Galectin-9 contributes to the survival of fully allogeneic skin grafts by modulating effector T cells and Tregs imbalance.

Allogeneic skin transplantation is an important clinical treatment for many diseases. Although Galectin-9 demonstrates multifaceted roles in modulating immune cell homeostasis and inflammation, its precise impact on balancing effector T cells and Tregs during allogeneic skin transplantation remains uncertain. This work was performed to evaluate the modulation of the survival time of allogeneic skin grafts by Gal-9 and to explore the critical mechanism involved in this process. Skin graft transplantation was conducted using C57BL/6 and BALB/c mice. Additionally, the levels of IL-2, IFN-γ, IL-4, and IL-17A were measured. Hematoxylin and eosin staining assay was performed to analyze the pathological conditions of skin grafts of experiment mice. The results revealed that Gal-9 noticeably prolonged the survival of the allogeneic skin graft and ameliorated the damage caused by acute immune rejection. Furthermore, Gal-9 resulted in selective reduction of effectors T cells such as Th1, and Th17. Simultaneously, Gal-9 didn't attenuate the protective function for allograft, which alleviated the immune rejection caused by abnormal immune imbalance. Gal-9 exhibited a therapeutic effect on the allogeneic skin graft by selectively reducing CD4+TIM-3+ T effector cells and inducing a shift from a Th1 to an anti-inflammatory Th2 response. Furthermore, Gal-9 did not attenuate the protective function. Our present study may represent a novel therapeutic candidate for modulating effector T cells and Tregs imbalance-based therapy of allograft transplantation.

LNCRNA XIST Inhibits miR-377-3p to Hinder Th17 Cell Differentiation through Upregulating ETS1.

Background: Th17 cell differentiation is involved in the development and progression of many diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Present study mainly focused on the role of LINC-XIST in Th17 cell differentiation. Methods: The naïve CD4+ T cells were isolated from human whole blood. Cells were cultured under Th17 cell-polarizing condition for 6 days. The expression of LINC-XIST and miR-153-3p was measured by qPCR. The relationship between LINC-XIST, miR-153-3p, and ETS1 was predicted by TargetScan website and authenticated by luciferase reporter assay. ELISA assays were conducted to evaluate the IL-17 concentration. Western blot was utilized to measure the protein expression of ETS1. Th17 cell frequency was examined by flow cytometry. Results: The expression of XIST markedly decreased and miR-153-3p expression markedly increased with Th17 cell differentiation. The mRNA expression of IL-17, IL-17 concentration, and Th17 cell frequency were observably decreased in overexpressed LINC-XIST group. Luciferase reporter assay authenticated that miR-153-5p was directly regulated by LINC-XIST. miR-153-3p inhibitor observably decreased IL-17 concentration, mRNA expression of IL-17, and Th17 cell frequency while si-XIST reversed this impact. ETS1 was confirmed to be regulated by miR-153-5p via luciferase reporter assay. In addition, ETS1 markedly decreased IL-17 mRNA expression, IL-17 concentration, and Th17 cell frequency while miR-153-5p mimic reversed this impact. Conclusion: LNCRNA XIST inhibited miR-377-3p to hinder Th17 cell differentiation through upregulating ETS1.

Reconstruction of the hepatic artery using the superior mesenteric artery for liver transplantation.

BACKGROUND: To investigate the application of the superior mesenteric artery (SMA) for the in vitro reconstruction of the hepatic artery for liver transplantation, and to improve the success rate and safety of donor liver transplantation. METHODS: The donor liver and the pancreas were obtained, and the SMA and its branches were used to reconstruct the hepatic artery. Liver transplantation was performed after reconstruction to understand the intraoperative situation after donor liver opening, as well as postoperative liver function. Color Doppler ultrasound of the transplanted liver was also performed. RESULTS: During the period from September 2016 to March 2020, a total of 98 pancreases were obtained. The common hepatic artery and gastroduodenal artery loop (CHA-GDA) were preserved to the donor pancreas, and only the proper hepatic artery (PHA) or left/right hepatic artery (LHA/RHA) were preserved to the donor liver. If the PHA of the donor liver was short or absent, the SMA was used for lengthening the PHA or in vitro reconstruction of the LHA/RHA, followed by implantation of the donor liver after reconstruction. A total of 17 cases of this type of donor liver required mesenteric artery lengthening or reconstruction. After opening, the donor liver was well-filled, bile secretion was normal, and liver function recovered as scheduled after surgery. Color Doppler ultrasound and CT angiography (CTA) of the transplanted liver revealed that hepatic arteries were normal without complications such as hepatic artery embolism. CONCLUSIONS: In vitro reconstruction of the hepatic artery with the SMA is an effective new method of vascular reconstruction, which ensures the blood flow of the hepatic artery, reduces the anastomosis difficulty of the arteries of the donor liver, and reduces the occurrence of vascular complications.

