Roles of immune microenvironment in the female reproductive maintenance and regulation: novel insights into the crosstalk of immune cells

Female fertility decline is an accumulative consequence caused by complex factors, among them, the disruption of the immune profile in female reproduction stands out as a crucial contributor. Presently, the effects of immune microenvironment (IME) on the female reproductive process have attracted increasing attentions for their dynamic but precisive roles. Immunocytes including macrophages, dendritic cells, T cells, B cells and neutrophils, with diverse subpopulations as well as high plasticity functioned dynamically in the process of female reproduction through indirect intercellular communication via specific cytokine release transduced by molecular signal networks or direct cell-cell contact to maintain the stability of the reproductive process have been unveiled. The immune profile of female reproduction in each stage has also been meticulously unveiled. Especially, the application of single-cell sequencing (scRNA-seq) technology in this process reveals the distribution map of immune cells, which gives a novel insight for the homeostasis of IME and provides a research direction for better exploring the role of immune cells in female reproduction. Here, we provide an all-encompassing overview of the latest advancements in immune modulation within the context of the female reproductive process. Our approach involves structuring our summary in accordance with the physiological sequence encompassing gonadogenesis, folliculogenesis within the ovaries, ovulation through the fallopian tubes, and the subsequent stages of embryo implantation and development within the uterus. Our overarching objective is to construct a comprehensive portrayal of the immune microenvironment (IME), thereby accentuating the pivotal role played by immune cells in governing the intricate female reproductive journey. Additionally, we emphasize the pressing need for heightened attention directed towards strategies that focus on immune interventions within the female reproductive process, with the ultimate aim of enhancing female fertility

Engineering microparticles based on solidified stem cell secretome with an augmented pro-angiogenic factor portfolio for therapeutic angiogenesis

Tissue (re)vascularization strategies face various challenges, as therapeutic cells do not survive long enough in situ, while the administration of pro-angiogenic factors is hampered by fast clearance and insufficient ability to emulate complex spatiotemporal signaling. Here, we propose to address these limitations by engineering a functional biomaterial capable of capturing and concentrating the pro-angiogenic activities of mesenchymal stem cells (MSCs). In particular, dextran sulfate, a high molecular weight sulfated glucose polymer, supplemented to MSC cultures, interacts with MSC-derived extracellular matrix (ECM) components and facilitates their co-assembly and accumulation in the pericellular space. Upon decellularization, the resulting dextran sulfate-ECM hybrid material can be processed into MIcroparticles of SOlidified Secretome (MIPSOS). The insoluble format of MIPSOS protects protein components from degradation, while facilitating their sustained release. Proteomic analysis demonstrates that MIPSOS are highly enriched in pro-angiogenic factors, resulting in an enhanced pro-angiogenic bioactivity when compared to naïve MSC-derived ECM (cECM). Consequently, intravital microscopy of full-thickness skin wounds treated with MIPSOS demonstrates accelerated revascularization and healing, far superior to the therapeutic potential of cECM. Hence, the microparticle-based solidified stem cell secretome provides a promising platform to address major limitations of current therapeutic angiogenesis approaches

Planar Chiral Ferrocene Cyclopalladated Derivatives Induce Caspase-Dependent Apoptosis and Antimetastasis in Cancer Cells

A series of planar chiral ferrocene cydopalladated compounds were synthesized and characterized. The absolute configurations of four compounds were determined by single-crystal X-ray analysis. The cytotoxic activities of the synthesized compounds and cisplatin exhibited different inhibition potencies on the viability of human liver, breast, and colon cancer cell lines. The dinuclear compound 7 was 16-fold more potent than cisplatin in hepatoma cells. Compound 7 was also more effective than cisplatin in the inhibition of hepatoma cell metastasis. Flow cytometry analysis and caspase activity assays indicated that compound 7 exerted antiproliferative activity in cancer cells through the induction of caspase-dependent apoptosis

Planar Chiral Ferrocene Cyclopalladated Derivatives Induce Caspase-Dependent Apoptosis and Antimetastasis in Cancer Cells

A series of planar chiral ferrocene cyclopalladated compounds were synthesized and characterized. The absolute configurations of four compounds were determined by single-crystal X-ray analysis. The cytotoxic activities of the synthesized compounds and cisplatin exhibited different inhibition potencies on the viability of human liver, breast, and colon cancer cell lines. The dinuclear compound <b>7</b> was 16-fold more potent than cisplatin in hepatoma cells. Compound <b>7</b> was also more effective than cisplatin in the inhibition of hepatoma cell metastasis. Flow cytometry analysis and caspase activity assays indicated that compound <b>7</b> exerted antiproliferative activity in cancer cells through the induction of caspase-dependent apoptosis

Assessment of the antitumor activity of a cyclopalladated ferrocene compound assisted by a dual-targeting drug delivery system

One cyclopalladated ferrocene compound CP was synthesized, which showed a good cell cytotoxicity. Assisted by a dual-targeting drug delivery system, the anticancer activity of CP to MDA-MB-468 remained unchanged, but the toxicity to non-tumorigenic cell line NIH3T3 was remarkably reduced. This provided a new path for the development of cyclopalladated ferrocene as an antitumor drug candidate

