ABSTRACT
Programmed cell death-1 (PD-1) and T-cell immunoglobulin mucin-3 (Tim-3) are important immune checkpoint receptors that prevent an overreacted maternal immune response to fetal antigens during pregnancy. Disruption of complex immune regulation mechanisms is associated with adverse pregnancy outcomes, including preeclampsia (PE). Our recent study showed that the Tim-3 pathway was involved in the regulation of decidual macrophage polarization. Decidual macrophages polarized to the M1 phenotype may impair uterine vessel remodeling during placentation, accounting for the occurrence of PE. Co-blockade of the PD-1/Tim-3 pathway was shown to successfully control tumor growth in preclinical cancer models. However, the effects of activating both PD-1 and Tim-3 pathways as a combined intervention strategy in PE are never reported. Herein, we observed the skew of decidual macrophage polarization toward the M1 phenotype in patients with PE and lipopolysaccharide (LPS)-induced PE-like rat model. Moreover, we found that the activation of PD-1/Tim-3 pathway by using PD-L1 and Gal-9 fusion proteins could alleviate the manifestation of the LPS-induced PE-like rats and protect their offspring. Compared with the single intervention, the combination of PD-L1and Gal-9 fusion proteins exhibited obvious advantages in the relief of PE-like symptoms, trophoblast invasion, and fetal vascular development, indicating a synergistic effect of the activated PD-1/Tim-3 pathway. The in vitro study also revealed that the combined intervention using PD-L1 and Gal-9 fusion proteins inhibited the LPS-induced M1 macrophage polarization via the synergic activation of the ERK/GSK3ß/ß-catenin signaling pathway. Together, our findings provide the first evidence that simultaneous activation of PD-1/Tim-3 signaling pathways may have an optimal protective effect and serve as a new potential target for PE intervention.
Subject(s)
Decidua/metabolism , MAP Kinase Signaling System , Macrophages/metabolism , Pre-Eclampsia/metabolism , Programmed Cell Death 1 Receptor/metabolism , Receptors, Cell Surface/metabolism , Animals , Decidua/pathology , Disease Models, Animal , Female , Humans , Lipopolysaccharides/toxicity , Pre-Eclampsia/chemically induced , Pre-Eclampsia/pathology , Pregnancy , Rats , Rats, Sprague-DawleyABSTRACT
Trophoblasts play critical roles in establishment and maintenance of a normal pregnancy. Their dysfunction in early pregnancy is closely related to pregnancy-related diseases, including recurrent pregnancy loss (RPL). Epigenetic modifications dynamically change during pregnancy; however, the role of the epigenetic modifier UHRF1 in trophoblast regulation remains unknown. This is the first study to show that UHRF1 expression was localized in the cytoplasm of cytotrophoblasts, syncytiotrophoblasts, and villi columns, and decreased in the villi of patients with RPL. The invasion and cell viability in a UHRF1 knockdown trophoblast cell line were significantly decreased. In addition, the mRNA expression profiles of Swan71 cells were partially altered by UHRF1 knockdown. The altered immune-related genes were screened out and the pro-inflammatory TH1-type chemokine/cytokines CXCL2 and IL-1ß were identified as the most promising targets of UHRF1 in the trophoblasts, which were significantly increased in the UHRF1 knockdown Swan71 cells, villi, and serum from patients with RPL. The macrophages treated with the supernatants of UHRF1 knockdown Swan71 cells were polarized to the M1 phenotype and secreted high levels of pro-inflammatory cytokines, which might be driven by the activated MyD88/NF-κB signaling pathway and mediated by the increased expression of CXCR2 and IL-1R1 (CXCL2 and IL-1ß receptors, respectively). In addition, the supernatants of UHRF1 knockdown Swan71 cells showed stronger chemotaxis to macrophages than those from the controls. Our findings highlight the previously unknown roles of UHRF1 as one of the key regulators on the trophoblasts and their cross-talk with local immune cells, and demonstrate a potential approach for RPL intervention.