CD4+ T Cell Immune Response to VP1 and VP3 in BK Virus Infected Recipients of Renal Transplantation.

OBJECTIVE: To investigate the characteristics of BK virus (BKV) specific cellular immune response in the recipients who have early infection with BKV after renal transplantation. METHODS: The recipients of renal allografts (n = 30) were divided into groups of BK virus nephropathy (BKVN), viruria, and viremia. The BKV load was observed with real-time fluorescence quantitative polymerase chain reaction in urine and blood every three months. The values of serum creatinine (SCr) were detected. The peripheral blood mononuclear cells (PBMCs) were cultivated with overlapping peptide pool containing BKV structural proteins VP1, VP2, and VP3, and regulatory proteins large tumor antigen (LT-Ag) and small tumor antigen (st-Ag), to stimulate in vitro specific cellular immunoresponse. Flow cytometry was used to measure the proliferation of CD3+/CD4+/CD8+ T and interferon [INF]-γ/interleukin [IL]-2/tumor necrosis factor [TNF]-α T cell subsets. RESULTS: The BKV infection increased SCr values in recipients of renal transplantation. CD4+ T cells were dominant (>90%) in the in vitro cellular immunoresponse to VP1, VP2, VP3, LT-Ag, and st-Ag. At the presence of viremia and BKVN, IL-2/IFN-γ+/TNF-α+ CD4+ T cells showed significantly decreased in vitro cellular immunoresponse to VP1, VP2, and VP3 (p < 0.05), but insignificantly changed to LT-Ag and st-Ag (p > 0.05). For the cases of viruria and viremia, IL-2/IFN-γ+/TNF-α+ CD4+ T cells showed significantly higher in vitro cellular immunoresponse to VP1, VP2, and VP3 than to LT-Ag and st-Ag (p < 0.05). The immunogenicity of VP1 and VP3 was significantly higher than that of VP2 (p < 0.05). CONCLUSIONS: The BKV infection increases SCr values, and CD4+ T cells are dominant in the in vitro BKV specific cellular immunoresponse in the recipients of renal transplantation. Viremia significantly decreased the immunoresponse to VP1, VP2, and VP3. There is the significantly stronger immunoresponse to VP1 and VP3 when compared with that to VP2, LT-Ag, and st-Ag, suggesting that VP1 and VP3 may be the major targets for the BKV specific immune response.

Ectopic expression of E3 ubiquitin-protein ligase 2 in glioma and enhances resistance to apoptosis through activating nuclear factor κ-light-chain-enhancer of B cells.

Nuclear factor κ-light-chain-enhancer of B cells (NF-κB) is one of the most important tumorigenic factors. Although it has been established that NF-κB is overly activated in human glioma cells, the molecular mechanisms that lead to the signal transduction to NF-κB and thereby the induction of resistance to apoptosis remain poorly understood. The present study demonstrated that mRNA and protein levels of E3 ubiquitin-protein ligase 2 (MIB2) were markedly upregulated in glioma cell lines and clinical samples. Immunohistochemical analysis also revealed high levels of MIB2 expression in glioma specimens. Ectopic overexpression of MIB2 was established in glioma cell lines to investigate its fundamental roles in the response of human glioma to apoptotic inducers. The results indicated that ultraviolet irradiation-induced cell apoptosis was inhibited with MIB2 overexpression in glioma cells. Notably, knockdown of MIB2 using RNA interference was able to increase the sensitivity of glioma cells to the pro-apoptotic agents. The present study identified that MIB2 induces NF-κB activation and facilitates the resistance of glioma cell to apoptosis. It was proposed that MIB2 may not only be an important hallmark to glioma disease progression, but that it may also offer novel clinical strategies to overcome resistance to cancer therapies.

