The Effect of Coenzyme Q10 on Liver Injury Induced by Valproic Acid and Its Antiepileptic Activity in Rats

Valproic acid (VPA) has toxic metabolites that can elevate oxidative stress markers, and the hepatotoxicity of VPA has been reported. Coenzyme Q10 (CoQ10) is one of the most widely used antioxidants. The effect of CoQ10 on epileptogenesis and VPA hepatotoxicity were examined. Rats were randomly divided into five groups: the control group received 0.5% methylcellulose by oral gavages daily and saline by intraperitoneal injection three times weekly. The PTZ group received 1% methylcellulose by gavages daily and 30 mg/kg PTZ by intraperitoneal injection three times weekly. The valproic acid group received 500 mg/kg valproic acid by gavage and 30 mg/kg PTZ, as above. The CoQ10 group received 200 mg/kg CoQ10 by gavages daily and 30 mg/kg PTZ, as above. The Valproic acid + CoQ10 group received valproic acid and CoQ10, as above. Results: CoQ10 exhibited anticonvulsant activity and potentiated the anticonvulsant effect of VPA. CoQ10 combined with VPA induced a more significant reduction in oxidative stress and improved the histopathological changes in the brain and liver compared to VPA treatment. In addition, CoQ10 reduced the level of toxic VPA metabolites. These findings suggest that the co-administration of CoQ10 with VPA in epilepsy might have therapeutic potential by increasing antiepileptic activity and reducing the hepatotoxicity of VPA.

A “Double-Locked” and Enzyme/pH-Activated Theranostic Agent for Accurate Tumor Imaging and Therapy

Theranostic agents for concurrent cancer therapy and diagnosis have begun attracting attention as a promising modality. However, accurate imaging and identification remains a great challenge for theranostic agents. Here, we designed and synthesized a novel theranostic agent H6M based on the “double-locked” strategy by introducing an electron-withdrawing nitro group into 1-position of a pH-responsive 3-amino-β-carboline and further covalently linking the hydroxamic acid group, a zinc-binding group (ZBG), to the 3-position of β-carboline to obtain histone deacetylase (HDAC) inhibitory effect for combined HDAC-targeted therapy. We found that H6M can be specifically reduced under overexpressed nitroreductase (NTR) to produce H6AQ, which emits bright fluorescence at low pH. Notably, H6M demonstrated a selective fluorescence imaging via successive reactions with NTR (first “key”) and pH (second “key”), and precisely identified tumor margins with a high S/N ratio to guide tumor resection. Finally, H6M exerted robust HDAC1/cancer cell inhibitory activities compared with a known HDAC inhibitor SAHA. Therefore, the NTR/pH-activated theranostic agent provided a novel tool for precise diagnosis and efficient tumor therapy.

Cinchona Alkaloid Derivatives modified Fe3O4 Nanoparticles for Enantioselective Ring Opening of meso- Cyclic Anhydrides

In the present work, the molecular framework of the quinidine was modified at the methoxy functional of C6’ carbon of quinoline moiety with a long-chain carboxylic acid group (-COOH) and...

Effects of hyperuricaemia, with the superposition of being overweight and hyperlipidaemia, on the incidence of acute kidney injury following cardiac surgery: a retrospective cohort study

ObjectivesAcute kidney injury (AKI) is a common complication of cardiac surgery. This study aimed to explore the effects of hyperuricaemia, being overweight and hyperlipidaemia as risk factors for AKI in patients following cardiac surgery (cardiac surgery-associated acute kidney injury (CSA-AKI)).DesignRetrospective observational study.SettingUniversity teaching, grade-A tertiary hospital in Shanghai, China.ParticipantsPatients who underwent cardiac surgery from July 2015 to December 2015 in Zhongshan Hospital, Fudan University.Main outcome measuresWe investigated the effect of hyperuricaemia, in combination with being overweight and hyperlipidaemia, on the risk of CSA-AKI.ResultsA total of 1420 patients were enrolled. The AKI incidence in the highest uric acid group was 44.4%, while that in the lowest uric acid group was 28.5% (p<0.001). Patients in the higher uric acid quartiles were more likely to be overweight and hyperlipidaemic at the same time (p<0.001). Multivariate logistic regression analysis showed that hyperuricaemia was an independent risk factor for AKI (OR=1.237, 95% CI 1.095 to 1.885; p=0.009); being overweight or hyperlipidaemia alone was not an independent risk factor, but the combination of being overweight and hyperlipidaemia was (OR=1.544, 95% CI 1.059 to 2.252; p=0.024). In the final model, the OR value increased to 3.126 when hyperuricaemia was combined with being overweight and hyperlipidaemia, and the Hosmer-Lemeshow test showed that all three models fit well (p=0.433, 0.638 and 0.597, respectively).ConclusionsThe combination of being overweight and having hyperlipidaemia was an independent risk factor, but being overweight or having hyperlipidaemia alone was not. The combination of hyperuricaemia, being overweight and hyperlipidaemia further increased the risk of CSA-AKI.

