Formyl peptide receptor 2 activation by mitochondrial formyl peptides stimulates the neutrophil proinflammatory response via the ERK pathway and exacerbates ischemia-reperfusion injury.

BACKGROUND: Ischemia-reperfusion injury (IRI) is an inevitable process in renal transplantation that significantly increases the risk of delayed graft function, acute rejection, and even graft loss. Formyl peptide receptor 2 (FPR2) is an important receptor in multiple septic and aseptic injuries, but its functions in kidney IRI are still unclear. This study was designed to reveal the pathological role of FPR2 in kidney IRI and its functional mechanisms. METHODS: To explore the mechanism of FPR2 in kidney IRI, the model rats were sacrificed after IRI surgery. Immunofluorescence, enzyme-linked immunosorbent assays, and western blotting were used to detect differences in the expression of FPR2 and its ligands between the IRI and control groups. WRW4 (WRWWWW-NH2), a specific antagonist of FPR2, was administered to kidney IRI rats. Kidney function and pathological damage were detected to assess kidney injury and recovery. Flow cytometry was used to quantitatively compare neutrophil infiltration among the experimental groups. Mitochondrial formyl peptides (mtFPs) were synthesized and administered to primary rat neutrophils together with the specific FPR family antagonist WRW4 to verify our hypothesis in vitro. Western blotting and cell function assays were used to examine the functions and signaling pathways that FPR2 mediates in neutrophils. RESULTS: FPR2 was activated mainly by mtFPs during the acute phase of IRI, mediating neutrophil migration and reactive oxygen species production in the rat kidney through the ERK1/2 pathway. FPR2 blockade in the early phase protected rat kidneys from IRI. CONCLUSIONS: mtFPs activated FPR2 during the acute phase of IRI and mediated rat kidney injury by activating the migration and reactive oxygen species generation of neutrophils through the ERK1/2 pathway.

Transplantation of Telocytes Attenuates Unilateral Ureter Obstruction-Induced Renal Fibrosis in Rats.

BACKGROUND/AIMS: Previous studies imply that telocytes may have a protective effect on fibrosis in various organs, including the liver, colon, and heart. The effect of telocytes on renal fibrosis remains unknown. Herein, this study was designed to investigate the effect of telocytes on renal fibrosis and the potential mechanisms involved. METHODS: In a unilateral ureteral obstruction (UUO)-induced renal fibrosis model, telocytes were injected via the tail vein every other day for 10 days. The degree of renal damage and fibrosis was determined using histological assessment. The expression of collagen I, fibronectin, epithelial-mesenchymal transition markers, and Smad2/3 phosphorylation was examined by western blot analyses. Real-time PCR and enzyme-linked immunosorbent assay were performed in vivo to detect the levels of transforming growth factor (TGF)-ß1 and various growth factors. RESULTS: Telocytes attenuated renal fibrosis, as evidenced by reduced interstitial collagen accumulation, decreased expression of fibronectin and collagen I, upregulation of E-cadherin, and downregulation of α-smooth muscle actin. Furthermore, telocytes decreased serum TGF-ß1 levels, suppressed Smad2/3 phosphorylation, and increased the expression of hepatocyte growth factor (HGF) in rat kidney tissue following UUO. Blockage of HGF counteracted the protective effect of telocytes on UUO-treated kidneys. Through the detection of HGF mRNA levels in vitro, we found that telocytes had no effect on HGF expression compared with renal fibroblasts. CONCLUSION: Telocytes attenuated UUO-induced renal fibrosis in rats, likely through enhancing the expression of HGF in an indirect manner.

Myeloid-derived suppressor cells in transplantation: the dawn of cell therapy.

Myeloid-derived suppressor cells (MDSCs) are a series of innate cells that play a significant role in inhibiting T cell-related responses. This heterogeneous population of immature cells is involved in tumor immunity. Recently, the function and importance of MDSCs in transplantation have garnered the attention of scientists and have become an important focus of transplantation immunology research because MDSCs play a key role in establishing immune tolerance in transplantation. In this review, we summarize recent studies of MDSCs in different types of transplantation. We also focus on the influence of immunosuppressive drugs on MDSCs as well as future obstacles and research directions in this field.

