Development of high-efficiency superparamagnetic drug delivery system with MPI imaging capability.

In this study, a high-efficiency superparamagnetic drug delivery system was developed for preclinical treatment of bladder cancer in small animals. Two types of nanoparticles with magnetic particle imaging (MPI) capability, i.e., single- and multi-core superparamagnetic iron oxide nanoparticles (SPIONs), were selected and coupled with bladder anti-tumor drugs by a covalent coupling scheme. Owing to the minimal particle size, magnetic field strengths of 270 mT with a gradient of 3.2 T/m and 260 mT with a gradient of 3.7 T/m were found to be necessary to reach an average velocity of 2 mm/s for single- and multi-core SPIONs, respectively. To achieve this, a method of constructing an in vitro magnetic field for drug delivery was developed based on hollow multi-coils arranged coaxially in close rows, and magnetic field simulation was used to study the laws of the influence of the coil structure and parameters on the magnetic field. Using this method, a magnetic drug delivery system of single-core SPIONs was developed for rabbit bladder therapy. The delivery system consisted of three coaxially and equidistantly arranged coils with an inner diameter of Φ50 mm, radial height of 85 mm, and width of 15 mm that were positioned in close proximity to each other. CCK8 experimental results showed that the three types of drug-coupled SPION killed tumor cells effectively. By adjusting the axial and radial positions of the rabbit bladder within the inner hole of the delivery coil structure, the magnetic drugs injected could undergo two-dimensional delivery motions and were delivered and aggregated to the specified target location within 12 s, with an aggregation range of about 5 mm × 5 mm. In addition, the SPION distribution before and after delivery was imaged using a home-made open-bore MPI system that could realistically reflect the physical state. This study contributes to the development of local, rapid, and precise drug delivery and the visualization of this process during cancer therapy, and further research on MPI/delivery synchronization technology is planned for the future.

A Fast and Reversible Responsive Bionic Transmembrane Nanochannel for Dynamic Single-Cell Quantification of Glutathione.

Biological channels can rapidly and continuously modulate ion transport behaviors in response to external stimuli, which play essential roles in manipulating physiological and pathological processes in cells. Here, to mimic the biological channels, a bionic nanochannel is developed by synergizing a cationic silicon-substituted rhodamine (SiRh) with a glass nanopipette for transmembrane single-cell quantification. Taking the fast and reversible nucleophilic addition reaction between glutathione (GSH) and SiRh, the bionic nanochannel shows a fast and reversible response to GSH, with its inner-surface charges changing between positive and negative charges, leading to a distinct and reversible switch in ionic current rectification (ICR). With the bionic nanochannel, spatiotemporal-resolved operation is performed to quantify endogenous GSH in a single cell, allowing for monitoring of intracellular GSH fluctuation in tumor cells upon photodynamic therapy and ferroptosis. Our results demonstrate that it is a feasible tool for in situ quantification of the endogenous GSH in single cells, which may be adapted to addressing other endogenous biomolecules in single cells by usage of other stimuli-responsive probes.

Organic Molecular Probe Enabled Ionic Current Rectification toward Subcellular Detection of Glutathione with High Selectivity, Sensitivity, and Recyclability.

Single-cell interrogation with the solid-state nanoprobes enables understanding of the linkage between cellular behavior and heterogeneity. Herein, inspired by the charge property of the organic molecular probe (OMP), a generic ionic current rectification (ICR) single-cell methodology is established, exemplified by subcellular detection of glutathione (GSH) with high selectivity, sensitivity, and recyclability. The as-developed nanosensor can transduce the subcellular OMP-GSH interaction via a sensitive ionic response, which stems from the superior specificity of OMP and its essential charge property. In addition, the nanosensor exhibits good reversibility, since the subsequent tandem reaction after the recognition can well recover the sensing surface. Given the diverse structures and tailorable charge properties of OMP, this work underpins a new and general method of OMP-based ICR single-cell analysis.

LINC00511/miRNA-143-3p Modulates Apoptosis and Malignant Phenotype of Bladder Carcinoma Cells via PCMT1.

