Apigenin ameliorates imiquimod-induced psoriasis in C57BL/6J mice by inactivating STAT3 and NF-κB

Psoriasis is a chronic autoimmune disease featured by patches on the skin.It is caused by malfunction of immune cells and keratinocytes with inflammation as one of its key features.Apigenin(API)is a natural flavonoid with anti-inflammatory and immunoregulatory properties.Therefore,we speculated that API can ameliorate psoriasis,and determined its effect on the development of psoriasis by using imiquimod(IMQ)-induced psoriasis mouse model.Our results showed that API attenuated IMQ-induced phenotypic changes,such as erythema,scaling and epidermal thickening,and improved splenic hyperplasia.Abnormal differentiation of immune cells was restored in API-treated mice.Mechanistically,we revealed that API is a key regulator of signal transducer activator of transcription 3(STAT3).API regulated immune responses by reducing interleukin-23(IL-23)/STAT3/IL-17A axis.Moreover,it suppressed IMQ-caused cell hyperproliferation by inactivating STAT3 through regulation of extracellular signal-regulated kinase 1/2 and nuclear factor-κB(NF-κB)pathway.Furthermore,API reduced expression of inflammatory cytokines through inactivation of NF-κB.Taken together,our study demonstrates that API can ameliorate psoriasis and may be considered as a strategy for psoriasis treatment.

Expression of Key Steroidogenic Enzymes in Human Placenta and Associated Adverse Pregnancy Outcomes

Steroid hormones,including progestagens,estrogens,androgens,corticosteroids,and their precursor cholesterol,perform essential functions in the successful establishment and maintenance of pregnancy and normal fetal development.As the core endocrine organ at the prenatal stage,the human placenta is involved in the biosynthesis,metabolism,and delivery of steroid hormones.Steroidogenic pathways are tightly regulated by placenta-intrinsic cytochrome P450 and hydroxysteroid dehydrogenase.However,the relationship between placental steroidogenic enzyme expression and adverse pregnancy outcomes is controversial.In this review,we summarize the possible upstream regulatory mechanisms of placental steroidogenic enzymes in physiologic and pathophysiologic states.We also describe the human placental barrier model and examine the potential of single-cell sequencing for evaluating the primary functions and cellular origin of steroidogenic enzymes.Finally,we examine the existing evidence for the association between placental steroidogenic enzyme dysregulation and adverse pregnancy outcomes.

Mechanisms of Immune Tolerance and Inflammation via Gonadal Steroid Hormones in Preterm Birth

In 2019,preterm births(PTB)accounted for approximately 0.66 million deaths globally.PTB is also associated with a significantly higher risk of mortality and long-term complications for newborns.Long-term studies associated several factors,including disruption of immune tolerance and inflammation,with PTB.However,the pathogenesis of PTB remains unclear.Gonadal steroid hormones are critical for pregnancy maintenance and regulation of immune and inflammatory responses.However,it is not clear how unbalanced gonadal steroid hormones,such as imbalanced estrogen/androgen or estrogen/progesterone contribute to PTB.In this review,we discuss how gonadal steroid hormones mediate dysfunction in immune tolerance and inflammatory responses,which are known to promote the occurrence of PTB,and provide insight into PTB prediction.

Integrative analysis of DNA methylation and gene expression identified cervical cancer-specific diagnostic biomarkers

Cervical cancer is the leading cause of death among women with cancer worldwide.Here,we performed an integrative analysis of Illumina HumanMethylation450K and RNA-seq data from TCGA to identify cervical cancer-specific DNA methylation markers.We first identified differentially methylated and expressed genes and examined the correlation between DNA methylation and gene expression.The DNA methylation profiles of 12 types of cancers,including cervical cancer,were used to generate a candidate set,and machine-learning techniques were adopted to define the final cervical cancer-specific markers in the candidate set.Then,we assessed the protein levels of marker genes by immunohistochemistry by using tissue arrays containing 93 human cervical squamous cell carcinoma samples and cancer-adjacent normal tissues.Promoter methylation was negatively correlated with the local regulation of gene expression.In the distant regulation of gene expression,the methylation of hypermethylated genes was more likely to be negatively correlated with gene expression,while the methylation of hypomethylated genes was more likely to be positively correlated with gene expression.Moreover,we identified four cervical cancer-specific methylation markers,cg07211381(RAB3C),cg12205729(GABRA2),cg20708961(ZNF257),and cg26490054(SLC5A8),with 96.2%sensitivity and 95.2%specificity by using the tenfold cross-validation of TCGA data.The four markers could distinguish tumors from normal tissues with a 94.2,100,100,and 100%AUC in four independent validation sets from the GEO database.Overall,our study demonstrates the potential use of methylation markers in cervical cancer diagnosis and may boost the development of new epigenetic therapies.

