Factors Related to Bone Metabolism in Kidney Transplant Recipients.

This study is aimed at establishing the prevalence of osteoporosis and osteopenia in kidney transplant recipients (KTRs) and determining the risk factors for bone mass loss. We invited KTRs who were under regular follow-up at Jiangxi Provincial People's Hospital Affiliated with Nanchang University to attend an assessment of osteoporotic risk assessed by questionnaire, biochemical profile, and dual-energy X-ray absorptiometry (DXA) scanning of the lumbar spine, total hip, and femoral neck. Binary logistic regression models were used to investigate the relationship between the different variables and bone mass density (BMD). A total of 216 patients satisfied the inclusion criteria. The group consisted of 156 men (72.22%) and 60 women (27.78%), and the mean age was 41.50 ± 9.98 years. There were 81 patients with normal bone mass (37.50%) and 135 patients with bone mass loss (62.50%). Logistic regression analysis showed that a higher phosphorus value and higher alkaline phosphatase concentration and a longer use of glucocorticoids were risk factors for bone mass loss in KTRs, and maintaining an appropriate weight and exercising an appropriate number of times per week helped to maintain bone mass.

Oleanolic Acid Improves the Symptom of Renal Ischemia Reperfusion Injury via the PI3K/AKT Pathway.

PURPOSE: The aim of this study was to investigate the therapeutic effect of oleanolic acid (OA) on the renal ischemia reperfusion injury (RIRI) and the possible mechanism. METHODS: The RIRI model was successfully established in rats. OA, LY294002 (a PI3K inhibitor), and OA combined with LY294002 were dosed to rats in 3 therapeutic groups, respectively. The blood was collected to detect the concentration of Cr and BUN by ELISA. The kidney of each rat was collected to detect the concentration of renal injury factor (Kim-1) and the HE staining was performed. Western blot was used to detect the expression level of PI3K, p-AKT, AKT, PDK1, Skp2, and p27 in the renal tissue homogenate. RESULTS: The symptom of vacuolar degeneration and interstitial edema was greatly improved in the rat kidney from the 3 therapeutic groups, compared with that from the RIRI model group. No significant difference was observed among the 3 therapeutic groups. The concentration of Cr in the 3 therapeutic groups was greatly lower than that in the RIRI model group. The expression level of p-AKT/AKT, PI3K, PDK1, Skp2, and p27 in OA group, LY294002 group, and OA combined with LY294002 group was significantly lower than that in the RIRI model group, respectively. CONCLUSION: OA could improve the symptom of RIRI, possibly by inhibiting PI3K/AKT signal pathway.

Incidence and risk factors for high-level BK viruria: a single center study in China.

BACKGROUND: BK virus allograft nephropathy is a serious complication after kidney transplantation, and the effect of pre-emptive intervention for high-level BK viruria has been verified, but protocols after kidney transplantation for early identification of high-level viruria are lacking. METHODS: This was a single-center study. The clinical data of the kidney transplant recipients and their donors in our center from January 1, 2015 to December 31, 2018, were collected. The patients were divided into the high-level BK viruria group (Group A) and a non-high-level BK viruria group (Group B) according to the qPCR results of BK virus DNA loads in urine samples. Significant variables were screened out by univariate analysis, and then the results were incorporated into a multivariate logistic regression model to analyze the independent risk factors for high-level BK viruria. RESULTS: A total of 262 recipients were included in the study. The incidence of high-level BK viruria was 13.4% (n = 35), and the median time of detection was 181 (range 91-1119) days. Univariate analysis showed that donor type ([Formula: see text] = 21.770, P < 0.001), history of ATG/ATG-F application ([Formula: see text] = 4.543, P = 0.033), acute rejection (AR) ([Formula: see text] = 8.313, P = 0.004) and delayed graft function (DGF) ([Formula: see text] = 21.170, P < 0.001) were related to high-level BK viruria. After the inclusion of the multivariate logistic regression model, the results showed deceased brain and cardiac donors (P = 0.032, OR = 3.927, 95% CI 1.122-13.746), AR (P = 0.022, OR = 4.709, 95% CI 1.253-17.697) and DGF (P = 0.001, OR = 6.682, 95% CI 2.288-19.518). CONCLUSIONS: Donation by deceased brain and cardiac patients, history of AR and DGF were independent risk factors for high-level BK viruria after kidney transplantation.

