Controlled In Situ Self-Assembly of Biotinylated Trans-Cyclooctene Nanoparticles for Orthogonal Dual-Pretargeted Near-Infrared Fluorescence and Magnetic Resonance Imaging.

A pretargeted strategy that decouples targeting vectors from radionuclides has shown promise for nuclear imaging and/or therapy in vivo. However, the current pretargeted approach relies on the use of antibodies or nanoparticles as the targeting vectors, which may be compromised by poor tissue penetration and limited accumulation of targeting vectors in the tumor tissues. Herein, we present an orthogonal dual-pretargeted approach by combining stimuli-triggered in situ self-assembly strategy with fast inverse electron demand Diels-Alder (IEDDA) reaction and strong biotin-streptavidin (SA) interaction for near-infrared fluorescence (NIR FL) and magnetic resonance (MR) imaging of tumors. This approach uses a small-molecule probe (P-Cy-TCO&Bio) containing both biotin and trans-cyclooctene (TCO) as a tumor-targeting vector. P-Cy-TCO&Bio can efficiently penetrate subcutaneous HeLa tumors through biotin-assisted targeted delivery and undergo in situ self-assembly to form biotinylated TCO-bearing nanoparticles (Cy-TCO&Bio NPs) on tumor cell membranes. Cy-TCO&Bio NPs exhibited an "off-on" NIR FL and retained in the tumors, offering a high density of TCO and biotin groups for the concurrent capture of Gd-chelate-labeled tetrazine (Tz-Gd) and IR780-labeled SA (SA-780) via the orthogonal IEDDA reaction and SA-biotin interaction. Moreover, Cy-TCO&Bio NPs offered multiple-valent binding modes toward SA, which additionally regulated the cross-linking of Cy-Gd&Bio NPs into microparticles (Cy-Gd&Bio/SA MPs). This process could significantly (1) increase r1 relaxivity and (2) enhance the accumulation of Tz-Gd and SA-780 in the tumors, resulting in strong NIR FL, bright MR contrast, and an extended time window for the clear and precise imaging of HeLa tumors.

Cascade In Situ Self-Assembly and Bioorthogonal Reaction Enable the Enrichment of Photosensitizers and Carbonic Anhydrase Inhibitors for Pretargeted Cancer Theranostics.

We report here a tumor-pretargted theranostic approach for multimodality imaging-guided synergistic cancer PDT by cascade alkaline phosphatase (ALP)-mediated in situ self-assembly and bioorthogonal inverse electron demand Diels-Alder (IEDDA) reaction. Using the enzymatic catalysis of ALP that continuously catalyses the dephosphorylation and self-assembly of trans-cyclooctene (TCO)-bearing P-FFGd-TCO, a high density of fluorescent and magnetic TCO-containing nanoparticles (FMNPs-TCO) can be synthesized and retained on the membrane of tumor cells. They can act as 'artificial antigens' amenable to concurrently capture lately administrated tetrazine (Tz)-decorated PS (775NP-Tz) and carbonic anhydrase (CA) inhibitor (SA-Tz) via the fast IEDDA reaction. This two-step pretargeting process can further induce FMNPs-TCO regrowth into microparticles (FMNPs-775/SA) directly on tumor cell membranes, which is analyzed by bio-SEM and fluorescence imaging. Thus, efficient enrichment of both SA-Tz and 775NP-Tz in tumors can be achieved, allowing to alleviate hypoxia by continuously inhibiting CA activity and improving PDT of tumors. Findings show that subcutaneous HeLa tumors could be completely eradicated and no tumor recurred after irradiation with an 808 nm laser (0.33 W cm-2 , 10 min). This pretargeted approach may be applied to enrich other therapeutic agents in tumors to improve targeted therapy.

Smart Lipid Nanoparticle that Remodels Tumor Microenvironment for Activatable H2S Gas and Photodynamic Immunotherapy.

