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Planta Medica Jun 2024The global increase in the incidence of wounds is concerning and fuels the search for new treatment options. The use of traditional medicinal plants in wound healing... (Review)
Review
The global increase in the incidence of wounds is concerning and fuels the search for new treatment options. The use of traditional medicinal plants in wound healing represents an appreciated available therapeutic possibility. This work introduces the VOLKSMED database, which contains plants and other materials used in Austrian folk medicine, either as monographs or mixtures. This work focuses on the monographs of the database. Concerning wound healing, sp., sp., and sp. are the most commonly used plants. The focus of this paper is set on selected lesser-known plants ( sp., sp., sp., ) and their status quo in literature concerning wound healing. A systematic search using the databases SciFinder, SCOPUS, and PubMed yielded substantial evidence for the wound healing potential of sp., sp., the Pinaceae and , as well as and clinical studies substantiate their use in Austrian folk medicine. According to the literature, especially and would be worth investigating in-depth since data concerning their wound healing effects - even though scarce - are convincing. In conclusion, the VOLKSMED database contains promising opportunities for further treatment options in the field of wound healing. Future research should consider the listed plants to support their traditional use in Austrian folk medicine and possibly promote the implementation of old knowledge in modern medicine.
Topics: Austria; Wound Healing; Medicine, Traditional; Humans; Plants, Medicinal; Phytotherapy; Databases, Factual; Plant Extracts
PubMed: 38843790
DOI: 10.1055/a-2225-7545 -
Placenta May 2024The maternal-fetal interface is composed of the placenta, which is affiliated with the fetus, and the maternal decidua. During pregnancy, the placenta is mainly... (Review)
Review
The maternal-fetal interface is composed of the placenta, which is affiliated with the fetus, and the maternal decidua. During pregnancy, the placenta is mainly responsible for nutrient transport and immune tolerance maintenance, which plays a key role in fetal growth and development and pregnancy maintenance. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that exists in various cell types at the maternal-fetal interface and is involved in multiple cellular processes. Recent studies have highlighted the role of AhR in regulating various physiological processes, including glucose and lipid metabolism, as well as tryptophan metabolism and immune responses, within non-pregnant tissues. This review shifts focus towards understanding how AhR modulation impacts metabolism and immune regulation at the maternal-fetal interface. This may implicate the development of pregnancy-related complications and the potential target of the AhR pathway for therapeutic strategies against poor pregnancy outcomes.
PubMed: 38830294
DOI: 10.1016/j.placenta.2024.05.134 -
Developmental Cell May 2024Embryonic stem cells (ESCs) can differentiate into all cell types of the embryonic germ layers. ESCs can also generate totipotent 2C-like cells and trophectodermal...
Embryonic stem cells (ESCs) can differentiate into all cell types of the embryonic germ layers. ESCs can also generate totipotent 2C-like cells and trophectodermal cells. However, these latter transitions occur at low frequency due to epigenetic barriers, the nature of which is not fully understood. Here, we show that treating mouse ESCs with sodium butyrate (NaB) increases the population of 2C-like cells and enables direct reprogramming of ESCs into trophoblast stem cells (TSCs) without a transition through a 2C-like state. Mechanistically, NaB inhibits histone deacetylase activities in the LSD1-HDAC1/2 corepressor complex. This increases acetylation levels in the regulatory regions of both 2C- and TSC-specific genes, promoting their expression. In addition, NaB-treated cells acquire the capacity to generate blastocyst-like structures that can develop beyond the implantation stage in vitro and form deciduae in vivo. These results identify how epigenetics restrict the totipotent and trophectoderm fate in mouse ESCs.
PubMed: 38823394
DOI: 10.1016/j.devcel.2024.05.009 -
Communications Biology May 2024Myeloid-derived suppressor cells (MDSCs) play a crucial role in maintaining maternal-fetal tolerance by expressing some immune-suppressive molecules, such as indoleamine...