Estimation of Mycophenolic Acid Area Under the Curve With Limited-Sampling Strategy in Chinese Renal Transplant Recipients Receiving Enteric-Coated Mycophenolate Sodium.

BACKGROUND: The enteric-coated mycophenolate sodium (EC-MPS), whose active constituent is mycophenolic acid (MPA), has been widely clinically used for organ transplant recipients. However, its absorption is delayed due to its special designed dosage form, which results in difficulty to monitor the exposure of the MPA in patients receiving the EC-MPS. This study was aimed at developing a relatively practical and precise model with limited sampling strategy to estimate the 12-hour area under the concentration-time curve (AUC0-12 h) of MPA for Chinese renal transplant recipients receiving EC-MPS. METHODS: A total of 36 Chinese renal transplant recipients receiving the EC-MPS and tacrolimus were recruited in this study. The time point was 2 weeks after the transplantation for all the patients. The MPA concentrations were measured with enzyme-multiplied immunoassay technique for 11 blood specimens collected predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the morning dose of EC-MPS. The measured AUC was calculated with these 11 points of MPA concentrations with the linear trapezoidal rule. Limited sampling strategy was used to develop models for estimated AUC in the model group (n = 18). The bias and precision of different models were evaluated in the validation group (n = 18). RESULTS: C4 showed the strongest correlation with the measured AUC. The best 3 time point equation was 6.629 + 8.029 × C0 + 0.592 × C3 + 1.786 × C4 (R = 0.910; P < 0.001), whereas the best 4 time point equation was 3.132 + 5.337 × C0 + 0.735 × C3 + 1.783 × C4 + 3.065 × C8 (R = 0.959; P < 0.001). When evaluated in the validation group, the 4 time point model had a much better performance than the 3 time point model: for the 4 time point model: R = 0.873, bias = 0.505 [95% confidence interval (CI), -10.159 to 11.170], precision = 13.370 (95% CI, 5.186-21.555), and 77.8% of estimated AUCs was within 85%-115% of the measured AUCs; for the 3 time point model: R = 0.573, bias = 6.196 (95% CI, -10.627 to 23.018), precision = 21.286 (95% CI, 8.079-34.492), and 50.0% of estimated AUCs was within 85%-115% of the measured AUCs. CONCLUSIONS: It demanded at least 4 time points to develop a relatively reliable model to estimate the exposure of MPA in renal transplant recipients receiving the EC-MPS. The long time span needed restricted its application, especially for the outpatients, but it could be a useful tool to guide the personalized prescription for the inpatients.

Renal telocytes contribute to the repair of ischemically injured renal tubules.

Telocytes (TCs), a distinct type of interstitial cells, have been identified in many organs via electron microscopy. However, their precise function in organ regeneration remains unknown. This study investigated the paracrine effect of renal TCs on renal tubular epithelial cells (TECs) in vitro, the regenerative function of renal TCs in renal tubules after ischaemia-reperfusion injury (IRI) in vivo and the possible mechanisms involved. In a renal IRI model, transplantation of renal TCs was found to decrease serum creatinine and blood urea nitrogen (BUN) levels, while renal fibroblasts exerted no such effect. The results of histological injury assessments and the expression levels of cleaved caspase-3 were consistent with a change in kidney function. Our data suggest that the protective effect of TCs against IRI occurs via inflammation-independent mechanisms in vivo. Furthermore, we found that renal TCs could not directly promote the proliferation and anti-apoptosis properties of TECs in vitro. TCs did not display any advantage in paracrine growth factor secretion in vitro compared with renal fibroblasts. These data indicate that renal TCs protect against renal IRI via an inflammation-independent pathway and that growth factors play a significant role in this mechanism. Renal TCs may protect TECs in certain microenvironments while interacting with other cells.

The protective effect of baicalin against renal ischemia-reperfusion injury through inhibition of inflammation and apoptosis.

