FBXW7 polymorphism asserts susceptibility to colorectal cancer.

FBXW7, belonging to the F-Box protein family, is considered a candidate cancer susceptibility gene. Our findings indicate that single nucleotide polymorphisms (SNPs) in the FBXW7 gene are linked to cancer risk, strengthening FBXW7's role in the pathogenesis of colorectal cancer. Our case-control study comprised of 450 patients diagnosed with colorectal cancer (CRC) and an equal number of 450 healthy subjects. FBXW7 SNPs rs2255137C>T and rs6842544C>T were genotyped using PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) and Single-Stranded Conformation Polymorphism (SSCP) techniques and further cross-checked by direct sequencing. Linkage disequilibrium and haplotype analyses of these SNPs were also assessed. The in-silico approach was used to reveal the functional analysis between the nonsynonymous variation (rs6842544) and CRC followed by its validation at the protein level by western blotting and reverse transcription-PCR. A significant association of colorectal cancer was detected with rs6842544 SNP. However, there was no association between FBXW7 rs2255137 polymorphism and CRC. The homozygous individuals carrying the C variant in FBXW7 rs6842544 showed a slightly higher risk for colorectal cancer (OR = 1.590, 95%CI = 0.39 âˆ¼ 2.89, p = 0.011). The haplotype CC identified in this study seemed to be associated with good prognosis (OR = 1.22, 95% CI = 1.00 âˆ¼ 1.47, p = 0.0013) whereas the TT haplotype was found to reduce the CRC risk (OR = 0.642, 95%CI = 0.48 âˆ¼ 0.84, p = 0.039). In-silico prediction proposed that the variant R133G is responsible for the lower expression of FBXW7. Additionally, the expression profiling of FBXW7 nonsynonymous SNP was significantly lower in primary CRC tissues than in the paired non-cancerous tissues at protein and mRNA levels. The study indicates that the FBXW7 rs6842544 is associated with the risk of development of CRC and could serve as a molecular biological marker to screen high-risk groups for CRC.

Interaction and antibacterial activity of ciprofloxacin with choline based ionic liquid and CTAB: A comparative spectroscopic study.

In this study, the complexation of potential chemo-therapeutic antibacterial drug, ciprofloxacin (CIP) with varying concentrations of surface active compounds (SACs) i.e., (N-(2-hydroxyethyl)-N,N-dimethyl-1-dodecanaminium bromide (12Cho.Br) and cetyltrimethylammonium bromide (CTAB) has been studied. Multispectroscopic techniques were exploited to carry out the study. The higher binding constant (Kb) value for CIP-CTAB than CIP-12Cho.Br obtained from fluorescence data revealed stronger binding of CTAB than 12Cho.Br, owing to the stronger hydrophobic-hydrophobic interaction betweeen CIP and CTAB compared to CIP and 12Cho.Br. The time resolve fluorescence decay shows changes in average lifetime (τavg) with the increasing concentration of 12Cho.Br and CTAB. The changes in τavg suggests that complex formation is taking place between CIP and 12Cho.Br / CTAB. Further, the formation of micelles by 12Cho.Br / CTAB and the effect of alkyl chain length was studied by dynamic light scattering (DLS) and zeta potential to confirm the drug complexation with 12Cho.Br and CTAB. The antibacterial activity has been performed for CIP and 12Cho.Br and CTAB. It was observed that in presence of lower concentrations of 12Cho.Br/ CTAB, the activity of the drug increased. The activity was also found cationic alkyl chain length dependent. Moreover, in-vitro cytotoxicity of CIP and its combinations with 12Cho.Br and CTAB was performed using MTT assay on HEK293 (Human embryonic kidney cells).

Formulation and development of novel lipid-based combinatorial advanced nanoformulation for effective treatment of non-melanoma skin cancer.

