A prediction model of delayed graft function in deceased donor for renal transplant: a multi-center study from China.

BACKGROUND: Kidneys obtained from deceased donors increase the incidence of delayed graft function (DGF) after renal transplantation. Here we investigated the influence of the risk factors of donors with DGF, and developed a donor risk scoring system for DGF prediction. METHODS: This retrospective study was conducted in 1807 deceased kidney donors and 3599 recipients who received donor kidneys via transplants in 29 centers in China. We quantified DGF associations with donor clinical characteristics. A donor risk scoring system was developed and validated using an independent sample set. RESULTS: The incidence of DGF from donors was 19.0%. Six of the donor characteristics analyzed, i.e., age, cause of death, history of hypertension, terminal serum creatinine, persistence of hypotension, and cardiopulmonary resuscitation (CPR) time were risk factors for DGF. A 49-point scoring system of donor risk was established for DGF prediction and exhibited a superior degree of discrimination. External validation of DGF prediction revealed area under the receiver-operating characteristic (AUC) curves of 0.7552. CONCLUSIONS: Our study determined the deceased donor risk factors related to DGF after renal transplantation pertinent to the Chinese cohort. The scoring system developed here had superior diagnostic significance and consistency and can be used by clinicians to make evidence-based decisions on the quality of kidneys from deceased donors and guide renal transplantation therapy.

Elimination of donor CD47 protects against vascularized allograft rejection in mice.

CD47 is a ubiquitously expressed transmembrane glycoprotein that plays a complex role in regulation of cell survival and function. We have previously shown that the interspecies incompatibility of CD47 plays an important role in triggering rejection of cellular xenografts by macrophages. However, the role of CD47 in solid organ transplantation remains undetermined. Here, we explored this question in mouse models of heart allotransplantation. We observed that the lack of CD47 in donor hearts had no deleterious effect on graft survival in syngeneic or single MHC class I-mismatched recipients, in which both wild-type (WT) and CD47 knockout (CD47 KO) mouse hearts survived long term with no sign of rejection. Paradoxically, elimination of donor CD47 was beneficial for graft survival in signal MHC class II- and class I- plus class II-mismatched combinations, in which CD47 KO donor hearts showed significantly improved survival compared to WT donor hearts. Similarly, CD47 KO donor hearts were more resistant than WT hearts to humoral rejection in α1,3-galactosyltransferase-deficient mice. Moreover, a significant prolongation of WT allografts was observed in recipient mice treated with antibodies against a CD47 ligand thrombospondin-1 (TSP1) or with TSP1 deficiency, indicating that TSP1-CD47 signaling may stimulate vascularized allograft rejection. Thus, unlike cellular transplantation, donor CD47 expression may accelerate the rejection of vascularized allografts.

Fenofibrate inhibits mTOR-p70S6K signaling and simultaneously induces cell death in human prostate cancer cells.

Fenofibrate is the most widely used lipid-lowering drug, but it seems to have anti-tumor effects in several tumor cell lines. However, there are only a few reports on its effects on human prostate cancer cells. Thus, we investigated the anti-proliferative effects of fenofibrate on human prostate cancer cells and potential mechanisms. The methods used include cell viability analysis with an MTT assay, as well as apoptosis and related signaling pathway analyses with flow cytometry and Western blotting. Fenofibrate inhibited PC-3 cell growth in dose- and time-dependent manners. The fenofibrate-induced cell death is predominantly apoptotic death that is mediated by both the caspase-3 activation and apoptosis-inducing factor (AIF) signaling pathways. Fenofibrate also increased the expression of Bad and decreased the expression of Bcl-2 and Survivin. Mechanistically, fenofibrate-induced cell death was associated with decreased p-p70S6K and the mammalian target of rapamycin (mTOR) phosphorylation levels. When further exploring the upstream mediators of mTOR/p70S6K, we found that fenofibrate increased p38 MAPK and AMPK phosphorylation but did not significantly change the phosphorylation levels of PI3K, AKT, and JNK. However, the inhibition of either p38 MAPK or AMPK with their specific inhibitor did not change the effect of fenofibrate-induced cell death. These findings suggested that fenofibrate indeed significantly inhibited the proliferation of PC-3 cells via apoptotic action, which is associated with the inactivation of the mTOR/p70S6K-dependent cell survival pathway. Although the mechanisms by which fenofibrate inactivates this pathway remains unclear, this study reveals great potential for its use for the clinical treatment of prostate cancers.