Ginkgolic Acid (GA) Inhibits the Growth of OCa by Inhibiting lncRNA MALAT1/JAK2 Axis

Objective. We aimed to observe the impact of ginkgolic acid (GA) on the proliferation and metastasis ability of ovarian cancer (OCa) cells and to further explore whether GA affects the malignant progress of OCa via regulating the lncRNA MALAT1/JAK2 axis. Methods. OCa cells SKOV3 and CAOV3 were administered with 1 ng/ml GA, 5 ng/ml GA, 10 ng/ml GA, 20 ng/ml GA, and DSMO as control, respectively. The cell proliferation and migration ability of the abovementioned cells in each group were measured by CCK-8 test and Transwell experiments. The expression levels of lncRNA MALAT1 and JAK2 protein were examined by qRT-PCR and western blot, respectively. Subsequently, in OCa cells treated with GA, lncRNA MALAT1 overexpression vector was transfected to continue to detect the proliferation activity and migration ability of each treatment group. Finally, the regulation of GA on activity of lncRNA MALAT1/JAK2 axis in OCa cells was further explored in nude mice. Results. Our data showed that the proliferation inhibition rate of cells at each ginkgolic acid concentration was higher than that of the control group ( P < 0.05 ), suggesting that GA has an inhibitory influence on the proliferation of OCa cells, in a dose-dependent way. GA was able to inhibit the proliferation rate and migration ability of OCa cells. Administration of ginkgolic acid downregulated the levels of lncRNA MALAT1 and JAK2 protein. Overexpression of lncRNA MALAT1 partially reversed the inhibited OCa proliferative capacity caused by GA treatment. Consistent with the results observed in vitro, we also found that the OCa tumor weight and volume of nude mice injected with lncRNA MALAT1 overexpression vector were enhanced and JAK2 protein level increased remarkably in comparison to the ginkgolic acid group. Conclusions. In summary, GA may exert its inhibitory effect on the proliferative and migratory capacities of OCa cells through suppressing the activity of lncRNA MALAT1/JAK2 axis.

Characterization of Saponins from Various Parts of Platycodon grandiflorum Using UPLC-QToF/MS

Platycodon grandiflorum (PG) is known as a high-potential material in terms of its biological activity. The objective of this report is to provide chromatographic and mass fragment ion data of 38 simultaneously identified saponins, including novel compounds, by analyzing them through ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QToF/MS). In so doing, we investigated their diverse conditions, including morphological parts (stems, roots, buds, and leaves), peeling (or not), and blanching of PG. The total contents of individual saponins indicated an order of roots (containing peel, 1674.60 mg/100 g, dry weight) > buds (1364.05) > roots (without peel, 1058.83) ≈ blanched roots (without peel, 945.17) ≈ stems (993.71) ≈ leaves (881.16). When considering three types of aglycone, the platycodigenin group (55.04 ~ 68.34%) accounted for the largest proportion of the total content, whereas the platycogenic acid A group accounted for 17.83 ~ 22.61%, and the polygalacic acid group represented 12.06 ~ 22.35%. As they are classified as major compounds, novel saponins might be utilized for their role in healthy food for human consumption. Additionally, during blanching, the core temperature of PG was satisfied with the optimal condition, thus activating the enzymes related to biotransformation. Furthermore, through the use of this comprehensive data, additional studies related to buds, as well as roots or the characterization of individual saponins, can be conducted in a rapid and achievable manner.

Meta-Analysis of Volatile Compounds from Vinegar Produced by the Slow Method and the Fast Method

Volatile compounds are one of the important characteristics of vinegar, where the content and composition of these compounds is an account for the aroma profile of vinegar. The difference in production technology used in making vinegar produces vinegar with different characteristics. There are two general methods commonly used in the production of vinegar, namely the slow method and the fast method. This meta-analysis was used to conclude several studies that examined the differences in volatile compounds in vinegar produced through the slow methods and the fast methods. From this study, it can be seen that comparison of volatile compounds characteristics in vinegar produced by the slow method and the fast method where the slow method tends to produce vinegar with a high concentration of acetate ester group and alcohol group, and the fast method tend to produced vinegar with a high concentration in a volatile acid group.