Non-melanoma skin cancer is one of the most common malignancies reported with high number of morbidities, demanding an advanced treatment option with superior chemotherapeutic effects. Due to high degree of drug resistance, conventional therapy fails to meet the desired therapeutic efficacy. To break the bottleneck, nanoparticles have been used as next generation vehicles that facilitate the efficient interaction with the cancer cells. Here, we developed combined therapy of 5-fluorouracil (5-FU) and cannabidiol (CBD)-loaded nanostructured lipid carrier gel (FU-CBD-NLCs gel). The NLCs were optimized using central composite design that showed an average particle size of 206 nm and a zeta potential of -34 mV. In addition, in vitro and ex vivo drug permeations studies demonstrated the effective delivery of both drugs in the skin layers via lipid structured nanocarriers. Also, the prepared FU-CBD-NLCs showed promising effect in-vitro cell studies including MTT assays, wound healing and cell cycle as compared to the conventional formulation. Moreover, dermatokinetic studies shows there was superior deposition of drugs at epidermal and the dermal layer when treated with FU-CBD-NLCs. In the end, overall study offered a novel combinatorial chemotherapy that could be an option for the treatment of non-melanoma skin cancer.

In Vitro Cytotoxicity and Interaction of Noscapine with Human Serum Albumin: Effect on Structure and Esterase Activity of HSA.

Noscapine is effective to inhibit cellular proliferation and induced apoptosis in nonsmall cell, lung, breast, lymphoma, and prostate cancer. It also shows good efficiency to skin cancer cells. In the current work, we studied the mechanism of interaction between the anticancer drug noscapine (NOS) and carrier protein human serum albumin (HSA) by using a variety of spectroscopic techniques (fluorescence spectroscopy, time-resolved fluorescence, UV-visible, fluorescence resonance energy transfer (FRET), Fourier transform infrared (FTIR), and circular dichroism (CD) spectroscopy), electrochemistry (cyclic voltammetry), and computational methods (molecular docking and molecular dynamic simulation). The steady-state fluorescence results showed that fluorescence intensity of HSA decreased in the presence of NOS via a static quenching mechanism, which involves ground state complex formation between NOS and HSA. UV-visible and FRET results also supported the fluorescence result. The corresponding thermodynamic result shows that binding of NOS with HSA is exothermic in nature, involving electrostatic interactions as major binding forces. The binding results were further confirmed through a cyclic voltammetry approach. The FRET result signifies the energy transfer from Trp214 of HSA to the NOS. Molecular site marker, molecular docking, and MD simulation results indicated that the principal binding site of HSA for NOS is site I. Synchronous fluorescence spectra, FTIR, 3D fluorescence, CD spectra, and MD simulation results reveal that NOS induced the structural change in HSA. In addition, the MTT assay study on a human skin cancer cell line (A-431) was also performed for NOS, which shows that NOS induced 80% cell death of the population at a 320 µM concentration. Moreover, the esterase-like activity of HSA with NOS was also done to determine the variation in protein functionality after binding with NOS.

New insights into the antioxidant and apoptotic potential of Glycyrrhiza glabra L. during hydrogen peroxide mediated oxidative stress: An in vitro and in silico evaluation.

Plant-derived substances (phytochemicals) are well recognized as sources of pharmacologically potent drugs in the treatment of several oxidative stress related disorders. Our study aims to evaluate the antioxidant and apoptotic effects of Glycyrrhiza glabra L. in both cell free and cell culture system. Plant fractions have been prepared with hexane, chloroform, ethyl acetate, methanol and water and their antioxidant properties are reviewed. Potent antioxidant activity has been well established in both in vitro and in silico studies which is believed to be responsible for the anticancerous nature of the plant. Results obtained indicate that methanol fraction of G. glabra L. exhibited maximum scavenging activity against DPPH and nitric oxide free radicals comparable to standard antioxidant L-AA. Administration of methanol fraction also considerably reduced the malondialdehyde produced due to lipid peroxidation in mammalian liver tissues. Moreover, the levels of antioxidant enzymes SOD, CAT, GST, GPx and GR in the oxidative stress induced tissues were refurbished significantly after treatment with plant's methanol fraction. Moreover, methanol fraction was found to be nontoxic to normal human cell line whereas it inhibited cancer cells HeLa and HepG2 considerably. Apoptosis was established by DAPI fluorescent staining and western blot analysis of pro apoptotic protein caspase-8, caspase-3 and anti-apoptotic protein Bcl-2.There is an up regulation in the levels of pro apoptotic caspase-8 and caspase-3 and down regulation of anti-apoptotic Bcl-2. Furthermore, GC-MS analysis of the methanol fraction revealed the presence of many compounds. In silico experiments using Autodock 4.2 tools showed strong affinity of plant compounds towards antioxidant enzymes (proteins) thus validating with the conclusions of antioxidant enzyme assays and establishing a role in cancer pathogenesis.