Diagnostic Value of Magnetic Resonance Imaging in Fetal Lateral Ventriculomegaly and the Relationship Between the Degree of Isolated Lateral Ventriculomegaly and Neonatal Prognosis

Objective::To assess the value of magnetic resonance imaging(MRI)in fetal lateral ventriculomegaly diagnosed with ultrasound,and to study the relationship between the degree of isolated lateral ventriculomegaly and neonatal prognosis.Methods::The pregnancy information and outcomes of 97 cases of fetal ventriculomegaly were retrospectively reviewed in the Tianjin Central Hospital of Gynecology Obstetrics from January 2016 to December 2017.The maternal age was 18-42 years,and the fetal gestational age at diagnosis was 19+4 to 37+3 weeks.MRI and ultrasound were used to compared the diagnosis of fetal lateral ventriculomegaly and evaluated the development of the nervous system after birth.Results::Among 97 pregnancy cases,associated central nervous system malformations were observed in 36 cases on ultrasound or ultrasound+MRI.Central nervous system malformations were diagnosed with ultrasound in 15 cases(15/36,41.7%)and with ultrasound+MRI in 25 cases(25/36,69.4%).Pearsonχ2 test was used to compare the detection rates between the groups,and the difference was statistically significant(P<0.05).We followed up 61 cases of isolated lateral ventriculomegaly for 1-3 years after birth.According to the width of the lateral ventricle of the fetus in middle pregnancy,the subjects were grouped as follows:mild 33 cases(lateral ventricle width 10.0-12.0 mm),moderate 23 cases(lateral ventricle width 12.1-15.0 mm),and severe 5 cases(lateral ventricle width>15.0 mm).The rate of normal growth and development in the mild group was 90.9%(30/33),that in the moderate group was 69.6%(16/23),and that in the severe group was 40.0%(2/5),and the difference between groups was statistically significant(P<0.05).Conclusion::Ultrasound combined with MRI can detect more central nervous system malformations,and the degree of isolated lateral ventriculomegaly is closely related to fetal prognosis.

Use of antenatal corticosteroids among infants with gestational age at 24 to 31 weeks in 57 neonatal intensive care units of China: a cross-sectional study

Background:Antenatal corticosteroids(ACS)can significantly improve the outcomes of preterm infants.This study aimed to describe the ACS use rates among preterm infants admitted to Chinese neonatal intensive care units(NICU)and to explore perinatal factors associated with ACS use,using the largest contemporary cohort of very preterm infants in China.Methods:This cross-sectional study enrolled all infants born at 24^(+0)to 31^(+6)weeks and admitted to 57 NICUs of the Chinese Neonatal Network from January 1st,2019 to December 30th,2019.The ACS administration was defined as at least one dose of dexamethasone and betamethasone given before delivery.Multiple logistic regressions were applied to determine the association between perinatal factors and ACS usage.Results:A total of 7828 infants were enrolled,among which 6103(78.0%)infants received ACS.ACS use rates increased with increasing gestational age(GA),from 177/259(68.3%)at 24 to 25 weeks’gestation to 3120/3960(78.8%)at 30 to 31 weeks’gestation.Among infants exposed to ACS,2999 of 6103(49.1%)infants received a single complete course,and 33.4%(2039/6103)infants received a partial course.ACS use rates varied from 30.2%to 100%among different hospitals.Multivariate regression showed that increasing GA,born in hospital(inborn),increasing maternal age,maternal hypertension and premature rupture of membranes were associated with higher likelihood to receive ACS.Conclusions:The use rate of ACS remained low for infants at 24 to 31 weeks’gestation admitted to Chinese NICUs,with fewer infants receiving a complete course.The use rates varied significantly among different hospitals.Efforts are urgently needed to propose improvement measures and thus improve the usage of ACS.

Immunomodulatory hybrid micro-nanofiber scaffolds enhance vascular regeneration

The inertness of synthetic polymer materials and the insufficient mechanical strength of reprocessed decellu-larized extracellular matrix(dECM)limited their promotive efforts on tissue regeneration.Here,we prepared a hybrid scaffold composed of PCL microfibers and human placental extracellular matrix(pECM)nanofibers by co-electrospinning,which was grafted with heparin and further absorbed with IL-4.The hybrid scaffold with improved hemocompatibility firstly switched macrophages to anti-inflammatory phenotype(increased by 18.1%)and then promoted migration,NO production,tube formation of endothelial cells(ECs),and migration and maturation of vascular smooth muscle cells(VSMCs),and ECM deposition in vitro and in vivo.ECs coverage rate increased by 8.6%and the thickness of the smooth muscle layer was 1.8 times more than PCL grafts at 12 wks.Our study realized the complementary advantages of synthetic polymer materials and dECM materials,and opened intriguing perspectives for the design and construction of small-diameter vascular grafts(SDVGs)and immune-regulated materials for other tissue regeneration.

Intrauterine Treatment of Monochorionic Triamniotic Triplet Pregnancy with Twin Reverse Arterial Perfusion Sequence

To editor:This study reports a pregnant woman who was naturally conceived with monochorionic triamniotic(MCTA)combined with twin reversed arterial perfusion(TRAP).An ultrasound revealed that one of the fetuses had a cardiac malformation,and a connection between the umbilical arteries was suspected.To reduce the acardiac fetus,radiofrequency ablation was performed at 17+3 weeks of pregnancy.At 36+4 weeks,two healthy infants were delivered via elective cesarean section.Postoperative examination revealed a direct connection between the umbilical arteries,with the placental perfusion acting as a direct pump.It is essential to identify the intrauterine status of the blood-supplying infant and vascular connections in order to achieve successful outcomes in pregnancies with complications,such as edema and heart failure.The studies involving human participants were reviewed and approved by Human Research Ethics Committee of Tianjin Central Hospital of Obstetrics and Gynecology.The patient provided her written informed consent to participate in this study.