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Sertoli cells (SCs) are vital to providing morphological and nutritional support for spermatogenesis. Defects in SCs often lead to infertility. SCs transplantation is a promising potential strategy to compensate for SC dysfunction. However, isolation of SCs from testes is impractical due to obvious and ethical limitations. Here, a molecular cocktail is identified comprising of pan‐BET family inhibitor (I‐BET151), retinoic acid, and riluzole that enables the efficient conversion of fibroblasts into functional Sertoli‐like cells (CiSCs). The gene expression profiles of CiSCs resemble those of mature SCs and exhibit functional properties such as the formation of testicular seminiferous tubules, engulfment of apoptotic sperms, supporting the survival of germ cells, and suppressing proliferation of primary lymphocytes in vitro. Moreover, CiSCs are sensitive to toxic substances, making them an alternative model to study the deleterious effects of toxicants on SCs. The study provides an efficient approach to reprogram fibroblasts into functional SCs by using pure chemical compounds.

Phenylethyl resorcinol (PR) is a potent tyrosinase inhibitor and a cosmeceutical skin lightening agent. However, the application of PR is limited by photoinstability and poor solubility. In this study, we formulated and optimized phenylethyl resorcinol loaded nanoliposomes (PR-NLPs) to improve the stability and effective delivery of PR. PR-NLPs were prepared by the ethanol injection method and optimized by a single factor experimental and Box–Behnken design. In addition, Diethylamino Hydroxybenzoyl Hexyl Benzoate (DHHB) as the UBA absorber was added to PR-NLPs, which significantly improved the photostability of PR. The mean size, polydispersity index (PDI), and zeta potential of the optimized PR-NLPs were 130.1 ± 3.54 nm, 0.225 ± 0.02, and −43.9 ± 3.44 mV, respectively. The drug encapsulation efficiency (EE) and loading efficiency (LC) of PR-NLPs were 96.81 ± 3.46% and 8.82 ± 0.6%, respectively. These PR-NLPs showed good physicochemical stability for 3 months at 4 °C and 25 °C in the dark. They showed typical sustained and prolonged drug-release behavior in vitro. The in vitro cytotoxicity assay and cellular uptake demonstrated that the PR-NLPs had excellent biocompatibility and cell transport ability. It significantly inhibited tyrosinase activity and reduced melanin production in B16F10 cells at concentrations of 20 or 30 μg/mL. Moreover, the PR-NLPs enhanced the PR into the skin. These results indicate that PR-NLPs can be used as a nanocarrier to improve the transdermal delivery of PR.

In the mammalian testis, two distinct populations of Sertoli cells (SCs), the immature SCs (ISCs) and adult SCs (ASCs), play significant roles in regulating the development and function of Leydig cells. However, the effect of different SC types on the function of Leydig cells is poorly understood. Here, our study showed that miR-145-5p expression was significantly different in SCs at different stages, with the highest expression observed in ISCs. Exosomes mediate the transfer of miR-145-5p from ISCs to Leydig cells. Overexpression of miR-145-5p in Leydig cells significantly downregulated steroidogenic gene expression and inhibited testosterone synthesis. Additionally, miR-145-5p functioned by directly targeted steroidogenic factor-1 (Sf-1) and downregulated the expression of SF-1, which further downregulated the expression of steroidogenic genes, induced accumulation of lipid droplets, and eventually suppressed testosterone production. These findings demonstrate that SC-derived miR-145-5p plays a significant role in regulating the functions of Leydig cells and may therefore serve as a diagnostic biomarker for male hypogonadism developmental abnormalities during puberty.

BackgroundThe direct application of umbilical cord‐derived mesenchymal stem cells (UCMSCs) for promoting skin wound healing and regeneration is challenging due to strict maintenance requirements and unpredictable differentiation results.MethodsWe developed dead but functional liquid nitrogen‐treated UCMSCs (LNT‐MSCs) by rapidly immersing live UCMSCs (live‐MSCs) in liquid nitrogen.ResultsThe LNT‐MSCs maintained similar cellular structures and surface markers to those of live‐MSCs. We evaluated the therapeutic effects of both live‐MSCs and LNT‐MSCs on full‐thickness skin wound healing in rats. Our results showed that the LNT‐MSCs accelerated wound closure by enhancing the proliferation and migration of skin cells, promoting angiogenesis, and inducing a favourable macrophage phenotype shift. The regenerative healing effect of LNT‐MSCs was comparable to that of live‐MSCs, making them a potential alternative strategy for accelerating wound closure that avoids unpredictable differentiation results and creates a ready‐to‐use cell bank for clinical applications.