The promotion of tissue engineering blood vessel patency by CGS21680 through regulating pro-inflammatory activities of endothelial progenitor cell.

The mobilization and homing of endothelial progenitor cells (EPCs) contribute to the rapid endothelialization of tissue engineering blood vessel (TEBV). Inflammation can affect TEBV patency, and monocytes/macrophages (MM) are the main effector cells. But it is not clear how EPCs interact with MM after TEBV transplantation. Our results showed acellular materials would not directly cause acute and severe inflammatory responses but activate E-selectin expression in homing EPCs, gradually promoting the polarization of MM to the M1. Adenosine A2a receptor agonist CGS21680 promoted the secretion of more proangiogenic factors from MM, inducing EPC migration and mobilization. CGS21680 could inhibit MM polarization to the M1 type through the down-regulation of EPC proinflammatory molecules, such as E-selectin. Chitosan/(2-hydroxypropyl)-ß-cyclodextrin nanoparticles were prepared to control the release of CGS-21680 and then modified to TEBVs through layer-by-layer assembly. Animal experiments showed that this TEBV can maintain patency for 6 months and good endothelialization was observed. In summary, our results showed the regulation of EPC pro-inflammatory activities is a new approach to enhance TEBV patency. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2634-2642, 2018.

mTOR masters monocyte development in bone marrow by decreasing the inhibition of STAT5 on IRF8.

Monocytes and macrophages play a key role in defending pathogens, removing the dead cells or cell debris, and wound healing. The mammalian target of rapamycin (mTOR) inhibitor rapamycin (RPM) is widely used in clinics to treat patients with organ transplantation or tumors. The role of mTOR in monocyte/macrophage development remains to be clarified. Here we found that mTOR intrinsically controls monocyte/macrophage development, as evidenced by the decreased percentages and cell numbers of CD11b+F4/80+ cells resulting from mTOR inhibition in SCID mice, mTOR-deficient mice, and mixed chimera mice, and the in vitro colony formation and monocyte/macrophage induction assays. However, Lyzs-mTOR knockout mice displayed normal levels of monocytes/macrophages, indicating that mTOR is not essential for the survival and maturation of monocytes/macrophages. Further studies showed that mTOR deficiency significantly reduced macrophage colony-stimulating factor receptor CD115 expression at the transcriptional and translational levels. The molecular mechanism studies indicate that the impaired monocyte/macrophage development caused by mTOR deficiency is mainly a result of the overactivated STAT5 and subsequent downregulation of IRF8, but not the altered cell metabolism and autophagy. Therefore, our work identifies that mTOR is an intrinsic master for monocyte/macrophage development at the early stages through regulating STAT5-IRF8-dependent CD115-expressing pathway. Long-term usage of RPM may cause a defect of myeloid progenitors in bone marrow.

Exosome-Modified Tissue Engineered Blood Vessel for Endothelial Progenitor Cell Capture and Targeted siRNA Delivery.

Instability and poor targeting causes the long-term patency of RNA-modified tissue engineering blood vessels (TEBVs) remaining unsatisfactory. RNA can be enriched in exosome and then delivered into targeted cells while whether exosome-modified TEBVs achieve RNA targeted delivery is unclear. Here, to promote the expression of klotho protein on the mesenchymal stem cell (MSC)-derived exosomes, klotho plasmids are first transfected into MSCs, and adenosine kinase (ADK) siRNA is then loaded into exosome (klotho/ADK siRNA-exosome) using electrotransfection. Flow chamber results show that klotho/ADK siRNA-exosome can effectively capture circulating endothelial progenitor cells (EPCs). Besides, the captured EPCs can endocytose this exosome, and then decompose it into klotho protein and ADK siRNA. Moreover, ADK siRNA promotes the paracrine of proangiogenic factors and adenosine from EPCs, which further facilitate proliferation and migration of endothelial cells. Based on polyethyleneimine-capped gold nanoparticles, exosome-modified TEBVs are constructed through layer-by-layer assembly. Animal experimental results show that klotho/ADK siRNA-exosome-modified TEBVs can maintain the patency up to one month, and good endothelialization is observed. In short, one exosome-modified TEBV is constructed, capture molecules on the surface of exosome capture the circulating EPCs, and the loaded RNA achieves its purpose of accurate treatment depending on the needs of patients.

