A Novel Small Molecular Inhibitor of DNMT1 Enhances the Antitumor Effect of Radiofrequency Ablation in Lung Squamous Cell Carcinoma Cells.

Radiofrequency ablation (RFA) is a relatively new and effective therapeutic strategy for treating lung squamous cell carcinomas (LSCCs). However, RFA is rarely used in the clinic for LSCC which still suffers from a lack of effective comprehensive treatment strategies. In the present work, we investigate iDNMT, a novel small molecular inhibitor of DNMT1 with a unique structure. In clinical LSCC specimens, endogenous DNMT1 was positively associated with methylation rates of miR-27-3p's promoter. Moreover, endogenous DNMT1 was negatively correlated with miR-27-3p expression which targets PSEN-1, the catalytic subunit of γ-secretase, which mediates the cleavage and activation of the Notch pathway. We found that DNMT1 increased activation of the Notch pathway in clinical LSCC samples while downregulating miR-27-3p expression and hypermethylation of miR-27-3p's promoter. In addition of inhibiting activation of the Notch pathway by repressing methylation of the miR-27-3p promoter, treatment of LSCC cells with iDNMT1 also enhanced the sensitivity of LSCC tumor tissues to RFA treatment. These data suggest that iDNMT-induced inhibition of DNMT-1 enhances miR-27-3p expression in LSCC to inhibit activation of the Notch pathway. Furthermore, the combination of iDNMT and RFA may be a promising therapeutic strategy for LSCC.

Evodiamine induces apoptosis and promotes hepatocellular carcinoma cell death induced by vorinostat via downregulating HIF-1α under hypoxia.

Hypoxia promotes HCC progression and therapy resistance, and there is no systemic treatment for HCC patients after sorafenib resistance. Thus, it is urgent to develop potential therapeutic regimens for HCC patients by targeting hypoxia signaling. In this study, we showed that evodiamine might be a potential therapeutic medicine for HCC by suppressing HIF-1α. In addition, evodiamine could sensitize the anti-HCC effect of vorinostat in HCC cells under hypoxia. Furthermore, evodiamine plus vorinostat accelerated the degradation of HIF-1α in HCC cells under hypoxia. In general, evodiamine might be a potential therapeutic candidate for HCC patients, and evodiamine combining with vorinostat might be an attractive chemotherapy strategy for HCC treatment.

Incidence, risk factors and treatment outcomes of drug extravasation in pediatric patients in China.

Yan YM, Gong M, Chen JL, Li D, Xu TT, Zou H, Li AQ, Fan QL, Lu QF. Incidence, risk factors and treatment outcomes of drug extravasation in pediatric patients in China. Turk J Pediatr 2017; 59: 162-168. Extravasation injury is a common phenomenon in hospitals. Failure to detect and treat extravasation injury can lead to irreversible local injuries, tissue necrosis and malfunction of the affected tissue. Until now, it is largely unknown about incidence, risk factors and treatment outcomes of extravasation in Chinese pediatric patients. The aim of this study is to explore the incidence, risk factors and summarize the characteristics and treatment outcomes of extravasation injuries resulting in drug extravasation among Chinese children in our hospital. The children undergoing infusion therapy (0-18 years) were enrolled in this study between December 2014 and June 2015 in Shanghai Children`s Hospital. The patients` information including age, gender, injection site, estimated volume of solution extravasated, patient symptoms, severity of extravasation injury, treatment methods, and outcomes was collected. Multivariate logistic regression was used to identify the independent risk factors for the development of extravasation. The incidence of extravasations in pediatric patients was 1.79% (18/1,004). The severity of extravasation was labeled with grade range from Grade 1 through Grade 4: 4 cases with Grade 1, 8 cases with Grade 2, 5 cases with Grade 3, and 1 case with Grade 4. The risk factors of extravasation include infused high volume/day (≥1000 ml), received operation, infused agents with high osmolarity and poor vein condition. The severity of extravasation was related to the large volumes of drug or special drugs (high-osmolarity, high-risk, low pH, etc). All extravasations were treated with physical, pharmacological and surgical intervention according to our standard operation protocols. Systematic implementation of intervention can alleviate the extravasation injuries and improve the patients` outcome.

Magnetic mesoporous Fe/carbon aerogel structures with enhanced arsenic removal efficiency.

