SLC5A3 is important for cervical cancer cell growth.

Novel molecular targets for cervical cancer must be identified. This study examined the role of SLC5A3, a myo-inositol transporter, in the pathogenesis of cervical cancer. Through boinformatics analysis, we showed that the SLC5A3 mRNA levels were upregulated in cervical cancer tissues. The upregulated SLC5A3 mRNA levels were negatively correlated with survival and progression-free interval. Genes co-expressed with SLC5A3 were enriched in multiple signaling cascades involved in cancer progression. In primary/established cervical cancer cells, SLC5A3 shRNA/knockout (KO) exerted growth-inhibitory effects and promoted cell death/apoptosis. Furthermore, SLC5A3 knockdown or KO downregulated myo-inositol levels, induced oxidative injury, and decreased Akt-mTOR activation in cervical cancer cells. In contrast, supplementation of myo-inositol or n-acetyl-L-cysteine or transduction of a constitutively active Akt1 construct mitigated SLC5A3 KO-induced cytotoxicity in cervical cancer cells. Lentiviral SLC5A3 overexpression construct transduction upregulated the cellular myo-inositol level and promoted Akt-mTOR activation, enhancing cervical cancer cell proliferation and migration. The binding of TonEBP to the SLC5A3 promoter was upregulated in cervical cancer. In vivo studies showed that intratumoral injection of SLC5A3 shRNA-expressing virus arrested cervical cancer xenograft growth in mice. SLC5A3 KO also inhibited pCCa-1 cervical cancer xenograft growth. The SLC5A3-depleted xenograft tissues exhibited myo-inositol downregulation, Akt-mTOR inactivation, and oxidative injury. Transduction of sh-TonEBP AAV construct downregulated SLC5A3 expression and inhibited pCCa-1 cervical cancer xenograft growth. Together, overexpressed SLC5A3 promotes growth of cervical cancer cells, representing as a novel therapeutic oncotarget for the devastating disease.

The efficacy of dexketoprofen for migraine attack: A meta-analysis of randomized controlled studies.

BACKGROUND: The efficacy of dexketoprofen for migraine attack remains controversial. We conduct a systematic review and meta-analysis to explore the influence of dexketoprofen supplementation versus placebo on pain control in migraine attack patients. METHODS: We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through March 2019 for randomized controlled trials (RCTs) assessing the effect of dexketoprofen supplementation versus placebo on pain control for migraine attack patients. This meta-analysis is performed using the random-effect model. RESULTS: Five RCTs involving 794 patients are included in the meta-analysis. Overall, compared with control group for migraine attack, dexketoprofen supplementation is associated with substantially increased pain free at 2 hours (RR = 1.90; 95% CI = 1.43-2.53; P < .0001), pain free at 48 hours (RR = 1.63; 95% CI = 1.07-2.49; P = .02), good or excellent treatment (RR = 1.48; 95% CI = 1.24-1.78; P < .0001) and pain relief at 2 hours (RR = 1.80; 95% CI = 1.17-2.77; P = .007), as well as reduced need for rescue drug (RR = 0.64; 95% CI = 0.43-0.94; P = .02), with no significant increase in adverse events (RR = 1.51; 95% CI = 0.87-2.62; P = .14). CONCLUSION: Dexketoprofen supplementation benefits to improve pain control at 48 hours and reduce the need for rescue drug in migraine attack patients.

Rapid prediction of yellow tea free amino acids with hyperspectral images.

Free amino acids are an important indicator of the freshness of yellow tea. This study investigated a novel procedure for predicting the free amino acid (FAA) concentration of yellow tea. It was developed based on the combined spectral and textural features from hyperspectral images. For the purposes of exploration and comparison, hyperspectral images of yellow tea (150 samples) were captured and analyzed. The raw spectra were preprocessed with Savitzky-Golay (SG) smoothing. To reduce the dimension of spectral data, five feature wavelengths were extracted using the successive projections algorithm (SPA). Five textural features (angular second moment, entropy, contrast, correlation, and homogeneity) were extracted as textural variables from the characteristic grayscale images of the five characteristic wavelengths using the gray-level co-occurrence matrix (GLCM). The FAA content prediction model with different variables was established by a genetic algorithm-support vector regression (GA-SVR) algorithm. The results showed that better prediction results were obtained by combining the feature wavelengths and textural variables. Compared with other data, this prediction result was still very satisfactory in the GA-SVR model, indicating that data fusion was an effective way to enhance hyperspectral imaging ability for the determination of free amino acid values in yellow tea.

