sST2 and Big ET-1 as Alternatives of Multi-Biomarkers Strategies for Prognosis Evaluation in Patients Hospitalized with Heart Failure.

Objective: To identify biomarkers with independent prognostic value and investigate the prognostic value of multiple biomarkers in combination in patients hospitalized with heart failure. Methods: A total of 884 consecutive patients hospitalized with heart failure from 2015 to 2017 were enrolled. Twelve biomarkers were measured on admission, and the relationships between biomarkers and outcomes were assessed. Results: During the median follow-up of 913 days, 291 patients (32.9%) suffered from primary endpoint events. Soluble suppression of tumorigenicity-2 (sST2) (per log [unit] increase, adjusted HR [95% CI]: 1.39 [1.13,1.72], P = 0.002) and big endothelin-1 (big ET-1) (per log [unit] increase, adjusted HR [95% CI]: 1.56 [1.23,1.97], P < 0.001) remained independent predictors of primary endpoint event after adjusting for other predictors including N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT). Both sST2 (C-statistic: 0.810 vs 0.801, P = 0.005, and 0.832 vs 0.826, P = 0.024, respectively) and big ET-1 (C-statistic: 0.829 vs 0.801, P = 0.001, and 0.843 vs 0.826, P < 0.001, respectively) significantly improved the predictive value for primary endpoint event at 1 year and 3 years. However, only big ET-1 (C-statistic: 0.852 vs 0.846, P = 0.014) significantly improved the predictive value at 3 months when added to clinical predictors and known biomarkers. According to the number of elevated biomarkers (including NT-proBNP, hs-cTnT, sST2, and big ET-1), patients with three or more elevated biomarkers had a higher risk of primary endpoint event compared to those with two elevated biomarkers (P = 0.001), as well as in patients with two elevated biomarkers compared to those with one elevated biomarker (P = 0.004). However, the risk of primary endpoint event was comparable between patients with one elevated biomarker and those with no elevated biomarker (P = 0.582). Conclusion: Multiple biomarkers in combination could provide a better prognostic value than a single biomarker. sST2 and big ET-1 could act as alternatives of multi-biomarkers strategies for prognosis evaluation beyond NT-proBNP and hs-cTnT in patients hospitalized with heart failure.

Mitochondria Targeted Nanoparticles Potentiate Tumor Chemo-Phototherapy by Toxic Oxidative Stress Mediated Oxeiptosis.

Insufficient accumulation of drug at the tumor site and the low drug response are the main reason for the unsatisfactory effect of cancer therapy. Delivery drugs exquisitely to subcellular level can be employed to reduce side effects, and expand the therapeutic window. Herein, a triphenylphosphine (TPP) modified lipid nanoparticles is designed which are loaded with the photosensitizer indocyanine green (ICG) and chemotherapeutic paclitaxel (PTX) for mitochondria-targeted chemo-phototherapy. Owing to the movement of majority mitochondria along microtubules in cytoplasm, mitochondrial targeting may enable PTX to act more effectively. Meanwhile, the existence of chemo-drug potentiates the phototherapy to achieve synergistic anti-tumor activity. As expected, mitochondria targeting nanomedicine (M-ICG-PTX NPs) showed improved mitochondria targeted cellular distribution and enhanced cell cytotoxicity in vitro. Also, M-ICG-PTX NPs exhibited higher tumor growth inhibition ability by promoting cell apoptosis and oxeiptosis pathway, and high effective inhibition of primary tumor growth and tumor metastasis. Taken together, M-ICG-PTX NPs may be promising nanoplatforms to achieve potent therapeutic effect for the combination of chemo- and photo-therapy (PTT).

Two Birds with One Stone: Copper-Based Adsorbents Used for Photocatalytic Oxidation of Hg0 (Gas) after Removal of PH3.

