Recognition of human telomeric G-quadruplex DNA by 1,5-disubstituted diethyl-amido anthraquinone derivative in different ion environments causing thermal stabilization and apoptosis.

Ligand binding to G-quadruplex (G4) structures at human telomeric DNA ends promotes thermal stabilization, disrupting the interaction of the telomerase enzyme, which is found active in 80-85% of cancers and serves as a molecular marker. Anthraquinone compounds are well-known G-quadruplex (G4) binders that inhibit telomerase and induce apoptosis in cancer cells. Our current investigation is based on 1,5-bis[3-(diethylamino)propionamido]anthracene-9,10-dione, a derivative of anthraquinone and its binding characterization with two different human telomeric DNA structures, wHTel26 and HTel22, in the effect of K+ and Na+ by using an array of biophysical, calorimetry, molecular docking and cell viability assay techniques. Binding constants (Kb) in the range of ∼105-107 M-1 and stoichiometries of 1:1, 2:1 & 4:1 were obtained from the absorbance, fluorescence, and circular dichroism study. Remarkable hypochromism (55, 97%) and ∼17 nm shift in absorbance, fluorescence quenching (95, 97%), the unaltered value of fluorescence lifetime, restoration of Circular Dichroism bands, absence of ICD band, indicated the external groove binding/binding somewhere at loops. This is also evident in molecular docking results, the ligand binds to groove forming base (G4, G5, G24, T25) and in the vicinity to TTA loop (G14, G15, T17) bases of wHTel26 and HTel22, respectively. Thermal stabilization induced by ligand was found greater in Na+ ion (27.5 °C) than (19.1 °C) in K+ ion. Ligand caused cell toxicity in MCF-7 cancer cell lines with an IC50 value of ∼8.4 µM. The above findings suggest the ligand, 1,5-bis[3-(diethylamino)propionamido]anthracene-9,10-dione could be a potent anticancer drug candidate and has great therapeutic implications.Binding of disubstituted amido anthraquinone derivative, 1,5-bis[3-(diethylamino)propionamido]anthracene-9,10-dione to human telomere HTel22 antiparallel conformation induced thermal stabilization.Communicated by Ramaswamy H. Sarma.

Identification and evaluation of antimicrobial and anti-arthritis activities of hydroethanolic extract of Rubus ellipticus leaves.

Rubus ellipticus is a native plant to India's tropical and subtropical regions and has been used as a traditional medicinal. The aim of study was to identify and evaluate the antimicrobial and anti-arthritis activities of hydroethanolic extract of R. ellipticus leaves (HEERE). The leaves were collected from the Narkanda Valley, India and were shade-dried and finely ground to produce the powder. The hydroethanolic extract was utilized for phytochemical analysis to determine the existence of carbohydrate, phenolic, terpenoid, flavonoid, saponin, glycoside, tannin, protein, and alkaloid. The HEERE was futher analyzed by gas chromatography-mass spectrometry (GC-MS) for the characterization of the phytoconstituents. The antimicrobial activity was tested against Escherichia coli, Staphylococcus aureus as well as Aspergillus niger. To assess its anti-arthritic activities, different doses of HEERE were given orally to complete Freund's adjuvant (CFA)-induced albino Wistar rats for twenty-one days. The GC-MS analysis of hydroethanolic extracts from leaves detected and identified the presence of 33 phytochemical compounds. HEERE showed significant effects against E. coli, S. aureus, and A. niger strains at 600 ppm. Our data indicated that HEERE 200 mg/kg was more effective than 50 mg/kg as anti-arthritis. Paw volume, ankle-joint diameter, the number leucocytes, and erythrocyte sedimentation rate (ESR) were all significantly reduced in experimental rats. Furthermore, when compared to respective standard drugs, the body weight, erythrocyte, hemoglobin, and synobium healing effect have all improved. These data demonstrated the potential of R. ellipticus for the long-term investigation of antimicrobial and anti-arthritic properties.

Green Synthesis, Characterization and Antimicrobial Activities of Copper Nanoparticles from the Rhizomes Extract of Picrorhiza kurroa.

BACKGROUND: Green synthesized nanoparticles from the solvent extract of various plant parts show better biological activities as compared to parent solvent plant extract. Traditionally rhizomes of Picrorhiza kurroa are used to cure various diseases like diarrhea, fever, jaundice, eye infection, skin problems, asthma, arthritis, cancer, diabetes, gastrointestinal problems. OBJECTIVE: The present study describes the synthesis of copper nanoparticles from a hydroethanolic extract of P. kurroa rhizomes (CuNPs-Pk) and their evaluation for antimicrobial activities against gram-negative, gram-positive bacterial, and fungal strains. METHODS: The solution of copper sulfate and hydroethanolic extract of rhizomes of P. kurroa was mixed with help of a magnetic stirrer at 60°C temperature for 1 h. The blue color of CuSO4.5H2O changed to brownish-black colored copper nanoparticles within 10 minutes. These nanoparticles were centrifuged at 4000 rpm for 20 min, washed with ethanol, followed by deionized water, dried, and were characterized by Ultra violet-visible (UV-Vis) absorption spectra, Fourier transform infrared spectroscopy (FTIR), Field emission scanning electron microscopy (SEM) and high-resolution transmission electron microscopy (TEM). Different concentrations of hydroethanolic extract of Picrorhiza kurroa rhizomes (HEEPk), CuNPs-Pk and copper oxide nanoparticles (bare CuO) ranging from 100-400 ppm had been studied against selected bacterial and fungal strains by using the well plate diffusion method. Ciprofloxin and fluconazole were used as standard and Dimethyl sulfoxide (DMSO) as a control for selected strains. RESULTS: The UV-Vis spectral studies confirmed the surface plasmon resonance of green-synthesized CuNPs-Pk. The particle size was found to be 275-285 nm. FTIR analysis of biosynthesis nanoparticles conformed the presence of various functional groups (flavonoids, glycosides, tannins, phenols). SEM and TEM of biosynthesized nanoparticles have predicted their spherical shape and their size (20-40 nm) and these particles have shown effective antimicrobial activities against selected pathogenic organisms viz. Escherichia coli, Staphylococcus aureus, and Aspergillus niger than that of HEEPk and bare CuO. CONCLUSION: The CuNPs-Pk shows effective antimicrobial activities against bacterial and fungal pathogens as compared to HEEPk and bare CuO.