Lower pole approach in retroperitoneal laparoscopic radical nephrectomy: a new approach for the management of renal vascular pedicle.

BACKGROUND: The objective of this study was to examine the effectiveness and safety of lower pole (LP) approach in retroperitoneal laparoscopic radical nephrectomy (LRN). METHODS: One hundred thirty-two renal cancer patients were scheduled for selective retroperitoneal LRN. The surgery parameters and outcomes were compared. Out of 132 patients, 78 (59.1%) patients underwent LRN via LP approach, while 54 (40.9%) patients underwent LRN via lateroposterior space (LPS) approach. RESULTS: Compared to LPS group, the LP group had a higher body mass index (27.0 ± 1.7 kg/m2 vs. 24.5 ± 1.8 kg/m2, P <  0.0001) and a larger tumor size (6.9 ± 3.5 cm vs. 4.1 ± 3.3 cm, P <  0.0001). The LP approach reduced the volumes of blood loss and transfusion significantly (135.3 ± 17.2 mL vs. 219.6 ± 30.9 mL, P <  0.0001; 55.6 ± 28.3 vs. 141.1 ± 50.4 mL, P <  0.0001) as compared to the LPS approach. The LP approach also decreased the risk of conversion to open procedure (1.3 vs. 7.4%, P <  0.05). CONCLUSIONS: The LP approach is an effective and safe alternative to the LPS approach for retroperitoneal LRN and might be more suitable for patients with obesity, large tumors, tumors located at the medial part of the kidney, or renal pedicular adhesion.

Distributed ISAR Subimage Fusion of Nonuniform Rotating Target Based on Matching Fourier Transform.

In real applications, the image quality of the conventional monostatic Inverse Synthetic Aperture Radar (ISAR) for the maneuvering target is subject to the strong fluctuation of Radar Cross Section (RCS), as the target aspect varies enormously. Meanwhile, the maneuvering target introduces nonuniform rotation after translation motion compensation which degrades the imaging performance of the conventional Fourier Transform (FT)-based method in the cross-range dimension. In this paper, a method which combines the distributed ISAR technique and the Matching Fourier Transform (MFT) is proposed to overcome these problems. Firstly, according to the characteristics of the distributed ISAR, the multiple channel echoes of the nonuniform rotation target from different observation angles can be acquired. Then, by applying the MFT to the echo of each channel, the defocused problem of nonuniform rotation target which is inevitable by using the FT-based imaging method can be avoided. Finally, after preprocessing, scaling and rotation of all subimages, the noncoherent fusion image containing all the RCS information in all channels can be obtained. The accumulation coefficients of all subimages are calculated adaptively according to the their image qualities. Simulation and experimental data are used to validate the effectiveness of the proposed approach, and fusion image with improved recognizability can be obtained. Therefore, by using the distributed ISAR technique and MFT, subimages of high-maneuvering target from different observation angles can be obtained. Meanwhile, by employing the adaptive subimage fusion method, the RCS fluctuation can be alleviated and more recognizable final image can be obtained.

Fenofibrate increases cardiac autophagy via FGF21/SIRT1 and prevents fibrosis and inflammation in the hearts of Type 1 diabetic mice.

