Design single-stranded DNA aptamer of cluster of differentiation 47 protein by stochastic tunnelling-basin hopping-discrete molecular dynamics method.

The formation of the Cluster of Differentiation 47 (CD47, PDB code: 2JJT)/signal regulatory protein α (SIRPα) complex is very important as it protects healthy cells from immune clearance while promoting macrophage phagocytosis for tumour elimination. Although several antibodies have been developed for cancer therapy, new function-blocking aptamers are still under development. This study aims to design the aptamer AptCD47, which can block the formation of the CD47/SIRPα complex. This study employs the MARTINI coarse-grained (CG) force field and the stochastic tunnelling-basin hopping-discrete molecular dynamics (STUN-BH-DMD) method to identify the most stable AptCD47/CD47 complexes. Coarse-grained molecular dynamics (CGMD) simulations were used to obtain root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF) analyses. The results demonstrate that the formation of AptCD47/CD47 complexes renders the CD47 structure more stable than the single CD47 molecule in a water environment. The minimum energy pathway (MEP) obtained by the nudged elastic band (NEB) method indicates that the binding processes of 5'-ATTCAATTCC-3' and 5'-AGTGCAATCT-3' to CD47 are barrierless, which is much lower than the binding barrier of SIRPα to CD47 of about 14.23 kcal/mol. Therefore, these two AptCD47/CD47 complexes can create a high spatial binding barrier for SIRPα, preventing the formation of a stable CD47/SIRPα complex. The proposed numerical process with the MARTINI CG force field can be used to design CD47 aptamers that efficiently block SIRPα from binding to CD47.Communicated by Ramaswamy H. Sarma.

Hepatic Angiosarcoma Post-Renal Transplantation: A Case Report.

BACKGROUND: DNA damage and oncogenic viruses increase the risk of cancer post-kidney transplantation, including skin cancer, Kaposi's sarcoma, oral cancer, and non-Hodgkin lymphoma. Here we report an uncommon case of liver angiosarcoma that occurred 8 years after kidney transplantation. This study strictly complied with the Helsinki Congress and the Istanbul Declaration regarding donor source. CASE REPORT: A 57-year-old female patient received a cadaver kidney transplantation 8 years ago. She followed a long-term regimen of tacrolimus, mycophenolate sodium, and everolimus, with good renal function. She received annual regular abdominal ultrasound examinations after kidney transplantation, which showed no findings. The patient suffered from several symptoms for approximately 2 weeks before a scheduled abdominal ultrasound: diarrhea, epigastric pain, abdominal fullness, tea-colored urine, and little stool passage. The abdominal computerized tomography showed multiple hepatic tumors in both the hepatic lobes with engorged vasculatures and mild hemoperitoneum. A liver biopsy revealed the histopathology of angiosarcoma. The patient suffered multiple organ failure within one month of treatment. CONCLUSIONS: Various post-transplant malignancies are not uncommon after transplantation, warranting periodic screenings for any symptoms in these patients.