Dichloroacetate enhances the antitumor effect of pirarubicin via regulating the ROS-JNK signaling pathway in liver cancer cells.

Aim: Liver cancer is one of the most common malignancies and has a high recurrence rate. However, current treatment strategies do not achieve satisfactory outcomes in the clinic. To explore a new strategy to enhance the effectiveness of chemotherapy in liver cancer, we investigated whether dichloroacetate (DCA) could enhance the sensitivity of liver cancer cells to pirarubicin (THP). Methods: Liver cancer cells were treated with DCA alone, THP alone, or DCA and THP combined. Cell viability was determined by the CCK-8 assay. Cell apoptosis was analyzed by flow cytometer. Reactive oxygen species (ROS) were detected using a CM-H2DCFDA fluorescence probe. Protein levels were identified by immunoblotting. Results: The results revealed that DCA significantly enhanced the antitumor effect of THP in liver cancer cells. Changes in morphology and adherence ability were observed, as well as decreased cell viability. The results of flow cytometry showed that the combination of THP and DCA significantly increased apoptosis of liver cancer cells. Moreover, compared with THP alone, combination treatment with DCA significantly increased THP-triggered ROS generation in liver cancer cells. The antioxidant N-acetyl-L-cysteine reversed the synergistic effect of DCA and THP on ROS generation, cell viability and apoptosis. Furthermore, phosphorylation of c-Jun N-terminal kinase (JNK) was significantly increased in the DCA and THP combination group. The effects of DCA and THP on cell viability and apoptosis were inhibited by the JNK inhibitor SP600125. Conclusion: The results obtained in the present study indicated that DCA enhanced the antitumor effect of THP in liver cancer cells via regulating the ROS-JNK signaling pathway.

Rapid Detection of Atrazine at Workplace with Near-Infrared Spectroscopy.

As a wildly used herbicide, Atrazine is mainly produced in China. In order to strengthen the routine detection of Atrazine exposure concentration and protect the health of occupational contact workers, it's of great importance to develop on-site rapid detection method. A self-assembled near infrared spectrometer was used to record spectra of laboratory prepared atrazine solutions with concentration range from 10 to 1 000 mg·L-1. The influences of different pretreatment methods, such as multiplicative scatter correction, standard normal variate, first order derivative (D1), second order derivative and their combinations, different variable selection methods, such as competitive adaptive reweighted sampling (CARS) and genetic algorithm (GA), different regression methods, such as partial least square (PLS) and support vector regression(nu-SVR), on the model prediction accuracy were investigated. Results show that D1 is the best pretreatment method; GA obtain better results than CARS on selecting highly related spectral variables; nu-SVR model perform better than PLS model. The nu-SVR model constructed with 16 spectral variables selected by GA obtained the best results, whose coefficient of determination for calibration, the coefficient of determination for validation, root mean square error of calibration, root mean square error of validation (RMSEV) and residual validation deviation (defined as SD/RMSEV where SD denotes standard deviation) are 1, 0.99, 17.54 mg·L-1, 25.42 mg·L-1 and 11.43, respectively. These results indicate near infrared spectroscopy combined with chemometrics has great potential to quantify Atrazine concentration at workplace. This research explores the feasibility of quantification Atrazine at workplace with near infrared spectroscopy for the first time, which has great reference value for similar work in the future.

Facilitating terminal discharge: fulfilling the hospitalised patient's wish for home death in the final hours.

BACKGROUND: Terminal discharge (TD) is the rapid discharge of a hospitalised patient when death is imminent. Its time-limited nature makes it challenging, particularly for ward nurses. AIM: To report the development of a structured TD framework, and determine if the framework can expedite TD processes and improve nurses' experience in conducting TDs. METHODS: A 3-phase audit was carried out in a Singapore hospital. The baseline and post intervention audits evaluated the time taken for TD, incidence of prescription errors, continuity of care, and timeliness of equipment arrangement. Nurse satisfaction was assessed through a written survey. Interventions encompassed the implementation of workflow changes and a TD guide. RESULTS: The mean time taken to complete TDs was shorter in the post-compared to pre-intervention phase (2.9±1.4 vs. 4.6±2.3 hours respectively, p<0.01). Approximately 89% of nurses who used the TD guide were satisfied that it made TDs easier. CONCLUSION: A structured TD framework is effective in expediting TDs and improving nurse satisfaction.