Hydrogen sulfide (H2S) has shown promise for gas therapy. However, it is still controversial whether H2S can remodel the tumor microenvironment (TME) and induce robust antitumor immunity. Here, a tumor-targeting and TME-responsive "smart" lipid nanoparticle (1-JK-PS-FA) is presented, which is capable of delivering and releasing H2S specifically in tumor tissues for on-demand H2S gas and photodynamic immunotherapy. 1-JK-PS-FA enables a burst release of H2S in the acidic TME, which promptly reduces the embedded organic electrochromic materials and consequently switches on near-infrared fluorescence and photodynamic activity. Furthermore, we found that high levels of H2S can reprogram the TME by reducing tumor interstitial fluid pressure, promoting angiogenesis, increasing vascular permeability, ameliorating hypoxia, and reducing immunosuppressive conditions. This leads to increased tumor uptake of 1-JK-PS-FA, thereby enhancing PDT efficacy and eliciting strong immunogenic cell death during 808 nm laser irradiation. Therefore, 1-JK-PS-FA permits synergistic H2S gas and photodynamic immunotherapy, effectively eradicating orthotopic breast tumors and preventing tumor metastasis and recurrence. This work showcases the capacity of H2S to reprogram the TME to enhance H2S gas and immunotherapy.

Ratiometric Near-Infrared Fluorescence Liposome Nanoprobe for H2S Detection In Vivo.

Accurate detection of H2S is crucial to understanding the occurrence and development of H2S-related diseases. However, the accurate and sensitive detection of H2S in vivo still faces great challenges due to the characteristics of H2S diffusion and short half-life. Herein, we report a H2S-activatable ratiometric near-infrared (NIR) fluorescence liposome nanoprobe HS-CG by the thin-film hydration method. HS-CG shows "always on" fluorescence signal at 816 nm and low fluorescence signal at 728 nm; the NIR fluorescence ratio between 728 and 816 nm (F728/F816) is low. Upon reaction with H2S, the fluorescence at 728 nm could be more rapidly turned on due to strong electrostatic interaction between enriched HS- and positively charged 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine (DPPC) doped in the liposome nanoprobe HS-CG, resulting in a large enhancement of F728/F816, which allows for sensitive visualization of the tumor H2S levels in vivo. This study demonstrates that this strategy of electrostatic adsorption between HS- and positively charged molecules provides a new way to enhance the reaction rate of the probe and H2S, thus serving as an effective platform for improving the sensitivity of imaging.

OCT3/4 enhances tumor immune response by upregulating the TET1-dependent NRF2/MDM2 axis in bladder cancer.

This study aimed to investigate the function of OCT3/4 on tumor immune escape in bladder cancer. Initially, the expression of OCT3/4, TET1, NRF2 and MDM2 was quantified in tumor tissues and cells, followed by gain- or loss-of-function studies to define their roles in cell migration, invasion and apoptosis and tumorigenicity in nude mice. Bladder cancer presented with abundant expression levels of OCT3/4, TET1, NRF2 and MDM2. We found that OCT3/4 promoted TET1 expression via binding to its promoter and that TET1 recruited MLL protein to NRF2 promoter and upregulated its expression, while NRF2 enhanced MDM2 expression. Upregulated MDM2 accelerated tumor immune escape in bladder cancer in mice. OCT3/4 knockdown suppressed the cell migration and invasion while inducing apoptosis, and consequently prevented tumor growth and immune escape in mice. Collectively, OCT3/4 may promote the progression of tumor immune escape in bladder cancer through acting as a promoter of the TET1/NRF2/MDM2 axis.

SIRT3 affects mitochondrial metabolic reprogramming via the AMPK-PGC-1α axis in the development of benign prostatic hyperplasia.