Wastewater treatment has drawn significant research attention due to its associated environmental issues. Adsorption is a promising method for treating wastewater. The development of an adsorbent with a high surface area is important. Therefore, we successfully developed mesoporous Fe/carbon aerogel (CA) structures with high specific surface areas of 48 7m(2)/g via the carbonization of composite Fe3O4/phenol-formaldehyde resin structures, which were prepared using a hydrothermal process with the addition of phenol. The mesoporous Fe/CA structures were further used for the adsorption of arsenic ions with a maximum arsenic-ion uptake of calculated 216.9 mg/g, which is higher than that observed for other arsenic adsorbents. Ferromagnetic behavior was observed for the as-prepared mesoporous Fe/CA structures with an excellent response to applied external magnetic fields. As a result, the adsorbent Fe/CA structures can be easily separated from the solution using an external magnetic field. This study develops the mesoporous Fe/CA structures with high specific surface areas and an excellent response to an applied external magnetic field to provide a feasible approach for wastewater treatment including the removal of arsenic ions.

Treatment of cutaneous injuries of neonates induced by drug extravasation with hyaluronidase and hirudoid.

OBJECTIVE: To analyze the effects of hyaluronidase and hirudoid treatment on drug extravasation in neonates. METHODS: The medical records of 13 neonates with drug extravasation treated with hyaluronidase and hirudoid between August 1(st), 2010 and May 1(st), 2012 were analyzed retrospectively. The treatment procedure for drug extravasation adhered to the protocol in neonatal department. The information including age, sex, weight, diagnosis, size of affected area, site of extravasation and treatment was collected. Findings : The extravasation injuries alleviated and the symptoms improved after treatment, no adverse drug effects were reported with use of hyaluronidase and hirudoid. CONCLUSION: The treatment appeared to be beneficial in the management of extravasations of various medications in neonates and may be useful in reducing the severity of cutaneous toxicosis. However, further studies with large samples are still needed to assess the effectiveness and safety of hyaluronidase and hirudoid.

A novel stacking method of repetitive large volume sample injection and sweeping MEKC for determination of androgenic steroids in urine.

In this research, a novel stacking capillary electrophoresis method, repetitive large volume sample injection and sweeping MEKC (rLVSI-sweeping MEKC) were developed to analyze the presence of three androgenic steroids considered as sport doping drugs, testosterone (T), epitestosterone (E) and epitestosterone glucuronide (EG) in urine. This method provides better sensitivity enhancement than the traditional large volume sample stacking-sweeping strategies due to sensitivity enhancement by repetitive injections. This multiple sampling method enhances sensitivity of monitoring of urine samples by UV detection (254 nm). Firstly, the phosphate buffer was filled into an uncoated fused silica capillary and the samples were injected into the capillary at 10 psi for 20s, and then stacked at -10 kV for 1 min using phosphate buffer containing SDS. The above injecting and stacking steps were repeated five times. Finally, separation was performed at -20 kV, using phosphate buffer containing methanol, SDS and (2-hydroxypropyl)-ß-cyclodextrin. Method validation showed that calibration plots were linear (r≥0.997) over a range of 5-200 ng mL(-1) for T, 20-200 ng mL(-1) for E and 0.5-500 ng mL(-1) for EG. The limits of detection were 1.0 ng mL(-1) for T, 5.0 ng mL(-1) for E and 200.0 pg mL(-1) for EG. When evaluating precision and accuracy, values of RSD and RE in intra-day (n=3) and inter-day (n=5) analysis were found to be less than 10.0%. Compared with the simple LVSS-sweeping, which is also a stacking strategy, this method further improves sensitivity up to 25 folds (~2500 folds with MEKC without preconcentration). This method was applied to monitor 10 athletes' urine, and did not detect any analyte. The novel stacking method was feasible for monitoring of doping by sportsmen.

Naringin attenuates acute lung injury in LPS-treated mice by inhibiting NF-κB pathway.

Naringin has been reported as an effective anti-inflammatory compound. We previously showed that naringin had antitussive effect on experimentally induced cough in guinea pigs. However, the effects and mechanism of naringin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice are not fully understood. In this study, our aim was to evaluate the anti-inflammatory activities of naringin on LPS-induced ALI in mice and clarify its underlying mechanisms of action. We found that in vivo pretreatment with naringin markedly decreased the lung wet weight to dry weight ratio, and led to significant attenuation of LPS-induced evident lung histopathological changes. Meanwhile, naringin significantly reduced bronchoalveolar lavage fluid (BALF) total cell and neutrophil (PMN) counts after LPS challenge. Furthermore, naringin inhibited myeloperoxidase (MPO: a marker enzyme of neutrophil granule) and inducible nitric oxide synthase (iNOS) activities in lung tissue and alleviated LPS-induced tumor neurosis factor-α (TNF-α) secretion in BALF in a dose-dependent manner. Additionally, Western blotting showed that naringin efficiently blunt NF-κB activation by inhibiting the degradation of IĸB-α and the translocation of p65. Taken together, these results suggest that naringin shows anti-inflammatory effects through inhibiting lung edema, MPO and iNOS activities, TNF-α secretion and pulmonary neutrophil infiltration by blockade of NF-κB in LPS-induced ALI.