Connexin 43 maintains tissue polarity and regulates mitotic spindle orientation in the breast epithelium.

Cell-cell communication is essential for tissue homeostasis, but its contribution to disease prevention remains to be understood. We demonstrate the involvement of connexin 43 (Cx43, also known as GJA1) and related gap junction in epithelial homeostasis, illustrated by polarity-mediated cell cycle entry and mitotic spindle orientation (MSO). Cx43 localization is restricted to the apicolateral membrane of phenotypically normal breast luminal epithelial cells in 3D culture and in vivo Chemically induced blockade of gap junction intercellular communication (GJIC), as well as the absence of Cx43, disrupt the apicolateral distribution of polarity determinant tight junction marker ZO-1 (also known as TJP1) and lead to random MSO and cell multilayering. Induced expression of Cx43 in cells that normally lack this protein reestablishes polarity and proper MSO in 3D culture. Cx43-directed MSO implicates PI3K-aPKC signaling, and Cx43 co-precipitates with signaling node proteins ß-catenin (CTNNB1) and ZO-2 (also known as TJP2) in the polarized epithelium. The distribution of Cx43 is altered by pro-inflammatory breast cancer risk factors such as leptin and high-fat diet, as shown in cell culture and on tissue biopsy sections. The control of polarity-mediated quiescence and MSO may contribute to the tumor-suppressive role of Cx43.

Anti-inflammatory bioactivities in plant extracts.

The medical ethnobotanical knowledge propagated over generations in the coastal regions of the Eastern Mediterranean, including Lebanon, is one that has built on several ancient cultures and civilizations of these regions. Recent interest in medical ethnobotany and the use of medicinal herbs in treating or preventing ailments has rejuvenated interest in folk medicine practices, especially those transcendent across generations. According to Eastern Mediterranean folk medicine practices, herbal remedies that treat many inflammation-related ailments were typically based on plant bioactive water extracts or decoctions. Studies have shown that active anti-inflammatory ingredients in water extracts include many natural chemicals such as phenols, alkaloids, glycosides, and carbohydrates. The intent of this manuscript is twofold: first, to review the literature that describes anti-inflammatory bioactivities in plant extracts of different plant genera; and second, to evaluate indigenous folk remedies used by folk doctors to treat inflammatory ailments in this region of the world. For this aim, the reported literature of five plant genera assumed to possess anti-inflammatory bioactivities and typically prescribed by folk doctors to treat inflammation-related ailments is reviewed.