Subject(s)
Abortion, Habitual , CCAAT-Enhancer-Binding Proteins , Trophoblasts , Ubiquitin-Protein Ligases , Abortion, Habitual/metabolism , CCAAT-Enhancer-Binding Proteins/genetics , CCAAT-Enhancer-Binding Proteins/metabolism , Cytokines/metabolism , Decidua/metabolism , Female , Humans , Macrophages/metabolism , Pregnancy , Trophoblasts/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolismABSTRACT
Autoimmune thyroiditis (AIT) is a common organ-specific autoimmune disease with a high incidence among women of childbearing age. Recent studies have reported that women with AIT are more susceptible to infertility, miscarriage and preterm birth. It has been investigated that abnormal changes in maternal immune system and maternal-fetal interface can dampen the immune tolerance between mother and fetus, which underlie the pathogenesis of adverse pregnancy outcomes. Hence, we summarize the immunological changes related to adverse reproductive outcomes in AIT and highlight the respective contributions of both humoral and cellular immune dysfunctions to pregnancy failures. Moreover, the direct impacts of AIT on maternal-fetal immune activation and biological influences to trophoblasts are discussed as well. All these associations require confirmation in larger studies, and the pathogenic mechanisms need to be better understood, which might provide useful information for clinical diagnosis and therapy of AIT.
Subject(s)
Abortion, Spontaneous/immunology , Infertility, Female/immunology , Maternal-Fetal Exchange/immunology , Premature Birth/immunology , Thyroiditis, Autoimmune/immunology , Antibodies , Female , Humans , Pregnancy , Thyroid Gland/immunologyABSTRACT
BACKGROUND: The objective of this prospective, multicentre, observational cohort study was to evaluate the association between admission hypothermia and neonatal outcomes in very low-birth weight (VLBW) infants in multiple neonatal intensive care units (NICUs) in China. METHODS: Since January 1, 2018, a neonatal homogeneous cooperative research platform-Shandong Neonatal Network (SNN) has been established. The platform collects clinical data in a prospective manner on preterm infants with birth weights (BWs) < 1500 g and gestational ages (GAs) < 34 weeks born in 28 NICUs in Shandong Province. These infants were divided into normothermia, mild or moderate/severe hypothermia groups according to the World Health Organization (WHO) classifications of hypothermia. Associations between outcomes and hypothermia were tested in a bivariate analysis, followed by a logistic regression analysis. RESULTS: A total of 1247 VLBW infants were included in this analysis, of which 1100 infants (88.2%) were included in the hypothermia group, 554 infants (44.4%) in the mild hypothermia group and 546 infants (43.8%) in the moderate/severe hypothermia group. Small for gestational age (SGA), caesarean section, a low Apgar score at 5 min and intubation in the delivery room (DR) were related to admission hypothermia (AH). Mortality was the lowest when their admission temperature was 36.5 ~ 37.5 °C, and after adjustment for maternal and infant characteristics, mortality was significantly associated with AH. Compared with infants with normothermia (36.5 ~ 37.5 °C), the adjusted ORs of all deaths increased to 4.148 (95% CI 1.505-11.437) and 1.806 (95% CI 0.651-5.009) for infants with moderate/severe hypothermia and mild hypothermia, respectively. AH was also associated with a high likelihood of respiratory distress syndrome (RDS), intraventricular haemorrhage (IVH), and late-onset neonatal sepsis (LOS). CONCLUSIONS: AH is still very high in VLBW infants in NICUs in China. SGA, caesarean section, a low Apgar score at 5 min and intubation in the DR were associated with increased odds of hypothermia. Moderate/severe hypothermia was associated with mortality and poor outcomes, such as RDS, IVH, LOS.