Highly Ordered Hierarchical Macro-Mesoporous Carbon-Supported Cobalt Electrocatalyst for Efficient Oxygen Evolution Reaction.

Metal-organic frameworks (MOFs) and their derivatives have been extensively employed in Oxygen Evolution Reaction (OER) catalysts due to their significantly larger specific surface areas, distinct metal centers, and well-organized porous structures. However, the microporous structure of MOFs and their derivatives presents mass transfer resistance, limiting their further development. Drawing inspiration from hierarchical structures allowing for the transport and exchange of substances in the biological world, we designed and fabricated biomimetic layered porous structures within ZIF-67 and its derivatives. Based on this, we achieved a three-dimensional ordered layered porous nitrogen-doped carbon-coated magnetic cobalt catalyst (3DOLP Co@NDC) with a biomimetic pore structure. It is found that the 3DOLP Co@NDC (352 mV @10 mA cm-1) was better than Co@NDC (391 mV @10 mA cm-1). The introduction of a three-dimensional ordered layered porous structure is conducive to increasing the specific surface area of the material, increasing the electrochemical active area, and improving the catalytic performance of the material. The introduction of a three-dimensional ordered layered porous structure would help to build a bionic grade pore structure. The existence of biomimetic grade pore structure can effectively reduce the mass transfer resistance, improve the material exchange efficiency, and accelerate the reaction kinetics.

PCNT is a prognostic biomarker correlated with tumor immune microenvironment in hepatocellular carcinoma and promotes tumor progression by inhibiting cell cycle arrest.

Pericentrin (PCNT), a core pericentriolar material protein during mitosis, is involved in tumorigenesis and development in various cancers. However, its role in hepatocellular carcinoma (HCC) remains unclear. Based on public databases and a cohort with 174 HCC patients, we found that PCNT mRNA and protein expression were elevated in HCC tissues and correlated with unfavorable clinicopathological characteristics and prognosis. In vitro experiments demonstrated that knockdown PCNT expression inhibited the cell viability, migration, and invasion capacity of HCC cells. Multivariate regression analysis suggested that a high PCNT level was an independent risk factor for poor prognosis. In addition, mutation analysis suggested that PCNT was positively correlated to TMB and MSI but negatively correlated to tumor purity. Moreover, PCNT was significantly negatively correlated with ESTIMATE, immune, and Stromal scores in HCC patients. The PCNT expression level was correlated with immune cell infiltration and immune checkpoint-related gene expression in the tumor microenvironment. The single-cell sequencing analysis suggested that higher PCNT expression level was detected in the malignant cells and immune cells (dendritic cells, monocytes, and macrophages cells) in HCC tissues. Enrichment analysis and functional experiments revealed PCNT promoted tumor progression by inhibiting cell cycle arrest. In conclusion, our studies suggested that PCNT can be a potential prognostic indicator correlated with tumor immune microenvironment, suggesting that PCNT can serve as a novel therapeutic target for HCC.

Three different anti-lipopolysaccharide factors identified from giant freshwater prawn, Macrobrachium rosenbergii.

Anti-lipopolysaccharide factor (ALF) is a type of basic protein and an important antimicrobial peptide that can bind and neutralize lipopolysaccharides (LPS). This protein shows a broad spectrum of antimicrobial activity. In this study, three forms of ALF designated as MrALF5, MrALF6, and MrALF7 were identified from giant freshwater prawn, Macrobrachium rosenbergii. MrALF5, MrALF6, and MrALF7 genes encode 133, 121, and 120 amino acids of the corresponding proteins, respectively. All these ALF proteins contain LPS-binding domain with two conserved cysteine residues. The genomic sequences of MrALF5 and MrALF7 were amplified. The genomic structures of MrALF5 and MrALF7 comprise three exons interrupted by two introns. Phylogenetic analysis showed that MrALF5, MrALF6, and MrALF7 were clustered into clade II. Evolutionary analysis showed that ALF genes from M. rosenbergii may suffer a rapid evolution. MrALF5 was expressed mainly in the hepatopancreas, gills, and heart. MrALF6 was mainly distributed in the intestine and hepatopancreas. The highest expression level of MrALF7 was detected in the hepatopancreas. MrALF6, as well as MrALF7, was downregulated by Escherichia coli challenge, and all three ALF genes were upregulated by Vibrio or white spot syndrome virus challenge. MrALF6 was also upregulated by Staphylococcus aureus challenge. In summary, the three isoforms of ALF genes may participate in the innate immune response against bacteria and virus infecting the giant fresh water prawn.

