Comparison of vacuum suction ureteroscopic laser lithotripsy and traditional ureteroscopic laser lithotripsy for impacted upper ureteral stones.

PURPOSE: To compare a novel vacuum suction ureteroscopic laser lithotripsy (VS-URS) with traditional ureteroscopic laser lithotripsy (T-URS) for impacted upper ureteral stones and to better define the potential benefits of VS-URS. METHODS: Between May 2019 and March 2021, 158 patients with impacted upper ureteral stones underwent ureteroscopic holmium-YAG laser lithotripsy. Of these, 76 underwent VS-URS and 82 underwent T-URS. In VS-URS procedures, the vacuum suction device is composed of a 5F ureteral catheter and a tee joint. The ureteral catheter is linked to the vacuum aspirator by the sidearm of the tee joint, and a 200 µm fiber is inserted through the tee joint and the ureteral catheter into the stone site for lithotripsy. RESULTS: When compared to the T-URS group, the VS-URS group had a shorter mean operation time (38.18 ± 6.37 min vs. 46.65 ± 5.66 min; P = 0.000), lower fever rate (3.9% vs. 14.6%; P < 0.022), less stone retropulsion (5.3% vs. 18.3%; P = 0.012), lower extra management rate (6.58% vs. 21.95%; P = 0.006), and a higher stone-free rate of the first postoperative day (88.2% vs. 72.0%; P = 0.011). There were no significant differences in stone-free rates 1 month after surgery between groups (94.7% vs. 92.7%; P = 0.748). CONCLUSIONS: VS-URS is an effective modality for impacted upper ureteral stones, and has a shorter operating time, lower fever rate, less stone retropulsion, and a higher primary stone-free rate compared with T-URS.

Double-Sheath Vacuum Suction Minimally Invasive Percutaneous Nephrolithotomy for Management of Large Renal Stones.

OBJECTIVES: This study aimed to describe a novel double-sheath vacuum suction minimally invasive percutaneous nephrolithotomy (mini-PCNL) to overcome the deficiencies of the conventional procedure. PATIENTS AND METHODS: Between March 2019 and December 2019, 65 patients (37 males and 28 females) with a mean age of 41 years (range 23-69) underwent mini-PCNL with double-sheath vacuum suction. It consisted of an F20 Y-shaped sheath as an outer sheath and an F16 Y-shaped sheath as an inner sheath, in which the inner sheath was longer than the outer sheath. The oblique arm of the outer sheath and the inner sheath was connected to the perfusion inflow and the vacuum suction, respectively. A 550-µm holmium-YAG laser was introduced for stone fragmentation through the working channel of the mini-nephroscope, which was no longer connected to the perfusion fluid. RESULTS: All procedures were successful. Mean operation time was 50.2 min (range 39-83). Mean hemoglobin decrease was 5.2 g/L (range 1.0-15.5), and no patient needed a blood transfusion. One patient (1.5%) with low fever (<38°C) at day 1 had returned to normal at day 2 without administration of antibiotics. There were no Clavien grade 2-4 complications. Mean postoperative hospital stay was 2.4 days (range 2-6). The initial stone-free rate of PCNL was 81.53% (53 of 65 patients). One month after surgery, the final stone-free rate increased to 90.77% (59/65 patients). CONCLUSIONS: The double-sheath vacuum suction mini-PCNL is a safe and effective modality for large renal stones, which might increase the efficiency of stone extraction with low intrapelvic pressure.

Double-sheath vacuum suction versus vacuum-assisted sheath minimally invasive percutaneous nephrolithotomy for management of large renal stones: single-center experience.