Bladder cancer has easy recurrence characteristics, but its occurrence and development mechanism are still unclear. Non-coding RNA is a kind of RNA that exists widely and cannot be translated into proteins, which has played a key role in the regulation of biological functions of tumor cells. However, the regulation mechanism of non-coding RNA on bladder tumors is not fully understood. By microarray analysis and database analysis, we found that LINC00511 was significantly highly expressed in bladder cancer. The expressions of LINC00511, miR-143-3p, and PCMT in bladder cancer tissues and cells were detected by quantitative reverse transcription-polymerase chain reaction. The relationship between the expressions of miR-143-3p and PCMT1 and the clinicopathological parameters of the tumor was analyzed. The proliferation and invasion of bladder cancer cells were detected by MTT assay and Transwell assay. The expression levels of E-cadherin and vimentin in bladder cancer cells were detected by Western blot. Cell apoptosis was detected by flow cytometry. In vivo, TCCSUP or SW780 cells were inoculated into BALB/c nude mice to detect tumor volume and weight. Bioinformatics and dual luciferase reporter gene were used to analyze the relationship between LINC00511 and miR-143-3p and its downstream target gene PCMT1. The results showed that LINC00511 could target miR-143-3p/PCMT1 to regulate the proliferation, migration, and apoptosis of bladder cancer TCCSUP or SW780 cells and promote the occurrence and development of bladder cancer.

Photocontrolled Nanopipette Biosensor for ATP Gradient Electroanalysis of Single Living Cells.

Emerging nanopipette tools have demonstrated substantial potential for advanced single-cell analysis, which plays vital roles from fundamental cellular biology to biomedical diagnostics. Highly recyclable nanopipettes with easy and quick regeneration are of special interest for precise and multiple measurements. However, existing recycle strategies are generally plagued by operational complexity and limited efficiency. Light, acting in a noncontact way, should be the ideal external stimulus to address this issue. Herein, we present the photocontrolled nanopipette capable of probing cellular adenosine triphosphate (ATP) gradient at single-cell level with good sensitivity, selectivity, and reversibility, which stems from the use of ATP-specific azobenzene (Azo)-incorporated DNA aptamer strands (AIDAS) and thereby the sensible transduction of variable nanopore size by the ionic currents passing through the aperture. Photoisomerized conformational change of the AIDAS by alternative UV/vis light stimulation ensures its noninvasive regeneration and repeated detection. Inducement and inhibition of the cellular ATP could also be probed by this nanosensor.

Role of p-ERK1/2 in Benign Prostatic Hyperplasia during Hyperinsulinemia.

PURPOSE: Using a rat model of hyperinsulinemia, the present study investigated the role of p-ERK1/2 in benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Forty male Sprague-Dawley rats were randomly selected and assigned to four groups: high fat diet (HFD)+BPH (n=10), HFD (n=10), BPH (n=10), and control (n=10) groups. Hyperinsulinemia was induced by HFD feeding, while BPH was induced using testosterone propionate. Plasma glucose, plasma insulin and bodyweight were examined weekly. Immunohistochemistry (IHC) and western blot analysis were used to analyze the expression of ERK1/2 and p-ERK1/2 in rat prostates. RESULTS: Plasma glucose and plasma insulin levels were significantly greater in the HFD+BPH and HFD groups, when compared to the other two groups (P<0.05). Prostate weights were significantly greater in the HFD+BPH, HFD and BPH groups, than in the control group (P<0.05). IHC and western blot analysis revealed that p-ERK1/2 expression was greater in the HFD+BPH group than in the other three groups (P<0.05). CONCLUSION: Androgens plus a hyperinsulinemic condition induced by HFD can result in prostatic cell hyperplasia, and this mechanism may be correlated to the upregulation of p-ERK1/2. Further investigations of this possibility are required.

Three-Dimensional TiO2@Cu2O@Nickel Foam Electrodes: Design, Characterization, and Validation of O2-Independent Photocathodic Enzymatic Bioanalysis.

This work reports the innovative design and application of a three-dimensional (3D) TiO2@Cu2O@nickel foam electrode synergized with enzyme catalysis toward the proof-of-concept study for oxygen-independent photocathodic enzymatic detection. Specifically, a 3D-nanostructured photoelectrode has great potential in the semiconductor-based photoelectrochemical (PEC) biological analysis. On the other hand, using various photocathodes, cathodic PEC bioanalysis, especially the photocathodic enzymatic detection, represents an attractive frontier in the field. Different from state-of-the-art photocathodic enzymatic studies that are oxygen-dependent, herein, we present the ingenious design, characterization, and implementation of 3D TiO2@Cu2O@nickel foam photocathodes for the first oxygen-independent example. In such a configuration, the Cu2O acted as the visible-light absorber, while the TiO2 shell would simultaneously function as a protective layer for Cu2O and as a desirable substrate for the immobilization of enzyme biomolecules. Especially, because of the proper band positions, the as-designed photocathode exhibited unique O2-independent PEC property. Exemplified by glucose oxidases, the as-developed sensor exhibited positive response to glucose with good performance. Because various oxidases could be integrated with the system, this protocol could serve as a universal O2-independent platform for many other targets. This work is also anticipated to catalyze more studies in the advanced 3D photoelectrodes toward innovative enzymatic applications.