Successful Rescue of a Patient with Acute Aconitine Poisoning Complicated by Polycystic Renal Hemorrhage.

INTRODUCTION: Aconitine is a highly toxic diterpenoid alkaloid, produced by plants of the Aconitum genus, that is still used in Chinese herbal medicines. Aconitine poisoning remains common in China and other parts of Asia. CASE REPORT: A 48-year-old man received a diagnosis of aconitine poisoning after ingesting herbal medicinal wine made with caowu, which is made from Aconitum kusnezoffii roots, and was admitted to our hospital' s emergency department. Electrocardiography and thoracoabdominal computed tomography showed cardiovascular toxicity from aconitine poisoning along with polycystic renal hemorrhaging. Because the arrhythmia was not controlled with lidocaine, blood purification with a reduced dosage of heparin was performed to treat the arrhythmia and to avoid increasing the bleeding of the polycystic renal hemorrhage. The patient recovered from aconitine poisoning and polycystic kidney hemorrhage. CONCLUSIONS: This case significantly advances our understanding of hemoperfusion with reduced heparin for the treatment of ventricular arrhythmia caused by aconitine poisoning.

Gender-related pharmacokinetics and absolute bioavailability of diosbulbin B in rats determined by ultra-performance liquid chromatography-tandem mass spectrometry.

ETHNOPHARMACOLOGICAL RELEVANCE: Diosbulbin B (DB) is the main constituent of furano-norditerpenes in Dioscorea bulbifera Linn., which is widely distributed in China and was usually used as a remedy for sore throat, struma and tumor. Owing to its potential antitumor activity, DB has been considered as a promising candidate for drug development. AIM OF THE STUDY: To study the pharmacokinetic properties and excretion of DB in rats by a sensitive UPLC-MS/MS method. Absolute bioavailability and gender-related pharmacokinetic properties, as well as excretion fractions of DB in urine and feces after oral and intravenous administrations would be addressed for the first time. MATERIALS AND METHODS: Sprague-Dawley rats were administrated orally (32mg/kg) and intravenously (0.5mg/kg) of DB, respectively. The concentrations of DB in rat plasma were determined by a sensitive and well-validated LC-MS/MS method. Main pharmacokinetic parameters including area under the plasma concentration-time curve (AUC), elimination half time (t1/2), mean residence time (MRT), apparent volume of distribution (Vd) and clearance rate (CL) were estimated using a non-compartmental pharmacokinetics data analysis software. Urine and feces of rats were collected within 48h after oral administration (32mg/kg) and detected by UPLC-MS/MS and HPLC, respectively. RESULTS: The standard curves of DB in rat plasma and urine showed good linearity in the concentration range of 1.0-515ng/mL in the method, with acceptable selectivity, precisions, recoveries, and stability. The oral absolute bioavailability of DB in female rats was 2.0%, significantly higher than that of males (0.3%) (p<0.05). Female rats demonstrated longer t1/2 and MRT (p<0.01), bigger Vd and higher CL (p<0.05) than males after intravenous administration of DB. Bigger but no significant difference in excretion fractions of urine and feces in female rats were observed, comparing to those in males. CONCLUSION: A simple and sensitive UPLC-MS/MS method was developed to determine the pharmacokinetic profiles of DB in rats, as well as the excretion in rat urine. Gender exerted a significant influence on the pharmacokinetics and bioavailability of DB in rats. Female rats showed significantly better absorption of DB than males after oral administration.

Systems toxicology used in nanotoxicology: mechanistic insights into the hepatotoxicity of nano-copper particles from toxicogenomics.