BACKGROUND: Sirtuin 3 (SIRT3) has been reported to share an association with mitochondrial metabolic reprogramming. However, the molecular mechanism underlying is not well understood, especially in benign prostatic hyperplasia (BPH). Therefore, the purpose of this study was to research whether SIRT3 can affect the progression of BPH via the regulation of mitochondrial metabolic reprogramming. METHODS: Following the development of a rat model of BPH using testosterone propionate (TP), we extracted prostate tissues from sham-operated and BPH rats. Subsequently, bioinformatics prediction was used to screen the genes differentially expressed in BPH. To verify the role played by SIRT3 in BPH, we injected AAV9-SIRT3 into rats, followed by TP treatment. Prostate epithelial cells (PEC) were treated with TP to assess the mitochondrial morphology, mitochondrial membrane potential, and expression of enzymes related to the oxidative phosphorylation pathway after SIRT3 expression alteration. Finally, we examined the expression of AMPK-PGC-1α pathway in tissues and cells. RESULTS: SIRT3 was reduced in the prostate tissues of BPH rats. After overexpression of SIRT3, mitochondrial morphology was more stable in prostate tissues of BPH rats and in TP-treated PEC, with significant increases in mitochondrial membrane potential and in the expression of oxidative phosphorylation-related enzymes in the cytoplasm. Moreover, SIRT3 significantly activated the AMPK-PGC-1α signaling pathway, which maintained the stability of mitochondrial membrane potential as well as mitochondrial structure, thus alleviating the symptoms of BPH. CONCLUSION: SIRT3 maintained the stability of mitochondrial membrane potential as well as mitochondrial structure by activating the AMPK-PGC-1α pathway, thereby alleviating the symptoms of BPH.

Twin Nanopipettes for Real-Time Electrochemical Monitoring of Cytoplasmic Microviscosity at a Single-Cell Level.

Cytoplasmic microviscosity (CPMV) plays essential roles in governing the diffusion-mediated cellular processes and has been recognized as a reliable indicator of the cellular response of many diseases and malfunctions. Current CPMV studies are exclusively established by probe-assisted optical methods, which nevertheless necessitate the complicated synthesis and delivery of optical probes into cells and thus the issues of biocompatibility and bio-orthogonality. Using twin nanopipettes integrated with a patch-clamp system, a practical electrochemical single-cell measurement is presented, which is capable of real-time and long-term CPMV detection without cell disruption. Specifically, upon the operation of the twin nanopipettes, the cellular CPMV status, which is correlated to cytoplasmic ionic mobility, could be sensibly transduced via the ionic current passing through the nanosystem. The average CPMV value of HeLa cells was detected as ca. 86 cP. Notably, the correlation between chemotherapy and CPMV alterations makes this approach possible for the real-time and long-term assessment of the evolution of external stimuli, as exemplified by the two natural products taxol and colchicine. Integrated with the patch-clamp setup, this study features the first use of twin nanopipettes for electrochemical CPMV monitoring of single living cells, and it is expected to inspire more interest in the exploitation of dual- and multiple nanopipettes for advanced single-cell analysis.

High power pump and signal combiner for backward pumping structure with two different fused fiber bundle designs by means of pretapered pump fibers.

We report on two high power backward (6 + 1) × 1 pump and signal combiners with different optical designs based on end-pumping technique, each achieving more than 95% coupling ratio of signal light, 98% coupling ratio of pump light, and a total pump power of 2.95kW. Both designs solve the problem of non-uniform arrangement in asymmetric fiber bundles by the pretreatment of the pump fibers and signal fiber. Asymmetric fiber bundle in backward pump and signal combiners means the pump input fibers and signal output fiber have different cladding diameters. Two 3D simulation models were built to calculate the parameters of the fused fiber bundles for matching the mode field diameter between the signal input and the output fibers. Both optical designs of backward combiners were developed based on the beam propagation method and confirmed by experimental results.

An inter-correlated cytokine network identified at the center of cytokine storm predicted COVID-19 prognosis.