Subject(s)
Hypothermia , Cesarean Section , China/epidemiology , Female , Humans , Hypothermia/epidemiology , Hypothermia/etiology , Infant , Infant, Newborn , Infant, Premature , Infant, Very Low Birth Weight , Intensive Care Units, Neonatal , Pregnancy , Prospective StudiesABSTRACT
PURPOSE: To assess changes in visual field (VF) values after gene therapy for Leber's hereditary optic neuropathy (LHON). METHODS: VF recovery, VF indices, and mean deviation in injected and uninjected eyes, before and after gene therapy, were examined in 2 groups of patients according to disease duration (≤2 years and > 2 years). Nine patients with LHON were treated by monocular intravitreal injection of AAV2-ND4. Finally, 7 patients were considered for subsequent comparisons; the first and second eyes were treated separately. RESULTS: There were no significant differences in VF indices and mean deviation between injected and uninjected eyes (p = 0.910 and p = 0.929, respectively). However, there was a significant difference before and after injection (p = 0.016 and p = 0.015, respectively). There was no significant difference in VF improvement between patients with ≤2 years' disease duration and those with a longer disease duration. CONCLUSION: There was a statistically significant VF improvement after gene therapy. This suggests that monocular intravitreal injection of AAV2-ND4 can improve binocular VF values. This study also suggests that gene therapy can be effective in patients with a disease duration of > 2 years.
Subject(s)
Genetic Therapy , Optic Atrophy, Hereditary, Leber/therapy , Visual Fields/physiology , Adolescent , Adult , Analysis of Variance , Child , Female , Genetic Vectors/administration & dosage , Humans , Intravitreal Injections , Male , Middle Aged , Optic Atrophy, Hereditary, Leber/physiopathology , Visual Acuity/physiology , Young AdultABSTRACT
BACKGROUND: A number of studies have indicated that the conversion of clopidogrel to its active metabolite is reduced in patients who carry the CYP2C19 *2, *3, *4 or *5 loss-of-function allele, resulting in decreased response of platelet to clopidogrel treatment and worse cardiovascular outcome. The aim of this study was to develop a novel biosensor-based microarray to visually detect CYP2C19 polymorphisms. METHODS: The target DNA was amplified from regions flanking the respective alleles using 5'-biotinylated reverse primer, and plasmids were prepared for the respective alleles. High stringency reversed hybridization, horseradish peroxidase-labeled streptavidin reaction, and color development, with multiple washes in different steps, were carried out and the results were recorded with an optical camera. The gene chips were tested for specificity, detection limit, intra- and inter-batch variations using the constructed plasmids. Finally, 88 clinical samples were assayed with this microarray as well as direct sequencing. RESULTS: The results could be seen with the naked eye. Concordance tests indicated that for alleles *2, *3, *4, and *5, the κ values between this assay and plasmids all reached 1.000. The detection limit was 5×10² cells/mL. Concordance test between direct sequencing and the microarray assay using 88 clinical samples gave rise to the κ value of 0.983, and p<0.01, indicating very high concordance. CONCLUSIONS: This novel biosensor-based microarray assay can amplify the signal in situ so that it can be detected by simple instruments or even the naked eyes. It is promising for clinical application in hospital laboratories.
Subject(s)
Biosensing Techniques , Cytochrome P-450 CYP2C19/genetics , Oligonucleotide Array Sequence Analysis , Polymorphism, Genetic/genetics , Humans , Sensitivity and SpecificityABSTRACT
BACKGROUND: Cry1Ab has emerged as a bio-insecticide to control Spodoptera litura (Lepidoptera: Noctuidae). However, the sublethal effects of Cry1Ab on the physiological changes and molecular level of S. litura have not been well documented. Our aims in this study were to assess the sublethal effect of Cry1Ab on S. litura, including midgut and Malpighian tubules as targets. RESULTS: After sublethal Cry1Ab exposure, distinct histological alterations were mainly observed in the midgut. Furthermore, the results of comparative RNA sequencing and tandem mass tag-based proteomics showed that, in the midgut, most differential expression genes (DEGs) were up-regulated and significantly enriched in the serine protease activity pathway, and up-regulated differential expression proteins (DEPs) were mainly associated with the oxidative phosphorylation pathway, whereas the down-regulated involved in the ribosome pathways. In the Malpighian tubules, DEGs and DEPs were significantly enriched in the ribosome pathway. We proposed that ribosome may act as a universal target in energy metabolism with other pathways via the results of protein-protein interaction analysis. Further, by verification of the mRNA expression of some Cry protein receptor and detoxification genes after Cry1Ab treatment, it was suggested that the ribosomal proteins (RPs) possibly participate in influencing the Bt-resistance of S. litura larvae under sublethal Cry1Ab exposure. CONCLUSION: Under sublethal Cry1Ab exposure, the midgut of S. litura was damaged, and the proteotranscriptomic analysis elucidated that Cry1Ab disrupted the energy homeostasis of larvae. Furthermore, we emphasized the potential role of ribosomes in sublethal Cry1Ab exposure. © 2024 Society of Chemical Industry.
