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.

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.

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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.

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. FASEB J. 33, 5425–5439 (2019). http://www.fasebj.org