10 research outputs found
Antinociceptive, antipyretic and anti-inflammatory effects of Clerodendrum phlomidis in mice and rats
The ethanolic extract of Clerodendrum phlomidis L. belonging to the family of Verbenaceae was evaluated for its antinociceptive, antipyretic and anti-inflammatory activity in mice and rats respectively. Analgesic activity was studied by using acetic acid-induced mouse withering test, hot water tail immersion method and eddy’s hot plate method in mice. The antipyretic activity was evaluated against yeast induced pyroxia in rat and anti-inflammatory activity was evaluated by carrageenan-induced hind paw edema and its probable mechanism evaluated in rats. The preliminary phytochemical screening and acute toxicity studies were carried out. C. phlomidis extract showed a dose dependent significant reduction of the number of writhes (
Synthetic lethal targeting of oncogenic transcription factors in acute leukemia by PARP inhibitors
Acute myeloid leukemia (AML) is mostly driven by oncogenic transcription factors,
which have been classically viewed as intractable targets using small molecule inhibitor
approaches. Here, we demonstrate that AML driven by repressive transcription factors
including AML1-ETO and PML-RARα are extremely sensitive to Poly (ADP-ribose)
Polymerase (PARP) inhibitor (PARPi), in part due to their suppressed expression of key
homologous recombination genes and thus compromised DNA damage response (DDR).
In contrast, leukemia driven by MLL fusions with dominant transactivation ability is
proficient in DDR and insensitive to PARP inhibition. Intriguing, depletion of an MLL
downstream target, Hoxa9 that activates expression of various HR genes, impairs DDR
and sensitizes MLL leukemia to PARPi. Conversely, Hoxa9 over-expression confers
PARPi resistance to AML1-ETO and PML-RARα transformed cells. Together, these
studies describe a potential utility of PARPi-induced synthetic lethality for leukemia
treatment and reveal a novel molecular mechanism governing PARPi sensitivity in AML
Selective separation of pyrite and chalcopyrite by biomodulation
Selective separation of pyrite from other associated ferrous sulphides at acidic and neutral pH has been a challenging problem. This paper discusses the utility of Acidithiobacillus ferrooxidans for the selective flotation of chalcopyrite from pyrite. Consequent to interaction with bacterial cells, pyrite remained depressed even in the presence of potassium isopropyl xanthate collector while chalcopyrite exhibited significant flotability. However, when the minerals were conditioned together, the selectivity achieved was poor due to the activation of pyrite surface by the copper ions in solution. The selectivity was improved when the sequence of conditioning with bacterial cells and collector was reversed, since the bacterial cells were able to depress collector interacted pyrite effectively, while having negligible effect on chalcopyrite. The observed behaviour is analysed and discussed in detail. The separation obtained was significant both at acidic and alkaline pH. This selectivity achieved was retained when the minerals were interacted with both bacterial cells and collector simultaneously