Unique Redox Reaction between CuO Photocathode and Cysteine: Insight into the Mechanism for Cathodic Photoelectrochemical Bioanalysis.

Previously reported copper oxide-based cathodic photoelectrochemical bioanalysis of cysteine had attributed the decrease of the photocurrents to the binding of cysteine onto the CuO surface. However, our latest investigation found that the previous explanation was not correct. This Letter presents the in-depth study of such phenomena and a new insight into the underlying mechanism. Specifically, the unique redox reaction between the CuO photocathode and cysteine produced [Cys-Cu(I)] and cystine, and the insoluble complex blocked the partial contact between the photoelectrode and the dissolved O2-containing electrolyte and reduced the effective working area of the photocathode, leading to the decrease of photocurrent.

Additive antitumor effect of arsenic trioxide combined with intravesical bacillus Calmette-Guerin immunotherapy against bladder cancer through blockade of the IER3/Nrf2 pathway.

BACKGROUND: As an inorganic compound used to treat various cancers and other diseases, arsenic trioxide (As2O3) has been reported to induce cellular apoptosis in certain kinds of cancers including bladder cancer. The aim of the present study was to elucidate the crucial cooperative role of As2O3 and intravesical bacillus Calmette-Guerin (BCG) immunotherapy and its ability to protect against bladder cancer by targeting the IER3/Nrf2 pathway. METHOD: Initially, an orthotopic bladder cancer model was established in mice by means of intravesical instillation of the human bladder cancer cell line 5637. The expression of IL-6/IL-8 in dendritic cells (DCs) and the proportion of CD4+ cells and ratio of CD4+/CD8+ T cells were subsequently determined. RT-qPCR and Western blot assay methods were employed to determine the expressions of IER3, Nrf2, NQO1, IL-6 and IL-8. Finally, tumor cell apoptosis and the volume and weight of the in vivo tumors were evaluated in an attempt to determine the contributory role of As2O3 in combination with BCG immunotherapy in treating bladder cancer. RESULTS: The additive effect of As2O3 and BCG was demonstrated to promote the expressions of IL-6/IL-8 among DCs. Additionally, the proportion of CD4+ cells, ratio of CD4+/CD8+ T cells and rate of tumor cell apoptosis were all elevated, while decreased in vivo tumor volume and weight were detected. Of importance, we determined the role that ad-shNrf2 (adenoviral vectors expressing shRNA against Nrf2) played in inhibiting the effects of As2O3 on bladder cancer. CONCLUSION: Taken together, the key findings of the present study provide evidence defining the effect of As2O3 on inducing the inhibitory effect of BCG on the development of bladder cancer via the IER3/Nrf2 pathway, highlighting the potential of As2O3 as a treatment option for bladder cancer through its enhancement of intravesical BCG.

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.

Minimally invasive percutaneous nephrolithotomy improves stone-free rates for impacted proximal ureteral stones: A systematic review and meta-analysis.

BACKGROUND: Urinary stones are common medical disorders and the treatment of impacted proximal ureteral stones (IPUS) is still a challenge for urologists. The aim of this study was to compare the efficacy and safety of minimally invasive percutaneous nephrolithotomy (MI-PCNL) and ureteroscopic lithotripsy (URL) in the treatment of IPUS via a meta-analysis. METHODS: We collected studies using PubMed, Embase, and Cochrane Library from 1978 to November 2016 and analyzed them using Stata 12.0 and RevMan 5.3. Odds ratios (ORs) and standard mean difference (SMD) were calculated for binary and continuous variables respectively, accompanied with 95% confidence intervals (CIs). All study procedures followed the PRISMA guidelines. RESULTS: Five prospective studies were included in our meta-analysis, with 242 MI-PCNL and 256 URL cases. MI-PCNL was associated with a longer postoperative hospital stay than URL (SMD, 3.14; 95% CI, 1.27 to 5.55). However, no significant difference was observed in operative time (SMD, -0.38; 95% CI, -3.15 to 2.38). In addition, MI-PCNL had higher initial (OR, 11.12; 95% CI, 5.56 to 22.24) and overall stone-free rates (OR, 8.70; 95% CI, 3.23 to 23.45) than URL, along with lower possibilities of surgical conversion (OR, 0.11; 95% CI, 0.03 to 0.49) and postoperative shock wave lithotripsy (OR, 0.06; 95% CI, 0.02 to 0.18). Regarding complications, no significant differences were observed between MI-PCNL and URL (OR, 1.39; 95% CI, 0.93 to 2.10), except for hematuria (OR, 4.80; 95% CI, 1.45 to 15.94). CONCLUSIONS: MI-PCNL is optimal and should be considered as the preferred treatment method for IPUS, as it has better efficacy and a safety profile similar to that of URL. However, further high quality studies with larger sample size are required in future.