PURPOSE: To compare double-sheath vacuum suction minimally invasive percutaneous nephrolithotomy (DS-mini-PCNL) with vacuum-assisted mini-PCNL (VS-mini-PCNL) and to better define the potential benefits of DS-mini-PCNL. METHODS: Between July 2019 and May 2020, 117 patients with large radiopaque renal stones underwent mini-PCNL. Of these, 63 underwent DS-mini-PCNL and 54 underwent VS-mini-PCNL. For VS-mini-PCNL, a F20 Y-shaped sheath was used and the oblique arm of the sheath was connected to the vacuum suction. For DS-mini-PCNL, the oblique arm of a F20 Y-shaped sheath (the outer sheath) and a F16 Y-shaped sheath (the inner sheath) was connected to the perfusion inflow and the vacuum suction, respectively. A 550-µm holmium-YAG laser was used for stone fragmentation. RESULTS: Compared with VS-mini-PCNL group, DS-mini-PCNL group had significantly shorter operative time (35.78 ± 7.77 min vs. 44.56 ± 13.19 min; P = 0.000) and significantly lower fever rate (1.6% vs. 11.1%; P = 0.048). It was not significantly different between the two groups despite the higher initial stone-free rate seen for DS-mini-PCNL group relative to VS-mini-PCNL group (87.7% vs. 81.5%, P = 0.346). Auxiliary procedure rates were 4.8% (three patients) in DS-mini-PCNL group and 16.7% (nine patients) in VS-mini-PCNL group, with a significant difference (P = 0.034). The difference in the final stone-free rate between the two groups was rendered insignificant (93.8% vs. 89.1%, P = 0.510). CONCLUSIONS: DS-mini-PCNL is a safe and effective modality for large renal stones, which could increase the efficiency of stone extraction and decrease infectious complications compared with VS-mini-PCNL.

Actinide Separation Inspired by Self-Assembled Metal-Polyphenolic Nanocages.

The separation of actinides has a vital place in nuclear fuel reprocessing, recovery of radionuclides, and remediation of environmental contamination. Here we propose a new paradigm of nanocluster-based actinide separation, namely, nanoextraction, that can achieve efficient sequestration of uranium in an unprecedented form of giant coordination nanocages using a cone-shaped macrocyclic pyrogallol[4]arene as the extractant. The U24-based hexameric pyrogallol[4]arene nanocages with distinctive [U2(PG)2] binuclear units (PG = pyrogallol) that rapidly assembled in situ in monophasic solvent were identified by single-crystal X-ray diffraction, MALDI-TOF mass spectrometry, NMR spectroscopy, and small-angle X-ray and neutron scattering. Comprehensive biphasic extraction studies showed that this novel separation strategy has enticing advantages such as fast kinetics, high efficiency, and good selectivity over lanthanides, thereby demonstrating its potential for efficient separation of actinide ions.

Negative-Pressure Ureteroscopic Holmium-YAG Laser Lithotripsy for Ureteral Stones.

OBJECTIVES: The aim of this study was to describe a novel negative-pressure laser lithotripsy device to overcome the deficiencies of the conventional procedure. PATIENTS AND METHODS: Between August 2018 and March 2019, 78 patients with a single ureteral stone underwent retrograde ureteroscopy with a Wolf 8F/9.8F rigid ureteroscope and a 200-µm holmium-YAG laser. The mean stone size was 11.8 mm, measured for the maximum length. The negative-pressure laser lithotripsy device consists of an F5 ureter catheter and a T joint. The closed tip of an F5 ureter catheter is cut off, and it is then inserted within one opening of the T joint. The 200-µm laser fiber is introduced into the ureteral catheter through the other opening of the T joint. The third opening of the T joint is connected to the negative-pressure pipe. The valve end of the Foley catheter is used for sealing the cap. Continuous suction and active irrigation throughout the lithotripsy could maintain adequate visibility. RESULTS: All ureteroscopic procedures were successful. The negative-pressure device showed good stone retention capabilities, with no observed stone migration. We did not observe any major complications. The stone-free rate was 97.44% (76/78), demonstrated on plain radiography of the kidney-ureter-bladder on the first postoperative day. The stone-free rate after 1 month was 100%. CONCLUSIONS: The negative-pressure ureteroscopic lithotripsy is easy and safe management for the ureteral stones. It might reduce the risk of stone fragment retropulsion, improve surgical vision, shorten the operative time, and decrease the renal pelvic pressure.

Clinical Efficacy Evaluation of a Novel Negative Pressure Ureteroscopic Lithotripsy for Ureteral Stones.