CuX/TiO2 adsorbents with CuO as the active component were prepared via a simple impregnation method for efficient purification of phosphine (PH3) under the conditions of low temperatures (90 °C) and low oxygen concentration (1%). The PH3 breakthrough capacity of optimal adsorbent (Cu30/TiO2) is 136.2 mg(PH3)·gsorbent-1, and the excellent dephosphorization performance is mainly attributed to its abundant sur face-active oxygen and alkaline sites, large specific surface area, and strong interaction between CuO and the support TiO2. Surprisingly, CuO is converted to Cu3P after the dephosphorization by CuX/TiO2. Since Cu3P is a P-type semiconductor with high added value, the deactivated adsorbent (Cu3P/TiO2) is an efficient heterostructure photocatalyst for photocatalytic removal of Hg0 (gas) with the Hg0 removal performance of 92.64% under visible light. This study provides a feasible strategy for the efficient removal and resource conversion of PH3 under low-temperature conditions and the alleviation of the environmental risk of secondary pollution.

Inflammatory biomarkers in assessing severity and prognosis of immune checkpoint inhibitor-associated cardiotoxicity.

AIMS: Inflammatory biomarkers, including CRP, the neutrophil-to-lymphocyte ratio (NLR), and the neutrophil-to-eosinophil ratio (NER), may predict outcomes in cancer. However, their value in immune checkpoint inhibitor (ICI) therapy-associated cardiotoxicity remains elusive. We aimed to characterize the relationship of inflammatory markers with severity of ICI-related cardiotoxicities (iRCs) and prognosis among patients with iRCs. METHODS: Patients who were diagnosed with iRCs between January 2019 and December 2021 were retrospectively enrolled and were dichotomized based on iRC severity into low-grade (grade 1-2) vs. high-grade (grade 3-4) groups. RESULTS: Forty-seven patients were included. The median time-to-event from first ICI infusion to onset of iRCs was 35 days (IQR: 19.0-65.5 days). When compared with respective baseline values, cardiac biomarkers and inflammatory markers were significantly elevated at onset of iRCs. Compared with low-grade iRCs, NER at iRC onset was significantly increased among patients with high-grade iRCs (Group × Time, P < 0.01). When grouped by the median NER (184.33) at iRC onset, NER ≥ 184.33 was associated with high-grade iRCs (OR: 10.77, P < 0.05) and had a 36.3% increased mortality compared to the lower NER group (HR: 2.67, P < 0.05). CONCLUSIONS: In patients who develop iRCs, NER is significantly elevated at iRC onset, and higher NER correlates with greater iRC severity and higher mortality. Larger datasets are needed to validate these findings.

Resource utilization of hazardous solid waste blast furnace dust: Efficient wet desulfurization and metal recovery.

Hazardous solid waste blast furnace dust (BFD) is rich in valuable metal components such as iron (Fe), zinc (Zn), manganese (Mn), and its recycling or harmless treatment is a major challenge. This paper creatively proposes the strategy of "treating waste with waste" by using BFD for desulfurization. The experimental results show that BFD slurry can achieve high-efficiency desulfurization and recovery of Zn resources. The characterization results indicate that ZnO and Fe2O3 in BFD slurry are the main active components of desulfurization, and the consumption of active components is the main reason for the decline of BFD slurry activity. Further semi-continuous experimental research shows that Zn, Fe, and Mn ions in BFD slurry play a crucial role in the catalytic oxidation of sulfur dioxide (SO2). Additionally, the effects of reaction temperature, stirring speed, inlet SO2 concentration, and inlet gas flow rate on the leaching rate of Zn and Fe were investigated. Under optimal conditions (SO2 concentration = 3000 mg‧m-3, reaction temperature = 40 °C, inlet gas flow rate = 300 mL‧min-1, solid-liquid ratio = 0.5 g/300 mL, stirring speed = 600 rpm), the desulfurization rate reaches 100%, and the maximum leaching rate of Zn can reach 44.6%. Based on the experimental and characterization results, the possible mechanism of BFD slurry desulfurization was proposed. This study provides a reference for the application of BFD in the field of wet desulfurization.

Hyperthermia-induced stellate cell deactivation to enhance dual chemo and pH-responsive photothermal therapy for pancreatic cancers.