BACKGROUND: Renal ischemia-reperfusion injury (IRI) increases the rates of acute kidney failure, delayed graft function, and early mortality after kidney transplantation. The pathophysiology involved includes oxidative stress, mitochondrial dysfunction, and immune-mediated injury. The anti-oxidation, anti-apoptosis, and anti-inflammation properties of baicalin, a flavonoid glycoside isolated from Scutellaria baicalensis, have been verified. This study therefore assessed the effects of baicalin against renal IRI in rats. METHODS: Baicalin was intraperitoneally injected 30 min before renal ischemia. Serum and kidneys were harvested 24 h after reperfusion. Renal function and histological changes were assessed. Markers of oxidative stress, the Toll-like receptor (TLR)2 and TLR4 signaling pathway, mitochondrial stress, and cell apoptosis were also evaluated. RESULTS: Baicalin treatment decreased oxidative stress and histological injury, and improved kidney function, as well as inhibiting proinflammatory responses and tubular apoptosis. Baicalin pretreatment also reduced the expression of TLR2, TLR4, MyD88, p-NF-κB, and p-IκB proteins, as well as decreasing caspase-3 activity and increasing the Bcl-2/Bax ratio. CONCLUSIONS: Baicalin may attenuate renal ischemia-reperfusion injury by inhibiting proinflammatory responses and mitochondria-mediated apoptosis. These effects are associated with the TLR2/4 signaling pathway and mitochondrial stress.

[Bone marrow mesenchymal stem cell-derived exosome protects kidney against ischemia reperfusion injury in rats].

OBJECTIVE: To explore the protective effects and mechanism of exosomes derived from bone marrow mesenchymal stem cells (BM-MSC) on ischemia reperfusion injury (IRI) in rats. METHODS: Rat-MSC were isolated, cultured and identified.Exosome was extracted from BM-MSC and observed under transmission electron microscope (TEM). The expression of surface molecular marker CD63 was tested by flow cytometry. Male Sprague-Dawley rats were randomly grouped into sham-operated (Sham), ischemia reperfusion (IR), MSC-treated (IR+MSC), MSC-derived exosome-treated (IR+MSC-ex) and fibroblast-derived exosome-treated (IR+F-ex) groups. The model for ischemia reperfusion injury was constructed. The serum levels of creatinine and blood urea nitrogen (BUN) were tested in each group. The histomorphological changes in of renal tissue samples were examined by hematoxylin and eosin-stained tissue samples. Cellular apoptosis was examined by terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) staining. The expression levels of proinflammatory cytokines interleukin 1ß and tumor necrosis factor α were examined by reverse transcription (RT)-PCR. And the expression level of caspase-3 was examined by Western blot. RESULTS: Rat BM-MSCs were successfully isolated and cultured. Dectection of surface markers revealed high expression levels of CD29 and CD44 and a low expression level of CD34. MSC differentiated successfully into osteoblasts and lipocytes after growing in osteoblast- and lipocyte-inducing media respectively. Typical appearances of exosome were observed under transmission electron microscope. CD63 was positive on flow cytometry. Compared with the IR group, the IR+MSC and IR+MSC-ex groups showed low levels of serum creatinine and BUN, mild pathological injury, decreased number of apoptotic cells and low expression of inflammatory factors and caspase-3 (IR group, 4 310 ± 616;IR+MSC group, 2 569 ± 530; IR+MSC-ex group, 3 144 ± 343, both P < 0.05). CONCLUSION: Rat BM-MSC-derived exosome protects against ischemia reperfusion injury with decreased inflammatory response and apoptosis in rats.

Atomic-level modulation of electron density in iron sulfides for enhancing sodium storage kinetics.

Iron sulfides (FeS2) are promising anode materials for sodium ion batteries (SIBs); however, their inferior electronic conductivity, large volume swelling, and sluggish sodium ion diffusion kinetics lead to unsatisfactory rate performance and cycling durability. Heteroatom doping plays a crucial role in modifying the physicochemical properties of FeS2 anodes to enhance its sodium storage. Herein, ultra-fine Ni-doped FeS2 nanocrystals derived from a metal-organic framework (MOF) and in-situ anchored on a nitrogen doped carbon skeleton (Ni-FeS2@NC) are proposed to enhance both structural stability and reaction kinetics. Material characterization, electrochemical performance, and kinetics analysis demonstrate the critical role of Ni doping in sodium storage, particularly in accelerating Na+ diffusion efficiency. The N-doped carbon derived from the MOF can buffer the volume expansion and enhance the structural stability of electrode materials during sodiation/desodiation processes. As expected, Ni-FeS2@NC exhibits a high reversible capacity of 656.6 ± 65.1 mAh g-1 at 1.0 A g-1 after 200 cycles, superior rate performance (308.8 ± 6.0 mAh g-1 at 10.0 A g-1), and long-term cycling durability over 2000 cycles at 1.0 A g-1. Overall, this study presents an effective approach for enhancing the sodium storage performance and kinetics of anode materials for high efficiency SIBs.

