Methylation alterations of imprinted genes in different placental diseases.

Background: Imprinted genes play important functions in placentation and pregnancy; however, research on their roles in different placental diseases is limited. It is believed that epigenetic alterations, such as DNA methylation, of placental imprinting genes may contribute to the different pathological features of severe placental diseases, such as pre-eclampsia (PE) and placenta accreta spectrum disorders (PAS).

Results: In this study, we conducted a comparative analysis of the methylation and expression of placental imprinted genes between PE and PAS using bisulfite sequencing polymerase chain reaction (PCR) and quantitative PCR, respectively.

Prediction of preeclampsia using maternal circulating mRNAs in early pregnancy.

Purpose: Preeclampsia (PE) is one of the most common and serious complications of pregnancy, and novel methods for the early prediction of PE are needed for clinical application.

Methods: In this study, a circulating cell-free RNA (cfRNA) panel of target genes for PE prediction was designed and validated in a case-control cohort and a nested case-control cohort. The QPCR was applied to quantify the copy number of cfRNA, and the data were normalized as multiples of the median.

α-mangostin derivatives ameliorated mouse DSS-induced chronic colitis via regulating Th17/Treg balance.

Th17 cell, an important subpopulation of helper T cell, plays an important role in the development of inflammatory bowel disease (IBD) and is thought to be a potential target for the treatment of IBD. In our previous study, we demonstrated that α-mangostin could relieve lupus nephritis via inhibiting Th17 cell function. In our preliminary study, we obtained four derivatives by adding chemical modification of α-mangostin which could also inhibit Th17 cell differentiation in vitro.

Screening of placenta accreta spectrum disorder using maternal serum biomarkers and clinical indicators: a case-control study.

Background: Placenta accreta spectrum (PAS) disorder is a major cause of postpartum hemorrhage-associated maternal and fetal death, and novel methods for PAS screening are urgently needed for clinical application.

Methods: The purpose of this study was to develop new methods for PAS screening using serum biomarkers and clinical indicators. A total of 95 PAS cases and 137 controls were enrolled in a case-control study as cohort one, and 44 PAS cases and 35 controls in a prospective nested case-control study were enrolled as cohort two.

Delivery of CD47 blocker SIRPα-Fc by CAR-T cells enhances antitumor efficacy.

Background: Chimeric antigen receptor (CAR) T cell therapy has been successfully applied in treating lymphoma malignancies, but not in solid tumors. CD47 is highly expressed on tumor cells and its overexpression is believed to inhibit phagocytosis by macrophages and dendritic cells. Given the antitumor activity against preclinical model of CD47-blocking to induce the innate and adaptive immune system in the tumor microenvironment, here we developed a CAR-T cell secreting CD47 blocker signal regulatory protein α (SIRPα)-Fc fusion protein (Sirf CAR-T) to boost CAR-T cell therapeutic effect in solid tumor therapy.

Uterine damage induces placenta accreta and immune imbalance at the maternal-fetal interface in the mouse.

Introduction: Placenta accreta spectrum (PAS) disorder is one of the major complications resulting in maternal death and serious adverse pregnancy outcomes. Uterine damage - principally that associated with cesarean section - is the leading risk factor for the development of PAS. However, the underlying pathogenesis of PAS related to uterine damage remains unclear.

Effects of paternal exposure to cigarette smoke on sperm DNA methylation and long-term metabolic syndrome in offspring.

Background: Although paternal exposure to cigarette smoke may contribute to obesity and metabolic syndrome in offspring, the underlying mechanisms remain uncertain.

Methods: In the present study, we analyzed the sperm DNA-methylation profiles in tobacco-smoking normozoospermic (SN) men, non-tobacco-smoking normozoospermic (N) men, and non-smoking oligoasthenozoospermic (OA) men. Using a mouse model, we also analyzed global methylation and differentially methylated regions (DMRs) of the DLK1 gene in paternal spermatozoa and the livers of progeny.

5,6,7,8-Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine derivative attenuates lupus nephritis with less effect to thymocyte development.

Retinoic‑acid‑receptor‑related orphan nuclear hormone receptor gamma t (RORγt), a critical transcriptional factor of Th17 cells, is a potential therapeutic target for Th17-mediated autoimmune diseases. In addition, RORγt is essential for thymocyte survival and lymph node development, and RORγt inhibition or deficiency causes abnormal thymocyte development, thymus lymphoma, and lymph node defect. Recent study demonstrated that specific regulation of Th17 differentiation related to the hinge region of RORγt.