Clinical significance of p16INK4A and p14ARF promoter methylation in renal cell carcinoma: a meta-analysis.

The inactivation of p16INK4A and p14ARF via promoter methylation has been investigated in various cancers. However, the clinical effects of p16INK4A and p14ARF promoter methylation on renal cell carcinoma (RCC) remain to be clarified. The pooled data were calculated and summarized. Finally, an investigation of 14 eligible studies with 1231 RCC patients and 689 control patients was performed. Methylated p16INK4A and p14ARF were observed to be significantly higher in RCC than in control subjects without malignancies (OR = 2.77, P = 0.005; OR = 11.73, P < 0.001, respectively). Methylated p16INK4A was significantly associated with the risk of RCC in the tissue subgroup, but not in the serum and urine subgroups. Methylated p16INK4A was significantly associated with tumor size. We did not find that p16INK4A promoter methylation was associated with sex, tumor grade, lymph node status, and tumor histology. Methylated p14ARF was significantly correlated with sex and tumor histology. Three studies reported that p16INK4A methylation was not significantly correlated with the prognosis of RCC. The results suggested that p16INK4A and p14ARF promoter methylation may be correlated with the carcinogenesis of RCC, and that methylated p14ARF , especially, can be a major susceptibility gene. We also found the different clinicopathological significance of 16INK4A and p14ARF in RCC. Additional studies with sufficient data are essential to further evaluate the clinical features and prognostic effect of p16INK4A and p14ARF promoter methylation in RCC.

Expression and genetic polymorphism of necroptosis related protein RIPK1 is correlated with severe hepatic ischemia-reperfusion injury and prognosis after hepatectomy in hepatocellular carcinoma patients.

OBJECTIVES: The goal of our study was to assess the prognostic impact of the necroptosis relative protein RIPK1 genetic polymorphism in ischemia-reperfusion injury and survival after hepatectomy in hepatocellular carcinoma (HCC) patients. METHODS: In this study, expression of RIPK1 and its genetic polymorphism(rs2272990) were examined in plasma of 44 HCC patients. All these patients were undergoing partial hepatectomy. The prognostic values of RIPK1 genetic polymorphism for tumor development and survival, and ischemia-reperfusion injury after hepatectomy were further determined. RESULTS: Plasma RIPK1 expressions were significantly increased in HCC patients, compared to the healthy control group. Totally 19 patients have the GA + AA genotype in the RIPK1 rs2272990 SNP site and 25 have GG genotype. There were no statistically significant intergroup differences observed in age, gender, AFP value, HBV positive, tumor size or cirrhosis. GG genotype had positive correlation with TNM classification (p= 0.033) and lymphatic metastasis (p= 0.027) and was significantly associated with severe hepatic ischemia-reperfusion injury and decreased survival rate after hepatectomy. CONCLUSION: In conclusion, the RIPK1 polymorphism is an indicator of hepatic injury and a novel prognostic biomarker for tumor development and survival of HCC recipients after hepatectomy.

Association Between Overweight and Renal Transplant Outcomes: A Meta-Analysis.