For pancreatic ductal adenocarcinoma (PDAC) treatment, the deactivation of pancreatic stellate cells (PSCs) by blocking the transforming growth factor ß (TGF-ß) pathway is a promising strategy to inhibit stroma, enhance drug penetration, and greatly amplify chemotherapeutic efficacy. It is known that photothermal therapy (PTT) locally depletes stroma and enhances permeability but whether and how PTT reacts in the molecular pathway to induce PSC deactivation in PDAC has rarely been investigated so far. Herein, C-G NPs are synthesized by loading both acid-responsive photothermal molecules and gemcitabine for investigating both the combinatory chemophotothermal therapy and the interaction between the PTT and TGF-ß pathway in PDAC. Notably, C-G NPs exhibit tumoral acidic pH-activated PTT and succeeded in deactivating PSCs and suppressing the expression level for both TGF-ß and collagen fiber. Furthermore, hyperthermia remodels the tumoral extracellular matrix, significantly improves NP penetration, and boosts the ultimate synergistic chemophotothermal therapeutic efficacy. Importantly, the molecular biology study reveals that hyperthermia leads to the decrease in the mRNA expression of TGF-ß1, SMAD2, SMAD3, α-SMA, and Collagen I in the tumor tissue, which is the key to suppress tumor progression. This research demonstrates that combinatory chemophotothermal therapy holds great promise for PDAC treatment.

N-Acetylcysteine Inhibits Patulin-Induced Apoptosis by Affecting ROS-Mediated Oxidative Damage Pathway.

Patulin (PAT) belongs to the family of food-borne mycotoxins. Our previous studies revealed that PAT caused cytotoxicity in human embryonic kidney cells (HEK293). In the present research, we systematically explored the detailed mechanism of ROS production and ROS clearance in PAT-induced HEK293 cell apoptosis. Results showed that PAT treatment (2.5, 5, 7.5, 10 µM) for 10 h could regulate the expression of genes and proteins involved in the mitochondrial respiratory chain complex, resulting in dysfunction of mitochondrial oxidative phosphorylation and induction of ROS overproduction. We further investigated the role of N-acetylcysteine (NAC), an ROS scavenger, in promoting the survival of PAT-treated HEK293 cells. NAC improves PAT-induced apoptosis of HEK293 cells by clearing excess ROS, modulating the expression of mitochondrial respiratory chain complex genes and proteins, and maintaining normal mitochondrial function. In addition, NAC protects the activity of antioxidant enzymes, maintains normal GSH content, and relieves oxidative damage. Additionally, 4 mM NAC alleviated 7.5 µM PAT-mediated apoptosis through the caspase pathway in HEK293 cells. In summary, our study demonstrated that ROS is significant in PAT-mediated cytotoxicity, which provides valuable insight into the management of PAT-associated health issues.

Involvement of NADPH oxidase in patulin-induced oxidative damage and cytotoxicity in HEK293 cells.

Patulin (PAT) is a kind of mycotoxins that commonly found in decayed fruits and their products. Our previous studies have shown that PAT induced cell apoptosis and the overproduction of reactive oxygen species (ROS) in human embryonic kidney (HEK293) cells. The present study aimed to further investigate the functional role of NADPH oxidase, one of the main cellular sources of ROS, in PAT-induced apoptosis and oxidative damage in HEK293 cells. We demonstrated that the protein and mRNA expression levels of NADPH oxidase catalytic subunit NOX2 and regulatory subunit p47phox were up-regulated under PAT stress. Inhibiting of NADPH oxidase with the specific antagonist diphenyleneiodonium (DPI) suppressed cytotoxicity and apoptosis induced by PAT as evidenced by the increase of cell viability, the decrease of LDH release and the inhibition of caspase activities. Furthermore, DPI re-established mitochondrial membrane potential (MMP) and enhanced cellular ATP content. Importantly, DPI supplementation elevated endogenous GSH contents as well as the ratio of GSH/GSSG. Meanwhile, the antioxidant-enzyme activities of GPx, GR, CAT and SOD were significantly promoted. Collectively, our results suggested that NADPH oxidase played a critical role in PAT-induced nephrotoxicity, and inhibition of NADPH oxidase by DPI attenuated cell injury and apoptosis via regulation of oxidative damage.

Transcriptomic and Proteomic Analysis Reveals Mechanisms of Patulin-Induced Cell Toxicity in Human Embryonic Kidney Cells.