OBJECTIVE: To evaluate the clinical efficacy of a novel negative pressure ureteroscopic lithotripsy (NP-URL) compared to standard ureteroscopic lithotripsy (S-URL) for treating ureteral stones. METHODS: A total of 284 patients diagnosed with ureteral stones and who underwent ureteroscopic lithotripsy between December 2020 and May 2022 at our hospital were included in the study. Among them, 146 cases underwent NP-URL and 138 cases underwent S-URL. The negative pressure device used in NP-URL consists of a 5F ureteric catheter and a tee joint. We evaluated the operative duration, stone-free rate, incidence of postoperative complications, stone retropulsion rate, and adjunct procedure rate between the two groups. RESULTS: The mean operative duration was significantly shorter in the NP-URL group compared to the S-URL group (30.17 ± 5.84 minutes vs 34.84 ± 6.62 minutes; P＜.05). Additionally, the NP-URL group had a lower incidence of postoperative fever (1.4% vs 8.7%; P＜.05), reduced stone retropulsion rate (3.4% vs 11.6%; P＜.05), and a statistically lower rate of adjunct procedures (5.5% vs 14.5%, P＜.05). The NP-URL group also demonstrated a higher primary stone-free rate (91.8% vs 81.9%; P＜.05). However, there was no significant difference in the final stone-free rate between the NP-URL and S-URL groups (P＞.05). CONCLUSION: NP-URL potentially reduces operative duration, significantly decreases the incidence of postoperative complications, and achieves better primary stone-free rates compared to S-URL.

A novel double-sheath negative-pressure versus conventional minimally invasive percutaneous nephrolithotomy for large kidney stone.

This study aims to evaluate the therapeutic efficacy of a novel double-sheath negative-pressure minimally invasive percutaneous nephrolithotomy (D-mPCNL) compared to conventional minimally invasive percutaneous nephrolithotomy (C-mPCNL) for large kidney stones. A total of 132 patients diagnosed with large kidney stones in our hospital were included in the study. Among them, sixty-eight patients underwent D-mPCNL, while sixty-four underwent C-mPCNL. Parameters such as operative duration, stone-free rate, incidence of postoperative complications, and the need for auxiliary procedures were evaluated between the two groups. Compared to the C-mPCNL group, the D-mPCNL group demonstrated a significantly shorter operative time (41.97 ± 8.24 min vs. 52.30 ± 13.72 min; P < 0.000), lower rates of auxiliary procedures (5.9% vs. 17.2%; P = 0.041), and lower fever rates (2.9% vs. 14.1%; P = 0.021). The group also had a significantly higher primary stone-free rate (85.3% vs. 70.3%; P = 0.038). However, there were no statistically significant advantages in terms of the final stone-free rate, hemoglobin drops, and stone composition in the D-mPCNL group (P > 0.05). D-mPCNL is a novel surgical method that is safe and effective, reducing operative time, improving stone-free efficiency, and decreasing postoperative complications.

Study on the mechanism of action of effective monomeric, berberine of Xianglian Pill in inhibiting human colon cancer cells based on fatty acid synthase target.

Background and aim: Xianglian Wan (XLW) as a classic prescription of traditional Chinese medicine protects digestive function; however, few studies have investigated its anti-colorectal cancer effects. This study verified that the effective monomer berberine of XLW plays an antitumo r role by regulating the acetyl-CoA carboxylase (ACC)/fatty acid synthase (FASN) lipid metabolism-related signaling pathway. Experimental procedure: The connection between XLW and FASN was identified through literature mining, bioinformatics and structural biology. In vivo experiments verified the rationality of the antitumor effect of berberine by regulating the ACC/FASN pathway, and in vitro experiments verified the regulatory relationship between berberine and FASN. Results and conclusion: The most frequent Chinese medicine component in XLW was Coptis chinensis. Berberine, the active ingredient of XLW, has a FASN binding site. FASN expression is higher in tumor tissues than in normal tissues. FASN is related to colorectal adenocarcinoma occurrence and patient survival time. Experiments showed that XLW, berberine and orlistat (FASN inhibitor) can cooperate with palmitic acid (PA) to inhibit tumors in mice. Berberine can downregulate FASN and ACC expression in tumor tissues and inhibit the increase in acetyl-CoA, the intermediate product of exogenous PA intake. The mechanism by which berberine inhibits colon cancer cell proliferation by lowering lipids is related to its downregulation of FASN protein expression. The ACC/FASN signaling pathway is a critical pathway through which berberine, the effective monomer of XLW, plays an antitumor role in colon cancer.