The Value of Contrast-Enhanced Ultrasonography and Contrast-Enhanced CT in the Diagnosis of Malignant Renal Cystic Lesions: A Meta-Analysis.

We compared the efficacy of contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CECT) for the diagnosis of renal cystic lesions via a meta-analysis to determine the value of CEUS in the prediction of the malignant potential of complex renal cysts. Eleven studies were evaluated: 4 control studies related to CEUS and CECT, 3 studies related to CEUS and 4 studies related to CECT. According to the random effects model, the pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio for CEUS/CECT were 0.95/0.90, 0.79/0.85, 4.39/5.00, and 0.10/0.15, respectively. The areas under the summary receiver operating characteristic (AUCs-SROC) curves for the two methods were 94.24% and 93.39%, and the estimated Q values were 0.8805 and 0.8698, respectively. Comparing the Q index values of CEUS and CECT revealed no significant difference between the two methods (P>0.05). When compared with conventional CECT, CEUS is also useful for diagnosing renal cystic lesions in the clinic.

Urinary nerve growth factor could be a biomarker for interstitial cystitis/painful bladder syndrome: a meta-analysis.

To examine whether urinary nerve growth factor (NGF) could serve as a biomarker for interstitial cystitis/painful bladder syndrome (IC/PBS), we conducted a comprehensive meta-analysis of 9 studies. Among the studies considered, patients with IC/PBS had higher urinary NGF and NGF/Cr levels compared to those of healthy people (SMD = 1.94, 95%CI = 0.79-3.08, P = 0.0009 and SMD = 1.79, 95%CI = 0.65-2.93, P = 0.002, respectively). In addition, there was a significant difference between patients with IC/PBS and patients with overactive bladder (OAB) symptoms with respect to the urinary NGF and NGF/Cr levels (SMD = -0.62, 95%CI = -1.00--0.24, P = 0.001 and SMD = -0.70, 95%CI = -1.01--0.39, P<0.0001, respectively). Furthermore, patients had a significantly lower urinary NGF level after successful treatment (SMD = 1.74, 95%CI = 0.32-3.17, P = 0.02). In conclusion, urinary NGF could be a useful biomarker for the diagnosis of OAB, a urinary biomarker for the differential diagnosis of IC/PBS and OAB (when a critical urinary NGF or NGF/Cr level is needed), and a predictive biomarker to help guide treatment.

[Inhibitory effect of cocoomyxa gloeobotrydifomis on benign prostate hyperplasia in aged rats and its action mechanism].

OBJECTIVE: To investigate the inhibitory effect of cocoomyxa gloeobotrydifomis (CGD) on benign prostate hyperplasia (BPH) in aged rats and its underlying mechanism. METHODS: Thirty SD male rats aged 21 months were equally randomized to three groups, aged control, low-dose CGD and high-dose CGD, the latter two groups fed on a diet with CGD at 50 and 100 mg per kg per d for 3 months, while the aged controls on normal laboratory chow. Another 10 3-month-old male rats were included in a young control group and fed on the same diet as the aged control rats. At the end of 3 months of CGD treatment, the prostates of all the rats were harvested and weighed. The histomorphological and interstitial changes of the prostatic tissue were observed by HE staining and Masson staining, respectively. The expressions of phosphorylated phosphoinositide-dependent kinase 1 (PDK1), phosphorylated Akt (Ser 473) and phosphorylated PTEN in the rat prostate were determined by Western blotting. RESULTS: The wet weight and index of the prostate were significantly higher in the aged controls than in the young controls ([1 220 +/- 140] vs [550 +/- 60] mg, P < 0.01; 2.08 +/- 0.17 vs 1.94 +/- 0.10, P < 0.05). High-dose CGD significantly inhibited the increase in the prostatic wet weight and index of the aged rats ([1 080 +/- 97] mg and 1.85 +/- 0.16) as compared with the aged controls (P < 0.01 and P < 0.05). The epithelium and interstitium, particularly the latter, were evidently thicker in the aged control than in the CGD-treated rats. The protein levels of phosphorylated PDK1 and Akt were significantly enhanced, while that of phosphorylated PTEN remarkably down-regulated in the aged rats as compared with the young ones. The expressions of phosphorylated PDK1 and Akt were significantly decreased, whereas that of phosphorylated PTEN markedly increased in both the low-dose and high-dose CGD groups. CONCLUSION: CGD can significantly inhibit BPH in aged rats through down-regulating the PI3K/Akt pathway.