Fabrication of biocompatible and mechanically reinforced graphene oxide-chitosan nanocomposite films.

BACKGROUND: Graphene oxide (GO)can be dispersed through functionalization, or chemically converted to make different graphene-based nanocomposites with excellent mechanical and thermal properties. Chitosan, a partially deacetylated derivative of chitin, is extensively used for food packaging, biosensors, water treatment, and drug delivery. GO can be evenly dispersed in chitosan matrix through the formation of amide linkages between them, which is different from previous reports focusing on preparing GO/chitosan nanocomposites through physical mixing. RESULTS: In this study, free-standing graphene oxide-chitosan (GO-chitosan) nanocomposite films have been prepared. The GO-chitosan films are biologically compatible and mechanically reinforced. Through the formation of amide linkages between GO's carboxylic acid groups and chitosan's amine groups, GO could be evenly dispersed within the chitosan matrix. We also characterized the GO-chitosan composite films using element analysis, Fourier transform infrared spectroscopy, X-ray photo electron spectroscopy, differential scanning calorimetry, and thermo gravimetric analysis. Compared to pristine chitosan film, the tensile strength of GO-chitosan film is improved by 2.5 folds and Young's modulus increases by nearly 4.6 folds. The glass transition temperature of GO-chitosan composite film shifts from 118°C to 158°C compared to the pristine chitosan, indicating its enhanced thermal stability. GO-chitosan composite film was also evaluated for its biocompatibility with C3H10T1/2 cells by in vitro fluorescent staining. The graphene oxide-reinforced chitosan composite films could have applications in functional biomaterials. CONCLUSION: The present study describes a useful and simple method to chemically attach biocompatible chitosan onto graphene oxide. We envision that the GO-chitosan film will open avenues for next-generation graphene applications in the realm of functional biomaterial.

Panax notoginseng saponins attenuate atherosclerosis via reciprocal regulation of lipid metabolism and inflammation by inducing liver X receptor alpha expression.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax notoginseng (Burk.) F.H. Chen has been used as a health product and natural remedy in traditional medicine for cardiovascular diseases for more than 1000 years in Asia, including China, Japan, and Korea. Panax notoginseng saponins (PNS) are the major effective ingredients extracted from Panax notoginseng. AIM OF THE STUDY: The purpose of this study was to investigate whether Panax notoginseng saponins (PNS) attenuated atherosclerosis by inducing liver X receptor alpha (LXRα) expression and to elucidate the mechanisms responsible for the effects. MATERIALS AND METHODS: The AS rats were treated once daily with PNS (100 mg/kg, i.p.), and pathological changes in the aorta were observed using Sudan IV staining. The expression of LXRα in the aortic wall was measured by Western blot analysis. THP-1 macrophages were cultured with PNS in the presence or absence of geranylgeranyl pyrophosphate ammonium salt (GGPP), an LXRα antagonist. The expression of LXRα and its target genes ATP-binding cassette A1 and G1 (ABCA1, ABCG1) were determined by qRT-PCR. The transcriptional activation of the LXRα gene promoter was analyzed by a reporter assay. The NF-κB DNA binding activity and the expression of interleukin (IL)-6, monocyte chemotactic protein-1 (MCP-1) was evaluated respectively by Trans-AM NF-κB ELISA and ELISA in THP-1 macrophages that were stimulated with LPS after treatment with PNS and GGPP. RESULTS: PNS treatment alleviated the typical pathological changes associated with atherosclerosis in rats. The expression of LXRα was increased in rat aortas after treatment with PNS. In vitro, PNS increased LXRα mRNA levels in THP-1 macrophages. The reporter assays showed that PNS enhanced transcriptional activation of the LXRα gene promoter and led to the upregulation of ABCA1 and ABCG1 expression. This upregulation could be reversed by treatment with GGPP. Additionally, PNS inhibited NF-κB DNA binding activity and reduced secretion of IL-6 and MCP-1 in LPS-stimulated THP-1 macrophages. These effects could be reversed by GGPP. CONCLUSIONS: The results indicated that the PNS-mediated attenuation of AS may, at least partly, due to LXRα uprergulation. The mechanisms of action included enhancement transcriptional activation of the LXRα gene promoter by PNS and subsequent upregulation of ABCA1 and ABCG1 and inhibition of NF-κB DNA binding activity.