Screening and confirmatory analysis of recombinant human erythropoietin for racing camels' doping control

Recombinant human erythropoietin (rHuEPO) belongs to the therapeutic class of erythropoiesis stimulating agents (ESAs) due to its implication in the creation pathway of red blood cells and thus enhancement of oxygenation. Because of this bioactivity, rHuEPO has been considered as a major doping agent in sports competitions for decades. Over the years, doping control laboratories designed several analytical strategies applied to human and animal samples to highlight any misuse. Even though multiple analytical approaches have been reported, none has yet been dedicated to racing camels. Here, we describe an analytical strategy to test camel plasma samples at screening using an ELISA assay and a targeted nano‐liquid chromatography–high‐resolution tandem mass spectrometry for confirmatory analysis. The method was validated and has been successfully applied to post‐race samples, allowing the detection of a positive case of rHuEPO administration.     

A density functional theory study on silver and bis-silver complexes with lighter tetrylene: are silver and bis-silver carbenes candidates for SARS-CoV-2 inhibition? Insight from molecular docking simulation

Ribavirin and remdesivir have been preclinically reported as potential drugs for the treatment of SARS-CoV-2 infection, while light silver tetrylene complexes (NHE_Ph–AgCl and (NHE_Ph–AgCl)₂ with E = C, Si, and Ge) have gained significant interest due to their promising applicability on the cytological scale. Firstly, the structures and bonding states of silver–tetrylene complexes (NHE–Ag) and bis-silver–tetrylene complexes (NHE–Ag-bis) were investigated using density functional theory (DFT) at the BP86 level with the def2-SVP and def2-TZVPP basis sets. Secondly, the inhibitory capabilities of the carbene complexes (NHC–Ag and NHC–Ag-bis) and the two potential drugs (ribavirin and remdesivir) on human-protein ACE2 and SARS-CoV-2 protease PDB6LU7 were evaluated using molecular docking simulation. The carbene ligand NHC bonds in a head-on configuration with AgCl and (AgCl)₂, whereas, the other NHE (E = Si and Ge) tetrylene ligands bond in a side-on mode to the metal fragments. The bond dissociation energy (BDE) of the NHE–Ag bond in the complex families follows the order of NHC–Ag > NHSi–Ag > NHGe–Ag and NHSi–Ag-bis > NHGe–Ag-bis > NHC–Ag-bis. The natural bond orbital analysis implies that the [NHE_Ph→AgCl] and [(NHE_Ph)₂→(AgCl)₂] donations are derived mainly from the σ- and π-contributions of the ligands. The docking results indicate that both the ACE2 and PDB6LU7 proteins are strongly inhibited by silver–carbene NHC–Ag, bis-silver–carbene NHC–Ag-bis, ribavirin, and remdesivir with the docking score energy values varying from −17.5 to −16.5 kcal mol⁻¹ and −16.9 to −16.6 kcal mol⁻¹, respectively. The root-mean-square deviation values were recorded to be less than 2 Å in all the calculated systems. Thus, the present study suggests that silver–carbene NHC–Ag and bis-silver–carbene NHC–Ag-bis complexes are potential candidates to inhibit ACE2 and PDB6LU7, and thus potentially conducive to prevent infection caused by the SARS-CoV-2 virus.

Simultaneous inhibition of silver–carbene complexes to ACE2 and PDB6LU7 is conducive for the prevention of SARS-CoV-2 infection: a virtual prediction.     

The effects of the nude (nu/nu) mutation on bleomycin-induced pulmonary fibrosis. A biochemical evaluation

Previous reports have suggested that the immune system is involved in the lung fibrogenic response to certain agents or treatments. In the present study, we have evaluated the impact of the athymic (nude) mutation on the development of pulmonary fibrosis in mice induced by a single intratracheal instillation of bleomycin (0.75 units/animal). Histologic examination revealed that cellular infiltration, fibroblast proliferation, and connective tissue accumulation were diminished in the nude mice when compared with euthymic (het) control mice. In contrast to control animals treated with saline, total lung hydroxyproline in the nude mouse was not significantly increased at 14 and 30 days after bleomycin treatment. Net collagen synthesis, as assessed by measuring the rate of incorporation of tritiated proline in an organ culture system, was increased above control values in both nude and euthymic mice at 14 days after bleomycin treatment, although these values returned to normal at 30 days. However, lung collagen synthetic rates, normalized to dry lung weights, were significantly higher at 14 days in euthymic bleomycin-treated control mice than in the nude bleomycin-treated animals. The data indicate that the nude athymic mutation protects, at least partially, against bleomycin-induced pulmonary fibrosis, thus suggesting a role for the cellular immune system in regulating the fibrogenic response to this drug.