Targeting regulatory T cells by curcumin: A potential for cancer immunotherapy

Immune system has critical roles in fighting against several diseases like cancer. Cancer cells evolve several ways to escape from the immune system to remain alive and trigger new phases of cancer progression. Regulatory T cells are one of the key components in tumor immune tolerance and contribute to the evasion of cancer cells from the immune system. Targeting regulatory T cells could provide new horizons in designing and development of effective therapeutic platforms for the treatment of various malignancies. Curcumin is the bioactive pigment of turmeric and a well-known phytochemical with a wide range of pharmacological activities. A growing body of evidence has demonstrated that curcumin affects manifold molecular pathways that are implicated in tumorigenesis and cancer metastasis. In this regard, some studies have indicated that this phytochemical could target regulatory T cells and convert them into T helper 1 cells, which possess anti-tumor effects. On the contrary, curcumin is able to increase the number of regulatory T cells in other conditions such as inflammatory bowel disease. Herein, we describe the anti-cancer roles of curcumin via targeting regulatory T cells. Moreover, we summarize the effects of curcumin on regulatory T cell population in other diseases. © 2019 Elsevier Lt

Molecular Actuators in Action: Electron-Transfer-Induced Conformation Transformation in Cofacially Arrayed Polyfluorenes

There is much current interest in the design of molecular actuators, which undergo reversible, controlled motion in response to an external stimulus (light, heat, oxidation, etc.). Here we describe the design and synthesis of a series of cofacially arrayed polyfluorenes (MeFnHm) with varied end-capping groups, which undergo redox-controlled electromechanical actuation. Such cofacially arrayed polyfluorenes are a model molecular scaffold to investigate fundamental processes of charge and energy transfer across a π-stacked assembly, and we show with the aid of NMR and optical spectroscopies, X-ray crystallography and DFT calculations that in the neutral state the conformation of MeFnH1 and MeFnH2 is open rather than cofacial, with a conformational dependence that is highly influenced by the local environment. Upon (electro)chemical oxidation, these systems undergo a reversible transformation into a closed fully π-stacked conformation, driven by charge-resonance stabilization of the cationic charge. These findings are expected to aid the design of novel wire-like cofacially arrayed systems capable of undergo redox-controlled actuation

Mesenchymal stem cell-derived exosomes: A new therapeutic approach to osteoarthritis?

Degenerative disorders of joints, especially osteoarthritis (OA), result in persistent pain and disability and high costs to society. Nevertheless, the molecular mechanisms of OA have not yet been fully explained. OA is characterized by destruction of cartilage and loss of extracellular matrix (ECM). It is generally agreed that there is an association between pro-inflammatory cytokines and the development of OA. There is increased expression of matrix metalloproteinase (MMP) and "a disintegrin and metalloproteinase with thrombospondin motifs" (ADAMTS). Mesenchymal stem cells (MSCs) have been explored as a new treatment for OA during the last decade. It has been suggested that paracrine secretion of trophic factors, in which exosomes have a crucial role, contributes to the mechanism of MSC-based treatment of OA. The paracrine secretion of exosomes may play a role in the repair of joint tissue as well as MSC-based treatments for other disorders. Exosomes isolated from various stem cells may contribute to tissue regeneration in the heart, limbs, skin, and other tissues. Recent studies have indicated that exosomes (or similar particles) derived from MSCs may suppress OA development. Herein, for first time, we summarize the recent findings of studies on various exosomes derived from MSCs and their effectiveness in the treatment of OA. Moreover, we highlight the likely mechanisms of actions of exosomes in OA. © 2019 The Author(s)

The role of fibromodulin in cancer pathogenesis: Implications for diagnosis and therapy

Fibromodulin (FMOD) is known as one of very important extracellular matrix small leucine-rich proteoglycans. This small leucine-rich proteoglycan has critical roles in the extracellular matrix organization and necessary for repairing of tissue in many organs. Given that the major task of FMOD is the modulation of collagen fibrillogenesis. However, recently observed that FMOD plays very important roles in the modulation of a variety of pivotal biological processes including angiogenesis, regulation of TGF-β activity, and differentiation of human fibroblasts into pluripotent cells, inflammatory mechanisms, apoptosis and metastatic related phenotypes. Besides these roles, FMOD has been considered as a new tumor-related antigen in some malignancies such as lymphoma, leukemia, and leiomyoma. Taken together, these findings proposed that FMOD could be introduced as diagnostic and therapeutic biomarkers in treatment of various cancers. Herein, for first time, we highlighted the various roles of FMOD in the cancerous conditions. Moreover, we summarized the diagnostic and therapeutic applications of FMOD in cancer therapy. © 2019 The Author(s)

Investigation of correlation of the variations in land subsidence (detected by continuous GPS measurements) and methodological data in the surrounding areas of Lake Urmia

Lake Urmia, a salt lake in the north-west of Iran, plays a valuable role in the environment, wildlife and economy of Iran and the region, but now faces great challenges for survival. The Lake is in immediate and great danger and is rapidly going to become barren desert. As a result, the increasing demands upon groundwater resources due to expanding metropolitan and agricultural areas are a serious challenge in the surrounding regions of Lake Urmia. The continuous GPS measurements around the lake illustrate significant subsidence rate between 2005 and 2009. The objective of this study was to detect and specify the non-linear correlation of land subsidence and temperature activities in the region from 2005 to 2009. For this purpose, the cross wavelet transform (XWT) was carried out between the two types of time series, namely vertical components of GPS measurements and daily temperature time series. The significant common patterns are illustrated in the high period bands from 180–218 days band (~6–7 months) from September 2007 to February 2009. Consequently, the satellite altimetry data confirmed that the maximum rate of linear trend of water variation in the lake from 2005 to 2009, is associated with time interval from September 2007 to February 2009. This event was detected by XWT as a critical interval to be holding the strong correlation between the land subsidence phenomena and surface temperature. Eventually the analysis can be used for modeling and prediction purposes and probably stave off the damage from subsidence phenomena

Curcumin: A new candidate for melanoma therapy?

Melanoma remains among the most lethal cancers and, in spite of great attempts that have been made to increase the life span of patients with metastatic disease, durable and complete remissions are rare. Plants and plant extracts have long been used to treat a variety of human conditions; however, in many cases, effective doses of herbal remedies are associated with serious adverse effects. Curcumin is a natural polyphenol that shows a variety of pharmacological activities including anti-cancer effects, and only minimal adverse effects have been reported for this phytochemical. The anti-cancer effects of curcumin are the result of its anti-angiogenic, pro-apoptotic and immunomodulatory properties. At the molecular and cellular level, curcumin can blunt epithelial-to-mesenchymal transition and affect many targets that are involved in melanoma initiation and progression (e.g., BCl2, MAPKS, p21 and some microRNAs). However, curcumin has a low oral bioavailability that may limit its maximal benefits. The emergence of tailored formulations of curcumin and new delivery systems such as nanoparticles, liposomes, micelles and phospholipid complexes has led to the enhancement of curcumin bioavailability. Although in vitro and in vivo studies have demonstrated that curcumin and its analogues can be used as novel therapeutic agents in melanoma, curcumin has not yet been tested against melanoma in clinical practice. In this review, we summarized reported anti-melanoma effects of curcumin as well as studies on new curcumin formulations and delivery systems that show increased bioavailability. Such tailored delivery systems could pave the way for enhancement of the anti-melanoma effects of curcumin. © 2016 UIC