Purpose Motility of spermatozoa helps not only in planning the type of infertility treatment but also directly reflects the success rate in assisted reproductive technology (ART). Previously, biotin, a water-soluble vitamin, has been shown to increase the motility and longevity of cryopreserved human spermatozoa. The present study was designed to understand the molecular basis of the beneficial effects of presence of biotin in sperm wash medium on early embryo development. Methods The effect biotin supplementation to sperm wash medium on the sperm parameters were assessed in swim-up fraction of normozoospermic and asthenozoospermic ejaculates collected from infertile men. Fertilization and early embryo development was studied using Swiss albino mice. Results Even though both biotin and pentoxifylline (PTX) enhanced the motility of spermatozoa from normozoospermic and asthenozoospermic samples, biotin group exhibited higher in vitro survival. Using mouse model, we observed that presence of biotin or PTX in sperm wash medium improved the fertilization rate and blastocyst rate compared to control. Blastocysts from these groups had significantly higher total cell number (P < 0.01) and lower apoptotic index. In silico target prediction revealed that GTPase HRas (HRas), tyrosine-protein phosphatase nonreceptor type 1 (PTP1B), and glucokinase are the probable targets for biotin. Solution-state Nuclear Magnetic Resonance (NMR) studies confirmed that biotin interacts both with human HRas and PTP1B. Conclusion Our results indicate that presence of biotin in sperm wash medium can improve the fertilization potential and preimplantation embryo development and can be considered as a safe alternate to PTX.
Summary
Emeraldine salt of polyaniline‐coated copper substrate was used as a cathode to study hydrogen evolution reaction in 1M H2SO4. Hydrogen evolution reaction in acidic medium followed Grotthus mechanism, where proton hops randomly on the surface of polyaniline. With Randles‐Sevcik equation, the average value of diffusion coefficient for H+ on polyaniline was calculated to be 2.66 times higher than that in the literature data. This higher value explicitly supported the rapid diffusion of H+ on polyaniline surface from the bulk electrolyte solution. With the help of a phenomenological thermodynamic approach demonstrated elsewhere, the solvent‐modified work function of polyaniline‐coated copper in acidic medium was calculated. The plot of exchange current density versus solvent‐modified work function of different metals and polyaniline‐coated copper indicated that at lower work function polyaniline‐coated copper showed higher exchange current density and the rate of hydrogen evolution was much higher on polyaniline‐coated copper than on copper. This was further confirmed by gas chromatography, and 13C and 1H nuclear magnetic resonance studies supported the mechanism proposed. From linear sweep voltammetry analysis, it was observed that the total capacity of hydrogen stored on polyaniline‐coated copper was approximately 1.85 times higher than that on copper.
The prime focus of the present study is to employ NMR relaxation measurement to address the intermolecular interactions, as well as motional dynamics, of drugs, viz., paracetamol and aspirin, encapsulated within the β-cyclodextrin (β-CD) cavity. In this report, we have attempted to demonstrate the applicability of nonselective (R), selective (R), and bi-selective (R) spin-lattice relaxation rates to infer dynamical parameters, for example, the molecular rotational correlation times (τ) and cross-relaxation rates (σ) of the encapsulated drugs. Molecular rotational correlation times of the free drugs were calculated using the selective relaxation rate in the fast molecular motion time regime (ωτ ≪ 1 and R/R ≈ 1.500), whereas that of the 1:1 complexed drugs were found from the ratio of R/R in the intermediate motion time regime (ωτ ∼ 1 and R/R ≈ 1.054), and these values were compared with each other to confirm the formation of inclusion complexes. Furthermore, the cross-relaxation rates were used to evaluate the intermolecular proton distances. Also, density functional theory calculations were performed to determine the minimum energy geometry of the inclusion complexes and the results compared with those from experiments. The report, thus, presents the possibility of utilizing NMR relaxation data, a more cost-effective experiment, to calculate internuclear distances in the case of drug-supramolecule complexes that are generally obtained by extremely time consuming two-dimensional nuclear Overhauser enhancement-based methods. A plausible mode of insertion of the drug molecules into the β-CD cavity has also been described based on experimental NMR relaxation data analysis.
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