Declined miR-181a-5p expression is associated with impaired natural killer cell development and function with aging.

MicroRNAs (miRNAs) regulate gene expression and thereby influence cell development and function. Numerous studies have shown the significant roles of miRNAs in regulating immune cells including natural killer (NK) cells. However, little is known about the role of miRNAs in NK cells with aging.

Pentacyclic triterpene compounds from loquat leaves reduce skin inflammation and epidermal hyperplasia in psoriasis via inhibiting the Th17 cells.

Psoriasis is a refractory inflammatory skin disease affecting 2 %-3 % of the world population, characterized by the infiltration and hyper-proliferation of inflammatory cells and aberrant differentiation of keratinocytes. Targeting the IL-23/ Th17 axis has been well recognized as a promising therapeutic strategy, as the IL-23/ Th17 signal plays a vital role in the pathology of psoriasis. Three pentacyclic triterpene compounds isolated from loquat leaves have been reported with significant inhibitory effects on RORγt transcription activity and Th17 cell differentiation, and excellent performance in preventing lupus nephritis pathogenesis.

Behavioral changes and brain epigenetic alterations induced by maternal deficiencies of B vitamins in a mouse model.

Rationale: B vitamins play essential roles in brain development and functionality; however, the effects of their deficiency during early life on mental health are not thoroughly understood.

Objectives: The objective of this study is to investigate the effects of a maternal deficiency of vitamin B6, B9 (folate), and B12 on behavioral changes in adult offspring.

Methods: Female C57BL/6 J mice were put on a diet lacking vitamin B6, B9, B12, or the above three vitamins from pregnancy to weaning.

CD27 enhances the killing effect of CAR T cells targeting trophoblast cell surface antigen 2 in the treatment of solid tumors.

Chimeric antigen receptor (CAR) T cell therapy, a type of adoptive cell therapy, has been successfully used when treating lymphoma malignancies, but not nearly as successful in treating solid tumors. Trophoblast cell surface antigen 2 (Trop2) is expressed in various solid tumors and plays a role in tumor growth, invasion, and metastasis. In this study, a CAR targeting Trop2 (T2-CAR) was developed with different co-stimulatory intercellular domains.

Placental trophoblast syncytialization potentiates macropinocytosis via mTOR signaling to adapt to reduced amino acid supply.

During pregnancy, the appropriate allocation of nutrients between the mother and the fetus is dominated by maternal-fetal interactions, which is primarily governed by the placenta. The syncytiotrophoblast (STB) lining at the outer surface of the placental villi is directly bathed in maternal blood and controls feto-maternal exchange. The STB is the largest multinucleated cell type in the human body, and is formed through syncytialization of the mononucleated cytotrophoblast.

Serum miRNA biomarker discovery for placenta accreta spectrum.

Placenta accreta spectrum (PAS) disorder is a major cause of maternal and fetal morbidity, and in vitro biomarkers are highly desired in clinic. This study enrolled three phases of 186 pregnant women, including controls, PAS patients, placenta previa (PP) patients, and pre-eclamptic (PE) patients. Initial miRNA array screened 42 out of 768 serum miRNAs in the screening phase, and then validated four miRNAs by quantitative RT-PCR in the training phase and validation phase.

Prenatal and neonatal factors for the development of childhood visual impairment in primary and middle school students: a cross-sectional survey in Guangzhou, China.

Objectives: In this cross-sectional survey, we sought to determine the prevalence of and the influence of prenatal and neonatal factors on childhood visual impairment without correction (VIUC) in a paediatric population from Guangzhou, China.

Setting: The health survey covered 11 administrative districts in Guangzhou, including 991 schools.

Participants: All of the primary and middle school students in Guangzhou were invited to complete an online questionnaire with the help of their parents.

Pregnancy immune tolerance at the maternal-fetal interface.

Pregnancy is a natural process that poses an immunological challenge because non-self fetus must be accepted. During the pregnancy period, the fetus as 'allograft' inherits maternal and also paternal antigens. For successful and term pregnancy, the fetus is tolerated and nurtured enjoying immune privileges that minimize the risk of being rejected by maternal immune system.

NRF2 deficiency increases obesity susceptibility in a mouse menopausal model.