The hyper-inflammatory response is thought to be a major cause of acute respiratory distress syndrome (ARDS) in patients with COVID-19. Although multiple cytokines are reportedly associated with disease severity, the key mediators of SARS-CoV-2 induced cytokine storm and their predictive values have not been fully elucidated. The present study analyzed maximal and early (within 10 days after disease onset) concentrations of 12-plex cytokines in plasma. We found consistently elevated plasma levels of IL-6, IL-8 and IL-5 in patients who were deceased compared with those who had mild/moderate or severe disease. The early plasma concentrations of IFN-a and IL-2 positively correlated with the length of the disease course. Moreover, correlation network analysis showed that IL-6, IL-8, and IL-5 located at the center of an inter-correlated cytokine network. These findings suggested that IL-8, IL-6, IL-5 might play central roles in cytokine storms associated with COVID-19 and that the early detection of multiple plasma cytokines might help to predict the prognosis of this disease.

Anticancer evaluation of a novel dithiocarbamate hybrid as the tubulin polymerization inhibitor.

Novel quinoline-dithiocarbamate hybrids were synthesized and designed by the molecular hybridization strategy. All these derivatives were evaluated for their antiproliferative activity against three selected cancer cell lines (MGC-803, HepG-2 and PC-3). Among them, compound 10c displayed the best antiproliferative activity against PC-3 cells with an IC50 value of 0.43 µM. Celluar mechanisms investigated that compound 10c could inhibit the migration against PC-3 cells by regulation the expression levels of E-cadherin and N-cadherin. Compound 10c induced morphological changes of PC-3 cells and regulated apoptosis-related proteins (Bcl-2, Bax and Cleaved-Parp). In addition, compound 10c inhibited tubulin polymerization in vitro with an IC50 value of 4.02 µM. Importantly, compound 10c inhibited the growth of PC-3 cells in vivo with the low toxicity toward mice. These results suggested that compound 10c might be an antitumor agent with potential for treating prostate cancer.

The status and characteristics of urinary stone composition in China.

OBJECTIVES: To explore characteristics of urinary stone composition in China, and determine the effects of gender, age, body mass index (BMI), stone location, and geographical region on stone composition. PATIENTS AND METHODS: We prospectively used Fourier-transform infrared spectroscopy to analyse stones from consecutive patients presenting with new-onset urolithiasis at 46 hospitals in seven geographical areas of China, between 1 June 2010 and 31 May 2015. Chi-squared tests and logistic regression analyses were used to determine associations between stone composition and gender, age, BMI, stone location, and geographical region. RESULTS: The most common stone constituents were: calcium oxalate (CaOx; 65.9%), carbapatite (15.6%), urate (12.4%), struvite (2.7%), and brushite (1.7%). CaOx and urate stones occurred more frequently in males, whereas carbapatite and struvite were more common in females (P < 0.01). CaOx and carbapatite were more common in those aged 30-50 and 20-40 years than in other groups. Brushite and struvite were most common amongst those aged <20 and >70 years. The detection rate of urate increased with age, whilst cystine decreased with age. Obese patients were more likely to have urate stones than carbapatite or brushite stones (P < 0.01). CaOx, carbapatite, brushite, and cystine stones were more frequently found in the kidney than other types, whereas urate and struvite were more frequent in the bladder (P < 0.01). Stone composition varied by geographical region. CONCLUSIONS: The most common stone composition was CaOx, followed by carbapatite, urate, struvite, and brushite. Stone composition differed significantly in patients grouped by gender, age, BMI, stone location, and geographical region.

Nanoporous Semiconductor Electrode Captures the Quantum Dots: Toward Ultrasensitive Signal-On Liposomal Photoelectrochemical Immunoassay.