OBJECTIVES: As the demand for kidney transplant allografts has increased, many centers are expanding the upper limit of acceptable body mass index for kidney donors. However, obesity is a risk factor for developing renal disease. Our goal was to quantify body mass index trends in donor nephrectomy patients and to institute nutrition counseling to promote sustainable weight loss to reduce the risk of metabolic syndrome-derived renal dysfunction. MATERIALS AND METHODS: Ninety patients who underwent donor nephrectomy between 2007 and 2012 consented to having height and weight data collected at multiple time points. After data collection, each patient underwent a standardized nutrition counseling session. One year later, body mass index was reassessed. RESULTS: Preoperatively, 52% of the patients were overweight or obese. The percentage of overweight and obese patients remained stable for 2 years after surgery. However, at 3, 4, and 5 years after surgery, these rates increased to 59%, 69%, and 91%. Each patient was counseled about obesity-related comorbidities and provided information about lifestyle modification. One year later, 94% of previously overweight patients and 82% of previously obese patients had a decrease in mean body mass index from 27.2 ± 4.0 kg/m2 to 25.1 ± 3.6 kg/m2. CONCLUSIONS: Living-donor nephrectomy patients are at risk of developing obesity, similar to the adult population. Nutrition counseling may be beneficial to help normalize body mass index in patients who have become overweight or obese to potentially prevent obesity-related comorbidities. All patients were evaluated by a nutrition specialist after surgery to review our donor nephrectomy nutrition brochure. Body mass index monitoring and primary care follow-up appear to be appropriate surveillance methods.

Prostate cancer downregulated SIRP-α modulates apoptosis and proliferation through p38-MAPK/NF-κB/COX-2 signaling.

The present study investigated the regulatory mechanism of signal-regulatory protein (SIRP)-α in the apoptosis and proliferation of prostate cancer (CaP) cells. The expression profile of SIRP-α in prostate cancer cells was analyzed using reverse transcription-quantitative polymerase chain reaction and western blotting. Then SIRP-α function in CaP cells was further analyzed with the overexpression and RNA interference of SIRP-α. The results revealed that SIRP-α expression levels were decreased in CaP tissues and cell lines, with androgen-independent CaP exhibiting a lower SIRP-α expression compared with androgen-dependent CaP. Overexpression of SIRP-α resulted in a significantly reduced number of live CaP cells by enhancing apoptosis, whereas SIRP-α silencing increased CaP cell proliferation. Mechanistically, SIRP-α decreases cyclooxygenase-2 (COX-2) expression and cytokine production by negatively regulating p38 mitogen-activated protein kinase and nuclear factor-κB pathway. Therefore, SIRP-α knockdown decreases cell apoptosis by enhancing COX-2 expression. The present results indicate that SIRP-α may function as a novel negative regulator to modulate cellular proliferation, survival and migration in CaP cells. The heightened sensitivity of cells restoring SIRP-α function could be exploited in the development of therapeutics that may potentiate the antineoplastic effects of conventional cytokines or chemotherapeutic agents.

Phenotype, development, and biological function of myeloid-derived suppressor cells.

CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs) are an important population of innate regulatory cells mainly comprising monocytic MDSCs (M-MDSCs) with a phenotype of CD11b+Ly6G-Ly6Chigh and granulocytic MDSCs (G-MDSCs) with a phenotype of CD11b+Ly6G+Ly6Clow in mice. They play crucial roles in the pathogenesis of cancers, chronic infections, autoimmune diseases, and transplantation. Various extracellular factors such as lipopolysaccharide (LPS), macrophage colony-stimulating factor (M-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), stem cell factor (SCF), interleukin (IL)-6, interferon gamma (IFNγ), IL-1ß, vascular endothelial growth factor (VEGF), Hsp72, IL-13, C5a, and prostaglandin E2 (PGE2) can induce MDSC differentiation, whereas IL-4 and all-trans-retinoic acid can inhibit this process. For the intracellular signals, signal transducer and activator of transcription (STAT) family members, C/EBPß and cyclooxigenase-2 (COX-2) promote MDSC function, whereas interferon regulatory factor-8 (IRF-8) and Smad3 downregulate MDSC activity. The immunosuppressive function of MDSCs is mediated through various effector molecules, primarily cellular metabolism-related molecules such as nitric oxide (NO), arginase, reactive oxygen species (ROS), transforming growth factor ß (TGFß), IL-10, indoleamine 2,3-dioxygenase (IDO), heme oxygenase-1 (HO-1), carbon monoxide (CO), and PGE2. In this article, we will summarize the molecules involved in the induction and function of MDSCs as well as the regulatory pathways of MDSCs.