Cobalt-Catalyzed Effective Access to Quinoxalines with Insights in Annulation of Terminal Alkynes and o-Phenylenediamines.

A novel methodology for the annulation of terminal alkynes and o-phenylenediamines by using a combination of a cobalt catalyst and oxygen as a terminal oxidant is reported. This method shows wide substrate scope and good functional group tolerance and provides a wide range of quinoxalines in good to high yields. The method is demonstrated by its gram-scale and broad potential applications. Furthermore, this protocol serves as a powerful tool for the late-stage functionalization of various complex bioactive molecules and drugs to provide a new class of molecules containing two distinct bioactive molecules directly linked. Detailed mechanistic studies reveal that the current reaction goes through a novel mechanism different from the previously reported glyoxal mechanism.

High cathepsin A protein expression predicts poor prognosis and tumor recurrence of hepatocellular carcinoma patients after curative hepatectomy.

Cathepsin A (CTSA) is overexpressed in various types of cancer and is linked to poor clinical outcomes. However, the clinical application of CTSA in HCC has not been explored. In this study, we examined the protein level of CTSA in the archived HCC samples from 161 patients by Immunohistochemistry (IHC). The high protein level of CTSA was significantly correlated to the poor clinicopathological parameters, such as TNM stage, serum AFP level, tumor differentiation, liver cirrhosis, Child-Pugh class, vascular invasion, tumor encapsulation, tumor recurrence, and patient death. In addition, multivariate Cox regression analysis indicated that high CTSA expression was an independent prognostic factor of OS and RFS. We also analyzed the area under the curve (AUC) of the time-dependent receiver operating characteristic (ROC) of CTSA expression for 1-, 3-, and 5-year OS and RFS prediction. Furthermore, we constructed a nomogram that exhibited excellent prediction performance, which was validated by the calibration curve and decision curve analysis. Together, our study demonstrated that CTSA protein level is strongly associated with poor clinical outcome of HCC patients and may be used as a potential diagnostic and prognostic biomarker in HCC.

GNG7 and ADCY1 as diagnostic and prognostic biomarkers for pancreatic adenocarcinoma through bioinformatic-based analyses.

Pancreatic adenocarcinoma (PAAD) is one of the most lethal malignant tumors in the world. The GSE55643 and GSE15471 microarray datasets were downloaded to screen the diagnostic and prognostic biomarkers for PAAD. 143 downregulated genes and 118 upregulated genes were obtained. Next, we performed gene ontology (GO) and The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis on these genes and constructed a protein-protein interaction (PPI) network. We screened out two important clusters of genes, including 13 upregulated and 5 downregulated genes. After the survival analysis, 3 downregulated genes and 10 upregulated genes were identified as the selected key genes. The KEGG analysis on 13 selected genes showed that GNG7 and ADCY1 enriched in the Pathway in Cancer. Next, the diagnostic and prognostic value of GNG7 and ADCY1 was investigated using independent cohort of the Cancer Genome Atlas (TCGA), GSE84129 and GSE62452. We observed that the expression of the GNG7 and ADCY1 was decreased in PAAD. The diagnostic receiver operating characteristic (ROC) analysis indicated that the GNG7 and ADCY1 could serve as sensitive diagnostic markers in PAAD. Survival analysis suggested that expression of GNG7, ADCY1 were significantly associated with PAAD overall survival (OS). The multivariate cox regression analysis showed that the expression of GNG7, ADCY1 were independent risk factors for PAAD OS. Our study indicated GNG7 and ADCY1 may be potential diagnostic and prognostic biomarkers in patients with PAAD.

