Skin-derived precursor conditioned medium alleviated photoaging via early activation of TGF-ß/Smad signaling pathway by thrombospondin1: In vitro and in vivo studies.

Photoaging is one major exogenous factor of skin aging. Efficacy and safety of current anti-photoaging therapies remained to be improved. Our previous studies indicated that skin-derived precursors (SKPs) alleviated photodamage by early activation of TGF-ß/Smad signaling pathway via thrombospondin1 (TSP1). However, the research concerning SKP conditioned medium (SKP-CM) has never been reported. In the current study, we aimed to explore the anti-photoaging effects of SKP-CM both in vitro and in vivo, and to elucidate the possible mechanisms. Mouse SKP-CM (mSKP-CM) collection was optimized by a comparative method. The concentration of protein and growth factors in mSKP-CM was detected using BCA protein assay kit and growth factor protein chip. The anti-photoaging effects of mSKP-CM and its regulation of key factors in the TGF-ß/Smad signaling pathway were explored using UVA + UVB photoaged mouse fibroblasts (mFBs) and nude mice dorsal skin. The research revealed that mSKP-CM contained significantly higher-concentration of protein and growth factors than mouse mesenchymal stem cell conditioned medium (mDMSC-CM). mSKP-CM alleviated mFBs photoaging by restoring cell viability and relieving senescence and death. ELISA, qRT-PCR, and western blot results implied the potential mechanisms were associated with the early activation of TGF-ß/Smad signaling pathway by TSP1. In vivo experiments demonstrated that compared with the topical intradermal mDMSC-CM injection and retinoic acid cream application, the photodamaged mice dorsal skin intradermally injected with mSKP-CM showed significantly better improvement. Consistent with the in vitro results, both western blot and immunohistochemistry results confirmed that protein expression of TSP1, smad2/3, p-smad2/3, TGF-ß1, and collagen I increased, and matrix metalloproteinases decreased. In summary, both in vitro and in vivo experiments demonstrated that mSKP-CM alleviated photoaging through an early activation of TGF-ß/Smad signaling pathway via TSP1. SKP-CM may serve as a novel and promising cell-free therapeutical approach for anti-photoaging treatment and regenerative medicine.

Ferroptosis in epithelial ovarian cancer: a burgeoning target with extraordinary therapeutic potential.

Epithelial ovarian cancer (EOC) is universally acknowledged as a terrifying women killer for its high mortality. Recent research advances support that ferroptosis, an emerging iron-dependent type of regulated cell death (RCD) triggered by the excessive accumulation of lipid peroxides probably possesses extraordinary therapeutic potential in EOC therapy. Herein, we firstly provide a very concise introduction of ferroptosis. Special emphasis will be put on the ferroptosis's vital role in EOC, primarily covering its role in tumorigenesis and progression of EOC, the capability of reversing chemotherapy resistance, and the research and development of related therapeutic strategies. Furthermore, the construction of ferroptosis-related prognostic prediction systems, and mechanisms of ferroptosis resistance in EOC are also discussed. Finally, we propose and highlight several important yet unanswered problems and some future research directions in this field.

The multifaceted roles of natural products in mitochondrial dysfunction.

Mitochondria are the primary source of energy production in cells, supporting the metabolic demand of tissue. The dysfunctional mitochondria are implicated in various diseases ranging from neurodegeneration to cancer. Therefore, regulating dysfunctional mitochondria offers a new therapeutic opportunity for diseases with mitochondrial dysfunction. Natural products are pleiotropic and readily obtainable sources of therapeutic agents, which have broad prospects in new drug discovery. Recently, many mitochondria-targeting natural products have been extensively studied and have shown promising pharmacological activity in regulating mitochondrial dysfunction. Hence, we summarize recent advances in natural products in targeting mitochondria and regulating mitochondrial dysfunction in this review. We discuss natural products in terms of their mechanisms on mitochondrial dysfunction, including modulating mitochondrial quality control system and regulating mitochondrial functions. In addition, we describe the future perspective and challenges in the development of mitochondria-targeting natural products, emphasizing the potential value of natural products in mitochondrial dysfunction.

The diagnostic and therapeutic prospects of exosomes in ovarian cancer.

Exosomes are nano-sized vesicles derived from the endosomal system and are involved in many biological and pathological processes. Emerging evidence has demonstrated that exosomes with cell-specific constituents are associated with the tumorigenesis and progression of ovarian cancer. Therefore, exosomes derived from ovarian cancers can be potential diagnostic biomarkers and therapeutic targets. In this review, we briefly present the biological characteristics of exosomes and the recent advances in isolating and detecting exosomes. Furthermore, we summarise the many functions of exosomes in ovarian cancer, hoping to provide a theoretical basis for clinical applications of exosomes in the diagnosis and treatment of ovarian cancer.