Collagen,the main component of mammal skin,has been traditionally used in leather manufacturing for thousands of years due to its diverse physicochemical properties.Collagen is the most abundant protein in mammals and the main component of the extracellular matrix(ECM).The properties of collagen also make it an ideal building block for the engineering of materials for a range of biomedical applications.Reproductive medicine,especially human fertility preservation strategies and reproductive organ regeneration,has attracted significant attention in recent years as it is key in resolving the growing social concern over aging populations worldwide.Collagen-based biomaterials such as collagen hydrogels,decellularized ECM(dECM),and bioengineering techniques including collagen-based 3D bio-printing have facilitated the engineering of reproductive tissues.This review summarizes the recent progress in apply-ing collagen-based biomaterials in reproductive.Furthermore,we discuss the prospects of collagen-based materials for engineering artificial reproductive tissues,hormone replacement therapy,and reproductive organ reconstruction,aiming to inspire new thoughts and advancements in engineered reproductive tissues research.
Macrophages acquire distinct phenotypes during tissue stress and inflammatory responses.Macrophages are roughly categorized into two different subsets named inflammatory M1 and anti-inflammatory M2 macrophages.We herein identified a unique pathogenic macrophage subpopulation driven by IL-23 with a distinct gene expression profile including defined types of cytokines.The freshly isolated resting mouse peritoneal macrophages were stimulated with different cytokines in vitro,the expression of cytokines and chemokines were detected by microarray,real-time PCR,ELISA and multiple colors flow cytometry.Adoptive transfer of macrophages and imiquimod-induced psoriasis mice were used.In contrast to M1-and M2-polarized macrophages,IL-23-treated macrophages produce large amounts of IL-17A,IL-22and IFN-γ.Biochemical and molecular studies showed that IL-23 induces IL-17A expression in macrophages through the signal transducer and activator of transcription 3(STAT3)-retinoid related orphan receptor-γ T (RORyT)pathway.T-bet mediates the IFN-γ production in IL-23-treated macrophages.Importantly,IL-23-treated macrophages signifi- cantly promote the dermatitis pathogenesis in a psoriasis-like mouse model.IL-23-treated resting macrophages express a distinctive gene expression prolife compared with M1 and M2 macrophages.The identification of IL-23-induced macrophage polarization may help us to understand the contribution of macrophage subpopulation in Th17-cytokines-related pathogenesis.
Spaceflight-associated immune system weakening ultimately limits the ability of humans to expand their presence beyond the earth's orbit. A mechanistic study of microgravity-regulated immune cell function is necessary to overcome this challenge. Here, we demonstrate that both spaceflight (real) and simulated microgravity significantly reduce macrophage differentiation, decrease macrophage quantity and functional polarization, and lead to metabolic reprogramming, as demonstrated by changes in gene expression profiles. Moreover, we identified RAS/ERK/NFκB as a major microgravity-regulated pathway. Exogenous ERK and NFκB activators significantly counteracted the effect of microgravity on macrophage differentiation. In addition, microgravity also affects the p53 pathway, which we verified by RT-qPCR and Western blot. Collectively, our data reveal a new mechanism for the effects of microgravity on macrophage development and provide potential molecular targets for the prevention or treatment of macrophage differentiation deficiency in spaceflight.
Lu ShiHongling TianPeng WangLing LiZhaoqi ZhangJiayu ZhangYong Zhao
Nowadays cloud architecture is widely applied on the internet.New malware aiming at the privacy data stealing or crypto currency mining is threatening the security of cloud platforms.In view of the problems with existing application behavior monitoring methods such as coarse-grained analysis,high performance overhead and lack of applicability,this paper proposes a new fine-grained binary program monitoring and analysis method based on multiple system level components,which is used to detect the possible privacy leakage of applications installed on cloud platforms.It can be used online in cloud platform environments for fine-grained automated analysis of target programs,ensuring the stability and continuity of program execution.We combine the external interception and internal instrumentation and design a variety of optimization schemes to further reduce the impact of fine-grained analysis on the performance of target programs,enabling it to be employed in actual environments.The experimental results show that the proposed method is feasible and can achieve the acceptable analysis performance while consuming a small amount of system resources.The optimization schemes can go beyond traditional dynamic instrumentation methods with better analytical performance and can be more applicable to online analysis on cloud platforms.
It is believed that the adaptive immune system responds to nonself entities with its specificity and memory properties.In contrast,the innate immune system lacks adaptive characteristics.Whether innate immune cells can generate adaptive immune features has always been an unanswered question.