Upregulation of miR-128 Mediates Heart Injury by Activating Wnt/ß-catenin Signaling Pathway in Heart Failure Mice.

Cardiac hypertrophy contributes to heart failure and is pathogenically modulated by a network of signaling cascades including Wnt/ß-catenin signaling pathway. miRNAs have been widely demonstrated to regulate gene expression in heart development. miR-128 was routinely found as a brain-enriched gene and has been functionally associated with regulation of cardiac function. However, its role and molecular mechanisms that regulate cardiac hypertrophy remain largely unclear. Adeno-associated virus serotype 9 (AAV9)-mediated constructs with miR-128 or anti-miR-128 were generated and delivered to overexpression or blockade of miR-128 in vivo followed by HF induction with isoproterenol (ISO) or transverse aortic constriction (TAC). Cardiac dysfunction and hypertrophy, coupled with involved gene and protein level, were then assessed. Our data found that miR-128, Wnt1, and ß-catenin expressions were upregulated in both patients and mice model with HF. Interference with miR-128 reduces Wnt1/ß-catenin expression in mouse failing hearts and ameliorates heart dysfunctional properties. We identified miR-128 directly targets to Axin1, an inhibitor of Wnt/ß-catenin signaling, and suppresses its inhibition on Wnt1/ß-catenin. Our study provides evidence indicating miR-128 as an inducer of HF and cardiac hypertrophy by enhancing Wnt1/ß-catenin in an Axin1-dependent nature. We thus suggest miR-128 has potential value in the treatment of heart failure.

Norethindrone causes cellular and hepatic injury in zebrafish by compromising the metabolic processes associated with antioxidant defence: Insights from metabolomics.

Progestins, such as norethindrone (NET), have been increasingly detected in aquatic environments due to their extensive use for medical applications. While NET is notorious for its endocrine disrupting effects, it has been recently shown to cause cellular damage, suggesting its potential impacts on the body defence of organisms. Hence, we examined the histological features and antioxidant defence of zebrafish (Danio rerio) after exposing to NET (50 ng/L and 500 ng/L) for 72 days, followed by analysing its metabolome to explore whether NET disturbs the metabolic processes responsible for antioxidant defence. While acute mortality was not triggered, we found that antioxidant defence was substantially weakened by NET at 500 ng/L (i.e. reduced SOD and GSH levels) and hence liver injury was inflicted (i.e. elevated ALT and MDA levels), as manifested by vacuolization of liver tissues and reduced number of normal cells in the liver. Metabolomic analysis showed that the metabolic processes responsible for antioxidant defence were disrupted by NET (e.g. upregulation of nervonyl carnitine and chenodeoxycholic acid 3-sulfate; downregulation of homolanthionine and acevaltrate) and these changes can undermine antioxidant defence by suppressing Nrf2-ARE and NF-κB pathways that contribute to the synthesis of SOD and GSH. This study demonstrates how NET can compromise the body defence of aquatic organisms via metabolic disruption, suggesting that the impacts of progestins on their fitness are more detrimental than previously thought.

Adult liver transplantation using pediatric donor livers after cardiac or brain death: A report of three cases.

The present study reports on the experience at Jiangxi Provincial People's Hospital (Nanchang, China) with liver transplantation in adults using pediatric donor livers, including indications, technique and results. A total of three cases of liver transplantation performed between April 2008 and May 2016 were retrospectively reviewed. Liver procurement and trimming, recipient selection, surgical tips, prevention and treatment of small-for-size syndrome, selection of immunosuppressive regimens, prevention and treatment of vascular complications and anticoagulant therapy were discussed. The three pediatric donors were 8, 8 and 10 years old. The three recipients were confirmed to have primary liver cancer. In recipient 1 (female; age, 39 years), jaundice persisted in the recipient after the liver transplantation. A reduced dose of FK506 was then given to gradually decrease the total bilirubin level to the normal range. Recipient 1 recovered and was discharged from hospital; however, the patient died of liver cancer recurrence and bone metastasis 6 years post-transplantation. In recipient 2 (male; age, 56 years), the recipient experienced sudden abdominal distension on postoperative day 7. The patient's clotting time was prolonged and the transaminase level was sharply increased, peaking on day 9. The patient was suspected of having small-for-size syndrome and was treated symptomatically. The patient experienced a significant improvement in symptoms on postoperative day 13 and regular postoperative follow-ups were performed until now and the patient is now in remission. In recipient 3 (male; age, 48 years), the recipient recovered well and the liver function returned to normal on postoperative day 3. The patient was discharged from hospital and has been in remission thus far. Adult liver transplantations from pediatric donors are feasible treatments. Systematic donor and recipient assessments, sound surgical skills and optimal postoperative treatments are essential for success in the transplantation of livers from pediatric donors into adult recipients. Considering the condition of the donor liver, the selection of recipients and appropriate surgical methods are particularly important in these cases.