Role of the CASP-9 Ex5+32 G>A polymorphism in susceptibility to cancer: A meta-analysis.

Failure of apoptosis is one of the hallmarks of cancer. As an execution-phase caspase, caspase-9 plays a crucial role during apoptosis. To examine whether the Ex5+32 G>A (rs1052576) polymorphism in the CASP-9 gene alters cancer risk, we conducted a comprehensive meta-analysis of 7 case-control studies consisting of a total of 1668 cancer cases and 2294 healthy controls. All studies considered, A allele and A allele carriers of Ex5+32 G>A in the CASP-9 gene had significant associations with cancer risk (OR=0.72, 95% CI, 0.58-0.89, P= 0.003; OR= 0.76, 95% CI, 0.63-0.92, P= 0.004; respectively). In the subgroup analysis, we found that the A allele of Ex5+32 G>A was a protective factor for cancer risk in Chinese and American populations (OR=0.60, 95% CI, 0.44-0.81, P<0.001; OR= 0.80, 95% CI, 0.69-0.94, P= 0.005; respectively). Similarly, we also found positive associations between A allele carriers of Ex5+32 G>A and cancer risk in Chinese and American populations (OR=0.63, 95% CI, 0.44-0.90, P= 0.01; OR= 0.78, 95% CI, 0.62-0.98, P=0.03; respectively). In addition, we identified that A allele and A allele carriers of Ex5+32 G>A may decrease the risk of cancer in the Asian population (OR=0.60, 95% CI, 0.44-0.81, P<0.001; OR= 0.63, 95% CI, 0.44-0.90, P= 0.01; respectively). In conclusion, this meta-analysis demonstrated that A allele and A allele carriers of the Ex5+32 G>A polymorphism in the CASP-9 gene may be protective factors for cancer risk.

[Transurethral thulium laser urethrotomy for urethral stricture].

OBJECTIVE: To evaluate the effect of endourethrotomy with thulium laser as a minimally invasive treatment for urethral stricture. METHODS: We treated 36 cases of urethral stricture or atresia by endourethrotomy with thulium laser, restored the urethral continuity by vaporization excision of the scar tissue, and observed the clinical effects and complications. RESULTS: The mean operation time was 35 min, ranging from 10 to 90 min. Smooth urination was achieved after 2-6 weeks of catheter indwelling, with no urinary incontinence. The patients were followed up for 4-24 (mean 12) months, during which 27 did not need any reintervention, 5 developed urinary thinning but cured by urethral dilation, 3 received another laser urethrotomy for previous negligence of timely urethral dilation, and the other 1 underwent open urethroplasty. CONCLUSION: Thulium laser urethrotomy is a safe and effective minimally invasive option for short urethral stricture, which is also suitable for severe urethral stricture and urethral atresia. Its short-term outcome is satisfactory, but its long-term effect remains to be further observed.

[Greenlight photoselective vaporization prostatectomy versus thulium laser vaporesection of the prostate for aged high-risk BPH patients with the prostate heavier than 80 g].

