Synthesis and spectroscopic characterization study of new palladium complexes containing bioactive O,O-chelated ligands: evaluation of the DNA/protein BSA interaction,in vitro antitumoural activity and molecular docking

[Pd{(C,N)–C₆H₄CH₂NH(Et) (Qu)] (2) and [Pd{(C,N)–C₆H₄CH₂NH(Et) (Nar)] (3) (Qu = Quercetin, Nar = Naringin) mononuclear palladium (II) complexes have been synthesized and characterized using elemental analysis, IR and electronic spectroscopy. The interaction of the prepared complexes with calf thymus DNA and bovine serum albumin (BSA), monitored by UV–visible and fluorescence titrations, respectively, have been carried out to better understand the mode of their action under biological conditions. Intercalative binding mode between the complexes and DNA is suggested by the binding constant (K_b) values of 2.5 × 10⁶ and 3.2 × 10⁶ for complexes 2 and 3, respectively. In particular, the in vitro cytotoxicity of the complexes on two cancer cells lines (bladder carcinoma TCC and breast cancer MCF7) showed that the compounds had broad spectrum, anti-cancer activity with low IC₅₀ values and the order of in vitro anticancer activities is consistent with the DNA-binding affinities. In the meantime, the quenching of tryptophan emission with the addition of complexes using BSA as a model protein indicated the protein binding ability. The quenching mechanisms of BSA by the complexes were static processes, according to the results obtained. The competitive binding using Warfarin, Digoxin and Ibuprofen site markers, which contain definite biding sites, demonstrated that the complexes bind to site I on BSA. Ultimately, the binding sites of DNA and BSA with the complexes have been determined by molecular modelling studies.     

Soluble guanylate cyclase isoenzymes: The expression of α1, α2, β1, and β2 subunits in the benign and malignant breast tumors

Soluble guanylate cyclase (sGC) encompasses α and β subunits. This study examined the expression of α1, α2, β1, and β2 subunits in the malignant and benign breast tumors using the Western blot analysis. Both benign and malignant tumors showed a significantly higher expression of the α1 subunit in comparison with normal tissues (p < 0.0001). In contrast, the expression of α2 and β2 sGC were significantly lower in these tumors than normal tissues (p < .0015 and p < .001, p < .007 and p < .0001, respectively). The expression level of α1 sGC was significantly correlated with ER + PR+ (p < .0001). A significant correlation was also detected for sGC-α1 and -α2 expression with c-erbB2-negative status (p < .01). However, the expression level of sGC was not associated with tumor stage, tumor grade, or other clinicopathological features. In conclusion, as the expression of α1 sGC is upregulated and α2 and β2 sGC are downregulated in malignant breast tumors. Variations in the expression of sGC isoenzymes may be suggested as an indicator to confirm the enzyme antitumor activity.     

Myricetin loaded in solid lipid nanoparticles induces apoptosis in the HT-29 colorectal cancer cells via mitochondrial dysfunction

Molecular Biology Reports - Among the flavonoids, Myricetin (MCN) has negligible side effects and anti-cancer properties. However, the therapeutic potential of MCN has been limited mainly by its...     

Elucidating the protein cold-adaptation: Investigation of the parameters enhancing protein psychrophilicity

To investigate the role of the critical parameters in adaptation of proteins to low temperatures, a comparative systematic analysis was performed. Several parameters were proposed to have contribution to cold adaptation of proteins. Among proposed parameters, total values of residual structure states, secondary structure states and oligomeric states were alike in both psychrophilic and mesophilic proteins. In addition, our results provided new quantitative information about the trends in the substitution preference of Ile, Phe, Tyr, Lys, Arg, His, Glu and Leu with most of amino acids and substitution avoidance of Gly, Thr and Ala with most of amino acids. These findings would help future efforts propose a strategy for designing psychrophilic proteins.     

Rat lung decellularization using chemical detergents for lung tissue engineering

Although pulmonary diseases account for a large number of deaths in the world, most have no treatment other than transplantation. New therapeutic methods for lung treatment include lung tissue engineering and regenerative medicine. Lung decellularization has been used to produce an appropriate scaffold for recellularization and implantation. We investigated 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS) with sodium dodecyl sulfate (SDS) and Triton X-100 detergents for effecting rat lung decellularization. We evaluated using conventional histology, immunofluorescence staining and SEM methods for removing nuclear material while leaving intact extracellular matrix proteins and three-dimensional architecture. We investigated different concentrations of CHAPS, SDS and Triton X-100 for different periods. We found that 2 mM CHAPS + 0/1% SDS for 48 h was the best among the treatments investigated. Our method can be used to produce an appropriate scaffold for recellularization by stem cells and for investigations ex vivo and in vivo.     

Dietary deoxynivalenol does not affect mineral element accumulation in breast and thigh muscles of broiler chicken

Deoxynivalenol (DON), a well-known contaminant of feed, can have negative effects on gut permeability and function in poultry, which then could affect major and trace element content of the broilers’ breast and thigh muscles, and ultimately reduce meat quality. To study this hypothesis, DON-contaminated diet was fed to broiler chicks. Two groups of birds were housed in metabolic cages with free access to water and feed, with or without DON (10 mg/kg). After 5 weeks, birds were dissected and samples of the breast and thigh muscles, feed and droppings were analysed for five macro (Ca, K, Mg, Na, and P) and ten micro elements (Al, Cr, Cu, Fe, Mn, Li, Mo, Ni, Pb, Rb, and Zn) by inductively coupled plasma optical emission spectrometry (ICP-OES) or inductively coupled plasma mass spectrometer (ICP-MS) methods. In both groups, increased (p?<?0.05) concentrations of Ca Na, Fe, Mn, and Zn were found in thigh muscles compared with the breast, whereas the concentrations of Mg, P, and Rb were higher in the breast muscles. DON had no effect on the elemental contents of the broilers’ breast and thigh muscles. In conclusion, DON at a level of 10 mg/kg feed to broiler chicken over of 5 weeks did not alter the macro or micro element composition in muscle meat.     

Cancer stem cells: A review from origin to therapeutic implications

Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), are elucidated as cells that can perpetuate themselves via autorestoration. These cells are highly resistant to current therapeutic approaches and are the main reason for cancer recurrence. Radiotherapy has made a lot of contributions to cancer treatment. However, despite continuous achievements, therapy resistance and tumor recurrence are still prevalent in most patients. This resistance might be partly related to the existence of CSCs. In the present study, recent advances in the investigation of different biological properties of CSCs, such as their origin, markers, characteristics, and targeting have been reviewed. We have also focused our discussion on radioresistance and adaptive responses of CSCs and their related extrinsic and intrinsic influential factors. In summary, we suggest CSCs as the prime therapeutic target for cancer treatment.