Antidepressant-like activity of oroxylin A in mice models of depression: A behavioral and neurobiological characterization.

Depression is a mood disorder which causes a huge economic burden to both families and societies. However, those monoamine-based antidepressants used in clinical practice have been found to have various limitations. Therefore, currently it is very necessary to explore novel antidepressant targets and medications. As a main active component extracted from Scutellariae radix, oroxylin A possesses many pharmacological functions such as anti-cancer, anti-inflammation and neuroprotection. Here, the present study aims to investigate whether oroxylin A possess antidepressant-like actions using the chronic unpredictable mild stress (CUMS) and chronic restraint stress (CRS) models of depression, forced swim test, tail suspension test, open field test, sucrose preference test, western blotting, immunofluorescence and viral-mediated gene interference. Our results revealed that treatment of oroxylin A fully prevented both the CUMS-induced and CRS-induced depressive-like behaviors in mice. Moreover, the protecting effects of oroxylin A against CUMS and CRS on mice behaviors were accompanied with a significant enhancement on the levels of brain-derived neurotrophic factor (BDNF), phosphorylated tyrosine kinase B (pTrkB), phosphorylated cAMP-response element binding protein (pCREB) and neurogenesis in the hippocampus. Furthermore, genetic knockdown of BDNF and TrkB in the hippocampus remarkably abolished the antidepressant-like efficacy of oroxylin A in both the CUMS and CRS models of depression, proving that the hippocampal BDNF-TrkB system participates in the antidepressant mechanism of oroxylin A. In summary, our findings are the first evidence showing that oroxylin A possesses potential of being an antidepressant candidate.

The Efficacy and Safety of Celecoxib in Addition to Standard Cancer Therapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The purpose of this meta-analysis was to evaluate the efficacy and safety of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, in addition to standard anticancer therapy. Randomized controlled trials (RCTs) that evaluated the efficacy and safety of celecoxib-combined cancer therapy were systematically searched in PubMed and Embase databases. The endpoints were overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), objective response rate (ORR), disease control rate (DCR), pathological complete response (pCR), and adverse events (AEs). The results of 30 RCTs containing 9655 patients showed limited benefits in celecoxib-combined cancer therapy. However, celecoxib-combined palliative therapy prolonged PFS in epidermal growth factor receptor (EGFR) wild-type patients (HR = 0.57, 95%CI = 0.35-0.94). Moreover, despite a slight increase in thrombocytopenia (RR = 1.35, 95%CI = 1.08-1.69), there was no increase in other toxicities. Celecoxib combined with adjuvant therapy indicated a better OS (HR = 0.850, 95%CI = 0.725-0.996). Furthermore, celecoxib plus neoadjuvant therapy improved the ORR in standard cancer therapy, especially neoadjuvant therapy (overall: RR = 1.13, 95%CI = 1.03-1.23; neoadjuvant therapy: RR = 1.25, 95%CI = 1.09-1.44), but not pCR. Our study indicated that adding celecoxib to palliative therapy prolongs the PFS of EGFR wild-type patients, with good safety profiles. Celecoxib combined with adjuvant therapy prolongs OS, and celecoxib plus neoadjuvant therapy improves the ORR. Thus, celecoxib-combined cancer therapy may be a promising therapy strategy.

[Clinic analysis of 16 patients of craniocerebral trauma with Labbé vein injury].