The risk of metabolic abnormalities in menopausal women increases significantly due to the decline in estrogen level. Nuclear factor E2-related factor 2 (NRF2) is an important oxidative stress sensor that plays regulatory role in energy metabolism. Therefore, an ovariectomized menopausal model in Nrf2-knockout (KO) mice was applied to evaluate the effect of Nrf2 deficiency on metabolism in menopausal females.

Chlorinated Polyfluoroalkylether Sulfonic Acids Exhibit Stronger Estrogenic Effects than Perfluorooctane Sulfonate by Activating Nuclear Estrogen Receptor Pathways.

Chlorinated polyfluoroalkylether sulfonic acids (Cl-PFESAs) have been shown to have potential thyroid hormone (TH) disruption effects. Here, we further investigated their estrogenic effects and underlying mechanisms. In vivo results revealed that exposure of zebrafish to Cl-PFESAs induced disorder of sex hormones during the early embryonic stages and caused histopathological lesions in the gonads of adult zebrafish relative to control groups.

Prenatal and neonatal factors involved in the development of childhood allergic diseases in Guangzhou primary and middle school students.

Background: Allergic diseases, such as asthma, dermatitis, rhinitis, and eczema, are highly prevalent in Chinese school children. Environmental factors, including air pollution and automobile exhaust, play an important role in the etiology of these diseases. However, prenatal and neonatal factors, such as gender, maternal diseases during pregnancy, and premature birth, may also be associated with allergic disease occurrence.

The Inhibitory Effects of Pentacyclic Triterpenes from Loquat Leaf against Th17 Differentiation.

Background: Loquat leaf is an herb that is commonly used in traditional Chinese medicine (TCM) for its anti-inflammatory properties. Numerous studies have demonstrated that Th17 cells play a fundamental role in mediating SLE pathological deterioration. In our study, we investigated the inhibitory effect of pentacyclic triterpenes from loquat leaf on T helper 17 (Th17) cells and the therapeutic efficacy of OA in Lupus nephritis (LN) development.

α-mangostin attenuates pristane-induced lupus nephritis by regulating Th17 differentiation.

Aim: α-mangostin, a polyphenolic xanthone derivative of mangosteen, has been reported to possess multiple therapeutic properties, such as anti-cancer, anti-allergy and anti-inflammatory activity. However, its anti-inflammatory effects in autoimmune diseases such as lupus nephritis (LN) remain unclear. In this study, we want to investigate the therapeutic effect of α-mangostin in LN.

Adolescent diabetes induced by multiple parental exposures to cigarette smoke condensate.

Parental exposure to cigarette smoke is closely related to the development of long-term metabolic diseases in the offspring. However, different exposure times at various developmental stages may cause these effects to vary. In this study, mice were exposed to cigarette smoke condensate (CSC) during the developmental time stages of paternal puberty or/and maternal pregnancy.

WITER: a powerful method for estimation of cancer-driver genes using a weighted iterative regression modelling background mutation counts.

Genomic identification of driver mutations and genes in cancer cells are critical for precision medicine. Due to difficulty in modelling distribution of background mutation counts, existing statistical methods are often underpowered to discriminate cancer-driver genes from passenger genes. Here we propose a novel statistical approach, weighted iterative zero-truncated negative-binomial regression (WITER, http://grass.

3-Acetyloxy-oleanolic Acid Attenuates Pristane-Induced Lupus Nephritis by Regulating Th17 Differentiation.

Th17 activity has been implicated in systemic lupus erythematosus (SLE), which is a systemic autoimmune disease with a typical clinical manifestation of lupus nephritis (LN). Retinoic acid receptor-related orphan receptor gamma t (RORt) has been shown to be important for Th17 differentiation. In this study, we evaluated the inhibition of RORt activity by 3-acetyloxy-oleanolic acid (AOA), a small molecule isolated from the root of , a traditional herb belonging to South China.

Influenza virus matrix protein M1 interacts with SLD5 to block host cell cycle.

Influenza virus matrix 1 protein (M1) is highly conserved and plays essential roles at many stages of virus life cycle. Here, we used a yeast two-hybrid system to identify the host protein SLD5, a component of the GINS complex, which is essential for the initiation of DNA replication in eukaryotic cells, as a new M1 interacting protein. M1 from several different influenza virus strains all interacted with SLD5.