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Preclinical and clinical findings suggest sexual dimorphism in cardiotoxicity induced by a chemotherapeutic drug, doxorubicin (DOX). However, molecular alterations leading to sex‐related differential vulnerability of heart to DOX toxicity are not fully explored. In the present study, RNA sequencing in hearts of B6C3F1 mice indicated more differentially expressed genes in males than females (224 vs. 19; ≥1.5‐fold, False Discovery Rate [FDR] < 0.05) at 1 week after receiving 24 mg/kg total cumulative DOX dose that induced cardiac lesions only in males. Pathway analysis further revealed probable inactivation of cardiac apelin fibroblast signaling pathway (p = 0.00004) only in DOX‐treated male mice that showed ≥1.25‐fold downregulation in the transcript and protein levels of the apelin receptor, APJ. In hearts of DOX‐treated females, the transcript levels of apelin (1.24‐fold) and APJ (1.47‐fold) were significantly (p < 0.05) increased compared to saline‐treated controls. Sex‐related differential DOX effect was also observed on molecular targets downstream of the apelin‐APJ pathway in cardiac fibroblasts and cardiomyocytes. In cardiac fibroblasts, upregulation of Tgf‐β2, Ctgf, Sphk1, Serpine1, and Timp1 (fibrosis; FDR < 0.05) in DOX‐treated males and upregulation of only Tgf‐β2 and Timp1 (p < 0.05) in females suggested a greater DOX toxicity in hearts of males than females. Additionally, Ryr2 and Serca2 (calcium handling; FDR < 0.05) were downregulated in conjunction with 1.35‐fold upregulation of Casp12 (sarcoplasmic reticulum‐mediated apoptosis; FDR < 0.05) in DOX‐treated male mice. Drug effect on the transcript level of these genes was less severe in female hearts. Collectively, these data suggest a likely role of the apelin‐APJ axis in sex‐related differential DOX‐induced cardiotoxicity in our mouse model. RNA sequencing in mouse hearts 1‐week after 24 mg/kg cumulative doxorubicin dose suggested a potential role of the apelin‐APJ pathway in sex‐related differential DOX‐induced cardiotoxicity. In males, the apelin receptor, APJ, was downregulated, whereas apelin and APJ were upregulated in females compared to saline‐treated counterparts. Downstream alterations were also seen, including significantly altered expression of Tgf‐β2, Sphk1, Serpine1, Ctgf, and Timp1 (fibrosis) in cardiac fibroblasts and Ryr2 and Serca2 (Ca2+ homeostasis) in cardiomyocytes with greater effects in males than females. [ABSTRACT FROM AUTHOR]

Semiconducting nanoparticles (quantum dots) have emerged as contrast agents for fluorescence microscopy with high quantum yields and photostability. Biosensing of molecule analysis is an important component of these methods and an electron transfer approach provides small molecule biosensing.

Radiolabeled biomolecules are routinely used for clinical diagnostics. Tc is the most commonly used radioactive tracer in radiopharmaceuticals. Re and Re are also commonly used as radioactive tracers in medicine. However, currently available methods for radiolabeling are lengthy and involve several steps in bioconjugation processes. In this work we present a strategy to engineer proteins that may selectively recognize the perrhenate (ReO) ion as a new way to label proteins. We found that a molybdate (MoO)-binding protein (ModA) from Escherichia coli can bind perrhenate with high affinity. Using fluorescence and isothermal titration calorimetry measurements, we determined the dissociation constant of ModA for ReO to be 541 nM and we solved a crystal structure of ModA with a bound ReO. On the basis of the structure we created a mutant protein containing a disulfide linkage, which exhibited increased affinity for perrhenate ( K = 104 nM). High-resolution crystal structures of ModA (1.7 Å) and A11C/R153C mutant (2.0 Å) were solved with bound perrhenate. Both structures show that a perrhenate ion occupies the molybdate binding site using the same amino acid residues that are involved in molybdate binding. The overall structure of the perrhenate-bound ModA is unchanged compared with that of the molybdate-bound form. In the mutant protein, the bound perrhenate is further stabilized by the engineered disulfide bond. [ABSTRACT FROM AUTHOR]