Effect of antithyroid antibodies on women with recurrent miscarriage: A meta-analysis.

PROBLEM: The effect of thyroid autoimmunity (TAI) on the prevalence of recurrent miscarriage (RM) is highly debatable. No meta-analysis has been published in the past decade to investigate the impact of TAI on women with RM. METHOD OF STUDY: Systemic literature search was conducted on PubMed, Embase, Cochrane, and Web of Science databases. English language literatures published between 1993 and 2019 were selected. We assessed the relationship between the prevalence of RM and thyroid peroxidase antibodies (TPO-Ab) or antithyroid antibodies (ATA) and evaluated the thyroid-stimulating hormone (TSH) level in TPO-Ab-positive women with RM. We also observed the treatment effect with levothyroxine (LT4) for RM. Review Manager 5.3 software was used to obtain the pooled odds ratios (OR). RESULTS: Analysis of 22 eligible studies revealed significant association between TPO-Ab and the prevalence of RM (OR = 1.85; 95% CI, 1.38 to 2.49; P < .001)(n ≥ 3), (OR = 1.82; 95% CI, 1.13 to 2.92; P = .01) (n ≥ 3). Women with ATA + had higher risk of RM (OR = 2.36; 95% CI, 1.71 to 3.25; P < .00001)(n ≥ 3), (OR = 2.34; 95% CI, 1.70 to 3.22; P < .00001)(n ≥ 2). RM women with TPO-Ab had higher TSH level when compared with those negative for TPO-Ab (random-effect SMD = 0.60; 95% CI, 0.31 to 0.90; P < .0001). We also found beneficial effects of LT4 supplementation on the outcome of live birth rate (LBR) among pregnant women with TPO-Ab (OR = 3.04; 95% CI, 0.69 to 13.36; P = .14). CONCLUSION: The presence of serum antithyroid antibodies does harms to women and can even lead to recurrent miscarriage; LT4 treatment may have beneficial to RM women.

Tumor-Associated Macrophages (TAMs): A Critical Activator In Ovarian Cancer Metastasis.

Tumor-associated macrophages (TAMs) that appear in every stage of cancer progression are usually tumor-promoting cells and are present abundantly in the tumor-associated microenvironment. In ovarian cancer, the overall and intratumoral M1/M2 ratio is a relatively efficient TAM parameter for predicting the prognosis of patients, especially for serous tissue type cancer. TAMs exhibit immunological checkpoint modulators, such as the B7 family and programmed death-ligand 1 (PD-L1), and play a key role in the development, metastasis and invasion of ovarian cancer, but the underlying mechanism is barely understood. Ovarian cancer is a severe gynecological malignancy with high mortality. Ovarian cancer-associated death can primarily be attributed to cancer metastasis. The majority of patients are diagnosed with wide dissemination in the peritoneum and omentum, limiting the effectiveness of surgery and chemotherapy. In addition, unlike other well-documented cancers, metastasis through vasculature is not a usual dissemination pathway in ovarian cancer. This review sheds light on TAMs and the main process and mechanism of ovarian cancer metastasis.

Intrauterine exposure to hyperglycemia retards the development of brown adipose tissue.