Myeloid-derived suppressor cells (MDSCs) play a crucial role in maintaining maternal-fetal tolerance by expressing some immune-suppressive molecules, such as indoleamine 2,3-dioxygenase (IDO). Toxoplasma gondii (T. gondii) infection can break the immune microenvironment of maternal-fetal interface, resulting in adverse pregnancy outcomes. However, whether T. gondii affects IDO expression in dMDSCs and the molecular mechanism of its effect are still unclear. Here we show, the mRNA level of IDO is increased but the protein level decreased in infected dMDSCs. Mechanistically, the upregulation of transcriptional levels of IDO in dMDSCs is regulated through STAT3/p52-RelB pathway and the decrease of IDO expression is due to its degradation caused by increased SOCS3 after T. gondii infection. In vivo, the adverse pregnancy outcomes of IDO infected mice are more severe than those of wide-type infected mice and obviously improved after exogenous kynurenine treatment. Also, the reduction of IDO in dMDSCs induced by T. gondii infection results in the downregulation of TGF-β and IL-10 expression in dNK cells regulated through Kyn/AhR/SP1 signal pathway, eventually leading to the dysfunction of dNK cells and contributing the occurrence of adverse pregnancy outcomes. This study reveals a novel molecular mechanism in adverse pregnancy outcome induced by T. gondii infection.
Topics: Animals; Female; Humans; Mice; Pregnancy; Decidua; Down-Regulation; Indoleamine-Pyrrole 2,3,-Dioxygenase; Killer Cells, Natural; Mice, Inbred C57BL; Myeloid-Derived Suppressor Cells; Toxoplasma; Toxoplasmosis
PubMed: 38822095
DOI: 10.1038/s42003-024-06365-5 -
Journal of Reproductive Immunology May 2024The pathogenesis of preeclampsia (PE) has not been elucidated, but immune imbalance is known to be one of the main pathogeneses. Dysfunction of decidual macrophages can...
The pathogenesis of preeclampsia (PE) has not been elucidated, but immune imbalance is known to be one of the main pathogeneses. Dysfunction of decidual macrophages can lead to PE, and the PD-1/PD-L1 signaling pathway is associated with macrophage polarization. However, the relationship between the influence of the PD-1/PD-L1 signaling pathway on macrophage polarization and the onset of PE has not been fully elucidated. In this study, we analyzed the expression of CD68, iNOS, CD206, PD-1 and PD-L1 and the coexpression of CD68PD-1 and CD68PD-L1 in the decidual tissue of PE patients (n= 18) and healthy pregnant women (n=20). We found that CD68 and iNOS expression was increased in the decidua of PE patients (P < 0.001) and that CD206, PD-1 and PD-L1 expression and CD68PD-1 and CD68PD-L1 coexpression were decreased (P < 0.001). To assess the influence of the PD-1/PD-L1 signaling pathway on macrophage polarization, we added an anti-PD-1 mAb (pembrolizumab) or an anti-PD-L1 mAb (durvalumab) during THP-1 differentiation into M1 macrophages. Then, we detected the polarization of CD68CD80 macrophages and the expression of iNOS. To examine the effect of macrophage polarization on the invasion ability of trophoblast cells, macrophages were cocultured with HTR8/SVneo cells, and the invasion ability of HTR8/SVneo cells was detected via transwell assays. We found that CD68CD80 macrophage polarization was enhanced (P<0.05) and that iNOS expression was greater (P<0.01) in the pembrolizumab group. In the durvalumab group, CD68CD80 macrophage polarization and iNOS expression were also increased (P<0.05 and P<0.001). Compared with that in the untreated group, the aggressiveness of HTR8/SVneo cells was decreased in both the pembrolizumab group (P < 0.01) and the durvalumab group (P < 0.001). These findings indicate that the PD-1/PD-L1 signaling pathway may play an important role in the pathogenesis of PE by influencing macrophage polarization and reducing the invasion ability of trophoblasts.
PubMed: 38810587
DOI: 10.1016/j.jri.2024.104258 -
Placenta Aug 2024Intrahepatic cholestasis of pregnancy (ICP) can result in adverse outcomes for both mother and fetus. Inflammatory (M1 subset) or anti-inflammatory (M2 subset)...