Liposomal photoelectrochemical (PEC) bioanalysis has recently emerged and exhibited great potential in sensitive biomolecular detection. Exploration of the facile and efficient route for advanced liposomal PEC bioanalysis is highly appealing. In this work, we report the split-type liposomal PEC immunoassay system consisting of sandwich immunorecognition, CdS quantum dots (QDs)-loaded liposomes (QDLL), and the release and subsequent capture of the QDs by a separated TiO2 nanotubes (NTs) electrode. The system elegantly operated upon the protein binding and lysis treatment of CdS QDLL labels within the 96-well plate, and then the CdS QDs-enabled sensitization of TiO2 NTs electrode. Exemplified by cardiac markers troponin I (cTnI) as target, the proposed system achieved efficient activation of TiO2 NTs electrode and thus the signal generation toward the split-type PEC immunoassay. This work features the first use of QDs for liposomal PEC bioanalysis and is expected to inspire more interests in the design and implementation of numerous QDs-involved liposomal PEC bioanalysis.

Synthetic promoter for efficient and muscle-specific expression of exogenous genes.

Synthetic promoters (SPs) have many advantages over their natural counterparts, especially with regard to transcriptional activity and tissue specificity. Here, we report a new strategy to construct SPs for efficient and muscle-specific gene expression. First, 19 nucleic acid motifs classified to 3 kinds of transcriptional regulatory elements were rationally selected. A recombinant promoter library was constructed by randomly assembling these motifs. Second, the transcriptional activities of ~1200 SPs were screened by intramuscular expression of several reporter genes in different cell lines for activity higher than that of the cytomegalovirus (CMV) promoter, with SP-301 finally identified as the strongest. A single intramuscular injection of mice with an SP-301 plasmid expressing mouse growth hormone releasing hormone accelerated mouse growth significantly over 24 days. Third, the muscle specificity of SP-301 was confirmed in transgenic mice. Finally, in comparison with the CMV promoter, SP-301 accelerated translocation and increased the level of plasmid in the nuclei of myoblast cells to a greater extent than in non-muscle cells. Altogether, the study has provided a more rational strategy to construct efficient and tissue-specific promoters, with the promoter SP-301 exhibiting promising potential for establishing an intramuscular gene expression system for therapeutic applications.

Ferroelectric Perovskite Oxide@TiO2 Nanorod Heterostructures: Preparation, Characterization, and Application as a Platform for Photoelectrochemical Bioanalysis.

This work reports the first synthesis and characterization of a ferroelectric perovskite oxide-based heterostructure as well as its application for photoelectrochemical (PEC) bioanalytical purposes. Specifically, exemplified by [KNbO3]1- x[BaNi1/2Nb1/2O3-δ] x (KBNNO), the ferroelectric perovskite oxides were prepared by solid-state synthesis, while the TiO2 nanorod (NR) arrays were obtained via a hydrothermal method. Using the technique of pulsed laser deposition (PLD), KBNNO were then deposited on TiO2 NRs to form KBNNO@TiO2 NR heterostructures. Various characterization techniques were applied to reveal compositional and structural information on the as-fabricated sample, and favorable alignment existed between the two components as displayed by the PEC test. In the detection of l-cysteine, the as-fabricated KBNNO@TiO2 NRs demonstrated good performance in terms of sensitivity and selectivity. This work revealed the potential of ferroelectric perovskite oxide and its heterostructures for innovative PEC bioanalytical applications, and we hope it will generate more interest in the development of various ferroelectrics-based heterostructures for advanced PEC bioanalysis.

PCMT1 is an unfavorable predictor and functions as an oncogene in bladder cancer.