Brown adipose tissue (BAT) is an exclusive tissue of nonshivering thermogenesis. It is fueled by lipids and glucose and involved in energy and metabolic homeostasis. Intrauterine exposure to hyperglycemia during gestational diabetes mellitus may result in abnormal fetal development and metabolic phenotypes in adulthood. However, whether intrauterine hyperglycemia influences the development of BAT is unknown. In this study, mouse embryos were exposed to the intrauterine hyperglycemia environment by injecting streptozocin into pregnant mice at 1 d post coitum (dpc). The structure of BAT was examined by hematoxylin and eosin staining and immunohistochemical analysis. The glucose uptake in BAT was measured in vivo by [18F]-fluoro-2-deoxyglucose-micro-positron emission tomography. The gene expression in BAT was determined by real-time PCR, and the 5'-C-phosphate-G-3' site-specific methylation was quantitatively analyzed. Intrauterine hyperglycemia exposure resulted in the impaired structure of BAT and decreased glucose uptake function in BAT in adulthood. The expressions of the genes involved in thermogenesis and mitochondrial respiratory chain in BAT, such as Ucp1, Cox5b, and Elovl3, were down-regulated by intrauterine hyperglycemia exposure at 18.5 dpc and at 16 wk of age. Furthermore, higher methylation levels of Ucp1, Cox5b, and Elovl3 were found in offspring of mothers with streptozotocin-induced diabetes. Our results provide the evidence for enduring inhibitory effects of intrauterine hyperglycemia on BAT development in offspring. Intrauterine hyperglycemia is associated with increased DNA methylation of the BAT specific genes in offspring, which support an epigenetic involvement.-Yu, D.-Q., Lv, P.-P., Yan, Y.-S., Xu, G.-X., Sadhukhan, A., Dong, S., Shen, Y., Ren, J., Zhang, X.-Y., Feng, C., Huang, Y.-T., Tian, S., Zhou, Y., Cai, Y.-T., Ming, Z.-H., Ding, G.-L., Zhu, H., Sheng, J.-Z., Jin, M., Huang, H.-F. Intrauterine exposure to hyperglycemia retards the development of brown adipose tissue.

Role of Aspergillus fumigatus-Specific IgE in the Diagnosis of Allergic Bronchopulmonary Aspergillosis.

INTRODUCTION: Allergic bronchopulmonary aspergillosis (ABPA) has been regarded as a rare disease in China due to the lack of quantitative detection of Aspergillus fumigatus-specific IgE (sIgE). We compared the diagnostic rate of ABPA among asthma patients with or without A. fumigatus-sIgE screening tests to evaluate the benefit of the tests in diagnosing ABPA. METHODS: We reviewed the detection rate of A. fumigatus-sIgE and the diagnostic rate of ABPA in 1842 asthma patients in the First Affiliated Hospital of Zhejiang University from 2014 to 2016. Additionally, we collected 144 asthma cases from November 2016 to March 2017 to detect the total serum IgE, A. fumigatus-sIgE and sIgE against mixed mold extract, the ABPA diagnostic rate of these patients was then compared with the total cohort. Total serum IgE, A. fumigatus-sIgE and sIgE against mixed mold extract were also tested in 30 patients identified with Aspergillus-positive sputum culture to analyze the incidence of ABPA. RESULTS: Among the 1,842 asthma cases, 566 were inspected for total IgE; 308 (55.40%) were total IgE-positive and 58 (10.43%) had total IgE > 1,000 IU/mL. In contrast, only 126 cases were tested for A. fumigatus-sIgE (6.84%), and 28 had A. fumigatus-sIgE > 0.35 kUA/L (22.22%). Eleven patients were finally diagnosed with ABPA. Of 1,842 asthma patients, only 0.6% were diagnosed with ABPA if the A. fumigatus-sIgE was not detected at first. Moreover, among the 144 asthma cases that were selected for total IgE, A. fumigatus-sIgE, and sIgE against mixed mold extract screening tests, 12 had total IgE > 1,000 IU/mL (8.33%), 11 had A. fumigatus-sIgE > 0.35 kUA/L (7.64%), and 14 had sIgE against mixed mold extract > 0.35 (9.72%); 7 of these patients were confirmed as having ABPA according to the ISHAM guidelines (4.86%) but only 2 without A. fumigatus-sIgE screening test were diagnosed with ABPA (1.39%) (p = 0.000). Of the 30 Aspergillus-positive sputum culture cases, 4 had A. fumigatus-sIgE > 0.35 kUA/L (13.33%), but none was diagnosed with ABPA. CONCLUSIONS: Routine A. fumigatus-sIgE screening for asthma patients can significantly improve the diagnostic rate of ABPA.

LINC01088 inhibits tumorigenesis of ovarian epithelial cells by targeting miR-24-1-5p.

