Molecular Mechanisms Responsible for In Vitro Cytotoxic Attributes of Conyza bonariensis Extract against Lymphoblastic Leukaemia Jurkat Cells.

BACKGROUND: Conyza bonariensis is known to have anti-cancer properties. OBJECTIVE: The current study investigated the in vitro pro-apoptotic properties of Conyza bonariensis (C. bonariensis) towards human lymphoblastic leukemia Jurkat cells. METHODS: Ariel parts of C. bonariensis were macerated in a non-polar (n-Hexane) solvent. MTS cell viability assay was employed to determine the cytotoxic activity of the extract towards human leukemia Jurket cells and normal Peripheral Blood Mononuclear Cells (PBMCs). The phytochemical composition of the extract was screened using HPLC method. Flow cytometric studies (FACS) were conducted to explore the pro-apoptotic potential of the extract. Western blot studies were employed to identify the molecular targets involved in the induction of apoptosis. RESULTS: The n-hexane extract showed selective cytotoxic activity towards Jurkat cells. FACS analysis indicated that the extract induced early and late apoptosis in Jurkat cells. Western blot studies revealed that the extract downregulated the expression of DNMT1, SIRT1, and UHRF1 with a simultaneous up-regulation of p73 and caspases-3 proteins expression. HPLC characterization of the extract revealed the presence of phenolic compounds. CONCLUSION: Overall, these findings demonstrate that the anti-cancer effects of a Conyza bonariensis extract towards human lymphoblastic leukemia Jurkat cells are due to the modulation of the activity of multiple oncogenic and tumor suppressor proteins. Phenolic contents of the extract are proposed to be responsible for these activities.

Development and validation of single analytical HPLC method for determination of flavoxate HCl in bulk, tablets and biological fluids.

A simple, sensitive and precise high performance liquid chromatographic (HPLC) method was developed and validated for determination of flavoxate HCI in raw material, tablets and biological fluids. The method followed by using the Zorbax XDB-C18 column containing Di-isobutyl n-octadeceylsilane (4.6mm×150mm, 5µm). The mobile phase consisted of acetonitrile: methanol: 0.15M sodium perchlorate (17:35:48 v/v) having pH 3. UV detection was carried out at 229nm at 40°C. Results indicated that the method has successfully established and validated in accordance with ICH guidelines acceptance criteria for linearity (0.03-7.5µg), accuracy (101.18-101.28%), robustness of column age and column lot (peak area %CV<0.04, purity %CV< 0.006) and robustness of HPLC condition (%CV<0.02), precision (intra and inter day precision assay, %CV values for peak area and percent purity of flavoxate HCl<2%) and system suitability parameters. The average noise, theoretical LOD and LOQ were found to be 0.01 mAU, 0.03 mAU and 0.6ng, respectively. The Coefficient of determination (r2) ranging from 0.03µg to 7.5µg, 0.99 which was within acceptable criteria of r2 & gt 0.99. The spiked recoveries of samples were 101.28, 101.18 and 101.18% respectively. All data revealed that this method can be used for in-vitro & in-vivo determination of flavoxate HCI in various pharmaceutical preparations.

Identifying volatile organic compounds used for olfactory navigation by homing pigeons.

Many bird species have the ability to navigate home after being brought to a remote, even unfamiliar location. Environmental odours have been demonstrated to be critical to homeward navigation in over 40 years of experiments, yet the chemical identity of the odours has remained unknown. In this study, we investigate potential chemical navigational cues by measuring volatile organic compounds (VOCs): at the birds' home-loft; in selected regional forest environments; and from an aircraft at 180 m. The measurements showed clear regional, horizontal and vertical spatial gradients that can form the basis of an olfactory map for marine emissions (dimethyl sulphide, DMS), biogenic compounds (terpenoids) and anthropogenic mixed air (aromatic compounds), and temporal changes consistent with a sea-breeze system. Air masses trajectories are used to examine GPS tracks from released birds, suggesting that local DMS concentrations alter their flight directions in predictable ways. This dataset reveals multiple regional-scale real-world chemical gradients that can form the basis of an olfactory map suitable for homing pigeons.

Impact of pharmacist's intervention on disease related knowledge, medication adherence, HRQoL and control of blood pressure among hypertensive patients.

The present study was aimed to evaluate the effect of educational intervention provided to the patients of hypertension through pharmacist with the goal to improve knowledge about hypertension, adherence to prescribed medicines, blood pressure control and HRQoL(Health Related Quality of Life).A total of 384 patients were assigned randomly into 2 groups including intervention and control groups each having 192 patients. Urdu versions of knowledge questionnaire regarding hypertension, medication adherence scale (MMAS-U) by Morisky and EuroQol scale (EQ-5D) were utilized. Each patient's blood pressure was measured. After educational intervention, an increase was found in mean knowledge score about hypertension (18.18 ± 4.00), adherence score (5.89 ± 1.90), HRQoL score (0.73 ± 0.12) and Visual Analogue Scale (VAS) score (69.39 ± 5.90) among the IG. The blood pressure control also improved and lower systolic (131.81 ± 10.98 mmHg) and diastolic blood pressures (83.75 ± 6.21 mmHg) were observed among the patients of IG. This study showed that educational programs are useful for patients in increasing patient's levels of knowledge about hypertension, improving adherence to prescribed medication and enhancing blood pressure control. This increase is in turn accountable to improve HRQoL.