OBJECTIVES: To study the mechanism of Labbé vein injury, and its effect on traumatic cerebral infarction and prognosis in patients of craniocerebral trauma. METHODS: The clinic imageology and data of 16 patients of craniocerebral trauma with Labbé vein injury approved intraoperatively from June 2006 to February 2009 were analyzed. To compare the effect of the intraoperative finding of Labbé vein damage and blood vessel treatment on traumatic cerebral infarction, and to analyze the traumatic cerebral infarction size and prognosis. RESULTS: All the 16 patients had acute subdural hematoma and(or) intracerebral hematoma. And 15 of all the 16 patients with Labbé vein injury suffered from skull fractures. All patients accepted hematoma cleaning and intracranial decompression procedure by removing skull. The preoperative Glasgow coma scale (GCS) were as following: 5 patients being between 9 - 12, 7 patients being between 6 - 8 and 4 patients being between 3 - 5. Eight patients had cerebral hernia before operations on admission, and among them, 3 patients had corectasis of both sides and 5 patients had corectasis of only one side, the other 8 patients had no corectasis. Postoperatively, 14 patients suffered from traumatic cerebral infarction of different grades. After follow-ups of 24 months, 8 patients had relatively good prognosis, with 4 patients having good recoveries and 4 having middle disability; the other 8 had bad prognosis, including 3 patients being seriously disable and 5 kept vegetative state. CONCLUSIONS: Impact injury and counterblow are the main reasons to the injury of Labbé vein, which consequently leads to serious traumatic cerebral infarction and bad prognosis. Intraoperatively, it is quite important to protect Labbé vein during the surgery, which should not be easily cut or obstructed by electric coagulation, and this is an effective way to improve the prognosis of these patients.

Emodin Inhibits Lipopolysaccharide-Induced Inflammation by Activating Autophagy in RAW 264.7 Cells.

OBJECTIVE: To investigate the effects of emodin on inflammation and autophagy in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and reveal its underlying mechanism. METHODS: 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay was conducted to find the appropriate dose for emodin. RAW264.7 cells pretreated with different concentrations (0-50 µmol/L) of emodin or vehicle for 2 h prior to exposure to LPS for 16 h. Cell morphology was examined and propidium iodide staining was used to examine cell cycle. Expressions of inflammation-related proteins [nuclear factor-kappaB (NF-κ B) and I-kappaB (I κ B)α] and autophagy-related proteins [light chain (LC)3, P62/sequestosome 1, mammalian target of rapamycin (mTOR), and p-mTOR] were examined using Western blot analysis. Expression of inflammation-related cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 were detected by enzyme-linked immunosorbent assay. Autophagy was examined with LC3B fluorescence intensity and aggregation. The effect of emodin on autophagy was conducted with an autophagy inhibitor, 3-methyladenine (3-MA). RESULTS: The expression of NF-κ B in LPS-induced cells was significantly increased (P<0.01) and simultaneously I κ B α decreased compared with the normal cell (P<0.05). The expressions of TNF-α, IL-ß, and IL-6 proteins in the LPS-induced RAW264.7 cells were significantly higher than in the normal cell (P<0.05 or P<0.01). LPS increased the percentage of cells in the G0/G1 phase, which was recovered by emodin at different doses (12.5, 25, and 50µ mol/L, P<0.05 or P<0.01). The medium-dose (25 µ ml/L) emodin decreased the expressions of NF-κ B, P62 and p-mTOR (P<0.01) and increased I κ B α expression, LC3B II/I ratio as well as LC3B fluorescence intensity (P<0.05 or P<0.01). Meanwhile, the enhanced autophagic effects of emodin, such as the increment of LC3B II/ratio and the decrement of P62 expression, were suppressed by autophagy inhibitor 3-MA. CONCLUSION: Emodin could inhibit inflammation of mice RAW264.7 macrophages induced by LPS, possibly through activating autophagy.

Transition Mechanism from Nonlamellar to Well-Ordered Lamellar Phases: Is the Lamellar Liquid-Crystal Phase a Must?

Understanding the self-assembly mechanisms of amphiphilic molecules in solutions and regulating their phase behaviors are of primary significance for their applications. To challenge the reported direct phase transitions from nonlamellar to ordered lamellar phases, the self-assembly and phase behavior of the 1-hexadecyl-3-methylimidazolium chloride aqueous dispersions were studied using a strategy of isothermal incubation after the temperature jump. A disordered lamellar phase (identified as the lamellar liquid-crystal (Lα) phase), serving as an intermediate, was found to bridge the transition from a spherical micellar (M) phase to a lamellar-gel (Lß) phase. Meanwhile, the nonsynchronicity in the tail and headgroup regions of the ionic liquid surfactant during the transition process was also unveiled, with the former being prior to the latter. The in-depth understanding of the self-assembly mechanisms may help push forward the related applications in the future.

