Electrochemical aptasensor based on the engineered core-shell MOF nanostructures for the detection of tumor antigens.

It is essential to develop ultrasensitive biosensors for cancer detection and treatment monitoring. In the development of sensing platforms, metal-organic frameworks (MOFs) have received considerable attention as potential porous crystalline nanostructures. Core-shell MOF nanoparticles (NPs) have shown different diversities, complexities, and biological functionalities, as well as significant electrochemical (EC) properties and potential bio-affinity to aptamers. As a result, the developed core-shell MOF-based aptasensors serve as highly sensitive platforms for sensing cancer biomarkers with an extremely low limit of detection (LOD). This paper aimed to provide an overview of different strategies for improving selectivity, sensitivity, and signal strength of MOF nanostructures. Then, aptamers and aptamers-modified core-shell MOFs were reviewed to address their functionalization and application in biosensing platforms. Additionally, the application of core-shell MOF-assisted EC aptasensors for detection of several tumor antigens such as prostate-specific antigen (PSA), carbohydrate antigen 15-3 (CA15-3), carcinoembryonic antigen (CEA), human epidermal growth factor receptor-2 (HER2), cancer antigen 125 (CA-125), cytokeratin 19 fragment (CYFRA21-1), and other tumor markers were discussed. In conclusion, the present article reviews the advancement of potential biosensing platforms toward the detection of specific cancer biomarkers through the development of core-shell MOFs-based EC aptasensors.

A homozygote variant in the tRNA splicing endonuclease subunit 54 causes pontocerebellar hypoplasia in a consanguineous Iranian family.

BACKGROUND: Homozygous loss-of-function mutations in TSEN54 (tRNA splicing endonuclease subunit 54; OMIM: 608755) cause different types of pontocerebellar hypoplasias (PCH) including PCH2, PCH4, and PCH5. The study aimed to determine the possible genetic factors contributing to PCH phenotypes in two affected male infants in an Iranian family. METHODS: We subjected two affected individuals in a consanguineous Iranian family. To systematically investigate the susceptible gene(s), whole-exome sequencing was performed on the proband and a novel identified variant was confirmed by Sanger sequencing. We also analyzed 26 relatives in three generations using PCR-restriction fragment length polymorphism (PCR-RFLP) followed and confirmed by Sanger sequencing. RESULTS: Physical and medical examinations confirmed PCH in the patients. Besides, the proband showed bilateral moderate sensorineural hearing loss and structural heart defects as the novel phenotypes. The molecular findings also verified that two affected individuals were homozygote for the novel synonymous variant, NM_207346.2: c.1170G>A; p.(Val390Val), in TSEN54. PCR-RFLP and Sanger sequencing elucidated that the parents and 16 relatives were heterozygote for the novel variant. CONCLUSION: We identified a novel synonymous variant, c.1170G>A, in TSEN54 associated with PCH in an Iranian family. Based on this study, we strongly suggest using "TSENopathies" to show the overlapped phenotypes among different types of PCH resulted from TSEN causative mutations.