The role of protein l-isoaspartate (d-aspartate) O-methyltransferase (PCMT1) in human cancer was generally cognized. The clinical significance and biological function of PCMT1 in bladder cancer is still unknown. PCMT1 mRNA and protein expression levels in bladder cancer tissues and cell lines were detected by qRT-PCR, immunohistochemistry, or western blot. The correlation between PCMT1 expression and clinicopathological factors was analyzed through immunohistochemistry in 108 bladder cancer patients. Loss-of-function and gain-of-function studies were conducted to explore the biological function of PCMT1 in bladder cancer cell lines in regulating cell proliferation, migration, and invasion. In our results, we found that PCMT1 was overexpressed in bladder cancer tissues compared with normal urothelium tissues in microarray datasets (GSE3167). Then, we confirmed PCMT1 mRNA and protein expression were increased in bladder cancer tissues and cell lines compared with paired normal urothelium tissues and normal uroepithelial cell line. PCMT1 protein expression was obviously correlated with clinical stage, muscularis invasion, lymph node metastasis, and distant metastasis. Survival analysis showed that PCMT1 protein high-expression was an independent unfavorable prognostic factor for bladder cancer patients. The in vitro experiments showed PCMT1 regulated bladder cancer cells migration and invasion through modulating epithelial-mesenchymal transition (EMT)-associated genes expression including E-cadherin, vimentin, Snail and Slug, but had no effect on proliferation. In conclusion, PCMT1 is an unfavorable prognostic biomarker and involves in cells migration and invasion through regulating EMT-associated genes. © 2018 IUBMB Life, 70(4):291-299, 2018.

Rab11 Functions as an Oncoprotein via Nuclear Factor kappa B (NF-κB) Signaling Pathway in Human Bladder Carcinoma.

BACKGROUND Elevated expression of Rab11 has been reported in different human cancers, including human bladder carcinoma. This study, we investigated the biological effects and mechanism of Rab11 overexpression in human bladder carcinoma for the first time. MATERIAL AND METHODS Rab11 expression in bladder cancer tissues was detected using immunohistochemistry and Western blot analysis. Then, Rab11 expression was inhibited in T24 cells and it was overexpressed in BIU-87 cells. The effects of Rab11 perturbations on cell growth rate and invasion were analyzed by CCK8, cell cycle assay, and matrix gel invasion assay. MMP-9, cyclin E, and cyclin D1 levels were studied using Western blot and qPCR. NF-κB activity was studied by luciferase assay. RESULTS High expression of Rab11 was detected in 41.5% (66/159) of tumor specimens. We found a significant correlation between high Rab11 expression and depth of tumor invasion (P=0.004). Rab11 overexpression was observed to promote the growth rate and invasiveness of cancer cells through upregulation of MMP9, cyclin E, and cyclin D1 levels. Rab11 overexpression further elevated NF-κB reporter activity and enhanced p-IκB expression. Use of BAY 11-7082, a noted NF-κB inhibitor, partially abolished overexpression of MMP9 and cyclin D1 by Rab11. CONCLUSIONS Our research proved that high Rab11 expression enhances cellular multiplication and invasiveness of bladder cancer, possibly by regulating the NF-κB signaling pathway.

Minimally invasive surgical treatment on delayed uretero-vaginal fistula.

OBJECTIVE: To evaluate the procedure of endoscopic surgery for ureterovaginal fistula (UVF) and its clinical efficacy. MATERIALS AND METHODS: A retrospective analysis of 46 patients needing treatment for UVF with endourology technology was conducted (all patients had unilateral ureteric injury, 27 left and 19 right). Transurethral retrograde ureteric stenting or realignment retrograde/antegrade approach stenting was used to treat the fistula, and the relation between treatment and prognosis was analyzed. RESULTS: One case failed, the patient undergoing percutaneous nephrostomy instead. Success was achieved in 45 cases, and urinary leakage was stopped 48 h after surgery. Of the 45 patients operated on, 16 had their double-J stents removed after 3-6 months, and 29 needed replacement every 6-12 months. In a postoperative follow-up of 6-36 months, 10 patients had recurrent stenosis needing ureteroscopic endoureterotomy or reexpansion with a balloon. No other complications occurred. CONCLUSIONS: Endoscopic surgery is an effective technology in the treatment of UVF, with the advantages of being effective, reliable, less invasive, and readily accepted by patients.