Patulin (PAT) is a natural mycotoxin that commonly contaminates fruits and fruit-based products. Previous work indicated that PAT-induced apoptosis in which reactive oxygen species (ROS) are involved in human embryonic kidney (HEK293) cells. To uncover novel aspects of the possible mechanism of PAT nephrotoxicity, the transcriptome and proteome profiles were investigated using the digital gene expression (DGE) and isobaric tags for relative and absolute quantitation (iTRAQ) proteomic approaches. A total of 127 genes and 85 proteins were found to express differentially in response to 5 µM PAT for 10 h in HEK293 cells. The most dramatic changes of expression were noticed with genes or proteins related to apoptosis, oxidative phosphorylation ribosome and cell cycle. Especially, the activation of caspase 3, UQCR11, active transport form and endocytosis appeared to be crucial in PAT kidney cytotoxicity. PAT also seemed to be associated with cancer and neuropathic disease as pathways associated with carcinogenesis, Alzheimer's disease and Parkinson's disease were induced. Overall, this study served to uncover overall insights associated with signaling pathway that modulated the PAT toxicity mechanism.

Intravenous Anesthetics Enhance the Ability of Human Bone Marrow-Derived Mesenchymal Stem Cells to Alleviate Hepatic Ischemia-Reperfusion Injury in a Receptor-Dependent Manner.

BACKGROUND/AIMS: The degree of hepatic ischemia-reperfusion injury (HIRI) is highly relevant to the incidence of postoperative liver failure and mortality. Bone marrow-derived mesenchymal stem cells (BM-MSCs) have been shown to migrate to the liver and restore the damaged liver. Intravenous anesthetics are commonly used in the perioperative period; however, it is not yet known whether they have an influence on the functions of BM-MSCs and eventually affect the recovery of HIRI. METHODS: A rat model of HIRI and a hypoxia-reoxygenation (H/R) model using L02 cells were generated, and human BM-MSCs (hBM-MSCs) were injected through the portal vein or co-cultured with L02 cells in a Transwell system, respectively. Three intravenous anesthetics, namely, dexmedetomidine, midazolam, and propofol, were given as pretreatments to hBM-MSCs. Quantitative real-time PCR for growth factors (HGF, FGF, VEGF, and IGF) and a migration assay were used to detect the paracrine and migration abilities of hBM-MSCs. NF-κB expression was detected using an immunofluorescence method. Furthermore, three receptor inhibitors, namely, yohimbine, PK11195, and bicuculline, were given to explore whether the three anesthetics worked in a receptor-dependent manner. RESULTS: Preconditioning with dexmedetomidine and midazolam, but not propofol, enhanced the efficacy of hBM-MSCs in HIRI. Dexmedetomidine and midazolam, but not propofol, changed the paracrine spectrum and NF-κB p65 nuclear translocation of hBM-MSCs co-cultured with L02 cells after H/R injury. All three anesthetics enhanced the migration ability of hBM-MSCs when cultured in L02 H/R conditioned medium. However, the addition of receptor antagonists resulted in an opposite tendency. CONCLUSIONS: The intravenous anesthetics dexmedetomidine and midazolam enhanced the liver protective effects of hBM-MSCs during HIRI more effectively than propofol, by binding with their receptors and regulating the paracrine effect, migration ability, and NF-κB p65 nuclear translocation of hBM-MSCs.

Uridine diphosphate-glucuronosyltransferase 2B15 D85Y gene polymorphism is associated with lower prostate cancer risk: a systematic review and meta-analysis.

UGT2B15 (uridine diphosphate-glucuronosyltransferase 2B15) catalyzes the conversion of lipophilic C19 steroid androgens such as dihydrotestosterone (DHT) into water-soluble metabolites that can be excreted. Studies of the association between the UGT2B15 gene D85Y polymorphism and prostate cancer have yielded contradictory results. We therefore systematically searched in the PubMed, EMBASE, Science Direct/Elsevier, CNKI, and Cochrane Library databases, and identified six relevant studies with which to perform a meta-analysis of the relation between UGT2B15 D85Y polymorphism and prostate cancer risk. Our meta-analysis revealed a significant association between UGT2B15 D85Y gene polymorphism and prostate cancer in all genetic models (P<0.05). The combined odds ratios and 95% confidence intervals were as follows: additive model, 0.53 and 0.32-0.88; dominant model, 0.51 and 0.33-0.79; recessive model, 0.76 and 0.60-0.96; co-dominant model, 0.55 and 0.35-0.86; and allele model, 0.70 and 0.55-0.89. These results are consistent with the idea that the UGT2B15 D85Y enzyme variant reduces the risk of prostate cancer by efficiently metabolizing dihydrotestosterone (DHT), which is associated with prostate cancer progression.