Circ_0049447 acts as a tumor suppressor in gastric cancer through reducing proliferation, migration, invasion, and epithelial-mesenchymal transition.

BACKGROUND: Although increasing abnormal expression of circular RNAs (circRNAs) has been revealed in various cancers, there were a small number of studies about circRNAs in gastric cancer (GC). Here, we explored the expression and function of a novel circRNA, circ_0049447, in GC. METHODS: A total of 80 GC tissues and non-tumorous tissues were collected from the First Affiliated Hospital of China Medical University. And all cells were cultured with 10% fetal bovine serum and incubated at 37°C and 5% CO2. The expression of circ_0049447 was quantified by real-time polymerase chain reaction. The biological function of circ_0049447 on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) was evaluated by cell counting kit-8 (CCK-8), colony formation assay, transwell migration and invasion assay, and Western blotting. Luciferase report assay was used to verify the direct binding between circ_0049447 and predicted microRNA (miRNA). Furthermore, a xenograft mouse model was used to validate the function of circ_0049447 in vivo. RESULTS: We demonstrated that circ_0049447 was downregulated in GC (P < 0.001). The area under the receiver operating characteristic curve reached 0.838, while sensitivity was 82.3% and specificity was 77.2%. CCK-8 and colony formation assay showed that overexpression of circ_0049447 could inhibit the proliferation (P < 0.05). Transwell migration and invasion assay showed upregulated circ_0049447 could impede migration in GC cells (P < 0.05). In addition, overexpression of circ_0049447 could impede GC cell EMT. Upregulation of miR-324-5p in GC specimens and direct binding between miR-324-5p with circ_0049447 proven by luciferase reporter assay indicated that circ_0049447 may inhibit GC by sponging certain miRNA. CONCLUSION: Circ_0049447 acts as a tumor suppressor in GC through reducing proliferation, migration, invasion, and EMT, and it is a promising biomarker for diagnosis.

[Establishment of loop-mediated isothermal amplification method for detection of Legionella pneumophila].

OBJECTIVE: To establish a simple and rapid molecular detection for Legionella pneumophila. METHODS: The loop-mediated isothermal amplification (LAMP) was applied for detection of Legionella pneumophila. A set of primers were designed to identify six special areas in mip gene of Legionella pneumophila. Genomic DNAs from 13 bacterial strains,including 8 Legionella pneumophila strains and 5 other bacterial strains were amplified by LAMP and general PCR method to evaluate the specificity and sensibility of LAMP. RESULT: All positive tubes produced visible white precipitation, and no precipitation was observed in others. By adding smart green fluorescent dye, all Legionella pneumophila positive tubes presented a strong green fluorescence, while others showed weak fluorescence. The detection rate of LAMP was higher than that of general PCR. The detection limits were 576fg with genomic DNA of Legionella pneumophila,and 8 cfu/mL with positive water samples. CONCLUSION: LAMP detection of Legionella pneumophila is an effective and low-cost method with high specificity and sensitivity requiring no special equipment.

Evaluation on pore structures of organosilicate thin films by grazing incidence small-angle X-ray scattering.

Nanoporous thin films fabricated by both a core-shell-shaped organic-inorganic hybrid sphere (octa(2,4-dinitrophenyl)silsesquioxane, ODNPSQ) and a four-leg-numbered surfactant (polyoxyethylene sorbitan monolaurate, Tween-20) for porogens in a higher molecular weight precursor (polyphenylsilsesquioxane, PPSQ) were characterized, respectively, by grazing incidence small-angle X-ray scattering (GISAXS), and the measured 2D GISAXS profiles were analyzed quantitatively by using a GISAXS formula based on the distorted wave Born approximation (DWBA). The fitted 2D GISAXS data show that the PPSQ porous thin films imprinted with ODNPSQ porogen exhibit sphere-shaped closed pores with the average pore size within a range of 1.18-3.12 nm and pore size distribution widths about 3.0 nm when the porogen loadings increase from 10 to 40 wt % and those imprinted with Tween-20 porogen give out an average pore size of 1.07-1.29 nm and pore size distribution widths about 2.0 nm with the porogen loading varying from 5 to 30 wt %. The nanoporous dielectric thin films imprinted with ODNPSQ porogen show a reducing to the molecular aggregation of porogens and significant antiphase separation behavior in the cross-linked matrix.

