Decoding the effect of photoperiodic cues in transducing kisspeptin-melatonin circuit during the pubertal onset in common carp.

This study unravels the intricate interplay between photoperiod, melatonin, and kisspeptin to orchestrate the pubertal onset of Common carp. Female fingerlings exposed to long days (LD) exhibited a hormonal crescendo, with upregulated hypothalamic-pituitary-ovarian (HPO) axis genes (kiss1, kiss1r, kiss2, gnrh2, gnrh3) and their downstream targets (lhr, fshr, ar1, esr1). However, the expression of the melatonin receptor (mtnr1a) diminished in LD, suggesting a potential inhibitory role. This hormonal symphony was further amplified by increased activity of key transcriptional regulators (gata1, gata2, cdx1, sp1, n-myc, hoxc8, plc, tac3, tacr3) and decreased expression of delayed puberty genes (mkrn1, dlk1). In contrast, short days (SD) muted this hormonal chorus, with decreased gnrh gene and regulator expression, elevated mtnr1a, and suppressed gonadal development. In in-vitro, estradiol mimicked the LD effect, boosting gnrh and regulator genes while dampening mtnr1a and melatonin-responsive genes. Conversely, melatonin acted as a conductor, downregulating gnrh and regulator genes and amplifying mtnr1a. Our findings illuminate the crucial roles of melatonin and kisspeptin as opposing forces in regulating pubertal timing. LD-induced melatonin suppression allows the kisspeptin symphony to flourish, triggering GnRH release and, ultimately, gonadal maturation. This delicate dance between photoperiod, melatonin, and kisspeptin orchestrates common carp's transition from juvenile to reproductive life.

Thermoresponsive liquid crystalline formulation of Exemestane: Design and structural characterization.

Exemestane (EXE), a drug used for the treatment of breast cancer, has limited aqueous solubility of 0.08 mg/mL and log P∼ 4.22. The only available marketed formulation in form of tablets possess limitations of poor oral absorption (∼ 42 %), low solubility, extensive hepatic metabolism and numerous adverse effects due to its peripheral absorption. In order to address these issues, an alternative route of topical application is attempted through a lamellar liquid crystal based formulation. Pluronic® was used as stabilizer due to its higher surface activity and gelling properties. The solubility enhancement of EXE was achieved using liquid crystal formulation. We have investigated the effect of concentration of oil, Smix (surfactant - cosurfactant mixture) and EXE on lattice parameter, rheology and drug release for various combinations of the formulation. The small angle x-ray scattering (SAXS) measurement demonstrated an evidence of a lamellar structure with lattice parameter ∼15 nm, which increases with corresponding increase in oil and EXE due to increase in hydrophobic interactions leading to an expansion of lamella. The inter lamellar distance decreases at higher surfactant concentration, due to the distribution of the same amount of oil and drug within larger concentration of surfactant molecules. The rheology measurement exhibited gel like properties at low shear rate indicating soft gel formation, which converts to Newtonian type flowing liquid at higher shear rate. At constant Smix with increasing oil content, the viscosity decreases, which is attributed to the dilution of the lamellar structures with oil. The temperature sweep rheology reveals a change in the viscosity near physiological temperature, which may be attributed to the structural transition of lamellae. The formulation remains gel like at room temperature, which aids in proper application to skin and converts it to free flowing liquid above 37 °C. The invitro drug release of optimized formulation for 24 h was ∼ 38 % at 37 °C, which increased to 50 % at 42 °C. Accordingly, this formulation containing thermoresponsive lamellar liquid crystal gels of EXE represents a viable option for hyperthermia induced enhanced drug release. The characteristic and advantageous features offered by this formulation includes improved bioavailability of EXE due to enhanced solubility, permeability and absorption.