Xenogeneic thymus transplantation can efficiently induce specific immune tolerance to donor antigens in athymic recipients. However, many nude mice suffer from autoimmune diseases (AID) for over 10 weeks after xenogeneic thymus transplantation. CD4+CD25+Foxp3+ regulatory T (Treg) cells were recently determined to play a pivotal role in keeping immune tolerance in humans and mice. Thus, we investigated this subpopulation of Treg cells in the periphery of pig thymus-grafted nude mice suffering from AID. Our results showed that the expression of Foxp3, CTLA-4 and GITR on mouse CD4+CD25+ T cells and the ratio of CD4+CD25+Foxp3+ Treg cells to CD4+ T cells were significantly decreased in the periphery of pig thymus-grafted nude mice suffering from AID, compared with healthy pig or mouse thymus-grafted nude mice. Furthermore, mouse CD4+CD25+ T cells in pig thymus-grafted nude mice suffering from AID showed more severe deficiency in immunosuppressive function compared with the counterpart in xenogeneic pig or syngeneic thymus-grafted nude mice without AID. Thus, the decreased frequency, altered phenotype and functional deficiency of mouse CD4+CD25+ Treg cells in pig thymus-grafted nude mice may contribute to the development of AID in this model.
Neutrophils are heterogeneous with distinct subsets,and can switch phenotypes to exert regulatory functions on immunity.We herein demonstrate that IL-23-treated neutrophils selectively produce IL-17A,IL-17F and IL-22,and display a distinct gene expression profile in contrast to resting and lipopolysaccharide-treated neutrophils.IL-17+neutrophils are present in the colons of mice with dextran sulfate sodium-induced colitis.Adoptive transfer of IL-23-treated neutrophils significantly promotes pathogenesis in this model.IL-23 induces neutrophil polarization through STAT3-dependent RORγt and BATF pathways.Thus,IL-23-induced neutrophil polarization expresses a unique cytokine-producing profile,which may contribute to IL-23-mediated inflammatory diseases.
CD4^(+)CD25^(+) T regulatory(Treg)cells are critical in inducing and maintaining immunological self-tolerance as well as transplant tolerance.The effect of low doses of whole-body irradiation(WBI)on CD41CD251Foxp31 Treg cells has not been determined.The proportion,phenotypes and function of CD4^(+)CD25^(+) Treg cells were investigated 0.5,5 and 15 days after euthymic,thymectomized or allogeneic bone marrow transplanted C57BL/6 mice received 2-Gy c-rays of WBI.The 2-Gy WBI significantly enhanced the ratios of CD41CD251 Treg cells and CD4^(+)CD25^(+)Foxp3^(+) Treg cells to CD41 T cells in peripheral blood,lymph nodes,spleens and thymi of mice.The CD41CD251 Treg cells of the WBI-treated mice showed immunosuppressive activities on the immune response of CD4^(+)CD25^(+) T effector cells to alloantigens or mitogens as efficiently as the control mice.Furthermore,2-Gy c-ray WBI significantly increased the percentage of CD4^(+)CD25^(+)Foxp3^(+) Treg cells in the periphery of either thymectomized mice or allogeneic bone marrow transplanted mice.The in vitro assay showed that ionizing irradiation induced less cell death in CD4^(+)CD25^(+)Foxp3^(+) Treg cells than in CD4^(+)CD25^(+) T cells.Thus,a low dose of WBI could significantly enhance the level of functional CD41CD251Foxp31 Treg cells in the periphery of naive or immunized mice.The enhanced proportion of CD41CD251Foxp31 Treg cells in the periphery by a low dose of WBI may make hosts more susceptible to immune tolerance induction.
Extracellular matrix(ECM)is characterized as widespread,abundant,and pluripotent.Among ECM members,collagen is widely accepted as one of the most prominent components for its essential structural property that can provide a scaffold for other components of ECM and the rich biological functions,which has been extensively used in tissue engineering.Emerging evidence has shown that the balance of ECM degradation and remodeling is vital to regulations of maternal-fetal interface including menstrual cycling,decidualization,embryo implantation and pregnancy maintenance.Moreover,disorders in these events may eventually lead to failure of pregnancy.Although the improvement of assisted conception and embryo culture technologies bring hope to many infertile couples,some unfavorable outcomes,such as recurrent implantation failure(RIF),recurrent pregnancy loss(RPL)or recurrent miscarriage(RM),keep troubling the clinicians and patients.Recently,in vitro three-dimensional(3D)model mimicking the microenvironment of the maternal-fetal interface is developed to investigate the physiological and pathological conditions of conception and pregnancy.The progress of this technology is based on clarifying the role of ECM in the endometrium and the interaction between endometrium and conceptus.Focusing on collagen,the present review summarized the degradation and regulation of ECM and its role in normal menstruation,endometrium receptivity and unsatisfying events occurring in infertility treatments,as well as the application in therapeutic approaches to improve pregnancy outcomes.More investigations about ECM focusing on the maternal-fetal interface interaction with mesenchymal stem cells or local immunoregulation may inspire new thoughts and advancements in the clinical application of infertility treatments.