Biomedical Potential of Ultrafine Ag Nanoparticles Coated on Poly (Gamma-Glutamic Acid) Hydrogel with Special Reference to Wound Healing

In wound care management, the prevention of wound infection and the retention of an appropriate level of moisture are two major challenges. Therefore, designing an excellent antibacterial hydrogel with a suitable water-adsorbing capacity is very important to improve the development of wound dressings. In this paper, a novel silver nanoparticles/poly (gamma-glutamic acid) (γ-PGA) composite dressing was prepared for biomedical applications. The promoted wound-healing ability of the hydrogels were systematically evaluated with the aim of attaining a novel and effective wound dressing. A diffusion study showed that hydrogels can continuously release antibacterial factors (Ag). Hydrogels contain a high percentage of water, providing an ideal moist environment for tissue regeneration, while also preventing contraction of the wound. Moreover, an in vivo, wound-healing model evaluation of artificial wounds in mice indicated that silver/γ-PGA hydrogels could significantly promote wound healing. Histological examination revealed that hydrogels can successfully help to reconstruct intact epidermis and collagen deposition during 14 days of impaired wound healing. Overall, this research could shed new light on the design of antibacterial silver/γ-PGA hydrogels with potential applications in wound dressing

Novel Biological Hydrogel: Swelling Behaviors Study in Salt Solutions with Different Ionic Valence Number

In this paper, poly γ-glutamic acid/ε-polylysine (γ-PGA/ε-PL) hydrogels were successful prepared. The γ-PGA/ε-PL hydrogels could be used to remove Na+, Ca2+, and Cr3+ from aqueous solution and were characterized by scanning electron microscopy. The performance of hydrogels were estimated under different ionic concentration, temperature, and pH. The results showed that the ionic concentration and the pH significantly influenced the swelling capacity of γ-PGA/ε-PL hydrogels. The swelling capacities of γ-PGA/ε-PL hydrogels were decreased with the increase of the ionic concentration. However, the swelling capacity of the γ-PGA/ε-PL hydrogel was increased with the increase of the pH. The swelling kinetics indicated that γ-PGA/ε-PL hydrogels presented a more limited swelling degree in metal ion solutions with higher ionic valence numbers than in ion solutions with lower ionic valence numbers. However, the swelling kinetics of γ-PGA/ε-PL hydrogels showed that they proposed a satisfactory description in NaCl and CaCl2 solutions. The adsorption process was fitted with a pseudo-second-order rate equation model. Moreover, the desorption kinetics of γ-PGA/ε-PL hydrogels showed that they could release most of the adsorption ions. Considering the biocompatibility, biodegradability, and ionic-sensitive properties, we propose that these γ-PGA/ε-PL hydrogels have high potential to be used in environmental protection, medical treatment, and other related fields

Customizable metal-phenolic supraparticles based on rationally designed building blocks

Metal-phenolic networks (MPNs) as a versatile platform for particle engineering have been well developed due to their integrated benefits of both metal ions and phenolic molecules. However, the approaches to broaden their applications are limited due to the single-driving force from the coordination of these two components. Herein, we developed a universal approach to introducing programmable assembles into MPNs to form metal-phenolic supraparticles based on the rationally designed phenolic building blocks. These as-prepared building blocks can first assemble into primary nanoparticles driven by various controllable intermolecular interactions (i.e., metal-organic coordination, host-guest interaction, and hydrophobic interaction), followed by particle assembly with metal ions to coat on different templates. The introduction of multiple assembly modalities into phenolic building blocks enriches the functionalities of these metal-phenolic supraparticles, such as dual-pH responsibility, light-controllable permeability, and rapid fluorescence labeling of living cells. Our work provides a conceptual and practical paradigm for customizing MPNs with hierarchical structures by importing various assembly strategies via rationally designed phenolic building blocks

Systemic Tumor Suppression via Macrophage‐Driven Automated Homing of Metal‐Phenolic‐Gated Nanosponges for Metastatic Melanoma

Abstract Cell‐based therapies comprising the administration of living cells to patients for direct therapeutic activities have experienced remarkable success in the clinic, of which macrophages hold great potential for targeted drug delivery due to their inherent chemotactic mobility and homing ability to tumors with high efficiency. However, such targeted delivery of drugs through cellular systems remains a significant challenge due to the complexity of balancing high drug‐loading with high accumulations in solid tumors. Herein, a tumor‐targeting cellular drug delivery system (MAGN) by surface engineering of tumor‐homing macrophages (Mφs) with biologically responsive nanosponges is reported. The pores of the nanosponges are blocked with iron‐tannic acid complexes that serve as gatekeepers by holding encapsulated drugs until reaching the acidic tumor microenvironment. Molecular dynamics simulations and interfacial force studies are performed to provide mechanistic insights into the “ON‐OFF” gating effect of the polyphenol‐based supramolecular gatekeepers on the nanosponge channels. The cellular chemotaxis of the Mφ carriers enabled efficient tumor‐targeted delivery of drugs and systemic suppression of tumor burden and lung metastases in vivo. The findings suggest that the MAGN platform offers a versatile strategy to efficiently load therapeutic drugs to treat advanced metastatic cancers with a high loading capacity of various therapeutic drugs