Characterisation of Tertiary Lymphoid Organs in Explanted Rejected Donor Kidneys.

PURPOSE: Tertiary lymphoid organs (TLOs) have been described within organ allografts, but whether they promote destructive or beneficial alloimmune responses remains controversial. This study aimed to characterize TLO distribution in human chronically rejected renal allografts and to explore their functions. METHODS: A total of 29 explanted chronically rejected and 12 acutely rejected renal allografts were analyzed by immunohistochemistry. The distribution of TLOs, T cells, follicular dendritic cells, B cells, and follicular regulatory T (Tfr) cells, as well as Ki67, peripheral lymph node addressin (PNAd), podoplanin, AID, IL-17, IL-21, IL-10, and C4d expression were detected by immunohistochemistry. Correlations between lymphoid neogenesis and the expression of IL-17, IL-21, C4d, podoplanin, IL-10, and Foxp3 were evaluated. In addition, the duration of graft function was compared between allografts that harbored or lacked TLOs. RESULTS: TLOs were detected in 27.6% of chronically rejected renal grafts, but they rarely had germinal centers. Lymphoid neogenesis negatively correlated with CXCR5 expression, and almost completely correlated with IL-17 expression. Those grafts that harbored a TLO functioned for an average of 5.98 years and those without a TLO lasted only about half as long with an average of 2.91 years. However, in grafts that harbored a TLO, Foxp3(+) cells were comparitively less than those without a TLO. Foxp3(+)CXCR5(+) Tfr cells and IL-10(+) cells were rare in grafts, irrespective of the presence of a TLO. CONCLUSION: TLOs in chronically rejected kidney allografts may be an epiphenomenon of the inflammatory process that is related to graft duration.

Renal graft biopsy assists diagnosis and treatment of renal allograft dysfunction after kidney transplantation: a report of 106 cases.

Acute antibody mediated rejection (AMR) is one of the most important complications after kidney transplantation. Renal graft biopsy is safe and reliable without adverse effects on the patients and transplanted kidneys, which was of great instructive significance in diagnosis and treatment of renal allograft dysfunction after renal transplantation. This paper reported a case series of 106 patients underwent renal allograft biopsies. All biopsies were evaluated according to the Banff 2007 schema. 52 examples were obtained within 1 month after transplantation, and there were another 20 examples in one to two months and other 34 examples in two to three months. Appropriate therapy was applied and clinical outcomes were observed. All patients received renal biopsies and anti-inflammatory and hemostasis treatment without complications. There were 2 cases of hyperacute rejection, and 15 cases of acute AMR. All Paraffin-embedded samples were stained by HE, periodic acid-Schiff (PAS), Masson, and immunohistochemistry (C4d, cd20, cd45RO, SV40). All samples were found C4d immunohistochemical staining positive. Patients with acute AMR were managed by steroid intravenous pulse therapy, Rabbit anti-thymocyte globulin intravenous pulse therapy, anti CD20 monoclonal antibody intravenous therapy and so on. Two cases of hyperacute rejection had renal failure, and received kidney excision; 12 cases in 15 cases of AMR recovered, another 2 cases did not recover with high-level creatine, and other 2 cases of renal allograft received excision.

Effectiveness and safety of calcineurin inhibitor withdrawal in kidney transplantation: a meta-analysis of randomized controlled trials.