Naked caspase 3 small interfering RNA is effective in cold preservation but not in autotransplantation of porcine kidneys.

BACKGROUND: Caspase 3 associated with apoptosis and inflammation plays a key role in ischemia-reperfusion injury. The efficacy of naked caspase 3 small interfering RNA (siRNA) has been proved in an isolated porcine kidney perfusion model but not in autotransplantation. MATERIALS AND METHODS: The left kidney was retrieved from mini pigs and infused with the University of Wisconsin solution with or without 0.3mg of caspase 3 siRNA into the renal artery with the renal artery and vein clamped for 24-h cold storage (CS). After right nephrectomy, the left kidney was autotransplanted into the right for 48 h without systemic treatment of siRNA. RESULTS: Fluorescent dye-labeled caspase 3 siRNA was visualized in the post-CS kidneys but was weakened after transplantation. The expression of caspase 3 messenger RNA and precursor was downregulated by siRNA in the post-CS kidneys. In the siRNA-preserved posttransplant kidneys, however, the caspase 3 messenger RNA and active subunit were upregulated with further decreased precursor but increased active caspase 3+ cells, apoptotic cells, and myeloperoxidase+ cells. Moreover, the renal tissue damage was aggravated by siRNA, whereas the renal function was not significantly changed. CONCLUSIONS: Naked caspase 3 siRNA administered into the kidney was effective in cold preservation but not enough to protect posttransplant kidneys, which might be because of systemic complementary responses overcoming local effects.

Telocytes in the human kidney cortex.

Renal interstitial cells play an important role in the physiology and pathology of the kidneys. As a novel type of interstitial cell, telocytes (TCs) have been described in various tissues and organs, including the heart, lung, skeletal muscle, urinary tract, etc. (www.telocytes.com). However, it is not known if TCs are present in the kidney interstitium. We demonstrated the presence of TCs in human kidney cortex interstitium using primary cell culture, transmission electron microscopy (TEM) and in situ immunohistochemistry (IHC). Renal TCs were positive for CD34, CD117 and vimentin. They were localized in the kidney cortex interstitial compartment, partially covering the tubules and vascular walls. Morphologically, renal TCs resemble TCs described in other organs, with very long telopodes (Tps) composed of thin segments (podomers) and dilated segments (podoms). However, their possible roles (beyond intercellular signalling) as well as their specific phenotype in the kidney remain to be established.

Hematopoietic stem cell transplantation induces immunologic tolerance in renal transplant patients via modulation of inflammatory and repair processes.

BACKGROUND: Inducing donor-specific tolerance in renal transplant patients could potentially prevent allograft rejection and calcineurin inhibitor nephrotoxicity. Combined kidney and hematopoietic stem cell transplant from an HLA-matched donor is an exploratory and promising therapy to induce immune tolerance. Investigation of molecular mechanisms involved in the disease is needed to understand the potential process of cell therapy and develop strategies to prevent this immunologic rejection. METHODS: We enrolled nine patients in a clinical study in which cryopreserved donor hematopoietic stem cells were infused on days 2, 4, and 6 after kidney transplantation. One month post-transplant, 4 plasma samples were collected from combined transplants (C + Tx), and 8 plasma samples from patients with kidney transplantation alone (Tx). High abundance proteins in plasma were depleted and the two-dimensional liquid chromatography-tandem mass spectrometry coupled with iTRAQ labeling was utilized to identify the protein profiling between the two groups. Clusters of up- and down-regulated protein profiles were submitted to MetaCore for the construction of transcriptional factors and regulation networks. RESULTS AND DISCUSSION: Among the 179 identified proteins, 65 proteins were found in C + Tx with at least a 2-fold change as compared with Tx. A subset of proteins related to the complement and coagulation cascade, including complement C3a,complement C5a, precrusors to fibrinogen alpha and beta chains,was significantly downregulated in C + Tx. Meanwhile, Apolipoprotein-A1(ApoA1), ApoC1, ApoA2, ApoE, and ApoB were significantly lower in Tx compared to C + Tx. Gene ontology analysis showed that the dominant processes of differentially expressed proteins were associated with the inflammatory response and positive regulation of plasma lipoprotein particle remodeling. CONCLUSIONS: Thus, our study provides new insight into the molecular events in the hematopoietic stem cell-induced immunologic tolerance.