INTRODUCTION
Intrahepatic cholestasis of pregnancy (ICP) can result in adverse outcomes for both mother and fetus. Inflammatory (M1 subset) or anti-inflammatory (M2 subset) macrophage polarisation is associated with various complications of pregnancy. However, the influence of ICP on macrophage numbers and polarisation remains unknown. This study analyses macrophage density and distribution in placentas of patients with ICP compared to controls. Clinical parameters were correlated to macrophage distribution and ursodeoxycholic acid use (UDCA).
METHODS
This study included routinely collected placental tissue samples of 42 women diagnosed with ICP and of 50 control pregnancies. Immunohistochemical staining was performed on placental tissue using CD68 antibody as a pan-macrophage marker, CD206 antibody as an M2 and HLA-DR antibody as an M1 macrophage marker. Macrophage density (cells/mm) and distribution (CD206/CD68 or CD206/CD68HLA-DR) in both decidua (maternal tissue) and villous parenchyma (fetal tissue) were compared between groups. Macrophage density and distribution were correlated to clinical parameters for ICP patients.
RESULTS
The density of CD68 macrophages differed significantly between groups in villous parenchyma. In both decidua and villous parenchyma, CD206/CD68 ratio was significantly lower in ICP patients compared to controls (p = 0.003 and p=<0.001, respectively). No difference was found based on UDCA use or in CD68HLA-DR cell density. Significant correlations were found between macrophage density and peak serum bile acids and liver enzymes.
DISCUSSION
In ICP patients, an immune shift was observed in both decidual and villous tissue, indicated by a lower CD206/CD68 ratio. ICP seems to affect placental tissue, however more research is required to understand its consequences.
Topics: Humans; Female; Pregnancy; Cholestasis, Intrahepatic; Pregnancy Complications; Adult; Placenta; Macrophages; Case-Control Studies; Ursodeoxycholic Acid
PubMed: 38810541
DOI: 10.1016/j.placenta.2024.05.129 -
Placenta Aug 2024Studies have shown that EMT (epithelial-mesenchymal transition) and energy metabolism influence each other, and it is unclear whether the trophoblast energy metabolism...
Decidual stromal cell-derived exosomes deliver miR-22-5p_R-1 to suppress trophoblast metabolic switching from mitochondrial respiration to glycolysis by targeting PDK4 in unexplained recurrent spontaneous abortion.
INTRODUCTION
Studies have shown that EMT (epithelial-mesenchymal transition) and energy metabolism influence each other, and it is unclear whether the trophoblast energy metabolism phenotype is dominated by glycolysis or mitochondrial respiration, and the relationship between trophoblast energy metabolism and EMT is still unclear.
METHODS
Exosomes were isolated from the DSC of URSA patients and their miRNA profile was characterized by miRNA sequencing. Wound healing assays and transwell assays were used to assess the invasion and migration ability of trophoblasts. Mitochondrial stress and glycolysis stress test were used to evaluate energy metabolism phenotype of trophoblast. Luciferase reporter assays, qRT-PCR and WB were conducted to uncover the underlying mechanism. Finally, animal experiments were employed to explore the effect of DSC-exos on embryo absorption in mice.
RESULTS
Our results showed that URSA-DSC-exos suppressed trophoblast EMT to reduce their migration and invasion, miR-22-5p_R-1 was the most upregulated miRNAs. URSA-DSC-exos can suppress trophoblast MGS (metabolic switch from mitochondrial respiration to glycolysis) and inhibit trophoblast migration and invasion by transferring miR-22-5p_R-1. Mechanistically, miR-22-5p_R-1 suppress trophoblast MGS and inhibit trophoblast EMT by directly suppressing PDK4 expression at the post-transcriptional level. Furthermore, in vivo experiment suggested that URSA-DSC-exos aggravated embryo absorption in mice. Clinically, PDK4 and EMT molecule were aberrant in villous of URSA patients, and negative correlations were found between miR-22-5p_R-1 and PDK4.
DISCUSSION
Our findings indicated that URSA-DSC-exos induced MGS obstacle playing an important role in intercellular communication between trophoblast and DSC, illuminating a novel mechanism in DSC regulation of trophoblasts and their role in URSA.
