analysis following cystometry at the end of the 6 week period. The histopathology was determined using Masson's trichrome staining. The mRNA and protein levels of pro‑fibrotic growth factors and extracellular matrix subtypes were assessed. pBOO debilitated bladder function and caused the parameters from cystometry to increase significantly compared with those in the control group (P

MicroRNAs (miRs) function as oncogenes and tumor suppressors, and have roles in most cellular processes. To date, the possible role of miR-27a, which is part of the miR-23a/27a/24-2 cluster, in malignant gliomas has remained elusive. Therefore, the present study aimed to explore the role of miR-27a in glioma and its potential target. Through transfection with miR-27a inhibitor or oligonucleotide mimics, the impact of miR-27a silencing or overexpression on the growth, apoptosis, cell cycle and invasiveness of U251 and U87MG cells was examined in vitro. The present study initially identified the potential target of miR-27a in glioma cells through a bioinformatics analysis, which was used for screening of the literature on the proteomics of gliomas. Prohibitin (PHB) was then confirmed as a target by absolute luciferase reporter assays, quantitative real-time polymerase chain reaction and western blot analysis. Treatment with miR-27a mimics oligonucleotides suppressed U251 cell proliferation, promoted apoptosis by inducing G2/M phase arrest, and impaired the invasive potential of U251 cells in vitro. In addition, miR-27a expression was downregulated in glioma tissues. A PHB-3'-untranslated region luciferase reporter assay confirmed PHB as a direct target gene of miR-27a. PHB mRNA expression was reversely correlated with levels of miR-27a in U251 cells. Overexpression of miR-27a in U251 cells at 72 h and 96 h post‑transfection with miR-27a mimics significantly decreased PHB protein expression by 17.2% and 43.9%, respectively. In conclusion, miR-27a was shown to be a significant tumor suppressor by targeting and decreasing PHB protein expression in glioma U251 cells. miR-27a targeting of PHB may be a novel potential therapeutic strategy for glioma.

Telomerase reverse transcriptase (TERT), encoded by the TERT gene, is an essential component of telomerase, essential for the maintenance of telomere DNA length, chro- mosomal stability and cellular immortality. The aim of the present study was to evaluate the association between common genetic variations across the TERT gene region and prostate cancer (PCa) aggressiveness in a Chinese population. A total of 12 TERT tagging single-nucleotide polymorphisms (SNPs) were genotyped on the Sequenom Mass-ARRAY iPLEX ® platform in a case-case study with 1,210 Chinese patients with PCa. Unconditional logistic regression was used to investigate the association of genotypes with PCa aggressiveness, Gleason grade and risk of developing early-onset PCa. It was observed that the C allele of the TERT intron 2 SNP (rs2736100) was significantly associated with reduced risk of PCa aggressive - ness (odds ratio (OR)=0.81; 95% confidence interval (CI): 0.66-0.99; P=0.037). This allele was also significantly corre - lated with a reduced risk of developing a tumor with a high Gleason score (>7; OR=0.83; 95% CI: 0.70-0.99; P=0.039). The T allele of the intron 4 SNP (rs10069690) was found to be significantly associated with a decreased risk for an aggres - sive form of PCa (OR=0.76; 95% CI: 0.59-0.97; P=0.030). In addition, the A allele of rs10078761 located at the 3' end of the TERT gene exhibited a statistically significant association with the reduced risk of developing a higher grade disease (OR=0.48; 95% CI: 0.28-0.81; P=0.006). However, no associa- tion between TERT polymorphisms and age at diagnosis was observed in the present study. The present findings demon - strated for the first time, to the best of our knowledge, that genetic variations across the TERT gene are associated with PCa aggressiveness in a Chinese Han population.