Removal of NO in flue gas simulated by the Fe2+/Cu2+-activated double oxidant system.

⋅OHThe wet denitrification technology has a good development prospect due to its simple system and mild reaction conditions, and related research has become a hot topic in the field of flue gas purification. In this work, a novel simultaneous removal technology of NO from flue gas using Fe2+/Cu2+-catalytic H2O2/(NH4)2S2O8 system was developed for the first time. The feasibility of this new flue gas cleaning technology was explored through a series of experiments and performance analyses. The mechanism of oxidation products, free radicals and simultaneous removal of NO was revealed. The effects of the main process parameters on the removal of NO were investigated. Relevant results demonstrated that the removal efficiency of NO was elevated when the concentration of (NH4)2S2O8 or reacting temperature increased, while it was decreased after increasing the raising of Fe2+, Cu2+ and H2O2 concentrations. The main radicals were and·SO4-, using the electron spin resonance technique in the solution, and played a very important role in NO removal. The main products were carried out by ion chromatography and elemental N material accountancy, and the results showed that it was sulfate and nitrate in the solution, which provided theoretical guidance for the subsequent treatment and resource utilization of the absorption solution. The results of the study provided a theoretical basis for the industrial application of wet denitrification.

Modelling of ammonia recovery from wastewater by air stripping in rotating packed beds.

The processes of ammonia recovery from ammonia nitrogen containing wastewater by air stripping in the laboratory-scale and the pilot-scale rotating packed bed (RPB) were simulated by the Aspen with the module of RADFRAC. For a more accurate description of the model, a variety of correlations for the RPB were introduced into the Aspen by the FORTRAN, such as the gas-liquid mass transfer rate, the liquid holdup, the heat transfer rate and the effective gas-liquid interfacial area, etc. The predicted data of ammonia recovery rate were consistent with the experimental results. To further optimize the operating conditions of ammonia recovery, the research also covered the effects of high gravity factor, gas to liquid ratio, pH and temperature on ammonia recovery rate. The promising results had suggested the established model could serve as a powerful tool to simulate the processes of ammonia recovery from the ammonia nitrogen containing wastewater by air stripping in the laboratory-scale and the pilot-scale RPB.

Diagnosis and Treatment of Early Transplant Renal Artery Stenosis: Experience From a Center in Eastern China.

Few studies have focused on the clinical characteristics of transplant renal artery stenosis (TRAS) with early onset. Sixteen cases diagnosed with TRAS in our center from January 2014 to August 2018 were retrospectively analyzed. Sixteen transplant patients without TRAS were selected as controls. The median diagnostic time for TRAS was 47.5 days after transplantation. No significant difference was observed between the TRAS group and the control group. The serum creatinine level (Scr), estimated glomerular filtration rate, systolic/diastolic blood pressure, graft artery peak systolic velocity (PSV), and resistive index of intersegmental artery (RI-ISA) between the 2 groups were (5.55 ± 3.49) and (1.89 ± 0.85) mg/dL; (17.83 ± 14.94) and (49.39 ± 19.96) mL/min; (143.50 ± 9.49)/(86.14 ± 7.38) and (130.38 ± 18.86)/(82.81 ± 12.52) mm Hg; (3.39 ± 1.57) and (1.31 ± 0.51) m/s; and (0.51 ± 0.10) and (0.67 ± 0.13), respectively. All showed statistical significance except the diastolic blood pressure. The Scr, estimated glomerular filtration rate, systolic/diastolic blood pressure, graft artery PSV, and RI-ISA in the TRAS group prior and after treatment were (5.55 ± 3.49) and (3.20 ± 1.50) mg/dL; (17.83 ± 14.94) and (25.60 ± 13.29) mL/min; (143.50 ± 9.49)/(86.14 ± 7.38) and (128.07 ± 16.16)/(75.71 ± 7.56) mm Hg; (3.39 ± 1.57) and (2.00 ± 1.04) m/s; and (0.51 ± 0.10) and (0.61 ± 0.10); all showed statistical significance. Receiver operating characteristic analysis showed an area under curve of 0.8616 for PSV and 0.8535 for RI-ISA in diagnosing TRAS. Patients with TRAS in our center showed a unique characteristic of early onset. The most prominent clinical symptom of TRAS is increasing Scr level instead of refractory hypertension. Screening of color Doppler flow imaging with a graft artery PSV >2.5 m/s and RI-ISA <0.5 could yield a preliminary diagnosis of TRAS. Percutaneous transluminal angioplasty/stenting could effectively improve allograft function as well as color Doppler flow imaging indexes.