Topics: Female; MicroRNAs; Trophoblasts; Humans; Glycolysis; Pregnancy; Exosomes; Animals; Mice; Mitochondria; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; Abortion, Habitual; Epithelial-Mesenchymal Transition; Adult; Decidua
PubMed: 38810540
DOI: 10.1016/j.placenta.2024.05.131 -
Molecular and Cellular Endocrinology Sep 2024Adequate extravillous trophoblast (EVT) invasion into the maternal decidua is important for human placental development. We identified that E2F transcription factor 8...
Adequate extravillous trophoblast (EVT) invasion into the maternal decidua is important for human placental development. We identified that E2F transcription factor 8 (E2F8) suppresses EVT invasion, and that tight junction protein-1 (TJP1) is a potential downstream target gene of E2F8. We investigated the role of TJP1 in the human placenta and regulation of TJP1 expression by E2F8. TJP1 expression decreased in E2F8 knockdown HTR-8/SVneo cells. TJP1 and E2F8 were co-expressed in villi in the first-trimester placenta and in EVTs and villi in the third-trimester placenta. TJP1 was significantly increased in the pre-eclamptic compared with control placenta. TJP1 knockdown increased the invasion of HTR-8/SVneo cells, while TJP1 overexpression inhibited cell invasion. Halo-E2F8 overexpression significantly increased TJP1 expression and TJP1 transcription compared with control placenta. Our findings suggest that E2F8 promotes TJP1 transcription, and that TJP1 expression by E2F8 inhibits EVT invasion. TJP1 and E2F8 may be related to pre-eclampsia pathogenesis.
Topics: Adult; Female; Humans; Pregnancy; Cell Line; Cell Movement; Gene Knockdown Techniques; Placenta; Pre-Eclampsia; Trophoblasts; Zonula Occludens-1 Protein; Repressor Proteins
PubMed: 38795825
DOI: 10.1016/j.mce.2024.112277 -
Cellular and Molecular Life Sciences :... May 2024Ovarian endometriosis is a common gynecological disease, and one of its most significant symptoms is infertility. In patients with endometriosis, defects in endometrial...
Ovarian endometriosis is a common gynecological disease, and one of its most significant symptoms is infertility. In patients with endometriosis, defects in endometrial decidualization lead to impaired endometrial receptivity and embryo implantation, thus affecting early pregnancy and women's desire to have children. However, the mechanisms underlying the development of endometriosis and its associated defective decidualization are unclear. We find that NEK2 expression is increased in the ectopic and eutopic endometrium of patients with endometriosis. Meanwhile, NEK2 interacts with FOXO1 and phosphorylates FOXO1 at Ser184, inhibiting the stability of the FOXO1 protein. Importantly, NEK2-mediated phosphorylation of FOXO1 at Ser184 promotes cell proliferation, migration, invasion and impairs decidualization. Furthermore, INH1, an inhibitor of NEK2, inhibits the growth of ectopic lesions in mouse models of endometriosis and promotes endometrial decidualization in mouse models of artificially induced decidualization. Taken together, these findings indicate that NEK2 regulates the development of endometriosis and associated disorders of decidualization through the phosphorylation of FOXO1, providing a new therapeutic target for its treatment.
Topics: Female; Endometriosis; Forkhead Box Protein O1; Humans; Animals; Phosphorylation; Mice; NIMA-Related Kinases; Endometrium; Cell Proliferation; Cell Movement; Decidua; Adult; Disease Models, Animal
PubMed: 38795132
DOI: 10.1007/s00018-024-05270-8 -
International Journal of Molecular... May 2024This Special Issue comprises original articles in the field of clinical studies whose major topics concern the genetic and immunological aspects of miscarriage and...
This Special Issue comprises original articles in the field of clinical studies whose major topics concern the genetic and immunological aspects of miscarriage and pre-eclampsia, the isolation of decidua macrophages and Hofbauer cells in the placenta for diagnostic purposes, and epigenetic mechanisms that trigger labor [...].
Topics: Humans; Pregnancy; Female; Placenta; Abortion, Spontaneous; Reproduction; Pre-Eclampsia; Macrophages; Decidua
PubMed: 38791171
DOI: 10.3390/ijms25105132