Subject(s)
Bacillus thuringiensis Toxins , Endotoxins , Hemolysin Proteins , Larva , Malpighian Tubules , Spodoptera , Animals , Spodoptera/drug effects , Spodoptera/genetics , Spodoptera/metabolism , Spodoptera/growth & development , Malpighian Tubules/drug effects , Malpighian Tubules/metabolism , Larva/drug effects , Larva/genetics , Larva/growth & development , Larva/metabolism , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Insect Proteins/metabolism , Insect Proteins/genetics , Transcriptome , Gastrointestinal Tract/drug effects , Gastrointestinal Tract/metabolism , Insecticides/toxicity , Proteome , Proteomics , Digestive System/drug effects , Digestive System/metabolismABSTRACT
Prostate cancer (PCa) is a common disease in elderly men, its incidence ranking the second among all malignancies in males in Western countries and increasing in China in the last decade. Tumor metastasis is the main cause of death of PCa patients. In the development and progression of tumor, the tumorous cells in the infiltration area interact with their microenvironment, undergo epithelial-mesenchymal transition (EMT) and consequently cause distant metastases. So to study the role of EMT in the development and progression of tumor is of great significance for the treatment of PCa. This article reviews the relevant literature of the last 3 years and gives an overview of the factors affecting EMT in prostate cancer, aiming at a therapeutic target.
Subject(s)
Epithelial-Mesenchymal Transition , Prostatic Neoplasms , Humans , MaleABSTRACT
Due to their crucial roles in embryo implantation, maternal-fetal tolerance induction, and pregnancy progression, immune checkpoint molecules (ICMs), such as programmed cell death-1, cytotoxic T-lymphocyte antigen 4, and T cell immunoglobulin mucin 3, are considered potential targets for clinical intervention in pregnancy complications. Despite the considerable progress on these molecules, our understanding of ICMs at the maternal-fetal interface is still limited. Identification of alternative and novel ICMs and the combination of multiple ICMs is urgently needed for deeply understanding the mechanism of maternal-fetal tolerance and to discover the causes of pregnancy complications. Leukocyte immunoglobulin-like receptor subfamily B (LILRB) is a novel class of ICMs with strong negative regulatory effects on the immune response. Recent studies have revealed that LILRB is enriched in decidual immune cells and stromal cells at the maternal-fetal interface, which can modulate the biological behavior of immune cells and promote immune tolerance. In this review, we introduce the structural features, expression profiles, ligands, and orthologs of LILRB. In addition, the potential mechanisms and functions mediated by LILRB for sustaining the maternal-fetal tolerance microenvironment, remodeling the uterine spiral artery, and induction of pregnancy immune memory are summarized. We have also provided new suggestions for further understanding the roles of LILRB and potential therapeutic strategies for pregnancy-related diseases.
Subject(s)
Immune Checkpoint Proteins , Pregnancy Complications , Female , Humans , Pregnancy , Embryo Implantation , Immune Tolerance , Immunoglobulins , Leukocytes , Maternal-Fetal Exchange , Leukocyte Immunoglobulin-like Receptor B1ABSTRACT
CD33 and MS4A6A genes play potential key roles in the pathogenesis of Alzheimer's disease (AD). One recent genome-wide association study has revealed that the rs3865444 polymorphism in the CD33 gene and rs610932 polymorphism in the MS4A6A gene are associated with susceptibility to AD in Caucasians. To evaluate the relationship between the polymorphism of the CD33, MS4A6A gene and AD in the ethnic Chinese Han, we conducted a case-control study (n = 383, age > 54) to determine the prevalence of single-nucleotide polymorphism of two genes in patients with AD in Chinese population of Mainland, and clarified whether these polymorphisms are risk factors for AD. The prevalence of the allele (T) in the rs3865444 polymorphism of the CD33 gene and allele (C) in rs610932 polymorphism of the MS4A6A gene was significantly different in AD patients and control subjects (P < 0.001, respectively), and the results were not influenced by age, gender, or APOE status. Our data revealed the allele (T) of the rs3865444 polymorphism of the CD33 gene and the allele (C) of the rs610932 polymorphism of the MS4A6A gene may contribute to AD risk in the Chinese Han population.