Enhanced methane production of vinegar residue by response surface methodology (RSM).

As the by-product of the vinegar production process, a large number of vinegar residue has been abandoned and caused a serious environmental pollution. Anaerobic digestion has been proved to be able to dispose and convert vinegar residue into bioenergy but still need to improve the efficiency. This study applied central composite design of response surface methodology to investigate the influences of feed to inoculum ratio, organic loading, and initial pH on methane production and optimize anaerobic digestion condition. The maximum methane yield of 203.91 mL gVS-1 and biodegradability of 46.99% were obtained at feed to inoculum ratio of 0.5, organic loading of 31.49 gVS L-1, and initial pH of 7.29, which was considered as the best condition. It has a very significant improvement of 69.48% for methane production and 52.02% for biodegradability compared with our previous study. Additionally, a high methane yield of 182.09 mL gVS-1 was obtained at feed to inoculum ratio of 1.5, organic loading of 46.22 gVS L-1, and initial pH of 7.32. And it is more appropriate to apply this condition in industrial application owing to the high feed to inoculum ratio and organic loading. Besides, a significant interaction was found between feed to inoculum ratio and organic loading. This study maximized the methane production of vinegar residue and made a good foundation for further study and future industrial application.

Colorimetric detection of glutathione in cells based on peroxidase-like activity of gold nanoclusters: A promising powerful tool for identifying cancer cells.

Glutathione (GSH), the most abundant biothiol in cells, not only plays a pivotal role in protective and detoxifying functions of the cell, but also serves as a very important mediator in many cellular functions. Especially, the difference of GSH level between cancer cells and normal cells is regarded as one of most important physiological parameters for cancer diagnosis. It is thereby extremely necessary to develop a simple, sensitive, and reliable analytical method for detection of GSH in cells. On the basis of the inhibition effect of GSH on the peroxidase-like activity of GSH stabilized gold nanoclusters, here a novel and facile strategy for colorimetric detection of cellular GSH level was well established. In this sensing system, GSH can effectively inhibit the oxidation of peroxidase substrate 3,3',5,5'-tetramethylbenzidine (TMB) to produce a blue colored product. Under the optimized conditions, the absorbance at 652 nm against GSH concentration shows a linear relationship within a range from 2 to 25 µM with detection limit of 420 nM. This excellent property allows our approach to be used to accurately evaluate the cellular GSH levels, and it is revealed that the overall GSH level in cancer cells was much higher than that in normal cells. The presented assay will enable a powerful tool for identifying cancer cells in a simple manner for biomedical diagnosis associated with GSH.

Hyperglycemia Aggravates Hepatic Ischemia Reperfusion Injury by Inducing Chronic Oxidative Stress and Inflammation.

Aim. To investigate whether hyperglycemia will aggravate hepatic ischemia reperfusion injury (HIRI) and the underlying mechanisms. Methods. Control and streptozotocin-induced diabetic Sprague-Dawley rats were subjected to partial hepatic ischemia reperfusion. Liver histology, transferase, inflammatory cytokines, and oxidative stress were assessed accordingly. Similarly, BRL-3A hepatocytes were subjected to hypoxia/reoxygenation (H/R) after high (25 mM) or low (5.5 mM) glucose culture. Cell viability, reactive oxygen species (ROS), and activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB) were determined. Results. Compared with control, diabetic rats presented more severe hepatic injury and increased hepatic inflammatory cytokines and oxidative stress. HIRI in diabetic rats could be ameliorated by pretreatment of N-acetyl-L-cysteine (NAC) or apocynin. Excessive ROS generation and consequent Nrf2 and NF-κB translocation were determined after high glucose exposure. NF-κB translocation and its downstream cytokines were further increased in high glucose cultured group after H/R. While proper regulation of Nrf2 to its downstream antioxidases was observed in low glucose cultured group, no further induction of Nrf2 pathway by H/R after high glucose culture was identified. Conclusion. Hyperglycemia aggravates HIRI, which might be attributed to chronic oxidative stress and inflammation and potential malfunction of antioxidative system.

Ureteroscopy and cystoscopy training: comparison between transparent and non-transparent simulators.

