Proteomics and transcriptomics explore the effect of mixture of herbal extract on diabetic wound healing process.

A new therapy strategy for relapsing patients who have received trastuzumab treatment urgently needs to be explored. HER2-specific chimeric antigen receptor (CAR)-expressing NK cells are being rapidly developed for solid tumor therapy, as they have many advantages over HER2-CAR-T cells. Endogenous soluble PD-1 (sPD-1) from the PD-1 extracellular domain blocks PD-1/PD-L1 interaction to promote cancer immunology. Herein, we engineered a new HER2-CAR-NK cell that co-expresses sPD-1 (designed as sPD-1-CAR-NK cells) and assessed its cytotoxic activities toward various cancer cells, activation of immunity and sPD-1 release in vitro and in mouse models bearing breast cancer cells with high HER2 expression, with or without trastuzumab resistance. We demonstrated that sPD-1-CAR-NK cells were able to release bioactive sPD-1, thereby enhancing the cytolytic activities of HER2-CAR-NK cells against HER2 and PD-L1 highly expressing target cells accompanied by increases in the secretion of perforin, granzyme B and IFN-γ. In vivo, sPD-1-CAR-NK cells had superior immunological anticancer efficacy compared to HER2-CAR-NK cells, and they had advantages over HER2-CAR-NK cells in the intraperitoneal injection of sPD-1. Moreover, the infiltration and activation of NK and T cells into tumor tissue were increased in mice with sPD-1-CAR-NK cells. There was no significant change in the body temperature, organ tissue and body weight in all groups except for the group with the PD-1 injection. Together, these data indicate that HER2-specific sPD-1-CAR-NK cells can transport sPD-1 into cancer tissues with high HER2 expression, further improving the efficacy of HER-CAR-NK cells without obvious side effects. sPD-1-CAR-NK is a promising cytotherapeutic agent for patients bearing HER2-positive breast cancer, including those with trastuzumab resistance.

/pdf/engineering-a-her2-car-nk-cell-secreting-soluble-programmed-mewj26q5.pdf

Engineering a HER2-CAR-NK Cell Secreting Soluble Programmed Cell Death Protein with Superior Antitumor Efficacy

Exploring the preparation of multifunctional hydrogels from a bionic perspective is an appealing strategy. Here, we prepared a multifunctional hydrogel dressing inspired by the characteristics of porous extracellular matrix produced during Acomys wound healing. These dressings were printed by Digital Light Processing (DLP) printing of hydrogels composed of gelatin methacrylate (GelMA), hyaluronic acid methacrylate (HAMA), and pretreated platelet-rich plasma (PRP) to shape out triply periodic minimal surface (TPMS) structures, which were freeze-dried for long-term storage. These dressings mimic the porous extracellular matrix of Acomys, while the freeze-drying technique effectively extended the storage duration of PRP viability. Through in vivo and in vitro experiments, the biomimetic dressings developed in this study modulated cell behavior and facilitated wound healing. Consequently, this research offers a novel approach for the advancement of regenerative wound dressings. This article is protected by copyright. All rights reserved.

Biomimetic Structure Hydrogel Loaded with Long-Term Storage Platelet-Rich Plasma in Diabetic Wound Repair.

The mechanisms of exosomes in diabetic foot ulcers healing: a detailed review.

Fibroblast growth factors (FGFs) are a versatile family of peptide growth factors that are involved in various biological functions, including cell growth and differentiation, embryonic development, angiogenesis, and metabolism. Abnormal FGF/FGF receptor (FGFR) signaling has been implicated in the pathogenesis of multiple diseases such as cancer, metabolic diseases, and inflammatory diseases. It is worth noting that macrophage polarization, which involves distinct functional phenotypes, plays a crucial role in tissue repair, homeostasis maintenance, and immune responses. Recent evidence suggests that FGF/FGFR signaling closely participates in the polarization of macrophages, indicating that they could be potential targets for therapeutic manipulation of diseases associated with dysfunctional macrophages. In this article, we provide an overview of the structure, function, and downstream regulatory pathways of FGFs, as well as crosstalk between FGF signaling and macrophage polarization. Additionally, we summarize the potential application of harnessing FGF signaling to modulate macrophage polarization. 

pdf/fibroblast-growth-factor-signaling-in-macrophage-1ofdlrsmx4.pdf

Fibroblast growth factor signaling in macrophage polarization: impact on health and diseases

Chronic non-healing wounds fail to progress beyond the inflammatory phase, characterized by a disorder of inflammation resolution. PD-1/PD-L1, a major co-inhibitory checkpoint signaling, plays critical roles in tumor immune surveillance and the occurrence of inflammatory or autoimmune diseases, but its roles in wound healing remains unclear. Here, we described a novel function of PD-L1 in fibroblast-like cells as a positive regulator of wound healing. PD-L1 dynamically expressed on the fibroblast-like cells in the granulation tissue during wound healing to form a wound immunosuppressive microenvironment, modulate macrophages polarization from M1-type to M2-type, and initiates resolution of inflammation, finally accelerate wound healing. Loss of PD-L1 delayed wound healing, especially in mice with LPS-induced severe inflammation. Furthermore, the mainly regulatory mechanism is that combination of FGF-2 and TGF-β1 promotes PD-L1 translation in fibroblasts through enhancing the eIF4E availability regulated by both PI3K-AKT-mTOR-4EBP1 and p38-ERK-MNK signaling pathways. Our results reveal the positive role of PD-L1 in wound healing, and provide a new strategy for the treatment of chronic wounds.

/pdf/fibroblast-like-cells-promote-wound-healing-via-pd-l1-252sb6ps.pdf

Fibroblast-like cells Promote Wound Healing via PD-L1-mediated Inflammation Resolution

Wound exudate holds great clinical and research potential in wound repair via paracrine signaling. In essence, exudate is modified serum that contains a high concentration of exosomes. The aim of this study was to investigate the role of serum-derived exosomes in scald wound healing of NIH mice skin and to explore the underlying mechanisms. Hence, we constructed a deep second-degree scald model in NIH mice, testing the benefits of exosomes in the scald wound healing. The scratch wound assay, apoptosis assay and MTT assay were conducted to assess the effects of serum-derived exosomes on migration, apoptosis and proliferation of HaCaT cells and fibroblasts. Our results showed that serum-derived exosomes injected subcutaneously entered cells and effectively accelerated wound healing processes in mice. Additionally, serum-derived exosomes optimized functions of cells related to skin injury repair by stimulating fibroblast proliferation, promoting HaCaT cell migration, and suppressing apoptosis of HaCaT cells induced by heat stress. Further study revealed that serum-derived exosomes enhanced phosphorylation of the serine-threonine kinase Akt in scalded skin tissue. These results suggest a potential clinical use of serum-derived exosomes for treating skin scald.

Serum-derived exosomes accelerate scald wound healing in mice by optimizing cellular functions and promoting Akt phosphorylation

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Fibroblast-like cells Promote Wound Healing via PD-L1-mediated Inflammation Resolution

Serum-derived exosomes accelerate scald wound healing in mice by optimizing cellular functions and promoting Akt phosphorylation