Renal cell carcinoma (RCC) has a high potential for bone metastasis; however, the molecular mechanisms underlying this metastasis have remained to be elucidated. The present study aimed to explore the expression levels of enhancer of zeste homolog 2 (EZH2), matrix metalloproteinase-2 (MMP2) and tissue inhibitor of metalloproteinase-2 (TIMP2) as determinants of RCC-associated bone metastasis. Their expression was evaluated in a newly generated RCC cell subline that has a high potential for bone metastasis, in tissue specimens from metastasized bone tissues from patients with RCC and in RCC tissues without metastasis. A total of 25 RCC tissue specimens without metastasis and 13 RCC tissue specimens with bone metastasis were acquired for immunohistochemical analysis of EZH2, MMP2 and TIMP2 protein expression. The expression levels of EZH2, MMP2 and TIMP2 mRNA and protein were analyzed in the ACHN and ACHN-BO5 cell lines using western blot and reverse transcription polymerase chain reaction (PCR) analyses. Methylation-specific PCR was also used to analyze TIMP2 promoter methylation. EZH2 and MMP2 proteins were found to be expressed at higher levels in tissues from patients where RCC had metastasized to the bone as compared with those in RCC patients without metastasis, whereas there was no significant difference in the expression of TIMP2 protein between the two tissues. Furthermore, the expression of EZH2 protein was correlated with MMP2 expression, but there was no significant correlation between the expression of EZH2 and TIMP2 proteins. The in vitro results using cell lines confirmed the ex vivo findings, indicating that the expression levels of EZH2 and MMP2 protein and mRNA were higher in ACHN-BO5 cells than those in ACHN cells. By contrast, TIMP2 protein and mRNA expression levels were lower in ACHN-BO5 cells than those in the parental ACHN cells. The TIMP2 promoter was highly methylated in ACHN-BO5 cells compared with that in ACHN cells. Upregulation of EZH2, MMP2 and TIMP2 expression was correlated with metastasis of RCC to bone tissues ex vivo and in vitro. Further studies are required in order to elucidate the mechanism underlying the altered expression of these genes.

The purpose of this study was to investigate the roles of bcl-2 chromosomal translocation and Bcl-2 protein expression in follicular lymphoma (FL) minimal bone marrow (BM) infiltration. We identified the same bcl-2/IgH fusion gene in paraffin-embedded lymph node (LN) samples and BM samples using immunohistochemistry (IHC), immunocytochemistry (ICC), cytologic morphology and fluorescence in situ hybridization (FISH). The presence of the Bcl-2/IgH fusion gene in the BM samples and paraffin-embedded LN samples from 56 patients with follicular lymphomas was detected using FISH. The Bcl-2 protein levels in BM and paraffin-embedded tissues were quantified using ICC and IHC, respectively. Approximately 78.6% (44/56) of the paraffin‑embedded LN tissue sections that underwent FISH analysis had a bcl-2/IgH translocation. The primary lesion was also positive for the bcl-2/IgH fusion gene, as were the BM minimal infiltrates. The bcl-2/IgH rearrangement occurred in 88.6% (39/44) of the BM specimens. The bcl-2/IgH recombination rate in stage III/IV cancers was significantly different to that observed in stage I/II cancers (p=0.041). In 59% (23/39) of the cases with t(14;18), Bcl-2 was found to be present as assessed by ICC. Positive Bcl-2 ICC staining and the t(14;18) translocation (as detected using FISH) were positively correlated (p=0.028). We then applied the FISH method to slides that had previously been morphologically evaluated using Wright-Giemsa staining; any slides with at least one abnormal cell were subjected to FISH analysis following staining. The assessment of bcl-2/IgH translocation status may contribute to the better detection of minimal BM infiltration by FL cells. Utilizing FISH and cytologic morphology techniques allows for earlier and more accessible BM examination.

The impact of adefovir dipivoxil (ADV) treatment on the immune system in patients with chronic hepatitis B (CHB) is unknown. The present study was designed to determine the expression of six cytokines, IL-2, IFN-γ, TNF-α, IL-4, IL-6 and IL-10, and their correlation with liver functions and clinical responses to ADV treatment. A total of 22 CHB patients were treated with ADV at a daily oral dose of 10 mg. Six cytokines, as well as AST, ALT and HBV DNA levels in blood samples were quantified prior to and following the treatment. A total of 10 healthy volunteers were enrolled as the control group. The six cytokines in CHB patients were significantly lower than in healthy individuals, and were increased significantly following 4, 12 and 24 weeks of ADV treatment. Although ALT, AST and HBV DNA were reduced following treatment, no correlation was found between these six cytokines and liver function or HBV DNA levels. The levels of the six cytokines in the group of patients with a complete clinical response were significantly higher than those in the group with a partial clinical response. ADV treatment increases the immunity of Th1/Th2 cells in CHB patients, and the increases in cytokines partly reflect the efficacy of the antiviral treatment.