BACKGROUND: Simulators have been widely used to train operational skills in urology, how to improve its effectiveness deserves further investigation. In this paper, we evaluated training using a novel transparent anatomic simulator, an opaque model or no simulator training, with regard to post-training ureteroscopy and cystoscopy proficiency. METHODS: Anatomically correct transparent and non-transparent endourological simulators were fabricated. Ten experienced urologists provided a preliminary evaluation of the models as teaching tools. 36 first-year medical students underwent identical theoretical training and a 50-point examination of theoretical knowledge. The students were randomly assigned to receive training with the transparent simulator (Group 1), the non-transparent simulator (Group 2) or detailed verbal instruction only (Group 3). 12 days after the training session, the trainees' skills at ureteral stent insertion and removal were evaluated using the Uro-Scopic Trainer and rated on an Objective Structured Assessment of Technical Skills (OSATS) scale. RESULTS: The new simulators were successfully fabricated in accordance with the design parameters. Of the ten urologists invited to evaluate the devices, 100% rated the devices as anatomically accurate, 90% thought both models were easy to use and 80% thought they were good ureteroscopy and cystoscopy training tools. The scores on the theoretical knowledge test were comparable among the training groups, and all students were able to perform ureteral stent insertion and removal. The mean OSATS scores of groups 1, 2 and 3 were 21.83 ± 3.64, 18.50 ± 4.03 and 15.58 ± 2.23 points, respectively, (p = 0.001). CONCLUSIONS: Simulator training allowed students to achieve higher ureteroscopic and cystoscopic proficiency, and transparent simulators were more effective than non-transparent simulators.

Regulation of autophagy of prostate cancer cells by ß-catenin signaling.

BACKGROUND/AIMS: Autophagy is a cellular degradation process for the recycling of damaged or superfluous intracellular compartments to provide an alternative energy source during periods of metabolic stress for maintaining cell homeostasis and viability. Although autophagy in different contexts have been shown to use similar signaling pathways, the exact molecular regulation of autophagy has been found to be cell-type dependent. METHODS: We used rapamycin to trigger autophagy and used nitric oxide (NO) to inhibit autophagy in prostate cancer cells. IWP-2 was used to inhibit ß-catenin signaling. Autophagy-associated proteins were examined by Western blot. RESULTS: We found that nitric oxide (NO), a potent cellular messenger, impaired rapamycin-induced autophagy in prostate cancer cells. Further analyses showed that NO induced nuclear accumulation of ß-catenin, a key factor of Wnt signaling pathway, to inhibit autophagy in prostate cancer cells. CONCLUSIONS: We demonstrate involvement of ß-catenin signaling in the regulation of autophagy of prostate cancer cells. Our results shed light on a previously unappreciated ß-catenin signaling pathway for regulating autophagy in prostate cancer.

Preclinical evaluation of a newly designed ureteral stent and magnetic retrieval catheter for minimally invasive stent removal.

OBJECTIVE: To develop a simple minimally invasive method for ureteral stent removal that does not require cystoscopy or fluoroscopic guidance. MATERIALS AND METHODS: We developed a novel ureteral stent comprising the main body of a stent and an iron oxide-coated net that was woven of processed polyester sutures. The ureteral stent was retrieved by a magnetic retrieval catheter with small hooks on the neck surface. Detailed analysis of the necessary mechanical and magnetic properties was performed, and we conducted retrieval tests of the ureteral stent from a specially designed urinary system model. RESULTS: The breaking strength and Young modulus of the processed polyester sutures were 10.12 ± 0.30 N and 9143 ± 7 N/tex, respectively. Thermogravimetric tests showed that the iron (III) oxide powders on the processed sutures accounted for 23% of the total weight. The magnetization value of the magnetic retrieval catheter was 578 emu/g. The dissolution times of polyvinyl alcohol wrapped the net in saline or urine were 24.2 ± 2.0 and 23.6 ± 3.1 hours, respectively. All stents in both the experimental and the control groups were successfully removed from the specially designed urinary model. However, the retrieval time in the experimental group was significantly shorter than that in the control group (38.6 ± 12.6 vs 59 ± 15.7 seconds; P <.05). CONCLUSION: Ureteral stent removal using a magnetic retrieval catheter with small capture devices is considered feasible. This technique is easy to learn and should be considered as suitable for use on an outpatient basis.