OBJECTIVE: To compare the effects of greenlight photoselective vaporization prostatectomy (PVP) and thulium laser vaporesection of the prostate (TmLRP) in the treatment of aged high-risk BPH patients with the prostate weighing > 80 g. METHODS: We included in this study 118 high-risk BPH patients aged 62-96 (mean 76) years with the prostate heavier than 80 g, 82 treated by PVP and the other 36 by TmLRP. Then we compared the operation time, intraoperative bleeding, complications, short-term effectiveness, and surgical cost between the two groups. RESULTS: All the patients tided over the perioperative period without blood transfusion and serious complications. The mean operation time, postoperative bladder irrigation time and surgical cost were significantly less in the TmLRP than in the PVP group (P < 0.05). Both the procedures remarkably improved the international prostatic symptom score (IPSS), quality of life (QOL), post void residual urine (PVR) and Qmax of the patients (P < 0.05), but with no significant differences between the two groups (P > 0.05). CONCLUSION: Both PVP and TmLRP are effective and safe for the treatment of aged high-risk BPH patients with the prostate heavier than 80 g, but the latter is superior for its shorter operation time and lower surgical cost.

The role of TRPC6 in HGF-induced cell proliferation of human prostate cancer DU145 and PC3 cells.

Hepatocyte growth factor (HGF) is a glycoprotein that induces prostate cancer cell proliferation, migration and invasion. The activation of transient receptor potential canonical 6 (TRPC6) channels is considered important in promoting prostate cancer cell proliferation. In this study, we assessed the role of endogenous TRPC6 channels in the HGF-induced cell proliferation of prostate cancer. Reverse transcription-PCR and Western blotting were used to investigate TRPC6 expression. Electrophysiological techniques (whole-cell patch clamp configuration) and Ca(2+) imaging analysis were used to investigate the channel activity in cells. The effects of TRPC6 channels on cell cycle progression, cell apoptosis and cell growth were also examined. TRPC6 and c-MET were expressed in DU145 and PC3 cells. In addition, functional TRPC6 channels were present in DU145 and PC3 cells, and TRPC6 knockdown suppressed TRPC-like currents evoked by oleoyl-2-acetyl-sn-glycerol (OAG). Inhibition of TRPC6 channels in DU145 and PC3 cells abolished OAG- and HGF-induced Ca(2+) entry. Furthermore, inhibition of TRPC6 channels arrested DU145 and PC3 cells at the G(2)/M phase and suppressed HGF-induced cell proliferation. Collectively, our results indicate that TRPC6 has an important role in HGF-induced DU145 and PC3 cell proliferation.

[Targeted delivery of bone marrow mesenchymal stem cells by ultrasound-mediated microbubble destruction].

OBJECTIVE: To investigate the feasibility of bone marrow mesenchymal stem cell (MSC) transplantation with ultrasound-targeted microbubble destruction. METHODS: Twenty-one Wistar rats were divided into MSCs-iv group (MSCs-iv), ultrasound+MSCs-iv group (US+MSCs-iv), ultrasound+microbubble+MSCs-iv group (US+MB+MSCs-iv) with intravenous MSC transfer, ultrasound and microbubble treatment as indicated. The skeletal muscles were obtained from the rats for microscopic examination with HE staining. The hindlimb gracilis and semimembranosus muscles were sampled 7 days after MSC transplantation, and the transplanted MSCs were detected by immunohistochemistry. The vital organs were collected from rats in US+MB+MSCs-iv group for immunohistochemistry. RESULTS: In US+MB+MSCs-iv group, HE staining demonstrated the presence of red blood cell leakage into the tissue space in the gracilis and semimembranosus muscles, and immunohistochemistry identified large numbers of transplanted MSCs in the the gracilis and semimembranosus muscles and the spleen, whereas no labeled cells were detected in the skeletal muscles in other groups. CONCLUSION: Ultrasound-targeted microbubble destruction provides a useful means for enhancing the efficiency of stem cell transplantation.

9-cis retinoic acid induces retinoid X receptor localized to the mitochondria for mediation of mitochondrial transcription.

We previously reported that 9-cis retinoic acid (RA) treatment induced an increase in mitochondrial (mt)DNA transcription. In order to extend these results, we tested various concentrations of 9-cis RA were used to treat 143B cells. Cells with low membrane potential treated with 9-cis RA showed significantly lower amounts of RXRalpha in mitochondria. We also found lower RXRalpha levels in mtDNA-depleted cells. Treating cells with 9-cis RA significantly increased expression of ND1, ND6, and COX I RNA. However, 9-cis RA-treatment did not appear to induce any significant changes in mtDNA copy number or mitochondrial mass. This study represents that 9-cis RA increases mtDNA transcription but not mtDNA replication, and it suggests that the effects of 9-cis RA on mitochondria are mediated by RXR localization to mitochondria. In addition, this is the first report that 9-cis RA regulation of RXR mitochondrial translocation depends on mitochondrial membrane potential and ATP.