Subject(s)
Alzheimer Disease/ethnology , Alzheimer Disease/genetics , Antigens, CD/genetics , Antigens, Differentiation, Myelomonocytic/genetics , Asian People/genetics , Membrane Proteins/genetics , Aged , Case-Control Studies , China/epidemiology , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Male , Polymorphism, Single Nucleotide , Sequence Analysis, DNA , Sialic Acid Binding Ig-like Lectin 3ABSTRACT
Energy metabolism plays a crucial role in the immune system. In addition to providing vital energy for cell growth, reproduction and other cell activities, the metabolism of nutrients such as glucose and lipids also have significant effects on cell function through metabolites, metabolic enzymes, and changing metabolic status. Interleukin-10 (IL-10), as a pleiotropic regulator, can be secreted by a diverse set of cells and can also participate in regulating the functions of various cells, thereby playing an essential role in the formation and maintenance of immune tolerance in pregnancy. Studies on the regulatory effects and mechanisms of IL-10 on immune cells are extensive; however, research from a metabolic perspective is relatively negligible. Here, we have discussed old and new data on the relationship between IL-10 and metabolism. The data show that alterations in cellular metabolism and specific metabolites regulate IL-10 production of immune cells. Moreover, IL-10 regulates immune cell phenotypes and functions by modulating oxidative phosphorylation and glycolysis. This review summarizes some earlier observations regarding IL-10 and its relationship with immune cells in pregnancy, and also presents recent research on the link between IL-10 and metabolism, highlighting the potential relationship between IL-10, immune cells, and energy metabolism during pregnancy.
Subject(s)
Immune Tolerance , Interleukin-10 , Pregnancy , Female , Humans , Pregnancy/immunology , Interleukin-10/physiologyABSTRACT
Macrophages are highly diverse cells and represent the major antigen-presenting cell at the maternal-fetal interface. Except for protecting the embryo with half of the paternal antigens from attack by the maternal immune system, decidua macrophages also have a critical role in implantation, trophoblast invasion, spiral artery remodeling, angiogenesis, and pathogen clearance. The classically activated (M1) and alternatively activated (M2) macrophages are the simplified classifications of macrophages, often applied to differentiate decidual macrophages. Particular phenotypes and functions of macrophages corresponding to each phase of the menstrual cycle and pregnancy are critical for establishing and maintaining pregnancy. Aberrant dynamics of decidual macrophages are associated with multiple pregnancy complications, such as recurrent pregnancy loss, preeclampsia, and preterm birth. Although various factors are related to decidual macrophage polarization, including cytokines, growth factors, hormones, and transcription factors, the potential regulatory mechanisms underlying decidual macrophage polarization are still unclear. Therefore, a thorough understanding of macrophage function and regulatory mechanism during pregnancy is critical to clarify the pathogenesis of pregnancy complications. In this review, we first describe an overview of the origin, phenotype, and function of macrophages in the uterus. Secondly, we propose emerging concepts explaining how macrophage polarization and functions are regulated, including immunometabolism, epigenetics, immune checkpoint, and microorganisms. Finally, we review the potential relationship among these novel factors in regulating the function of the immune system.
