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.

KCa3.1 protein is part of a heterotetrameric voltage-independent potassium channel, the activity of which depends on the intracellular calcium binding to calmodulin. KCa3.1 is immensely significant in regulating immune responses and primarily expressed in cells of hematopoietic lineage. It is one of the attractive pharmacological targets that are known to inhibit neuroinflammation. KCa3.1 blockers mediate neuroprotection through multiple mechanisms, such as by targeting microglia-mediated neuronal killing. KCa3.1 modulators may provide alternative treatment options for neurological disorders like ischemic stroke, Alzheimer disease, glioblastoma multiforme, multiple sclerosis and spinal cord injury. This review is an attempt to draw attention towards KCa3.1 channel, which was never exploited to its full potential as a viable therapeutic candidate against various neurological disorders.

mPTF1 demonstrated lower genotoxicity, higher affinity for PDEs, & reasonable pharmacokinetic, druglikeness & ADMET properties compared to Pentoxifylline.

Ischemic stroke is the leading cause of mortality and morbidity worldwide for which the assemblage of therapeutic interventions has remained outstandingly limited. Several new insights into the causes of neuronal death during ischemic event have led to the identification of some important novel targets for intervention. This article highlights some of the promising protein targets, which are in the validation process and have the potential to get translated into viable neurotherapeutics against ischemic stroke.

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