The present study emphasizes the molecular interactions between human brain acetylcholinesterase (AChE) and the natural ligand Huperzine-B and its comparison to 'AChE-Tolserine interactions'. Docking between Huperzine-B and AChE was performed using 'Autodock4.2'. Hydrophobic interactions and hydrogen bonds both play an equally important role in the correct positioning of Huperzine-B within the 'catalytic site' of AChE to permit docking. However, docking of Tolserine to AChE is largely dominated by hydrophobic interactions. Such information may aid in the design of versatile AChE-inhibitors, and is expected to aid in safe clinical use of Huperzine-B. Scope still remains in the determination of the three-dimensional structure of AChE-Huperzine-B complex by X-ray crystallography to validate the described data. Furthermore, this study confirms that Huperzine-B is a more efficient inhibitor of human brain AChE compared to tolserine with reference to Ki and ΔG values.
Transferrin receptor (TFRC) is the major mediator for iron entry into a cell. Under excessive iron conditions, TFRC is expected to be reduced to lower iron uptake and toxicity. However, the mechanism whereby TFRC expression is maintained at high levels in iron-enriched cancer cells and the contribution of TFRC to cancer development are enigmatic. Here the work shows TFRC is induced by adenomatous polyposis coli (APC) gene loss-driven 𝜷-catenin activation in colorectal cancer, whereas TFRC-mediated intratumoral iron accumulation potentiates 𝜷-catenin signaling by directly enhancing the activity of tankyrase. Disruption of TFRC leads to a reduction of colonic iron levels and iron-dependent tankyrase activity, which caused stabilization of axis inhibition protein 2 (AXIN2) and subsequent repression of the 𝜷-catenin/c-Myc/E2F Transcription Factor 1/DNA polymerase delta1 (POLD1) axis. POLD1 knockdown, iron chelation, and TFRC disruption increase DNA replication stress, DNA damage response, apoptosis, and reduce colon tumor growth. Importantly, a combination of iron chelators and DNA damaging agents increases DNA damage response and reduces colon tumor cell growth. TFRC-mediated iron import is at the center of a novel feed-forward loop that facilitates colonic epithelial cell survival. This discovery may provide novel strategies for colorectal cancer therapy.
Curcumin, a bright yellow colored phytochemical is the principal and active ingredient - curcuminoids present in the plant Curcuma longa which belonging to the family Zingiberaceae. Curcumin has said to be metabolized in intestine and liver and metabolizes to form glucuronide and sulfate conjugate thus exhibiting its restricted oral bioavailability. It has been studied till Phase-II clinical study, but its bioavailability is still an issue (Biological Classification System-IV {BCS-Class-IV}). Nonetheless, curcumin can be successfully formulated for oral administration, but care needs to be taken with formulation design to ensure consistent bioavailability. There are numerous studies in support of excellent antioxidant activity, safe toxicity profile and bioavailability of conventional and modulated curcumin. The aim of the present study was to investigate the antioxidant potential, acute toxicity profile and bioavailability of water soluble part of curcumin. Objective of research is to determine the antioxidant potential and acute toxicity of aqueous soluble part of curcumin .
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