Structure-Activity Relationship of Methyl 4-Aminobenzoate Derivatives as Being Drug Candidate Targeting Glutathione Related Enzymes: in Vitro and in Silico Approaches

A thiol compound, glutathione, is essential for healthy cell defence against xenobiotics and oxidative stress. Glutathione reductase (GR) and glutathione S-transferase (GST) are two glutathione-related enzymes that function in the antioxidant and the detoxification systems. In this study, potential inhibitory effects of methyl 4-aminobenzoate derivatives on GR and GST were examined in vitro. GR and GST were isolated from human erythrocytes with 7.63 EU/mg protein and 5.66 EU/mg protein specific activity, respectively. It was found that compound 1 (methyl 4-amino-3-bromo-5-fluorobenzoate with K_i value of 0.325±0.012 μM) and compound 5 (methyl 4-amino-2-nitrobenzoate with K_i value of 92.41±22.26 μM) inhibited GR and GST stronger than other derivatives. Furthermore, a computer-aided method was used to predict the binding affinities of derivatives, ADME characteristics, and toxicities. Derivatives 4 (methyl 4-amino-2-bromobenzoate) and 6 (methyl 4-amino-2-chlorobenzoate) were estimated to have the lowest binding energies into GR and GST receptors, respectively according to results of in silico studies.     

Dampening HOTAIR sensitizes the gastric cancer cells to oxaliplatin through miR-195-5p and ABCG2 pathway

Long non-coding RNAs (lncRNA) have an extensive role in the progression and chemoresistance of gastric cancer (GC). Deeply study the regulatory role of lncRNAs could provide potential therapeutic targets. The aim of this study is to explore the regulatory role of HOTAIR in the progression and oxaliplatin resistance of GC. The expression of HOTAIR in GC and cell lines were detected by using qRT-PCR. Cell proliferation and apoptosis were analysed by CCK-8, EdU incorporation and flow cytometry. Luciferase reporter assay was used to identify the interaction between HOTAIR and ABCG2 (ATP-binding cassette (ABC) superfamily G member 2, ABCG2) via miR-195-5p. The regulatory functions were verified by using molecular biology experiments. HOTAIR was significantly overexpressed in GC and associated with poor prognosis. Knock-down of HOTAIR inhibited the GC cells proliferation and oxaliplatin resistance, while overexpression of HOTAIR showed opposite functions. Further studies found that HOTAIR acted as a competing endogenous RNA (ceRNA) to absorb miR-195-5p and elevated the expression of ABCG2, which leads to resistance of GC cells to oxaliplatin. Taken together, our findings demonstrated that HOTAIR regulates ABCG2 induced resistance of GC to oxaliplatin through miR-195-5p signalling and illustrate the great potential of developing new therapeutic targets for GC patients.     

HPLC-DAD Analysis and Versatile Bioactivities of Turkish Sunflower Honeys Using Chemometric Approaches

Sunflower honey (SH) is bright yellow, fragrant, pollen-flavoured, slightly herbaceous and has a unique taste. The present research aims to examine the enzyme inhibitory, antioxidant, anti-inflammatory, antimicrobial and anti-quorum sensing activities and phenolic compositions of 30 sunflower honeys (SHs) produced from several regions of Turkey with chemometric study. SAH from Samsun exhibited the best antioxidant activity in β-carotene linoleic acid (IC₅₀: 7.33±0.17 mg/mL) and CUPRAC (A_0.50: 4.94±0.13 mg/mL) assays, anti-urease activity (60.63±0.87 %) and anti-inflammatory activity against COX-1 (73.94±1.08 %) and COX-2 (44.96±0.85 %). SHs exhibited mild antimicrobial activity against the test microorganisms while they showed high quorum sensing inhibition zones measured in the range of 42–52 mm against the CV026 strain. The phenolic composition was determined by high performance liquid chromatography with diode array detection (HPLC-DAD) system and levulinic, gallic, p-hydroxybenzoic, vanillic and p-coumaric acids were identified in all studied SHs. The classification of SHs was performed the using PCA and HCA. This study revealed that phenolic compounds and biological properties are effective in classification of SHs according to their geographical origin. The results suggest that studied SHs could be valued as potential agents with versatile bioactivities in oxidative stress-related disease, microbial infections, inflammation, melanoma, and peptic ulcer.     