BACKGROUND: The purpose was to compare the effectiveness and safety of calcineurin inhibitors (CNIs) withdrawal and continued therapies in kidney transplant recipients. METHODS: We searched the PubMed, MEDLINE, Springer, Elsevier Science Direct, Cochrane Library and Google Scholar up to May 2014. Risk ratio (RR) or weighted mean difference (WMD) and their 95 % confidence intervals (CIs) were calculated in fixed-effects model or random-effects model when appropriate. Besides, sensitivity analysis was performed based on the addition of sirolimus in initial immunosuppression protocols. RESULTS: Total seven studies with 1071 kidney transplant recipients received CNIs withdrawal therapy (experimental group) and 792 kidney transplant recipients received CNIs continued therapy (control group) were included in the meta-analysis. The overall estimates of acute rejection rate (RR = 1.64, 95 % CI: 1.19-2.27, P = 0.003), mean measured glomerular filtration rate (WMD = 9.50, 95 % CI = 2.96-16.03, P = 0.004), thrombocytopenia (RR = 3.39, 95 % CI: 2.27-5.05, P < 0.00001) and hypertension (RR = 0.56, 95 % CI: 0.40-0.78, P = 0.0006) showed that there were significant differences between the CNIs withdrawal and continued therapies in kidney transplant recipients, while no significant differences were found between groups in survival rate, graft survival rate, diabetes, hypercholesterolemia, hypertriglyceridemia and malignancies. In addition, two studies, in which sirolimus was not used in initial immunosuppression protocol, were excluded in sensitivity analysis and the results were still consistent with the overall analysis. CONCLUSIONS: CNIs withdrawal therapy in kidney transplant recipients could significantly decrease risk of hypertension and improve glomerular filtration rate, accompanying with increased risk of acute rejection and thrombocytopenia, compared with the CNIs continued therapy.

[Expression of T lymphocyte cytokines in peripheral blood of renal transplant recipients].

OBJECTIVE: To evaluate the clinical values of T-lymphocyte cytokines in renal transplant acute rejection. METHODS: A total of 31 recipients with renal transplantation and 15 healthy volunteers from January 2010 to January 2012 were enrolled and divided into acute rejection group (n = 11) and stable renal allograft function group (n = 20) according to the inclusion criteria. Peripheral blood was collected from the patients before transplantation, 1, 7, 14, 28 day after transplantation and acute rejection onset. Cytometric bead array (CBA) was used to monitor the levels of interleukin-17 (IL-17), interferon-gamma (IFN-γ), tumor necrosis factor (TNF), interleukin(IL)-10, IL-6, IL-4 and IL-2. The associations of the changes and levels of cytokines in 3 groups were examined with Pearson correlation analysis. RESULTS: The levels of IL-17A, TNF, IL-10 and IL-2 in recipients before transplantation were (3.40 ± 1.29) , (1.79 ± 0.53) , (2.73 ± 0.65) and (1.79 ± 1.02) ng/L respectively and decreased significantly compared to healthy volunteers ((4.52 ± 2.01), (3.36 ± 1.09) , (3.91 ± 0.42) , (3.12 ± 1.07) ng/L respectively, all P < 0.05). However the levels of IFN-γ, IL-6 and IL-4 showed no significant changes between two groups (all P > 0.05). In acute rejection group after transplantation, the levels of IL-17A, IFN-γ, IL-10 and IL-6 were (9.47 ± 4.75) , (5.01 ± 2.23) , (12.20 ± 5.79) , (6.55 ± 3.45) ng/L respectively and increased significantly compared to the renal allograft function group ((4.39 ± 1.26), (2.90 ± 0.87),(5.68 ± 2.25) and (2.10 ± 0.70) ng/L respectively, all P < 0.05); the level of IL-17A was correlated with those of IFN-γ and IL-4 (Pearson r = 0.519, 0.395, both P < 0.01), the level of IFN-γ was correlated with those of IL-4 and IL-2 (r = 0.276, 0.335, all P < 0.05) , the level of TNF was correlated with that of IL-4 (r = 0.423, P < 0.05) and the level of IL-10 was correlated with that of IL-6 (r = 0.361, P < 0.05). CONCLUSIONS: Cytokines play an important role in acute rejection of renal transplant. And further understanding of its mechanism may provide experimental and preventive rationales.

Serum levels of CXCR3 ligands predict T cell-mediated acute rejection after kidney transplantation.