Subject(s)
Pregnancy Complications , Premature Birth , Decidua , Female , Humans , Infant, Newborn , Macrophage Activation , Macrophages , Pregnancy , Premature Birth/metabolismABSTRACT
Lactic acid (LA) metabolism in the tumor microenvironment contributes to the establishment and maintenance of immune tolerance. This pathway is characterized in tumor associated macrophages. However, the role and pathway of LA metabolism at maternal-fetal interface during early pregnancy, especially in decidual macrophage differentiation, are still unclear. Herein, for the first time, we discovered that LA can trigger either M2 or M1 macrophage polarization via oxidative phosphorylation and glycolysis regulation under normoxia or hypoxia, respectively. Also, LA metabolism played a vital role in decidual macrophages-mediated recurrent pregnancy loss (RPL), through HIF-1α/SRC/LDHA pathway. Moreover, blockade of LA intake with AZD3965 (MCT-1 inhibitor) could rescue pregnancy in an abortion-prone mouse model, suggesting a potential therapeutic target in RPL. Collectively, the present study identifies the previously unknown functions of LA metabolism in the differentiation of decidual macrophages in early normal pregnancy and RPL, and provides a potential therapeutic strategy in RPL by manipulating decidual macrophages' functions through LA metabolic pathway.
Subject(s)
Abortion, Spontaneous/metabolism , Lactic Acid/metabolism , Macrophages/metabolism , Pregnancy/metabolism , Trophoblasts/metabolism , Adult , Animals , Cell Differentiation , Disease Models, Animal , Female , Humans , L-Lactate Dehydrogenase/metabolism , Male , Maternal-Fetal Exchange , Mice , Mice, Inbred BALB C , Mice, Inbred CBA , Mice, Inbred DBA , Signal Transduction , src-Family Kinases/metabolismABSTRACT
OBJECTIVE: To observe the effect of Zhulian needle insertion by slow twirling technique on the contents of hydrogen peroxide (H2O2) and malondialdehyde (MDA) and apoptosis rate in kidney tissue of aging model rats and explore the potential mechanism of such needling technique. METHODS: A total of 40 adult male SD rats were randomized into a blank control group, a model control group, a Zhulian needling technique group and a routine acupuncture group, 10 rats in each one. Except the blank control group, the sub-acute aging rat models were established by intraperitoneal injection with 10% D-galactose solution, 5 mL/kg in the rats of the other groups. In the Zhulian needling technique group and the routine acupuncture group, Zhulian needle insertion by slow twirling technique and the routine acupuncture technique were exerted at "Guanyuan" (CV 4) and "Zusanli" (ST 36) respectively. The needles were retained for 30 min, once a day, for 28 days totally. After intervention, the content of H2O2 in kidney tissue was detected by colorimetry, the content of MDA in kidney tissue was detected by thiobarbituric acid method and the apoptosis rate of kidney cells was detected by terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling. RESULTS: Compared with the blank control group, the contents of H2O2 and MDA in kidney tissue and kidney cell apoptosis rate were all increased in the model control group (P<0.05). Compared with the model control group, the contents of H2O2 and MDA in kidney tissue and kidney cell apoptosis rate were all reduced in the Zhulian needling technique group and the routine acupuncture group (P<0.05), and these indexes in the Zhulian needling technique group were all lower than the routine acupuncture group (P<0.05). CONCLUSION: Zhulian needle insertion by slow twirling technique delays aging probably by regulating peroxidation and apoptosis.
Subject(s)
Acupuncture Therapy , Needles , Acupuncture Points , Aging , Animals , Apoptosis , Hydrogen Peroxide , Kidney , Male , Rats , Rats, Sprague-DawleyABSTRACT
Alzheimer's disease (AD) is the main cause of dementia, and its pathogenesis is still not clear. Peptidyl arginine deiminases 4(PAD4) as one of the important members of PAD family, is the only protein with nuclear transfer function, it can regulate the expression of many proteins through citrullinating histone. PAD4 can also interact with many transcription factors, involved in regulating gene expression. PAD4 expression is closely related to the inflammatory factors secreted, cell autophagy, tumorigenesis and other neurodegenerative diseases. More importantly, PAD4 and its citrullinated protein were found in cortical and hippocampal neurons of AD patients. To study the expression and regulatory pathway of PAD4 in vivo and in vitro experiments on AD may be of helpful to elucidate the pathogenesis of AD. Meanwhile, detection of anti-citrullinated antibody will have potential value as novel biomarkers of AD.