Quantitative Detection of 15 Serum Bile Acid Metabolic Products by LC/MS/MS in the Diagnosis of Primary Biliary Cholangitis

To determine 15 bile acid metabolic products in human serum by liquid chromatography-tandem mass spectrometry (LC/MS/MS) and value their diagnostic outcome in primary biliary cholangitis (PBC). Serum from 20 healthy controls and 26 patients with PBC were collected and went LC/MS/MS analysis of 15 bile acid metabolic products. The test results were analyzed by bile acid metabolomics, and the potential biomarkers were screened and their diagnostic performance was judged by statistical methods such as principal component and partial least squares discriminant analysis and area under curve (AUC). 8 differential metabolites can be screened out: Deoxycholic acid (DCA), Glycine deoxycholic acid (GDCA), Lithocholic acid (LCA), Glycine ursodeoxycholic acid (GUDCA), Taurolithocholic acid (TLCA), Tauroursodeoxycholic acid (TUDCA), Taurodeoxycholic acid (TDCA), Glycine chenodeoxycholic acid (GCDCA). The performance of the biomarkers was evaluated by the AUC, specificity and sensitivity. In conclusion, DCA, GDCA, LCA, GUDCA, TLCA, TUDCA, TDCA and GCDCA were identified as eight potential biomarkers to distinguish between healthy people and PBC patients by multivariate statistical analysis, which provided reliable experimental basis for clinical practice.     

Antioxidant and Antidiabetic Properties of Extracts from Three Underutilized Food Plants of North East India

Three underutilized leafy vegetables Sarcochlamys pulcherrima (Roxb.) Gaudich (SP), Ipomoea aquatica Forssk. (IA) and Zanthoxylum rhetsa (Roxb.) DC (ZR) were extracted with different solvents viz. 95 % ethyl alcohol, methanol and hot water. The extracts were evaluated for their antioxidant potential via DPPH, ABTS and FRAP assay along with electroanalytical studies using cyclic voltammetry. The antidiabetic potential was determined by recording their α-amylase and α-glucosidase inhibitory assay. The total phenolic content (TPC), total flavonoid content (TFC) and the liquid chromatography-mass spectrometry (LC/MS) based phytochemical profiles of the extracts were also determined. All three extracts of SP exhibited significant antioxidant capacity. The antidiabetic potential of the IA and ZR extracts was found to be higher than or at par with that of standard acarbose. LC/MS studies reveal the presence of hitherto reported antioxidant and antidiabetic compounds like gamma-aminobutyric acid, cinnamic acid, caffeic acid, α-viniferin, piperlonguminine, niacin, kaempferol, etc., in the extracts.     

High-Resolution Performance of Polycaprolactone Functionalized with Guanidinium Ionic Liquid for Gas Chromatography

This work firstly reported a new polycaprolactone based material functionalized with guanidinium ionic liquid (PCL-GIL) as the stationary phase with high resolution performance for capillary gas chromatography (GC). It is composed of polycaprolactone (PCL) and guanidinium ionic liquid (GIL) with amphiphilic conformation. The PCL-GIL capillary column coated by static method exhibited high column efficiency of 3942 plates/m and moderate polarity. As a result, the PCL-GIL column exhibited high-resolution capability. For a mixture of 27 analytes with a wide ranging polarity and outperformed the PCL-2OH and HP-35 columns, showing its advantageous separation capability for analytes of diverse types. Moreover, the PCL-GIL column showed high resolving capability for various positional isomers and cis-/trans-isomers, including alkylbenzenes, chlorobenzenes, naphthalenes, bromonitrobenzenes, chloronitrobenzenes, benzaldehydes, phenols, alcohols, respectively. In a word, PCL derivatized by GIL units as a new type of stationary phase has a promising future in GC separations.     

Climatic niche divergence explains angiosperm diversification across clades in China

Diversification rates are critically important for understanding patterns of species richness among clades. However, the effects of climatic niche width on plant diversification rates remain to be elucidated. Based on the phylogenetic, climatic, and distributional information of angiosperms in China, a total of 26 906 species from 182 families were included in this study. We aimed to test relationships between diversification rate and climatic niche width and climatic niche width related variables (including climatic niche divergence, climatic niche position, geographic extent, and climatic niche evolutionary rate) using phylogenetic methods. We found that climatic niche divergence had the largest unique contribution to the diversification rate, while the unique effects of climatic niche width, climatic niche position, geographic extent, and climatic niche evolutionary rate on the diversification rate were negligible. We also observed that the relationship between diversification rate and climatic niche divergence was significantly stronger than the null assumption (artefactual relationship between diversification and clade-level climatic niche width by sampling more species). Our study supports the hypothesis that wider family climatic niche widths explain faster diversification rates through a higher climatic niche divergence rather than through higher geographic extent, higher climatic niche evolutionary rate, or separated climatic niche position. Hence, the results provide a potential explanation for large-scale diversity patterns within families of plants.