KLF6 contributes to myeloid cell plasticity in the pathogenesis of intestinal inflammation.

Inflammatory bowel disease (IBD) is associated with dysregulated macrophage responses, such that quiescent macrophages acquire a pro-inflammatory activation state and contribute to chronic intestinal inflammation. The transcriptional events governing macrophage activation and gene expression in the context of chronic inflammation such as IBD remain incompletely understood. Here, we identify Kruppel-like transcription factor-6 (KLF6) as a critical regulator of pathogenic myeloid cell activation in human and experimental IBD. We found that KLF6 was significantly upregulated in myeloid cells and intestinal tissue from IBD patients and experimental models of IBD, particularly in actively inflamed regions of the colon. Using complementary gain- and loss-of-function studies, we observed that KLF6 promotes pro-inflammatory gene expression through enhancement of nuclear factor κB (NFκB) signaling, while simultaneously suppressing anti-inflammatory gene expression through repression of signal transducer and activator of transcription 3 (STAT3) signaling. To study the in vivo role of myeloid KLF6, we treated myeloid-specific KLF6-knockout mice (Mac-KLF6-KO) with dextran sulfate sodium (DSS) and found that Mac-KLF6-KO mice were protected against chemically-induced colitis; this highlights the central role of myeloid KLF6 in promoting intestinal inflammation. Collectively, our results point to a novel gene regulatory program underlying pathogenic, pro-inflammatory macrophage activation in the setting of chronic intestinal inflammation.

Importance of office hysteroscopy screening to diagnose endometrial carcinoma in menopausal women.

Uterine cancer is today the upcoming neoplasia in gynaecological oncology. In Western countries endometrial cancer is mostly diagnosed after menopause and often becomes apparent with atypical uterine bleeding. Because of the great importance of such disease a series of accurate diagnostic analyses which require an adequate expenditure by hospital structures become necessary. Transvaginal sonography (TVS) remains the first choice to diagnose atypical bleeding because it is less invasive and highly bearable by the patients. TVS exam allows the selection of all patients who have an endometrial thickness more than 5 mm and/or with an inhomogeneous endometrial line thickness, who would then undergo further analyses. To achieve the diagnosis, office hysteroscopy carried out in an outpatient departments, is the most useful exam. Such exam allows a complete overview of the uterine cavity with possible detection of smaller lesions and a specific sampling of histological material. Hysteroscopy is today an indispensable aid in last resort diagnosis of endometrial cancer and is highly tolerated by patients.