First Total Synthesis and Bioactivity Study of Dumortierinoside A and Concinnoside D: Two Representative D/E-Ring Simultaneously Functionalized Oleanane-Type Triterpene Saponins.

Efficient chemical synthesis of D/E-ring-functionalized oleanane-type saponins (DERFOS) is highly challenging in carbohydrate chemistry, but more challenging is the access to D/E-ring simultaneously functionalized oleanane-type saponins (DERSFOSs) by chemical synthesis. Based on the MCEPT glycosylation protocol, the DMNPA group for robust stereocontrol of glycosidic linkages, as well as Yu-modified Schonecker-Baran oxidation, the first total synthesis of dumortierinoside A and concinnoside D, the two representatives of DERSFOSs, was achieved from easily accessible feedstock. The longest linear sequences are 24 and 25 steps (counting from oleanolic acid), with the overall yields being 2.

Excess heme orchestrates progesterone resistance in uterine endometrial cancer through macrophage polarization and the IL-33/PAX8/PGR axis.

Progesterone is an important drug for hormone therapy in uterine endometrial cancer (UEC). However, the therapeutic efficacy of progestogen is often limited by resistance, and the underlying mechanism remains unknown. In this study, we observed heme metabolism is more active in progesterone-insensitive patients.

Functional identification of mango MiEXPLA1a2 and MiEXPA4e1 genes in transgenic Arabidopsis and tomato.

Expansin (EXP) is an intrinsic regulator of plant cell expansion, and have been shown to play a role in each stages of plant growth and development. But has not yet been fully studied in mango. In this experiment, two pairs of homologous genes MiEXPA1s and MiEXPA4s were firstly excavated from mango genome.

Transposition element MERVL regulates DNA demethylation through TET3 in oxidative-damaged mouse preimplantation embryos.

Transposable elements (TEs) comprise approximately half of eukaryotic genomes and significantly contribute to genome plasticity. In this study, we focused on a specific TE, MERVL, which exhibits particular expression during the 2-cell stage and commonly serves as an indicator of embryonic totipotency. However, its precise role in embryo development remains mysterious.

NK cells: shielding senescence homeostasis in the decidua during early pregnancy.

Decidualization, the transformation of endometrial stromal cells into specialized decidual cells, is essential for embryo implantation and pregnancy maintenance. This process involves immune cell infiltration, especially decidual natural killer (dNK) cells, which regulate immune responses and support tissue remodeling. Recent findings suggest that cellular senescence during decidualization is not just a byproduct but plays a functional role in enhancing uterine receptivity.

Creatine promotes endometriosis progression by inducing M2 polarization of peritoneal macrophages.

In Brief: Endometriosis (EM) is a chronic inflammatory disease with unclear pathogenesis, in which peritoneal macrophages play a pivotal role. This study demonstrates that creatine (CR) induces M2 polarization of peritoneal macrophages, promoting angiogenesis, fibrogenesis and lesion progression in EM, offering new insight into potential therapeutic strategies.

Abstract: EM is a chronic inflammatory disease characterized by the growth of endometrium-like tissues outside the uterine cavity, with an unclear pathogenesis.

Fatty Acid Metabolism Disruptions: A Subtle yet Critical Factor in Adverse Pregnancy Outcomes.

The establishment and maintenance of pregnancy encompass a series of complex and high-energy-consuming physiological processes, resulting in a significant energy demand. Fatty acids, one of the most essential nutrients, play a crucial role in energy supply via oxidation and perform critical biological functions such as anti-inflammatory and anti-oxidant effects, which substantially impact human health. Disordered fatty acid metabolism can cause anomalies in fetal growth and development, as well as a range of pregnancy problems, which can influence the health of both the mother and the fetus.

Emerging Roles of IL-27 in Trophoblast Cells and Pregnancy Complications.

Problem: Pregnancy complications such as spontaneous abortion, preeclampsia, and preterm birth persist, despite current interventions aimed at their prevention and treatment largely proving unsuccessful. Interleukin-27 (IL-27), composed of p28 and EBI3 subunits, binds to IL-27R, which consists of gp130 and IL-27Rα (also known as WSX-1 or TCCR), and plays a pivotal role in tumor development and inflammation regulation. At the maternal-fetal interface, IL-27 expression has been detected in trophoblasts, endometrial stromal cells, and decidual cells.

A Hypoxia-Decidual Macrophage Regulatory Axis in Normal Pregnancy and Spontaneous Miscarriage.

The significance of hypoxia at the maternal-fetal interface is proven to be self-explanatory in the context of pregnancy. During the first trimester, low oxygen conditions play a crucial role in processes such as angiogenesis, trophoblast invasion and differentiation, and immune regulation. Recently, there has been increasing research on decidual macrophages, which contribute to the maintenance of immune tolerance, placental and fetal vascular development, and spiral artery remodeling, to investigate the effects of hypoxia on their biological behaviors.

Active Heme Metabolism Suppresses Macrophage Phagocytosis via the TLR4/Type I IFN Signaling/CD36 in Uterine Endometrial Cancer.

Background: Uterine endometrial cancer (UEC) is a common gynecological estrogen-dependent carcinoma, usually accompanied by intermenstrual bleeding. Active heme metabolism frequently plays an increasingly important role in many diseases, especially in cancers. Tumor-associated macrophages (TAMs) are the major population in the immune microenvironment of UEC.

Impaired IL-27 signaling aggravates macrophage senescence and sensitizes premature ovarian insufficiency induction by high-fat diet.