Effects of MoO3 and CeO2 doping on the decomposition and reactivity of NH4HSO4 on V2O5/TiO2 catalysts.

The deposition of NH4HSO4 on catalysts is one of the key issues for selective catalytic reduction of NOx. In this study, NH4HSO4 was preloaded on catalysts, and the effects of MoO3 and CeO2 doping on the decomposition and reactivity of NH4HSO4 on V2O5/TiO2 catalysts are studied. The results show that the introduction of MoO3 and CeO2 significantly promoted NOx conversion on the V2O5/TiO2 catalysts. Doping with MoO3 could effectively enhance the S and H2O resistance of the catalysts. Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analysis indicate that it is the strong chemical interactions between NH4HSO4 and the catalysts that are adverse to the decomposition of NH4HSO4. However, doping with MoO3 apparently inhibits these interactions, which significantly decrease the decomposition temperature of NH4HSO4. In situ FTIR experiments show that the NH4+ in preloaded NH4HSO4 could react with gaseous NO on catalysts, and doping with MoO3 could facilitate the reaction rate.

CXCL16 is activated by p-JNK and is involved in H2O2-induced HK-2 cell injury via p-ERK signaling.

Acute kidney injury (AKI) leads to an abrupt deterioration of renal function. CXC chemokine ligand 16 (CXCL16) is a CXC-soluble chemokine and a cell surface scavenger receptor that is involved in tissue injury and inflammation. It is induced in AKI patients, but the molecular mechanism remains unclear. In this study, we have worked to determine the function of CXCL16 and to investigate the involvement of ERK and JNK signaling in AKI. We used H2O2 and recombinant human CXCL16 protein (rh CXCL16) to treat the human renal tubular epithelial cell line, HK-2, in vitro. The present results indicate that H2O2 inhibits proliferation, induces apoptosis, and up-regulates expression of CXCL16 and the CXCL16 receptor, CXCR6, in HK-2 cells. Furthermore, H2O2-induced proliferation inhibition, apoptosis, and inflammation in HK-2 cells were ameliorated by NAC (N-acetyl cysteine, the ROS scavenger) and SP600125 (the JNK inhibitor). The expression levels of CXCL16 and CXCR6 were also positively correlated with the phosphorylation level of JNK (p-JNK). Additionally, rh CXCL16 treatment led to effects like those of H2O2 treatment in HK-2 cells, with symptoms being effectively improved by CXCR6 siRNA and the ERK inhibitor (PD98059). In addition, rh CXCL16-induced HK-2 cell apoptosis, inflammation, and collagen deposition were lessened by CXCR6 siRNA and PD98059 treatment. In summary, the present results have indicated that CXCL16 is involved in H2O2-induced HK-2 cell injury, that CXCL16 is activated by p-JNK, and that the regulatory function of CXCL16 is involved in the phosphorylation of ERK.

Sites of gastrointestinal lesion induced by mycophenolate mofetil: a comparison with enteric-coated mycophenolate sodium in rats.