Fenofibrate (FF), as a peroxisome-proliferator-activated receptor α (PPARα) agonist, has been used clinically for decades to lower lipid levels. In the present study, we examined whether FF can be repurposed to prevent the pathogenesi of the heart in Type 1 diabetes and to describe the underlying mechanism of its action. Streptozotocin (STZ)-induced diabetic mice and their age-matched control mice were treated with vehicle or FF by gavage every other day for 3 or 6 months. FF prevented diabetes-induced cardiac dysfunction (e.g. decreased ejection fraction and hypertrophy), inflammation and remodelling. FF also increased cardiac expression of fibroblast growth factor 21 (FGF21) and sirtuin 1 (Sirt1) in non-diabetic and diabetic conditions. Deletion of FGF21 gene (FGF21-KO) worsened diabetes-induced pathogenic effects in the heart. FF treatment prevented heart deterioration in the wild-type diabetic mice, but could not do so in the FGF21-KO diabetic mice although the systemic lipid profile was lowered in both wild-type and FGF21-KO diabetic mice. Mechanistically, FF treatment prevented diabetes-impaired autophagy, reflected by increased microtubule-associated protein 1A/1B-light chain 3, in the wild-type diabetic mice but not in the FGF21-KO diabetic mice. Studies with H9C2 cells in vitro demonstrated that exposure to high glucose (HG) significantly increased inflammatory response, oxidative stress and pro-fibrotic response and also significantly inhibited autophagy. These effects of HG were prevented by FF treatment. Inhibition of either autophagy by 3-methyladenine (3MA) or Sirt1 by sirtinol (SI) abolished FF's prevention of HG-induced effects. These results suggested that FF could prevent Type 1 diabetes-induced pathological and functional abnormalities of the heart by increasing FGF21 that may up-regulate Sirt1-mediated autophagy.

Hypothermic Machine Perfusion in DCD Kidney Transplantation: A Single Center Experience.

INTRODUCTION: Donation after cardiac death (DCD) began in 2011 after the program hosted by the First Affiliated Hospital of Sun Yat-sen University in China. The aim of this study is to report on our experience regarding the method of preserving donated kidneys for DCD kidney transplantation. MATERIAL AND METHODS: A total of 37 donors and 73 primary kidney transplant recipients during the period 2011-2014 in the Urology Center of the First Hospital of Jilin University were enrolled in the study. Recipients were assigned to traditional static cold storage (SCS) group and hypothermic machine perfusion (HMP) group based on the preservation environment of donated kidneys after organ harvest. Clinical data were collected for each group. RESULT: The HMP group had a lower rate of delayed graft function (DGF), better postoperative recovery and kidney function compared with that of SCS group. There is no significant difference in postoperative rejection incidence between the 2 groups. CONCLUSIONS: DCD kidneys stored by hypothermic machine contribute to a lower rate of DGF and promoted the rehabilitation progress.

Advantages of caudal block over intrarectal local anesthesia plus periprostatic nerve block for transrectal ultrasound guided prostate biopsy.

OBJECTIVE: To compare caudal block with intrarectal local anesthesia plus periprostatic nerve block for transrectal ultrasound guided prostate biopsy. METHODS: One hundred and ninety patients scheduled for transrectal ultrasound guided prostate biopsy were randomized equally into Group-A who received caudal block (20 ml 1.2% lidocaine) and Group-B who received intrarectal local anesthesia (0.3% oxybuprocaine cream) plus periprostatic nerve block (10 ml 1% lidocaine plus 0.5% ropivacaine) before biopsy. During and after the procedure, the patients rated the level of pain/discomfort at various time points. Complications during the whole study period and the patient overall satisfaction were also evaluated. RESULTS: More pain and discomfort was detected during periprostatic nerve block than during caudal block. Pain and discomfort was significantly lower during prostate biopsy and during the manipulation of the probe in the rectum in Group-A than in Group-B. No significant differences were detected in the pain intensity after biopsy and side effects between the two groups. CONCLUSIONS: Caudal block provides better anesthesia than periprostatic nerve block plus intrarectal local anesthesia for TRUS guided prostate biopsy without an increase of side effects.

