Berberine attenuates epithelial mesenchymal transition in bleomycin-induced pulmonary fibrosis in mice via activating AR and mitigating the SDF-1/CXCR4 signaling.

Aims: Berberine is endowed with anti-oxidant, anti-inflammatory and anti-fibrotic effects. This study explored the role of adenosine A receptor (AR) activation and SDF-1/CXCR4 signaling suppression in the protective effects of berberine in bleomycin-induced pulmonary fibrosis in mice.

Main Methods: Pulmonary fibrosis was generated in mice by injecting bleomycin (40 U/kg, i.

Estradiol-17β upregulates pyruvate kinase M2 expression to coactivate estrogen receptor-α and to integrate metabolic reprogramming with the mitogenic response in endometrial cells.

Context: Proliferating cells reprogram their cellular glucose metabolism to meet the bioenergetic and biosynthetic demands and to maintain cellular redox homeostasis. Pyruvate kinase M (PKM) is a critical regulator of this metabolic reprogramming. However, whether estradiol-17β (E2) reprograms cellular metabolism to support proliferation of human primary endometrial stromal cells (hESCs) and the molecular basis of this reprogramming are not well understood.

2-Methoxyestradiol causes functional repression of transforming growth factor β3 signaling by ameliorating Smad and non-Smad signaling pathways in immortalized uterine fibroid cells.

Objective: To investigate the effects and the mechanism of action of 2-methoxyestradiol (2ME(2)) on transforming growth factor (TGF) β3-induced profibrotic response in immortalized human uterine fibroid smooth muscle (huLM) cells.

Design: Laboratory study.

Setting: University research laboratory.

Catechol-o-methyltransferase expression and 2-methoxyestradiol affect microtubule dynamics and modify steroid receptor signaling in leiomyoma cells.

Context: Development of optimal medicinal treatments of uterine leiomyomas represents a significant challenge. 2-Methoxyestradiol (2ME) is an endogenous estrogen metabolite formed by sequential action of CYP450s and catechol-O-methyltransferase (COMT). Our previous study demonstrated that 2ME is a potent antiproliferative, proapoptotic, antiangiogenic, and collagen synthesis inhibitor in human leiomyomas cells (huLM).

Effect of tumor necrosis factor-alpha on estrogen metabolism and endometrial cells: potential physiological and pathological relevance.

Context: Estrogen and its metabolites play a critical role in the pathophysiology of the endometrium. The bioavailability of estrogen and estrogen metabolites in endometrial tissues depends on the expression of enzymes involved in estrogen biosynthesis and metabolism. Substantial evidence indicates that estrogen-dependent endometrial disorders are also associated with proinflammatory milieu.