Enhanced arsenic tolerance and secondary metabolism by modulation of gene expression and proteome profile in Artemisia annua L. after application of exogenous salicylic acid.

This study was designed to investigate the effect of exogenous application of salicylic acid (SA) on proteins pattern and secondary metabolites in arsenic (As) stressed Artemisia annua. A. annua was treated by As 100 µM, SA 100 µM and combined treatment of SA 100 µM + As 100 µM upto 3 days. Significant accumulation of As was observed in roots than shoots at As 100 µM treatment. Under As treatment, oxidative stress was induced as indicated by increased TBARS content. Biomass, carotenoid, flavonoids were enhanced whereas total chlorophyll pigment was reduced under As treatment. Combined treatment of SA 100 µM + As 100 µM was more effective for increment of biomass, total chlorophyll content, and flavonoids as compared to As 100 µM treatment. Protein profiling revealed 20 differentially abundant proteins by 2-DE PAGE and MALDI-TOF-MS analysis. Identified proteins were related to photosynthesis, energy metabolism, transcriptional regulators, secondary metabolism, lipid metabolism, transport proteins and unknown/hypothetical proteins. All identified proteins were significantly increased in abundance under combined treatments of SA 100 µM + As 100 µM. The expression analysis of key genes involved in biosynthesis of lipid metabolism, signal molecule, transcriptional regulators, artemisinin biosynthetic genes, isoprenoids pathway, terpenes and flavonoids pathway were significantly upregulated under combined treatments of SA 100 µM + As 100 µM, suggesting a fine linkage in regulation of primary and secondary metabolism to modulate tolerance capacity and to improve phytoremediation property of A. annua against arsenic toxicity.

Exogenous salicylic acid-mediated modulation of arsenic stress tolerance with enhanced accumulation of secondary metabolites and improved size of glandular trichomes in Artemisia annua L.

The present study was undertaken to find out individual and interactive effects of arsenic (As) and salicylic acid (SA) on an important medicinal plant, Artemisia annua. As uptake and its accumulation was detected and found to be maximum in roots at higher As concentration (150 µM). Under As treatments, H2O2 and MDA content were induced. Biomass and chlorophyll content were negatively affected under As treatments. Furthermore, enzymatic (SOD, CAT, APX, and GR) and non-enzymatic antioxidants were also enhanced under As treatments. Exogenous application of SA reduced the extent of H2O2 and O2- generation and lipid peroxidation, while reverted biomass and chlorophyll content to overcome oxidative stress. Simultaneous application of SA with As increased endogenous SA level, artemisinin, and dihydroartemisinic acid as compared with individual As treatment and pre-application of SA with As treatments. The expression of four key artemisinin biosynthetic pathway genes, i.e., ADS, CYP71AV1, DBR2, and ALDH1 were upregulated at a maximum in plants simultaneously treated with SA and As. Similar pattern of artemisinin accumulation and glandular trichome size was observed which attest that SA has a stimulatory impact on artemisinin biosynthesis under As stress. Our study suggests that exogenous application of SA and As together induced more tolerance in A. annua than a comparable dose of SA pre-treatment. The study may provide a platform with dual benefits by developing As-tolerant plants to be used for phytoremediation of arsenic from As-contaminated soil and obtaining high artemisinin-producing A. annua plants.

Bilateral hypopyon as the presenting feature of chronic myeloid leukemia.

PURPOSE: To report bilateral hypopyon as an unusual presenting feature of chronic myeloid leukemia (CML). DESIGN: Observational case report. METHODS: A 68-year-old male presenting with bilateral hypopyon uveitis underwent hematological investigations and cytology of hypopyon. RESULTS: Blood smear revealed increased leucocyte count with presence of abnormal cells (myelocytes, band forms, and promyelocytes) suggestive of CML. Cytopathology of hypopyon revealed predominance of lymphocytes and few plasma cells. CML was confirmed by hematological investigations. Patient was initiated on chemotherapy under the care of an oncologist and is stable. CONCLUSIONS: Elderly patients presenting with hypopyon uveitis should be investigated to rule out masquerade syndrome.