EFFECT OF PREOPERATIVE INTRAVENOUS OXYCODONE ON LOW-DOSE ROPIVACAINE SPINAL ANESTHESIA COMBINED WITH INTRATHECAL FENTANYL.

BACKGROUND: Low-dose ropivacaine combined with intrathecal fentanyl can provide adequate anaesthesia with minimal haemodynamic variation. Preemptive analgesia can enhance analgesic effect of spinal anaesthesia without obvious side effects. AIMS: To assess the efficacy of preoperative intravenous oxycodone on transurethral resection of prostate (TURP) under 10 mg ropivacaine spinal anaesthesia combined with intrathecal 25 pg fentanyl. METHODS: Sixty patients undergoing TURP were randomly divided into two groups: Group o (n=30), in which the patients were administered 0.1 mg.kg-1 oxycodone intravenously 10 min prior to the operation for 2 min, and Group C (n=30) in which the patients were administered intravenously a similar volume of 0.9% saline. The participants were injected with hyperbaric 10 mg ropivacaine and 25 µg fentanyl intrathecally. The block characteristics, hemodynamic values, the tramadol consumption and adverse effects were analyzed. RESULTS: The peak level of sensory block was lower in Group C. Time to the first analgesic request and time to two-segment regression of sensory block were shorter in Group C. Fewer patients in Group 0 were given postoperative analgesics. CONCLUSION: Preoperative intravenous oxycodone can prolong analgesic effect of this method and postoperative analgesia.

The imbalance between Tregs, Th17 cells and inflammatory cytokines among renal transplant recipients.

BACKGROUND: A significant barrier to organ transplantation is the cellular rejection that occurs and mediated by antibodies, T cells, and innate immune cells. This study was aimed to determine the number of CD4(+)CD25(+)Foxp3(+) Treg, CD4(+)IFN-γ(-)IL-17(+) Th17, CD4(+)IFN-γ(+)IL-17(-) Th1 and CD4(+)IFN-γ(+)IL-17(+) Th1/17 cells in renal transplant recipients (RTR). METHODS: Renal transplantation was performed for a total of 35 patients with end-stage renal failure. The number of CD4(+)CD25(+)Foxp3(+) Treg, CD4(+)IFN-γ(-)IL-17(+) Th17, CD4(+)IFN-γ(+)IL-17(-) Th1 and CD4(+)IFN-γ(+)IL-17(+) Th1/17 cells, and the serum level of IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10, and IL-17 were measured in pre- and post-transplant patients and 10 healthy controls (HC) using flow cytometry and Cytometric Bead Array (CBA). The association between the number of different subsets of CD4(+) T-cells and clinical parameters were analyzed among the pre- and post-transplant patients, and the healthy controls. RESULTS: The number of CD4(+)IFN-γ(-)IL-17(+) Th17, CD4(+)IFN-γ(+)IL-17(-) Th1 and CD4(+)IFN-γ(+)IL-17(+) Th1/17 cells were significantly increased in patients with End-Stage Renal Failure (ESRF) compared to the HC. Stratification analysis indicated that AMR (Acute antibody mediated acute rejection), AR (acute rejection) and CR (chronic rejection) groups displayed greater number of CD4(+)IFN-γ(-)IL-17(+) Th17, CD4(+)IFN-γ(+)IL-17(-) Th1 and CD4(+)IFN-γ(+)IL-17(+) Th1/17 cells as well as high level of serum IL-2, IFN-γ, TNF-α and IL-17. But, the AMR, AR and CR groups have shown lower level of CD4(+)CD25(+)Foxp3(+) T cells and serum IL-10 compared to transplant stable (TS) patients. Moreover, the number of Tregs were negatively correlated with the number of Th17 cells in RTR patients. The number of Tregs and Th17 cells were positively correlated with the eGFR and serum creatinine values, respectively. CONCLUSION: The imbalance between different types of CD4(+) T cells and dysregulated inflammatory cytokines may contribute towards renal transplantation rejection.