The roles of long non-coding RNAs (lncRNAs), a class of long non-protein-coding RNAs, in the tumorigenesis of ovarian epithelial cells remain unknown. In this study, we discovered that the expression of long intergenic non-coding RNA 1088 (LINC01088) was clearly reduced in benign epithelial ovarian tumor tissues compared to matched normal ovarian tissues. This was shown by global cDNA gene chip scanning and real-time qPCR, and validated in 42 clinical specimens. Furthermore, we found that LINC01088 inhibited the growth of ovarian cancer xenografts in nude mice. Correlation analysis between LINC01088 and mircoRNAs (miRNAs) conducted using primary clinical samples and RNA co-precipitation experiments revealed that miR-24-1-5p was one of the targets of LINC01088. Overexpression of miR-24-1-5p facilitated cell proliferation both in vitro and in vivo, however, LINC01088 could partially reverse the cell proliferation induced by miR-24-1-5p. Finally, we demonstrated that p21 activated kinase 4 (PAK4) was one of the downstream key targets of miR-24-1-5p by luciferase reporter assay and Western blotting; and our results showed a remarkable decrease in cell proliferation after overexpression of PAK4. We conclude that LINC01088 might function as a tumor suppressor, inhibiting the tumorigenesis of ovarian epithelial cells through LINC01088/ miR-24-1-5p/ PAK4 axis.

Structural basis for the specific recognition of dual receptors by the homopolymeric pH 6 antigen (Psa) fimbriae of Yersinia pestis.

The pH 6 antigen (Psa) of Yersinia pestis consists of fimbriae that bind to two receptors: ß1-linked galactosyl residues in glycosphingolipids and the phosphocholine group in phospholipids. Despite the ubiquitous presence of either moiety on the surface of many mammalian cells, Y. pestis appears to prefer interacting with certain types of human cells, such as macrophages and alveolar epithelial cells of the lung. The molecular mechanism of this apparent selectivity is not clear. Site-directed mutagenesis of the consensus choline-binding motif in the sequence of PsaA, the subunit of the Psa fimbrial homopolymer, identified residues that abolish galactosylceramide binding, phosphatidylcholine binding, or both. The crystal structure of PsaA in complex with both galactose and phosphocholine reveals separate receptor binding sites that share a common structural motif, thus suggesting a potential interaction between the two sites. Mutagenesis of this shared structural motif identified Tyr126, which is part of the choline-binding consensus sequence but is found in direct contact with the galactose in the structure of PsaA, important for both receptor binding. Thus, this structure depicts a fimbrial subunit that forms a polymeric adhesin with a unique arrangement of dual receptor binding sites. These findings move the field forward by providing insights into unique types of multiple receptor-ligand interactions and should steer research into the synthesis of dual receptor inhibitor molecules to slow down the rapid progression of plague.

Crystallization and preliminary X-ray diffraction analysis of PsaA, the adhesive pilin subunit that forms the pH 6 antigen on the surface of Yersinia pestis.

Yersinia pestis has been responsible for a number of high-mortality epidemics throughout human history. Like all other bacterial infections, the pathogenesis of Y. pestis begins with the attachment of bacteria to the surface of host cells. At least five surface proteins from Y. pestis have been shown to interact with host cells. Psa, the pH 6 antigen, is one of them and is deployed on the surface of bacteria as thin flexible fibrils that are the result of the polymerization of a single PsaA pilin subunit. Here, the crystallization of recombinant donor-strand complemented PsaA by the hanging-drop vapor-diffusion method is reported. X-ray diffraction data sets were collected to 1.9 Šresolution from a native crystal and to 1.5 Šresolution from a bromide-derivatized crystal. These crystals displayed the symmetry of the orthorhombic space group P222(1), with unit-cell parameters a = 26.3, b = 54.6, c = 102.1 Å. Initial phases were derived from single isomorphous replacement with anomalous scattering experiments, resulting in an electron-density map that showed a single molecule in the crystallographic asymmetric unit. Sequence assignment was aided by residues binding to bromide ions of the heavy-atom derivative.