Subject(s)
Alzheimer Disease , Citrullination , Humans , Hydrolases/genetics , Hydrolases/metabolism , Protein-Arginine Deiminase Type 4 , Protein-Arginine Deiminases/genetics , Protein-Arginine Deiminases/metabolismABSTRACT
INTRODUCTION: Maternal metabolism undergoes dynamic changes during pregnancy. A deviation from this physiological metabolic status might be involved in the pathogenesis of pregnancy complications, such as recurrent pregnancy loss (RPL). Decidua is an important uterine tissue, which provides immunological protection as well as nutritional support to the developing embryo during early pregnancy. Previous studies have shown that aberrant metabolism of the decidua is related to the etiology of RPL. However, the metabolic profile of the decidua in RPL has not yet been fully elucidated. METHODS: In the current study, decidual samples from RPL patients (n = 23) and normal pregnancy (NP) women (n = 30) were collected, and hydrophilic and hydrophobic metabolites were extracted and measured using a liquid chromatography electrospray ionization tandem mass spectrometry system. Besides, the mRNA expression of several critical enzymes involved in sphingolipid metabolism and glycerophospholipid metabolism was detected. RESULTS: The OSC-PLS-DA scores plot illustrates that metabolic differences are present in the decidual tissue of RPL patients compared with that of NP women. Combining multivariate analysis with univariate statistical analysis, a total of 62 metabolites related to RPL were selected, including carnitine, glycerophospholipids, sphingomyelin (SM), ceramide, organic acids and their derivatives, and amino acid metabolomics. KEGG analysis showed that abnormalities in multiple metabolic pathways occurred in RPL decidua, including vitamin digestion and absorption, tryptophan metabolism, citrate cycle, arginine biosynthesis, glycerophospholipid metabolism, sphingolipid metabolism, and sphingolipid signaling pathway. Increased SM synthase and decreased Phospholipase A2 Group IIE mRNA levels were detected in RPL compared with NP group. DISCUSSION: Disruption of decidual metabolism, especially glycerophospholipid metabolism and sphingolipid metabolism, might be involved in the occurrence of RPL.
Subject(s)
Abortion, Habitual/metabolism , Decidua/metabolism , Glycerophospholipids/metabolism , Metabolome , Sphingolipids/metabolism , Adult , Carnitine/analogs & derivatives , Carnitine/metabolism , Case-Control Studies , Female , Group II Phospholipases A2/metabolism , Humans , Lipidomics , Pregnancy , Transferases (Other Substituted Phosphate Groups)/metabolismABSTRACT
A successful pregnancy is a complex and unique process comprised of discrete events, including embryo implantation, placentation, and parturition. To maintain the balance between maternal-fetal immune tolerance and resistance to infections, the maternal immune system must have a high degree of stage-dependent plasticity throughout the period of pregnancy. Innate immunity is the frontline force for the establishment of early anti-infection and tolerance mechanisms in mammals. Belonging to the innate immune system, a subset of T cells called γδT cells (based on γδT cell receptors) are the main participants in immune surveillance and immune defense. Unlike traditional αßT cells, γδT cells are regarded as a bridge between innate immunity and acquired immunity. In this review, we summarize current knowledge on the functional plasticity of γδT cells during pregnancy. Furthermore, we discuss the roles of γδT cells in pathological pregnancies.
Subject(s)
Adaptive Immunity , Histocompatibility, Maternal-Fetal , Immune Tolerance , Immunity, Innate , Intraepithelial Lymphocytes/immunology , Pregnancy Complications/immunology , Receptors, Antigen, T-Cell, gamma-delta/immunology , Animals , Female , Humans , Intraepithelial Lymphocytes/metabolism , Phenotype , Pregnancy , Pregnancy Complications/metabolism , Pregnancy Complications/physiopathology , Receptors, Antigen, T-Cell, gamma-delta/metabolism , Signal TransductionABSTRACT
We present a 28-year-old man with an early onset of recurrent respiratory papillomatosis at 1 year. The patient had undergone 31 operations over a period of 7 years. After the diagnosis of tracheal papillomatosis, he received a four-time treatment of T-tube insertion combined with laser fulguration. During the last operation, pathologic findings showed moderate dysplasia with malignancy potential. Conformal radiotherapy was then given at 5000 cGY, targeting the tracheal tumor bed. The patient experienced complete remission with no complications. His condition has lasted for 20 years, and has continued up through the time of this report.