CLINICAL RESEARCH REGARDING PREEMPTIVE ANALGESIC EFFECT OF PREOPERATIVE KETAMINE AFTER TRANSURETHRAL RESECTION OF PROSTATE.

OBJECTIVE: To investigate whether a single intravenous dose of ketamine before transurethral resection of prostate (TURP) led to reduced postoperative pain and tramadol consumption. METHODOLOGY: Sixty patients undergoing elective TURP were randomized into one of two groups: the ketamine group (Group K, n = 30) received intravenous 0.5 mg/kg ketamine 10 min before surgery, and the control group (Group C, n = 30) received an equivalent volume of normal saline 30 min before surgery. A standardized general anesthesia method was used with a laryngeal mask airway device in all patients. Data on pain intensity, incidence of lower urinary tract discomfort, time to the first analgesic requirement, tramadol analgesia and consumption, overall patient satisfaction and side effects were recorded for 24 h after extubation of the patients. RESULTS: Group K had significantly decreased postoperative pain scores at 1, 2, 6, and 12 h. The number of patients who required postoperative analgesia was fewer and postoperative tramadol consumption was significantly less in Group K as compared with Group C. There was no significant difference in the incidence of lower urinary tract discomfort or any of side effects. The patients in Group K were more satisfied. CONCLUSION: Preemptive 0.5 mg/kg ketamine has a definitive role of preemptive analgesia for TURP without influence of LUT discomfort or an increase of adverse effects.

Zinc rescue of Akt2 gene deletion-linked murine cardiac dysfunction and pathological changes is metallothionein-dependent.

We have demonstrated that zinc supplementation provides cardiac protection from diabetes in mice, but its underlying mechanism remains unclear. Since zinc mimics the function of insulin, it may provide benefit to the heart via stimulating Akt-mediated glucose metabolism. Akt2 plays an important role in cardiac glucose metabolism and mice with Akt2 gene deletion (Akt2-KO) exhibit a type 2 diabetes phenotype; therefore, we assumed that no cardiac protection by zinc supplementation from diabetes would be observed in Akt2-KO mice. Surprisingly, despite Akt2 gene deletion, zinc supplementation provided protection against cardiac dysfunction and other pathological changes in Akt2-KO mice, which were accompanied by significant decreases in Akt and GSK-3ß phosphorylation. Correspondingly, glycogen synthase phosphorylation and hexokinase II and PGC-1α expression, all involved in the regulation of glucose metabolism, were significantly altered in diabetic hearts, along with a significantly increased expression of Akt negative regulators: PTEN, PTP1B, and TRB3. All these molecular, pathological, and functional changes were significantly prevented by 3-month zinc supplementation. Furthermore, the stimulation of Akt-mediated glucose metabolic kinases or enzymes by zinc treatment was metallothionein-dependent since it could not be observed in metallothionein-knockout mice. These results suggest that zinc preserves cardiac function and structure in Akt2-KO mice presumably due to its insulin mimetic effect on cardiac glucose-metabolism. The cardioprotective effects of zinc are metallothionein-dependent. This is very important since zinc supplementation may be required for patients with Akt2 gene deficiency or insulin resistance.

Imbalance of different types of CD4(+)Foxp3(+) T cells in renal transplant recipients.