Azacitidine Omega-3 Self-Assemblies: Synthesis, Characterization, and Potent Applications for Myelodysplastic Syndromes

5-Azacitidine, a cytidine analogue used as a hypomethylating agent, is one of the main drugs for the treatment of myelodysplastic syndromes (MDSs) and acute myeloid leukemia (AML) in the elderly. However, after administration, it exhibits several limitations, including restricted diffusion and cellular internalization due to its hydrophilicity, and a rapid enzymatic degradation by adenosine deaminase. The aim of this study was to improve the drug cell diffusion and protect it from metabolic degradation via the synthesis of amphiphilic prodrugs and their potential self-assembly. Azacitidine was conjugated to two different omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The carboxylic acid group of the omega-3 fatty acids was effectively conjugated to the amine group of the azacitidine base, yielding two amphiphilic prodrugs. Nanoprecipitation of the obtained prodrugs was performed and self-assemblies were successfully obtained for both prodrugs, with a mean diameter of 190 nm, a polydispersity index below 0.2 and a positive zeta potential. The formation of self-assemblies was confirmed using pyrene as a fluorescent dye, and the critical aggregation concentrations were determined: 400 µM for AzaEPA and 688 µM for AzaDHA. Additionally, the stability of the obtained self-assemblies was studied and after 5 days their final stable arrangement was reached. Additionally, cryo-TEM revealed that the self-assemblies attain a multilamellar vesicle supramolecular structure. Moreover, the obtained self-assemblies presented promising cytotoxicity on a leukemia human cell line, having a low IC50 value, comparable to that of free azacitidine.

Antioxidant Activity of Amino Acid Sodium and Potassium Salts in Vegetable Oils at Frying Temperatures

Previous studies reported that several amino acids had strong antioxidant activity in vegetable oils under frying conditions. In this study, the carboxylic acid group of amino acids was converted to a carboxylate group (-COO-Na+ or -COO-K+), a heating study was conducted with amino acid salts in soybean oil at 180 ºC. Sodium salts of amino acids including alanine, phenylalanine, and proline and disodium glutamate had significantly stronger antioxidant activity than the corresponding amino acids, and potassium salts had stronger antioxidant activity than sodium salts. Potassium salts of alanine and phenylalanine more effectively retained tocopherols in soybean oil than the corresponding amino acids during heating. Phenylalanine potassium salt had stronger antioxidant activity than phenylalanine in other vegetable oils including olive, high oleic soybean, canola, avocado, and corn oils. Phenylalanine potassium salt at 5.5. mM more effectively prevented oil oxidation than tert-butyl hydroquinone (TBHQ), a synthetic antioxidant, at its legal concentration limit (0.02%) indicating its feasibility as a new antioxidant for frying.

Comparative Study on Vit. E & Mefenamic acid vs Mefenamic acid alone on mean reduction in pain in Primary Dysmenorrhea

Background: Pelvic pain around the time of mensturation without any identifiable pathologic lesion present from menarche is called primary dysmenorrhea. The pain is believed to be related to prostaglandin (PG). Women with dysmenorrhoea have a relatively high concentration of PGF 2 alpha in menstrual fluid and suppression of PG synthesis has become the main treatment. Aim: To compare mean reduction in pain in patients presenting with primary dysmenorrhea given vitamin E & Mefenamic acid versus Mefenamic acid alone. Results: It was a randomized controlled trial which was conducted in Department of Obstetrics & Gynecology, THQ Raiwind Hospital, Lahore for 6 months duration w.e.f 01/02/2017 to 31/07/2017. In this study, 18(36%) in Vitamin-E group and 21(42%) in Mefenamic acid group were between 15-20 years while 32(64%) in Vitamin-E group and 29(58%) in Mefenamic acid group were between 21-25 years, mean±sd was calculated as 20.86±2.92 and 20.66±2.86 years respectively, mean dysmenorrheal pain at baseline was recorded as 50.06±10.27 in Vitamin-E group and 50.14±10.28 in Mefenamic acid group, p value < 0.754, showing that both groups are insignificant, mean dysmenorrheal pain after treatment was recorded as 20.50±10.04 in Vitamin-E group and 30.22±10.28 in Mefenamic acid group, p value was < 0.002 showing significant difference between the two group, comparison of mean reduction in dysmenorrheal pain after treatment was recorded as 20.56±0.91 in Vitamin-E group and 10.92±0.75 in Mefenamic acid group, p value was < 0.000, showing significant difference. Conclusion: We concluded that there is a significant mean reduction in dysmenorrhic pain in patients given Mefenamic Acid + Vitamen E as compared to patients given Mefenamic Acid alone. Keywords: Dysmenorrhic pain, Mefenamic Acid + Vitamen E, mean reduction in dysmenorrhic pain