Comparative transcriptomics characterized the distinct biosynthetic abilities of terpenoid and paeoniflorin biosynthesis in herbaceous peony strains.

The herbaceous peony (Paeonia lactiflora Pall.) is a perennial flowering plant of the Paeoniaceae species that is widely cultivated for medical and ornamental uses. The monoterpene glucoside paeoniflorin and its derivatives are the active compounds of the P. lactiflora roots. However, the gene regulation pathways associated with monoterpene and paeoniflorin biosynthesis in P. lactiflora are still unclear. Here, we selected three genotypes of P. lactiflora with distinct morphologic features and chemical compositions that were a result of long-term reproductive isolation. We performed an RNA-sequencing experiment to profile the transcriptome changes of the shoots and roots. Using de novo assembly analysis, we identified 36,264 unigenes, including 521 genes responsible for encoding transcription factors. We also identified 28,925 unigenes that were differentially expressed in different organs and/or genotypes. Pathway enrichment analysis showed that the P. lactiflora unigenes were significantly overrepresented in several secondary metabolite biosynthesis pathways. We identified and profiled 33 genes responsible for encoding the enzymescontrolling the major catalytic reactions in the terpenoid backbone and in monoterpenoid biosynthesis. Our study identified the candidate genes in the terpenoid biosynthesis pathways, providing useful information for metabolic engineering of P. lactiflora intended for pharmaceutical uses and facilitating the development of strategies to improve marker-assist P. lactiflora in the future.

Engineered Recombinant Escherichia coli Probiotic Strains Integrated with F4 and F18 Fimbriae Cluster Genes in the Chromosome and Their Assessment of Immunogenic Efficacy in Vivo.

F4 (K88) and F18 fimbriaed enterotoxigenic Escherichia coli (ETEC) are the predominant causes of porcine postweaning diarrhea (PWD), and vaccines are considered the most effective preventive approach against PWD. Since heterologous DNA integrated into bacterial chromosomes could be effectively expressed with stable inheritance, we chose probiotic EcNc (E. coli Nissle 1917 prototype cured of cryptic plasmids) as a delivery vector to express the heterologous F4 or both F4 and F18 fimbriae and sequentially assessed their immune efficacy of anti-F4 and F18 fimbriae in both murine and piglet models. Employing the CRISPR-cas9 technology, yjcS, pcadA, lacZ, yieN/trkD, maeB, and nth/tppB sites in the chromosome of an EcNc strain were targeted as integration sites to integrate F4 or F18 fimbriae cluster genes under the Ptet promotor to construct two recombinant integration probiotic strains (RIPSs), i.e., nth integration strain (EcNcΔnth/tppB::PtetF4) and multiple integration strain (EcNc::PtetF18x4::PtetF4x2). Expression of F4, both F4 and F18 fimbriae on the surfaces of two RIPSs, was verified with combined methods of agglutination assay, Western blot, and immunofluorescence microscopy. The recombinant strains have improved adherence to porcine intestinal epithelial cell lines. Mice and piglets immunized with the nth integration strain and multiple integration strain through gavage developed anti-F4 and both anti-F4 and anti-F18 IgG immune responses. Moreover, the serum antibodies from the immunized mice and piglets significantly inhibited the adherence of F4+ or both F4+ and F18+ ETEC wild-type strains to porcine intestinal cell lines in vitro, indicating the potential of RIPSs as promising probiotic strains plus vaccine candidates against F4+/F18+ ETEC infection.