AIMS: To determine the number of CD4(+)CD25(-)Foxp3(+), CD4(+)CD25(+)Foxp3(+) and CD4(+)CXCR5(+)Foxp3(+) T cells in renal transplant recipients that are transplanted stable (TS), or experiencing accelerated rejection (ALR), or acute rejection (AR). METHODS: Renal transplantation was conducted in 28 patients with end-stage renal failure (ESRF). The number of peripheral CD4(+)CD25(-)Foxp3(+), CD4(+)CD25(+)Foxp3(+), or CD4(+)CXCR5(+)Foxp3(+) T cells and the serum levels of interleukin-10 (IL-10) were measured in pre- and post-transplant patients and these results were compared to 10 healthy controls (HC). Correlation between CD4(+)CD25(+)Foxp3(+) and estimated glomerular filtration rate (eGFR), CD4(+)CD25(-)Foxp3(+) and serum creatinine (Cr) levels, or Cr and IL-10 levels in TS patients was also determined. RESULTS: The number of CD4(+)CD25(-)Foxp3(+) T cells was significantly increased in patients with ESRF, as compared to HC. Stratification analysis demonstrated that TS patients contained greater numbers of CD4(+)CD25(+)Foxp3(+) and CD4(+)CXCR5(+)Foxp3(+) T cells, higher levels of serum IL-10, and fewer numbers of CD4(+)CD25(-)Foxp3(+) T cells than ESRF patients. In contrast, ALR and AR patients contained fewer numbers of CD4(+)CD25(+)Foxp3(+) and CD4(+)CXCR5(+)Foxp3(+) T cells, greater numbers of CD4(+)CD25(-)Foxp3(+) T cells, and lower levels of serum IL-10 than ESRF patients. In TS patients, the numbers of CD4(+)CD25(+)Foxp3(+) and CD4(+)CD25(-)Foxp3(+) T cells were positively correlated with eGFR and serum Cr levels, respectively. CONCLUSION: An imbalance of different types of CD4(+)Foxp3(+) T cells might be involved in renal transplant rejection.

Blind Super-Resolution Via Meta-Learning and Markov Chain Monte Carlo Simulation.

Learning based approaches have witnessed great successes in blind single image super-resolution (SISR) tasks, however, handcrafted kernel priors and learning based kernel priors are typically required. In this paper, we propose a Meta-learning and Markov Chain Monte Carlo based SISR approach to learn kernel priors from organized randomness. In concrete, a lightweight network is adopted as kernel generator, and is optimized via learning from the MCMC simulation on random Gaussian distributions. This procedure provides an approximation for the rational blur kernel, and introduces a network-level Langevin dynamics into SISR optimization processes, which contributes to preventing bad local optimal solutions for kernel estimation. Meanwhile, a meta-learning based alternating optimization procedure is proposed to optimize the kernel generator and image restorer, respectively. In contrast to the conventional alternating minimization strategy, a meta-learning based framework is applied to learn an adaptive optimization strategy, which is less-greedy and results in better convergence performance. These two procedures are iteratively processed in a plug-and-play fashion, for the first time, realizing a learning-based but plug-and-play blind SISR solution in unsupervised inference. Extensive simulations demonstrate the superior performance and generalization ability of the proposed approach when comparing with state-of-the-arts on synthesis and real-world datasets.

Meta-learning based blind image super-resolution approach to different degradations.

Although recent studies on blind single image super-resolution (SISR) have achieved significant success, most of them typically require supervised training on synthetic low resolution (LR)-high resolution (HR) paired images. This leads to re-training necessity for different degradations and restricted applications in real-world scenarios with unfavorable inputs. In this paper, we propose an unsupervised blind SISR method with input underlying different degradations, named different degradations blind super-resolution (DDSR). It formulates a Gaussian modeling on blur degradation and employs a meta-learning framework for solving different image degradations. Specifically, a neural network-based kernel generator is optimized by learning from random kernel samples, referred to as random kernel learning. This operation provides effective initialization for blur degradation optimization. At the same time, a meta-learning framework is proposed to resolve multiple degradation modelings on the basis of alternative optimization between blur degradation and image restoration, respectively. Differing from the pre-trained deep-learning methods, the proposed DDSR is implemented in a plug-and-play manner, and is capable of restoring HR image from unfavorable LR input with degradations such as partial coverage, noise addition, and darkening. Extensive simulations illustrate the superior performance of the proposed DDSR approach compared to the state-of-the-arts on public datasets with comparable memory load and time consumption, yet exhibiting better application flexibility and convenience, and significantly better generalization ability towards multiple degradations. Our code is available at https://github.com/XYLGroup/DDSR.