Subject(s)
Laser Therapy , Neoplasm Recurrence, Local/radiotherapy , Neoplasm Recurrence, Local/surgery , Papilloma/radiotherapy , Papilloma/surgery , Tracheal Neoplasms/radiotherapy , Tracheal Neoplasms/surgery , Adult , Humans , Male , Radiotherapy, AdjuvantABSTRACT
The 2019 novel coronavirus disease (COVID-19) was first detected in December 2019 and became epidemic in Wuhan, Hubei Province, China. COVID-19 has been rapidly spreading out in China and all over the world. The virus causing COVID-19, SARS-CoV-2 has been known to be genetically similar to severe acute respiratory syndrome coronavirus (SARS-CoV) but distinct from it. Clinical manifestation of COVID-19 can be characterized by mild upper respiratory tract infection, lower respiratory tract infection involving non-life threatening pneumonia, and life-threatening pneumonia with acute respiratory distress syndrome. It affects all age groups, including newborns, to the elders. Particularly, pregnant women may be more susceptible to COVID-19 since pregnant women, in general, are vulnerable to respiratory infection. In pregnant women with COVID-19, there is no evidence for vertical transmission of the virus, but an increased prevalence of preterm deliveries has been noticed. The COVID-19 may alter immune responses at the maternal-fetal interface, and affect the well-being of mothers and infants. In this review, we focused on the reason why pregnant women are more susceptible to COVID-19 and the potential maternal and fetal complications from an immunological viewpoint.
Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/complications , Coronavirus Infections/immunology , Disease Susceptibility/immunology , Pneumonia, Viral/complications , Pneumonia, Viral/immunology , Pregnancy Complications, Infectious/immunology , COVID-19 , China , Coronavirus Infections/pathology , Female , Humans , Pandemics , Pneumonia, Viral/pathology , Pregnancy , Pregnancy Complications, Infectious/virology , Premature Birth/etiology , SARS-CoV-2ABSTRACT
PROBLEM: This study aims to determine the expression and localization of programmed cell death 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) in the testes of mice at different developmental stages. METHOD OF STUDY: By means of RT-qPCR, Western blot and immunofluorescence, the expression and localization of PD-1 and PD-L1 were detected in the testicular tissues of mice at different postnatal times: P7, P14, P21, P28, P35, and adulthood. Meanwhile, the level of soluble PD-L1 (sPD-L1) was evaluated by ELISA in the testicular interstitial fluid (IF) of the adult mice, culture supernatants of TM4 cell lines (Sertoli cells lines), and primary Sertoli cells at P14. RESULTS: Pd-1 mRNA levels were unexpectedly low. From P7 to P21, there was limited PD-1 protein detected while PD-1 was evident at P28 and afterward at significantly higher levels than at P14 and P21 (P < 0.05). Despite being found in the interstitial area at P7, P14, and P21, PD-1 was also detected in the germ cells of the seminiferous tubules after P28. Pd-l1 mRNA exhibited age-related changes, peaking at P21, while PD-L1 protein was constitutively expressed at any stage, specifically localized in the nucleus of Sertoli cells. Moreover, the level of sPD-L1 in IF was significantly higher than that in the culture supernatants of both TM4 and primary Sertoli cells at P14. CONCLUSIONS: PD-1 and PD-L1 were present in the testicular tissue of adult mice. The expression and localization of PD-1 fluctuated with age, and PD-1 was mainly localized to advanced germ cells, suggesting that it may play a role in spermiogenesis. PD-L1 was constitutively expressed in the nucleus of Sertoli cells, which could secrete sPD-L1 into the testicular interstitial space and thus may be involved in testicular immune privilege.