Platelet-derived growth factor receptor beta: a novel urinary biomarker for recurrence of non-muscle-invasive bladder cancer.

Non-muscle-invasive bladder cancer (NMIBC) is one of the most common malignant tumors in the urological system with a high risk of recurrence, and effective non-invasive biomarkers for NMIBC relapse are still needed. The human urinary proteome can reflect the status of the microenvironment of the urinary system and is an ideal source for clinical diagnosis of urinary system diseases. Our previous work used proteomics to identify 1643 high-confidence urinary proteins in the urine from a healthy population. Here, we used bioinformatics to construct a cancer-associated protein-protein interaction (PPI) network comprising 16 high-abundance urinary proteins based on the urinary proteome database. As a result, platelet-derived growth factor receptor beta (PDGFRB) was selected for further validation as a candidate biomarker for NMIBC diagnosis and prognosis. Although the levels of urinary PDGFRB showed no significant difference between patients pre- and post-surgery (n = 185, P>0.05), over 3 years of follow-up, urinary PDGFRB was shown to be significantly higher in relapsed patients (n = 68) than in relapse-free patients (n = 117, P<0.001). The levels of urinary PDGFRB were significantly correlated with the risk of 3-year recurrence of NMIBC, and these levels improved the accuracy of a NMIBC recurrence risk prediction model that included age, tumor size, and tumor number (area under the curve, 0.862; 95% CI, 0.809 to 0.914) compared to PDGFR alone. Therefore, we surmise that urinary PDGFRB could serve as a non-invasive biomarker for predicting NMIBC recurrence.

Screening biomarkers of prostate cancer by integrating microRNA and mRNA microarrays.

OBJECTIVE: In this study, we screened microRNA (miRNA) target genes of prostate cancer by integrating miRNA and mRNA expression profiles after target prediction and performed function enrichment analysis for selected candidate genes. METHODS: The miRNA expression profile (GSE36802) and mRNA expression profile (GSE36801) were downloaded from the Gene Expression Omnibus database. We processed data and identified the differentially expressed miRNAs and mRNAs with R packages. Verified targets of miRNAs were identified through miRecods and miRTarBase. Then, software of Search Tool for the Retrieval of Interacting Genes was used to construct the interaction network of target genes. Finally, we performed function enrichment analysis for genes in the interaction network with the Functional Classification Tool. RESULTS: A total of 22 upregulated and 8 downregulated miRNAs were detected in this study, of which, hsa-mir-31 was the most overexpressed miRNA in prostate cancer. Both ITGA5 and RDX, two target genes of hsa-mir-31, were found to be differentially expressed from mRNA profiles by overexpressing hsa-mir-31. The cell adhesion molecule was found to be the most significant pathway enriched by ITGA5 and RDX. CONCLUSION: Overexpression of hsa-mir-31 can be a significant marker to distinguish cancer tissues from benign tissues. The targets such as ITGA5 and RDX regulated by hsa-mir-31 are candidate genes of prostate cancer, which provide new treatment strategies for its gene therapy.

Prolonged survival time of allografts by the oral administration of RDP58 linked to the cholera toxin B subunit.

Oral administration, which has been identified as a tool for boosting physiological immunoregulatory mechanisms in an antigen-specific manner, is a more convenient way than classical parenteral injection methods. RDP58 is derived from specific regions of class-I MHC molecules and is known to have immunomodulatory effects after intraperitoneal injection or intravenous administration. To determine whether the oral administration of RDP58 conjugated to the cholera toxin B subunit (CTB) can better induce peripheral tolerance than the use of traditional methods, we used various feeding regimens and methods of administration using equivalent doses of antigen during rat kidney transplantation. The results showed that RDP58-GC/CTB treatment increased the activity of Haem oxygenase-1 (HO-1) in vivo and significantly improved the survival and histopathology of allograft kidney tissue relative to the oral administration of RDP58 alone. These results suggest that the administration of RDP58 linked to CTB outweighs the benefits of oral administration of RDP58 alone for prolonging the survival time of kidney transplantation. This study supports the potential therapeutic use of oral administration of RDP58 linked to CTB as a platform molecule in the treatment of allograft rejection.