Therapeutic effect of MG-132 on diabetic cardiomyopathy is associated with its suppression of proteasomal activities: roles of Nrf2 and NF-κB.

MG-132, a proteasome inhibitor, can upregulate nuclear factor (NF) erythroid 2-related factor 2 (Nrf2)-mediated antioxidative function and downregulate NF-κB-mediated inflammation. The present study investigated whether through the above two mechanisms MG-132 could provide a therapeutic effect on diabetic cardiomyopathy in the OVE26 type 1 diabetic mouse model. OVE26 mice develop hyperglycemia at 2-3 wk after birth and exhibit albuminuria and cardiac dysfunction at 3 mo of age. Therefore, 3-mo-old OVE26 diabetic and age-matched control mice were intraperitoneally treated with MG-132 at 10 µg/kg daily for 3 mo. Before and after MG-132 treatment, cardiac function was measured by echocardiography, and cardiac tissues were then subjected to pathological and biochemical examination. Diabetic mice showed significant cardiac dysfunction, including increased left ventricular systolic diameter and wall thickness and decreased left ventricular ejection fraction with an increase of the heart weight-to-tibia length ratio. Diabetic hearts exhibited structural derangement and remodeling (fibrosis and hypertrophy). In diabetic mice, there was also increased systemic and cardiac oxidative damage and inflammation. All of these pathogenic changes were reversed by MG-132 treatment. MG-132 treatment significantly increased the cardiac expression of Nrf2 and its downstream antioxidant genes with a significant increase of total antioxidant capacity and also significantly decreased the expression of IκB and the nuclear accumulation and DNA-binding activity of NF-κB in the heart. These results suggest that MG-132 has a therapeutic effect on diabetic cardiomyopathy in OVE26 diabetic mice, possibly through the upregulation of Nrf2-dependent antioxidative function and downregulation of NF-κB-mediated inflammation.

The role of zinc in the prevention of diabetic cardiomyopathy and nephropathy.

Zinc (Zn) is one of the essential trace elements and has numerous physiological functions. Zn acts as an antioxidant and also as a part of other antioxidant related proteins, such as metallothionein (MT) and Zn-copper superoxide dismutase. Zn deficiency often occurs in patients with diabetes. Therefore, the effect of Zn deficiency or Zn supplementation on diabetes-induced cardiac and renal pathogeneses has been explored. Diabetes was induced by streptozotocin (STZ) in mice and rats. Zn deficiency was induced by chronic treatment of diabetic mice with Zn chelator N,N,N,N-Tetrakis(2-pyridylmethyl)-1,2-ethylenediamine (TPEN) for 4 months. For Zn supplementation study, diabetic mice or rats were treated with Zn for 3 months. Inflammation, fibrosis, and histopathological changes in the heart and kidney of these diabetic mice and rats were examined by western blotting assay, immunohistochemical and fluorescent staining. Results showed that diabetes induced cardiac and renal oxidative damage, inflammation and fibrosis, which were reversed by Zn supplementation that also induced cardiac and renal MT synthesis. Furthermore, Zn deficiency was found to significantly enhance the renal damage induced by diabetes. Several clinical observations also support the preventive effect of Zn in the development of diabetic cardiomyopathy and nephropathy. Therefore, Zn plays an important role in the protection of the heart and kidney against diabetes-induced oxidative damage, inflammation, and fibrosis. These studies suggested that diabetic patients should be monitored and treated for Zn deficiency to avoid the acceleration of diabetes-induced cardiac and renal injury.

Bis(4-cyano-1-methyl-pyridinium) bis-(1,2-dicyano-ethene-1,2-dithiol-ato-κS,S')cuprate(II).