Premature ovarian insufficiency (POI) critically affects female reproductive health, with obesity being a significant and recognized risk factor. Interleukin-27 (IL-27), known for its role in immune modulation and inflammation, has garnered attention in metabolic syndrome research. Nonetheless, the role of these immunometabolic factors on the initiation of POI remains to be unraveled.

Abnormal HCK/glutamine/autophagy axis promotes endometriosis development by impairing macrophage phagocytosis.

The presence of extensive infiltrated macrophages with impaired phagocytosis is widely recognised as a significant regulator for the development of endometriosis (EMs). Nevertheless, the metabolic characteristics and the fundamental mechanism of impaired macrophage phagocytosis are yet to be clarified. Here, we observe that there is the decreased expression of haematopoietic cellular kinase (HCK) in macrophage of peritoneal fluid from EMs patients, which might be attributed to high oestrogen and hypoxia condition.

Heme metabolism and HO-1 in the pathogenesis and potential intervention of endometriosis.

Endometriosis (EM) is one of the diseases related to retrograded menstruation and hemoglobin. Heme, released from hemoglobin, is degraded by heme oxygenase-1 (HO-1). In EM lesions, heme metabolites regulate processes such as inflammation, redox balance, autophagy, dysmenorrhea, malignancy, and invasion, where macrophages (Mø) play a fundamental role in their interactions.

Validation of mitochondrial biomarkers and immune dynamics in polycystic ovary syndrome.

Problem: Polycystic ovary syndrome (PCOS), a prevalent endocrine-metabolic disorder, presents considerable therapeutic challenges due to its complex and elusive pathophysiology.

Method Of Study: We employed three machine learning algorithms to identify potential biomarkers within a training dataset, comprising GSE138518, GSE155489, and GSE193123. The diagnostic accuracy of these biomarkers was rigorously evaluated using a validation dataset using area under the curve (AUC) metrics.

Accumulation of γδT cells in the decidua is promoted by RANKL which upregulates ICAM-1 via NF-κB.

In Brief: The mechanism underlying the accumulation of γδT cells in the decidua, which helps maintain maternal-fetal immunotolerance in early pregnancy, is unknown. This study reveals that DSC-derived RANKL upregulates ICAM-1 expression via the NF-κB pathway to enable γδT cell accumulation in the early decidua.

Abstract: Decidual γδT (dγδT) cells help maintain maternal-fetal immunotolerance in early pregnancy.

Chitosan alleviates ovarian aging by enhancing macrophage phagocyte-mediated tissue homeostasis.

Background: Age-related changes in the ovarian microenvironment are linked to impaired fertility in women. Macrophages play important roles in ovarian tissue homeostasis and immune surveillance. However, the impact of aging on ovarian macrophage function and ovarian homeostasis remains poorly understood.

Current advancements in diagnosing and managing cavovarus foot in paediatric patients.

The cavovarus deformity is a pathological condition characterised by an anomalous elevation of the longitudinal arch. This condition results from a significant hindfoot varus and forefoot equinus deformity. This phenomenon comprises diverse anomalies and therapies and exhibits a prevalence of 25% within the populace.

Novel Insights into Prokineticin 1 Role in Pregnancy-related Diseases.

Prokineticin 1 (PROK1) is a secreted protein involved in a range of physiological activities such as cell proliferation, migration, angiogenesis, and neuronal cell proliferation. Emerging evidences show that PROK1/PROK receptors (PROKRs) are expressed by trophoblasts, and decidual stroma cells at the maternal-fetal interface. PROK1 plays a critical role in successful pregnancy establishment by regulating the decidualization, implantation and placental development.

Recent Advances in Folates and Autoantibodies against Folate Receptors in Early Pregnancy and Miscarriage.

Though firstly identified in cerebral folate deficiency, autoantibodies against folate receptors (FRAbs) have been implicated in pregnancy complications such as miscarriage; however, the underlying mechanism needs to be further elaborated. FRAbs can be produced via sensitization mediated by folate-binding protein as well as gene mutation, aberrant modulation, or degradation of folate receptors (FRs). FRAbs may interfere with folate internalization and metabolism through blocking or binding with FRs.

The Relationship between Cadmium Exposure and Mortality in Postmenopausal Females: A Cohort Study of 2001-2018 NHANES.

Cadmium is one of the most harmful elements to human health, and the health of postmenopausal females is an important public health issue. However, the correlation between exposure to cadmium and the survival status of postmenopausal women is currently not fully clear. This research intended to explore the correlation between cadmium exposure and mortality among postmenopausal females using a representative sample of the population in the U.

Association of serum 25-hydroxyvitamin D levels with all-cause and cause-specific mortality among postmenopausal females: results from NHANES.

Background: Vitamin D deficiency is common among the population, but its relationship with mortality of postmenopausal females is unclear. The aim of this study is to explore the association between serum 25-Hydroxyvitamin D (25(OH)D) and all-cause and cause-specific mortality among postmenopausal women in the United States.

Methods: 6812 participants of postmenopausal females from the National Health and Nutrition Examination Survey (2001-2018) were included in this study.

An abnormal LPA/LPAR1-NHE1 axis leads to the autophagy deficiency of trophoblast cells in recurrent spontaneous abortion.

In Brief: Autophagy is important for trophoblast cells at the maternal-fetal interface during early pregnancy. This study suggests that trophoblast cells can promote the autophagy under a regulation of the LPA/LPAR 1-NHE1 axis.

Abstract: The autophagy of trophoblasts is necessary for developing and maintaining a healthy pregnancy.