The early diagnosis of acute rejection is crucial for graft survival after kidney transplantation. The interferon-γ (IFNγ)-CXCR3-chemokine-dependent inflammatory loop plays a pivotal role in the recruitment of T lymphocytes during acute rejection. Previously published studies have typically focused on the CXCR3 receptor rather than on its ligands. In the present study, we used Luminex assays to detect the levels of CXCR3 ligands, monokine induced by IFNγ (MIG), IFN-induced protein 10 (IP-10) and IFN-induced T­cell chemoattractant (I-TAC), in the serum of renal allograft recipients. According to a renal biopsy performed one month after kidney transplantation, 32 recipients were diagnosed with T cell-mediated acute rejection and 38 patients were evaluated as stable. Serum was collected after the diagnosis of acute rejection or one month after transplantation. The concentrations of MIG (median, 4,271 pg/ml), IP-10 (median, 686.7 pg/ml) and I-TAC (median, 44.32 pg/ml) in the serum during an acute rejection episode were significantly higher compared with those of the stable patients (MIG, P=0.0002; IP-10, P=0.0001; I-TAC, P=0.0103; vs. the stable function group, P<0.05). Based on the receiver-operating characteristic (ROC) curve, the joint detection of MIG, IP-10 and I-TAC in the serum using Luminex analysis may constitute a non-invasive and efficient method for the early prediction of T cell-mediated acute rejection following kidney transplantation.

Dynamic expression changes between non-muscle-invasive bladder cancer and muscle-invasive bladder cancer.

AIMS AND BACKGROUND: Despite elaborate characterization of the risk factors, bladder cancer is still a major epidemiological problem whose incidence continues to rise each year. We aim to investigate the dynamic expression changes between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). METHODS: The gene expression profile GSE13507 was obtained from the Gene Expression Omnibus, and the R package was used to identify gene expression signatures (GESs) between NMIBC and MIBC. Gene ontology enrichment analysis was performed for GES function analysis. We used miRTarBase and TargetScan to identify the differentially regulated microRNAs, and TfactS to identify transcription factors between NMIBC and MIBC. Bionet was used to identify the differentially expressed subnetwork. RESULTS: A total of 802 upregulated NMIBC GESs and 668 downregulated MIBC GESs were identified. Functional enrichment analysis revealed that the MIBC GESs were majorly involved in cell cycle and inflammatory response. miR-29c and miR-9 were regarded as key microRNAs in MIBC. SMAD3 in MIBC and SMAD5 and SMAD7 in NMIBC were potential activated transcription factors. In addition, a subnetwork that was considered to capture the differences between MIBC and NMIBC was identified, of which GRB2 and UBC were the hub nodes. CONCLUSIONS: Some key microRNAs, activated transcription factors and hub nodes have been identified in this study, which may be used as potential biomarkers or targets for the diagnosis, treatment and detection of bladder cancer at different stages.

The association between fish consumption and risk of renal cancer: a meta-analysis of observational studies.

BACKGROUND: Several case-control studies and cohort studies have investigated the association between fish intake and renal cancer risk, however, they yielded conflicting results. To our knowledge, a comprehensive assessment of the association between fish consumption and risk of renal cancer has not been reported. Hence, we conducted a systematic literature search and meta-analysis to quantify the association between fish consumption and renal cancer. METHODS: A systematic search was performed using the PubMed, Embase, and Cochrane Library Central database for case-control and cohort studies that assessed fish intake and risk of renal cancer. Two authors independently assessed eligibility and extracted data. Fixed-effect and random-effect models were used to estimate summary relative risks (RR) and the corresponding 95% confidence intervals (CIs). Subgroup analyses, sensitivity analysis and cumulative meta-analysis were also performed. RESULTS: A total of 12 case-control studies and three cohort studies published between 1990 and 2011 were included in the meta-analysis, involving 9,324 renal cancer cases and 608,753 participants. Meta-analysis showed that fish consumption did not significantly affect the risk of renal cancer (RR=0.99, 95% CI [0.92,1.07]). In our subgroup analyses, the results were not substantially affected by study design, region, gender, and confounder adjustments. Furthermore, sensitivity analysis confirmed the stability of results. CONCLUSIONS: The present meta-analysis suggested that there was no significant association between fish consumption and risk of renal cancer. More in-depth studies are warranted to report more detailed results, including stratified results by fish type, preparation method, and gender.