BACKGROUND: Immunosuppressant drugs for renal transplant mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS) cause gastrointestinal (GI) disorders. The specific site of GI tract targeted by MMF and EC-MPS remains unclear. METHODS: In this study, we investigated the effects of MMF and EC-MPS on stomach, duodenum, jejunum, ileum, colon and rectum using a rat model. Rats were randomized into five groups: control, MMF (100 mg/kg·d), mofetil (30 mg/kg·d), EC-MPS (72 mg/Kg·d), mofetil + EC-MPS. Each group was treated with drugs once a day for 7 days through intra-gastric gavage. Diarrhea grade of each rat were measured every day, as well as the body weight. Blood was collected by tail nick and Seven days later, the rats were sacrificed, GI tissues were collected for Histological research. RESULTS: The results showed that diarrhea grade and weight loss were significantly higher in MMF group than other groups. The pathological score of MMF group was significantly higher than EC-MPS group and EC-MPS + mofetil group in jejunum and ileum tissues, but not other segments of GI tract. Absorption of EC-MPS is delayed, compared to that of MMF. MPAG concentration in duodenum, jejunum and ileum tissues of MMF group is higher than EC-MPS group. Mofetil may increase the magnitude of MPA absorption. CONCLUSIONS: Our data suggested that MMF might target jejunum and ileum and induce GI injury. EC-MPS causes less injury in GI tract than MMF, probably due to its kinetic property.

Gene Therapy in Kidney Transplantation: Evidence of Efficacy and Future Directions.

Allograft loss remains a severe clinical problem after kidney transplantation. The molecular mechanism of graft loss is a complex process involving T and/or B cell activation, inflammation responses, autophagy and apoptosis. Since these pathways are involved in immune responses in kidney transplant rejection, application of genetic interference to inhibit specific pathways could present an effective targeted gene therapy method. Recent studies have successfully attempted to use gene therapy to target the key molecules involved in immune responses during transplantation. This strategy has the potential to silence target genes associated with a variety of diseases, including those that trigger allograft loss following organ transplantation. In this review, we have discussed evidence of the clinical applicability of gene therapy in kidney transplantation based on known associations between kidney diseases and genes participating in the underlying mechanisms. The molecules contributing to immune responses and inflammatory injury are further highlighted as potential targets in future clinical therapy for renal transplantation.

Removal of heavy metal ions by magnetic chitosan nanoparticles prepared continuously via high-gravity reactive precipitation method.

This study aimed to provide a continuous method for the preparation of magnetic Fe3O4/Chitosan nanoparticles (Fe3O4/CS NPs) that can be applied to efficient removal of heavy metal ions from aqueous solution. Using a novel impinging stream-rotating packed bed, the continuous preparation of Fe3O4/CS NPs reached a theoretical production rate of 3.43kg/h. The as-prepared Fe3O4/CS NPs were quasi-spherical with average diameter of about 18nm and saturation magnetization of 33.5emu/g. Owing to the strong metal chelating ability of chitosan, the Fe3O4/CS NPs exhibited better adsorption capacity and faster adsorption rates for Pb(II) and Cd(II) than those of pure Fe3O4. The maximum adsorption capacities of Fe3O4/CS NPs for Pb(II) and Cd(II) were 79.24 and 36.42mgg-1, respectively. In addition, the Fe3O4/CS NPs shown excellent reusability after five adsorption-desorption cycles. All the above results provided a potential method for continuously preparing recyclable adsorbent with a wide prospect of application in wastewater treatment.

Dynamic change of glomerular filtration rate in the early stage is associated with kidney allograft status: a preliminary report.

BACKGROUND: This study aimed to investigate the relationship between the dynamic changes of estimated glomerular filtration rate (eGFR) in the early stage post renal transplantation and renal allograft dysfunction. METHODS: We selected 9 patients with interstitial fibrosis and tubular atrophy (IF/TA) and 11 patients with stable renal function based on the Banff 2007 classification system. Pathology of the patients was evidenced with renal biopsy results. Glomerular filtration rate (GFR) was calculated continuously for 14 days post-transplantation by using an estimated GFR (eGFR) formula adjusted into Chinese. Linear regression was employed, and eGFR slopes were compared. Prisoners or organs from prisoners were not used in this study. RESULTS AND CONCLUSION: The eGFR slope in the IF/TA group was significantly higher than that in the stable group (P < 0.01), and a cut-off value of 5.11 mL/min/1.73 m(2)/d was a reliable clinical value in a receiver operating characteristic (ROC) curve. On the basis of the ROC area under the curve, predictive accuracy of the eGFR slope was excellent (0.848). In conclusion, the eGFR in IF/TA increased faster within a period of 14 days post-transplantation, suggesting that reperfusion in the early stage may damage the glomerular filtration membrane to some extent. Furthermore, reperfusion might adversely affect long-term renal allograft survival.