Drugs and metabolites are transported in the blood by plasma proteins, such as human serum albumin (HSA). The uridine analog 2'dFUrd, which is a cytotoxic prodrug metabolite of capecitabine, has remarkable activity against solid tumors when administered orally. We report the results of an in vitro experimental study on the interactions of 2'-dFUrd with the N-isoform (at pH 7.4) and B-isoform (at pH 9.0) of HSA, investigated using fluorescence spectroscopy, circular dichroism (CD), isothermal titration calorimetry (ITC), differential scanning calorimetry (DSC), and molecular docking. The binding constant (Kb) was higher for the N-isoform than for the B-isoform. Thermodynamic parameters, such as enthalpy change (ΔH°), entropy change (ΔS°), and Gibbs free energy change (ΔG°), were also calculated for both isoform interactions using calorimetric techniques. The thermostabilities of HSA and the HSA-2'dFUrd complex were found to be higher for the N-isoform. The interaction of 2'dFUrd with HSA was also explored in molecular docking studies, which revealed that 2'dFUrd was bound to the Sudlow site I in subdomain IIA through multiple modes of interaction, such as hydrophobic interactions and hydrogen bonding. These results suggest that 2'dFUrd has higher binding affinity for the N-isoform of HSA.

Abstract Currently, many gastrointestinal diseases are a major reason for the increased mortality rate of children and adults every year. Additionally, these patients may cope with the high cost of the parenteral nutrition (PN), which aids in the long-term survival of the patients. Other treatment options include surgical lengthening, which is not sufficient in many cases, and intestinal transplantation. However, intestinal transplantation is still accompanied by many challenges, including immune rejection and donor availability, which may limit the transplant’s success. The development of more safe and promising alternative treatments for intestinal diseases is still ongoing. Stem cell-based therapy (SCT) and tissue engineering (TE) appear to be the next promising choices for the regeneration of the damaged intestine. However, suitable stem cell source is required for the SCT and TE process. Thus, in this review we discuss how intestinal stem cells (ISCs) are a promising cell source for small intestine diseases. We will also discuss the different markers were used to identify ISCs. Moreover, we discuss the dominant Wnt signaling pathway in the ISC niche and its involvement in some intestinal diseases. Additionally, we discuss ISC culture and expansion, which are critical to providing enough cells for SCT and TE. Finally, we conclude and recommend that ISC isolation, culture and expansion should be considered when SCT is a treatment option for intestinal disorders. Therefore, we believe that ISCs should be considered a cell source for SCT for many gastrointestinal diseases and should be highlighted in future clinical applications.