In some studies, nano-copper particles have been found to be acutely toxic to exposed mice, with the liver and kidney being the target tissues. However, the characteristics of subacute toxicity from repeated nano-copper exposure in rats and the molecular mechanism of its hepatotoxicity at the genomic level remain unclear. We investigated the mechanisms of nano-copper-induced hepatotoxicity, which were identified from hepatic gene expression profiles that were phenotypically anchored to conventional toxicological outcomes, and identified biomarkers of nanotoxicity caused by nano-copper. Male Wistar rats were administered nano-copper or micro-copper at different doses for five days. Subsequently, we examined conventional toxicological parameters including body weight, clinical chemistry, and histopathology, and also used microarrays to identify gene expression changes in rat liver. High dose nano-copper induced increases in alanine aminotransferase, aspartate aminotransferase, triglyceride, total bilirubin, total bile acid levels, and a decrease in body weight. Histopathological studies of the liver indicated scattered, dotted hepatocytic necrosis in all rats in the high dose nano-copper group. Identified genes from the group receiving the high dose were functionally categorized, and results showed that genes related to oxidoreductase activity, metabolism, and signal transduction were involved in the development of the observed phenotypes. The results also suggest that altered gene expression patterns induced by exposure to a low, subtoxic dose of nano-copper may reveal signs of cell stress or subtle cell injury indicative of overt toxicity at higher doses. Results in this study provide new insights into the toxicology of nano-copper particles and illustrate how toxicogenomic approaches are providing an unprecedented amount of mechanistic information on molecular responses to nano-copper, as well as how they are likely to impact hazard and risk assessment. Gene expression changes are likely to be more sensitive indicators of potential adverse effects than traditional measurements of toxicity.

Integrated metabolomic analysis of the nano-sized copper particle-induced hepatotoxicity and nephrotoxicity in rats: a rapid in vivo screening method for nanotoxicity.

Despite an increasing application of copper nanoparticles, there is a serious lack of information concerning their impact on human health and the environment. In this study, the biochemical compositions of urine, serum, and extracts of liver and kidney tissues of rats treated with nano-copper at the different doses (50, 100, and 200 mg/kg/d for 5 d) were investigated using (1)H NMR techniques with the pattern recognition methods. Serum biochemical analysis and histopathological examinations of the liver and kidney of all the rats were simultaneously performed. All the results indicated that the effects produced by nano-copper at a dose of 100 or 50 mg/kg/d were less than those induced at a higher dose of 200 mg/kg/d. Nano-copper induced overt hepatotoxicity and nephrotoxicity at 200 mg/kg/d for 5 d, which mainly involved scattered dot hepatocytic necrosis and widespread renal proximal tubule necrosis. Increased citrate, succinate, trimethylamine-N-oxide, glucose, and amino acids, accompanied by decreased creatinine levels were observed in the urine; furthermore, elevated levels of lactate, 3-hydroxybutyrate, acetate, creatine, triglycerides, and phosphatide and reduced glucose levels were observed in the serum. The predominant changes identified in the liver tissue aqueous extracts included increased lactate and creatine levels together with reduced glutamine and taurine levels, and the metabolic profile of the kidney tissue aqueous extracts showed an increase in lactate and a drop in glucose. In the chloroform/methanol extracts of the liver and kidney tissues, elevated triglyceride species were identified. These changes suggested that mitochondrial failure, enhanced ketogenesis, fatty acid beta-oxidation, and glycolysis contributed to the hepatotoxicity and nephrotoxicity induced by nano-copper at 200 mg/kg/d for 5 d. An increase in triglycerides in the serum, liver and kidney tissues could serve as a potential sensitive biomarker reflecting the lipidosis induced by nano-copper. The data generated from the current study completely supports the fact that an integrated metabolomic approach is promising for the development of a rapid in vivo screening method for nanotoxicity.

Lignans from bark of Larix olgensis var. koreana.

Six new lignans (2-7) were isolated from the bark of Larix olgensis var. koreana, and their structures were determined on the basis of their spectroscopic data. Seven known lignans were also obtained and identified as (+)-lariciresinol 9'-p-coumarate (1), (+)-lariciresinol, (-)-secoisolariciresinol, (+)-isolariciresinol, vladinol D, sesquipinsapol B, and ehletianol C. Compound 1 showed weak inhibition against K562, SHG44, HCT-8, A549, and PC-3M tumor cells with IC50 values of 2.9, 21.4, 32.9, 33.8, and 28.0 microg/mL, respectively.

[Studies on chemical constituents in bark of Larix olgensis var. koreana].

OBJECTIVE: To study the chemical constituents in bark of Larix olgensis var. koreana. METHOD: The compounds were isolated with silica gel column chromatography and their structures were elucidated on the basis of spectral analysis (IR, EI-MS, 1H-NMR, 13C-NMR). RESULT: Eight compounds were isolated and identified as isopimaric acid (I), beta-sitosterol (II), 24R,5alpha-stigmast-3,6-dione (III), larixol (IV), ferulic acid (V), lariciresinol (VI), secroisolariciresinol (VII) and isolariciresinol (VIII). CONCLUSION: All the compounds were isolated from this plant for the first time.