Effects of touchscreen gesture's type and direction on finger-touch input performance and subjective ratings.

This study examined how finger-touch input performance (i.e. task completion time, failure status, and error rate) and subjective ratings (i.e. performance and physical demand) are influenced by touchscreen gestures' type and direction. Twenty participants performed one-touch (i.e. drag and swipe) and two-touch (i.e. pinch and spread) gesture tasks on a tablet, using several major directions (i.e. eight directions for one-touch and four directions for two-touch gestures). The results showed that swipe was approximately 4.5 times faster than drag, but pinch and spread showed no significant difference in task completion time. Dragging and pinching showed more failures or higher error rates compared to swiping and spreading, respectively. One-touch gestures in the horizontal directions were rated to have higher performance and lower physical demand than those in the vertical and diagonal directions. Two-touch gestures in the horizontal directions took the shortest time but caused more failures and higher error rates. Practitioner Summary: This study provides evidence for the effects of touchscreen gestures' type and direction on human performance and subjective ratings, which varied depending on the number of fingers used. Designers should arrange related touchscreen components accordingly, to improve touch-finger input performance and reduce user workload.

Drag-reducing polymers increase exercise tolerance in an ischemic hind-limb rat model.

OBJECTIVE: Drag-reducing polymers are long-chain, blood soluble macromolecules that can improve microcirculation in vivo. This study aimed to examine the effects of drag-reducing polymers on exercise tolerance in a rat model of hind-limb ischemia. METHODS: After adaptive running training, bilateral femoral artery ligation models were established in 64 Wistar rats. During an exhaustive exercise, polyethylene oxide or normal saline was intravenously injected to each group (n = 32) at 4 mL/h for 10 min. The exhaustive exercise time was recorded, and lactic acid levels in gastrocnemius muscle and serum were measured. Serum levels of nitric oxide, creatine kinase and lactate dehydrogenase were measured as biomarkers of physical fatigue. RESULTS: Compared with saline-treated control group, rats in polyethylene oxide-treated group had longer exhaustive exercise time (774.7 ± 171.5 s vs. 687.6 ± 166.1 s, p = 0.043), and lower lactic acid level in gastrocnemius muscle (p < 0.01) but no significant difference in serum lactic acid level between two groups was observed (p > 0.05). Nitric oxide level was higher in polyethylene oxide group than in controls (p < 0.05), but no significant differences in serum creatine kinase and lactate dehydrogenase levels between two groups were observed (p > 0.05). CONCLUSION: Drag-reducing polymers contribute to the enhancement of exercise endurance and exert anti-fatigue effect.

Clinical significance and biological roles of TRIM24 in human bladder carcinoma.

Tripartite motif-containing 24 (TRIM24), also known as transcription intermediary factor 1-alpha (TIF1α), is a chromatin-associated protein which as been has been implicated in carcinogenesis. However, its expression profile and biological roles in human bladder carcinoma has not been investigated. In this study, we examined its expression in 95 bladder cancer specimens. We found that TRIM24 expression was upregulated in 39 of 95 (41.1 %) specimens compared with normal control. TRIM24 overexpression was associated with local invasion and advanced grade of bladder cancer. In addition, we transfected TRIM24 plasmid into BIU-87 cell line and TRIM24 siRNA into 5637 cell line. Colony formation, CCK-8, and transwell assay were used to assess its biological roles in bladder cancer cells. The result showed that TRIM24 could facilitate cancer cell growth and invading ability. Western blot analysis demonstrated that TRIM24 upregulated cyclin D1, cyclin E, p-IκBα, and p-AKT expression, suggesting TRIM24 activates NF-κB and AKT pathways. In addition, NF-κB inhibitor reversed the effect of TRIM24 on cyclin D1. In conclusion, TRIM24 is overexpressed in human bladder cancer and facilitates bladder cancer growth and invasion, possibly through NF-κB and AKT signaling pathways.