The title ion-pair compound, (C(7)H(7)N(2))(2)[Cu(C(4)N(2)S(2))(2)], was obtained by the direct reaction of CuCl(2)·2H(2)O, disodium maleonitrile-dithiol-ate (Na(2)mnt) and 4-cyano-1-methyl-pyridinium iodide. The anion and one pyridinium cation lie entirely on a mirror plane, whereas for the other cation, a crystallographic mirror plane runs through the N and para-C atoms of the pyridine ring, the methyl C atom, and the cyano group. In the crystal, ions are linked into a three-dimensional network by C-H⋯N hydrogen bonds.

Comprehensive Analysis and Identification of an Immune-Related Gene Signature with Prognostic Value for Prostate Cancer.

BACKGROUND: The tumor microenvironment (TME) has recently been proven to play a crucial role in the development and prognosis of tumors. However, the current knowledge on the potential of the TME in prostate cancer (PCa) remains scarce. PURPOSE: This study aims to elucidate the value of TME-related genes for PCa prognosis by integrative bioinformatics analysis. MATERIALS AND METHODS: We downloaded the immune and stromal scores of PCa samples via the ESTIMATE and correlated these scores to clinicopathological characteristics and recurrence-free survival (RFS) of patients. Based on these scores, the TME-related differentially expressed genes were identified for functional enrichment analysis. Cox regression analyses were performed to identify prognostic genes and establish a predictive risk model. Moreover, gene set enrichment analysis (GSEA) was performed to evaluate the relationship between risk score and immune pathway. RESULTS: The stromal and immune scores were associated with clinicopathological characteristics and RFS in PCa patients. In total, 238 intersecting differentially expressed genes were identified. Functional enrichment analysis further revealed that these genes dramatically participated in the immune-related pathways. The immune-related risk model was built with C-type lectin domain containing 7A (CLEC7A) and collagen type XI alpha 1 chain (COL11A1) using Cox regression analyses. Kaplan-Meier survival analysis showed that the expression levels of CLEC7A and COL11A1 were significantly associated with the RFS. Further, the RFS time in high-risk group was significantly shorter than that in low-risk group. The areas under the curve for the risk model in predicting 3- and 5-year RFS rates were 0.694 and 0.731, respectively. GSEA suggested that immunosuppression existed in high-risk PCa patients. CONCLUSION: CLEC7A and COL11A1 were selected to build a predictive risk model, which may help clinicians to assess the prognosis of PCa patients and select appropriate targets for immunotherapy.

Survival and function of CD47-deficient thymic grafts in mice.

BACKGROUND: We have previously shown that the interspecies incompatibility of CD47 plays an important role in triggering rejection of xenogeneic hematopoietic cells by macrophages. However, it remains unknown whether CD47 incompatibility also contributes to the rejection of non-hematopoietic xenografts. AIMS: Here, we investigated the role of CD47 in preventing macrophage-mediated rejection of thymic epithelial cells in a mouse model of thymic transplantation across the CD47 barrier. METHODS: Wild-type (WT) and CD47 KO mice were thymectomized and treated with T cell-depleting mAbs, and implanted with fetal thymus from syngeneic WT or CD47 KO donors. RESULTS: Transplantation of CD47 KO mouse thymus led to T cell recovery in thymectomized, T cell-depleted WT mice. Similar to the control WT mouse thymic grafts, CD47 KO mouse thymic grafts showed a normal distribution of thymocyte subsets, and almost all of the thymocytes were recipient origin. Furthermore, histological analysis confirmed long-term survival of CD47 KO mouse thymic epithelial cells in WT mouse recipients. CONCLUSIONS: These results demonstrate that, unlike hematopoietic cells, CD47 KO mouse thymus can survive and function in WT mice. Furthermore, our data implicate that the role of CD47 in xenograft rejection may differ for different types of xenografts, and that CD47 incompatibility is unlikely to impede thymic xenotransplantation, a potential approach to inducing xenotolerance, by triggering macrophage-mediated rejection.