Human bone marrow-derived mesenchymal stem cell-secreted exosomes overexpressing microRNA-34a ameliorate glioblastoma development via down-regulating MYCN.

PURPOSE: Exosomes play important roles in intercellular communication through signaling pathways affecting tumor microenvironment modulation and tumor proliferation, including those in glioblastoma (GBM). As yet, however, limited studies have been conducted on the inhibitory effect of human bone marrow-derived mesenchymal stem cell (hBMSC)-derived exosomes on GBM development. Therefore, we set out to assess the role of hBMSC secreted exosomes, in particular those carrying microRNA-34a (miR-34a), in the development of GBM. METHODS: Microarray-based expression analysis was employed to identify differentially expressed genes and to predict miRNAs regulating MYCN expression. Next, hBMSCs were transfected with a miR-34a mimic or inhibitor after which exosomes were isolated. Proliferation, apoptosis, migration, invasion and temozolomide (TMZ) chemosensitivity of exosome-exposed GBM cells (T-98G, LN229 and A-172) were measured in vitro. The mechanism underlying MYCN regulation was investigated using lentiviral transfections. The in vivo inhibitory effect of exosomal miR-34a was measured in nude mice xenografted with GBM cells through subcutaneous injection of hBMSCs with an upregulated miR34a content. RESULTS: We found that poorly-expressed miR-34a specifically targeted and negatively regulated the expression of MYCN in GBM cells. In addition we found that miR-34a was delivered to T-98G, LN229 and A-172 GBM cells via hBMSC-derived exosomes. Exogenous overexpression of miR-34a in hBMSC-derived exosomes resulted in inhibition of GBM cell proliferation, invasion, migration and tumorigenesis in vitro and in vivo, while promoting the chemosensitivity of GBM cells to TMZ by silencing MYCN. CONCLUSIONS: From our data we conclude that hBMSC-derived exosomes overexpressing miR-34a may be instrumental for the therapeutic targeting and clinical management of GBM.

Hippocampal PPARα is involved in the antidepressant-like effects of venlafaxine in mice.

Although thought as a serotonin and norepinephrine reuptake inhibitor (SNRI), the antidepressant mechanisms of venlafaxine remain unknown. Previous reports have shown the role of peroxisome proliferator activated receptor α (PPARα) in depression. In this study, we investigated whether the antidepressant-like effects of venlafaxine require PPARα. We first examined whether repeated venlafaxine administration reversed the effects of chronic unpredictable mild stress (CUMS) and chronic restraint stress (CRS) on PPARα in the hippocampus and medial prefrontal cortex (mPFC). Then, the pharmacologcial inhibitors of PPARα, GW6471 and MK886, were used to assay if the protecting effects of venlafaxine against chronic stress were prevented by PPARα blockade. Furthermore, gene knockdown of PPARα by AAV-PPARα-shRNA was also used. It was found that venlafaxine treatment fully restored the decreasing effects of CUMS and CRS on the hippocampal PPARα expression. Pharmacological inhibition of PPARα significantly attenuated the antidepressant-like effects of venlafaxine in mice. Moreover, gene knockdown of hippocampal PPARα also fully abolished the antidepressant-like actions of venlafaxine in mice. Collectively, hippocampal PPARα is an antidepressant target of venlafaxine.

Circulating Noncoding RNAs Have a Promising Future Acting as Novel Biomarkers for Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common malignant tumors worldwide, causing a large number of cancer-related deaths each year. Patients are usually diagnosed at advanced and incurable stages due to the lack of suitable screening methods for early detection. Noncoding RNAs (ncRNAs), including small and long noncoding RNAs (lncRNA), are known to have significant regulatory functions, and accumulating evidence suggests that circulating ncRNAs have potential applications as noninvasive biomarkers for diagnosing CRC, evaluating its prognosis, or predicting chemosensitivity in the general population. In this review, we summarize the origins of circulating ncRNAs and provide details of single and multiple circulating ncRNAs that might have roles as diagnostic and prognostic biomarkers in CRC. We end by discussing circulating ncRNAs that may distinguish patients with resistance to chemotherapy.