[The corrosion of pure iron in five different mediums].

The sectional test was adopted in this study to investigate the corrosion of pure iron in 0.15 mol/L NaCl solution, Ringer solution, PBS(-) solution, SBF solution and M199 cell culture medium at three different times. The result shows that different mediums have different corrosion effects on pure iron. The arrangement according to the medium's corrosion ability from the strongest to weakest is 0.15 mol/L NaCl solution (Ringer solution), PBS(-) solution, SBF solution and M199 cell culture medium. The results of scanning electron microscopy and energy dispersive X-ray spectrum analyses show that the addition of HPO4(2-), H2POC4-, Ca2+, Mg2+, SO4(2-) and the organic component can inhibit the corrosion to some degree.

Pd-Catalyzed Intramolecular Chemoselective C(sp2)-H and C(sp3)-H Activation of N-Alkyl- N-arylanthranilic Acids.

A controllable palladium-catalyzed intramolecular C-H activation of N-alkyl- N-arylanthranilic acids has been developed. The methodology allows selective synthesis of 1,2-dihydro-(4 H)-3,1-benzoxazin-4-ones and carbazoles from the same starting materials and palladium catalyst. The selectivity is controlled by the oxidant. Silver oxide promotes C(sp3)-H activation/C-O cyclization to provide 1,2-dihydro-(4 H)-3,1-benzoxazin-4-ones, while copper acetate contributes to C(sp2)-H activation/decarboxylative arylation to afford carbazoles. This protocol is demonstrated by its wide substrate scope and good functional group tolerance.

Exenatide Reduces Graft Injury in a Rat Transplantation Model Using Kidneys Donated after Cardiac Death.

Besides being used in the therapy of type 2 diabetes, exenatide reduces cerebral ischemia-reperfusion (I/R) injury. We evaluated the potential effects of exenatide on inhibition of apoptosis in kidney grafts donated after cardiac death and on reduction of I/R injury after kidney transplantation (KTx) in a rat model. We used a rat syngeneic KTx model with kidney grafts obtained after cardiac death, and apoptosis was detected in the graft before KTx. Graft function, rat survival, morphologic examination, and activation of inflammatory molecules were analyzed after KTx. By the end of the cold storage, exenatide pretreatment donors had significantly reduced caspase pathway activation, terminal deoxynucleotidyl transferase dUTP nick-end labeling--positive cells, release of mitochondrial porin proteins into the cytosol, and expression of cleaved caspase-3 and poly (ADP-ribose) polymerase in kidney grafts. Exenatide pretreatment improved renal function survival rate with lower scores of acute tubular necrosis, infiltrating macrophages, and interstitial fibrosis as well as reduced messenger RNA expression of inflammatory mediators (tumor necrosis factor α, interleukin-6, interleukin-1ß, and intercellular adhesion molecule-1) after KTx. Our study showed that exenatide reduced I/R injury in kidneys donated after cardiac death in a rat transplantation model and improved recipient survival and graft function.

A comprehensive analysis of cancer-driving mutations and genes in kidney cancer.

An accumulation of driver mutations is important for cancer formation and progression, and leads to the disruption of genes and signaling pathways. The identification of driver mutations and genes has been the subject of numerous previous studies. The present study was performed to identify cancer-driving mutations and genes in renal cell carcinoma (RCC), prioritizing noncoding variants with a high functional impact, in order to analyze the most informative features. Sorting Intolerant From Tolerant (SIFT), Polymorphism Phenotyping version 2 (Polyphen2) and MutationAssessor were applied to predict deleterious mutations in the coding genome. OncodriveFM and OncodriveCLUST were used to detect potential driver genes and signaling pathways. The functional impact of noncoding variants was evaluated using Combined Annotation Dependent Depletion, FunSeq2 and Genome-Wide Annotation of Variants. Noncoding features were analyzed with respect to their enrichment of high-scoring variants. A total of 1,327 coding mutations in clear cell RCC, 258 in chromophobe RCC and 1,186 in papillary RCC were predicted to be deleterious by all three of MutationAssessor, Polyphen2 and SIFT. In total, 77 genes were positively selected by OncodriveFM and 1 by OncodriveCLUST, 45 of which were recurrently mutated genes. In addition, 10 signaling pathways were recurrently mutated and had a high functional impact bias (FM bias), and 31 novel signaling pathways with high FM bias were identified. Furthermore, noncoding regulatory features and conserved regions contained numerous high-scoring variants, and expression, replication time, GC content and recombination rate were positively correlated with the densities of high-scoring variants. In conclusion, the present study identified a list of cancer-driving genes and signaling pathways, features like regulatory elements, conserved regions, replication time, expression, GC content and recombination rate are major factors that affect the distribution of high-scoring non-coding mutations in kidney cancer.

