Novel developments in the study of estrogen in the pathogenesis and therapeutic intervention of lymphangioleiomyomatosis.

OBJECTIVE: This study aimed to enhance the understanding of the role of estrogen in lymphangioleiomyomatosis(LAM) and to conclude the impact of estrogen-altering events on the condition and recent advances in estrogen-based treatments for LAM. RESULTS: LAM development is strongly linked to mutations in the tuberous sclerosis gene (TSC1/2) and the presence of estrogen. Estrogen plays a significant role in the spread of TSC2-deficient uterine leiomyoma cells to the lungs and the production of pulmonary LAM. Menstruation, pregnancy, estrogen medication, and other events that cause an increase in estrogen levels can trigger the disorder, leading to a sudden worsening of symptoms. Current findings do not support using estrogen-blocking therapy regimens. However, Faslodex, which is an estrogen receptor antagonist, presents new possibilities for future therapeutic approaches in LAM. CONCLUSION: Estrogen is crucial in the development and spread of LAM. The use of estrogen inhibitors or estrogen receptor antagonists alone does not provide good control of the disease or even poses a greater risk, and the use of a combination of mTOR receptor inhibitors, complete estrogen receptor antagonists, estrogen inhibitors, and autophagy inhibitors targeting important signaling pathways in LAM pathogenesis may be of greater benefit to the patient.

Identification of a novel immune-related long noncoding RNA in carp primary macrophages associated with bisphenol A' s immunoregulatory effects.

Increasing evidence suggests that long non-coding RNAs (lncRNAs) play pivotal roles in various biological processes. However, current studies on lncRNAs mostly focus on mammalian species, with little research on the functional roles of lncRNAs in teleost fish. Here, we identified a novel intergenic lncRNA (linc-93.2) in the head kidney primary macrophages of common carp (Cyprinus carpio) after exposure to a typical environmental endocrine disrupting chemical, bisphenol A (BPA). As a result, linc-93.2 was more than 3,619 bp in length and predominantly localized to the nucleus of primary macrophages other than cytoplasm, with the highest expression level in spleen followed by head kidney among different organs. Bioinformatic analysis predicted a cis-target gene, dennd1b, and 20 trans-target genes including hsp70, gna13 and rasgap, were potentially regulated by linc-93.2; NFκB and estrogen receptor (ERα) binding sites were located in the promoter region upstream of its transcription start site, which together suggested the involvement of linc-93.2 in immune and neurological functions in fish. Based on that, the expression level of linc-93.2 was determined in macrophages following acute lipopolysaccharide (LPS) and BPA treatments, both of which significantly induced linc-93.2 and IL-1ß expression in cells. Moreover, a NF-κB inhibitor PDTC significantly reduced linc-93.2 expression in macrophages, but co-exposure of macrophages to PDTC with BPA or LPS could significantly rescue linc-93.2 expression, consistent with the observation on that LPS or BPA alone significantly induced both linc-93.2 and its target gene expression. Interestingly, linc-93.2 and its target gene expression was significantly suppressed by an ER antagonist ICI 182,780, however, the co-exposure of macrophages to ICI 182,780 with BPA failed to attenuate their declined expression. Overall, the current study demonstrated that linc-93.2, a novel immune-related lncRNA, may participate in the immune processes of common carp macrophages via the NF-κB and ER pathway. The results presented in this study enhance our understanding of the immunotoxin mechanisms of BPA in teleost fish.

Shugan Liangxue Decoction () Down-Regulates Estrogen Receptor α Expression in Breast Cancer Cells.

OBJECTIVE: To observe the effect of Shugan Liangxue Decoction (, SGLXD) on estrogen receptor α (ERα) in human breast cancer cells. METHODS: The effect of SGLXD (0.85-5.10 mg/mL) on the proliferation of breast cancer cells were evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The nuclear ERα protein levels in MCF-7, T47D and ZR-75-1 cells which treated by SGLXD for 24 h were examined by western blot and immunofluorescence assay. MCF-7 and MDA-MB-231 cells were treated by 17ß-estradiol (E2) with or without SGLXD, for 24 h, and the E2 targeted genes c-myc and bcl-2 protein product was evaluated by western blot. RESULTS: SGLXD showed dose-dependent inhibition on the proliferation of MCF-7, T47D and ZR-75-1 cells, but did not inhibit the proliferation of MDA-MB-231 cells. Furthermore, the promotive effect on cell growth induced by E2 was also significantly inhibited by SGLXD treatment. With the treatment of 1.70, 3.40, 5.10 mg/mL SGLXD, the nuclear ERα protein level was reduced to 88.1%, 70.4% and 60.9% in MCF-7 cells, and was decreased to 43.0%, 38.4% and 5.9% in ZR-75-1 cells as compared with the control group. In T47D cells, the nuclear ERα protein was down-regulated to 51.3% and 4.3% by 3.40 and 5.10 mg/mL SGLXD treatment. The down-regulative effect of SGLXD on nuclear ERα was confirmed by immunofluorescence assay. SGLXD decreased the protein product of c-myc and bcl-2. CONCLUSIONS: SGLXD may exhibit selective inhibition effect on the proliferation of ER positive breast cancer cells. SGLXD reduced the nuclear ERα expression and the protein product of E2 target gene c-myc and bcl-2.