Attenuation of renal ischemia/reperfusion injury by oleanolic acid preconditioning via its antioxidant, anti­inflammatory, and anti­apoptotic activities.

Ischemia/reperfusion (I/R)­associated acute kidney injury is a major clinical problem in both native and transplanted kidneys. Renal I/R, and subsequent renal injury, may be attributed to oxidative stress, inflammation, and apoptosis. Oleanolic acid (OA) is a natural product, which possesses antioxidant, anti­inflammatory, and anti­apoptotic activities. The present study aimed to examine the effects of OA preconditioning on renal I/R and the possible underlying mechanisms. In a renal I/R model, rats were administered OA (12.5, 25 and 50 mg/kg) for 15 consecutive days prior to bilateral renal I/R induction. Serum samples and kidneys were then collected and stored for subsequent determination. The results of the present study demonstrated that OA significantly and dose­dependently attenuated I/R­induced renal damage. OA prevented renal I/R injury, as evidenced by decreased levels of blood urea nitrogen, creatinine, kidney injury molecule­1 and lactate dehydrogenase. In addition, OA defended against oxidative stress, as reflected by decreased levels of methane dicarboxylic aldehyde, increased activities of superoxide dismutase, catalase and glutathione peroxidase, and increased glutathione (GSH) levels. Levels of proinflammatory cytokines, interferon­Î³, interleukin (IL)­6) and myeloperoxidase, were also reduced by OA, whereas the anti­inflammatory cytokine IL­10 was increased. Furthermore, OA prevented I/R­induced apoptotic cell death, and prevented decreases in the mRNA expression levels of nuclear factor erythroid 2­related factor 2 (Nrf2) and γ­glutamylcysteine ligase (GCLc). Conversely, buthionine sulphoximine attenuated the protective effects of OA on renal I/R injury. These results indicated that OA preconditioning may prevent I/R­induced renal damage via antioxidant, anti­inflammatory, and anti­apoptotic activities. Stabilization of Nrf2/GCLc signaling and subsequent maintenance of the GSH pool is critical for the protective effects of OA against renal I/R injury. The present study reported a novel therapeutic strategy for the treatment of renal I/R injury.

Strontium coating by electrochemical deposition improves implant osseointegration in osteopenic models.

Osteopenia, a preclinical state of osteoporosis, restricts the application of adult orthodontic implant anchorage and tooth implantation. Strontium (Sr) is able to promote bone formation and inhibit bone absorption. The aim of the present study was to evaluate a new method for improving the success rate of dental implantation. In this study, an electrochemical deposition (ECD) method was used to prepare a Sr coating on a titanium implant. The coating composition was investigated by energy dispersive X-ray spectroscopy and X-ray diffraction, and the surface morphology of the coating was studied using scanning electron microscopy. A total of 24 Sprague-Dawley rats received bilateral ovariectomy (OVX) and an additional 12 rats underwent a sham surgery. All rats were then implanted in the bilateral tibiae with titanium mini-implants with or without a Sr coating. The results of histological examination and a fluorescence double labeling assay showed strong new bone formation with a wider zone between the double labels, a higher rate of bone mineralization and better osseointegration in the OVX rats that received Sr-coated implants compared with the OVX rats that received uncoated implants. The study indicates that Sr coatings are easily applied by an ECD method, and that Sr coatings have a promoting effect on implant osseointegration in animals with osteopenia.