Several immune and immunocompetent cells, including dendritic cells, macrophages, adipocytes, natural killer cells, T cells, and B cells, are significantly correlated with the complex discipline of oncology. Cytotoxic innate and adaptive immune cells can block tumor proliferation, and others can prevent the immune system from rejecting malignant cells and provide a favorable environment for tumor progression. These cells communicate with the microenvironment through cytokines, a chemical messenger, in an endocrine, paracrine, or autocrine manner. These cytokines play an important role in health and disease, particularly in host immune responses to infection and inflammation. They include chemokines, interleukins (ILs), adipokines, interferons, colony-stimulating factors (CSFs), and tumor necrosis factor (TNF), which are produced by a wide range of cells, including immune cells, such as macrophages, B-cells, T-cells, and mast cells, as well as endothelial cells, fibroblasts, a variety of stromal cells, and some cancer cells. Cytokines play a crucial role in cancer and cancer-related inflammation, with direct and indirect effects on tumor antagonistic or tumor promoting functions. They have been extensively researched as immunostimulatory mediators to promote the generation, migration and recruitment of immune cells that contribute to an effective antitumor immune response or pro-tumor microenvironment. Thus, in many cancers such as breast cancer, cytokines including leptin, IL-1B, IL-6, IL-8, IL-23, IL-17, and IL-10 stimulate while others including IL-2, IL-12, and IFN-γ, inhibit cancer proliferation and/or invasion and enhance the body’s anti-tumor defense. Indeed, the multifactorial functions of cytokines in tumorigenesis will advance our understanding of cytokine crosstalk pathways in the tumor microenvironment, such as JAK/STAT, PI3K, AKT, Rac, MAPK, NF-κB, JunB, cFos, and mTOR, which are involved in angiogenesis, cancer proliferation and metastasis. Accordingly, targeting and blocking tumor-promoting cytokines or activating and amplifying tumor-inhibiting cytokines are considered cancer-directed therapies. Here, we focus on the role of the inflammatory cytokine system in pro- and anti-tumor immune responses, discuss cytokine pathways involved in immune responses to cancer and some anti-cancer therapeutic applications.

Obesity and breast cancer are two major health issues that could be categorized as sincere threats to human health. In the last few decades, the relationship between obesity and cancer has been well established and extensively investigated. There is strong evidence that overweight and obesity increase the risk of postmenopausal breast cancer, and adipokines are the central players in this relationship. Produced and secreted predominantly by white adipose tissue, adiponectin is a bioactive molecule that exhibits numerous protective effects and is considered the guardian angel of adipokine. In the obesity–cancer relationship, more and more evidence shows that adiponectin may prevent and protect individuals from developing breast cancer. Recently, several updates have been published on the implication of adiponectin in regulating tumor development, progression, and metastases. In this review, we provide an updated overview of the metabolic signaling linking adiponectin and breast cancer in all its stages. On the other hand, we critically summarize all the available promising candidates that may reactivate these pathways mainly by targeting adiponectin receptors. These molecules could be synthetic small molecules or plant-based proteins. Interestingly, the advances in genomics have made it possible to create peptide sequences that could specifically replace human adiponectin, activate its receptor, and mimic its function. Thus, the obvious anti-cancer activity of adiponectin on breast cancer should be better exploited, and adiponectin must be regarded as a serious biomarker that should be targeted in order to confront this threatening disease.

Obesity, a recognized risk factor for breast cancer in postmenopausal women, is associated with higher mortality rates regardless of menopausal status, which could in part be explained by therapeutic escape. Indeed, adipose microenvironment has been described to influence the efficiency of chemo- and hormonal therapies. Residual cancer stem cells could also have a key role in this process. To understand the mechanisms involved in the reduced efficacy of hormonal therapy on breast cancer cells in the presence of adipose secretome, human adipose stem cells (hMAD cell line) differentiated into mature adipocytes were co-cultured with mammary breast cancer cells and treated with hormonal therapies (tamoxifen, fulvestrant). Proliferation and apoptosis were measured (fluorescence test, impedancemetry, cytometry) and the gene expression profile was evaluated. Cancer stem cells were isolated from mammospheres made from MCF-7. The impact of chemo- and hormonal therapies and leptin was evaluated in this population. hMAD-differentiated mature adipocytes and their secretions were able to increase mammary cancer cell proliferation and to suppress the antiproliferative effect of tamoxifen, confirming previous data and validating our model. Apoptosis and cell cycle did not seem to be involved in this process. The evaluation of gene expression profiles suggested that STAT3 could be a possible target. On the contrary, leptin did not seem to be involved. The study of isolated cancer stem cells revealed that their proliferation was stimulated in the presence of anticancer therapies (tamoxifen, fulvestrant, doxorubicine) and leptin. Our study confirmed the role of adipocytes and their secretome, but above all, the role of communication between adipose and cancer cells in interfering with the efficiency of hormonal therapy. Among the pathophysiological mechanisms involved, leptin does not seem to interfere with the estrogenic pathway but seems to promote the proliferation of cancer stem cells.

Filipendula ulmaria is a plant commonly used for the treatment of several pathologies, such as diarrhoea, ulcers, pain, stomach aches, fevers, and gout. Our study focused on the use of F. ulmaria for the treatment of gout disease. We first studied the chemical composition of a methanolic extract of the aerial parts and demonstrated its xanthine oxidase (XO) inhibitory activity. Then, we performed a fractionation and evaluated the most XO inhibitory active fractions by UV measurement. Purification of some fractions allowed the determination of the inhibitory activity of pure compounds. We demonstrated that spiraeoside, a glycosylated flavonoid, possesses an activity around 25 times higher than allopurinol, used as a reference in the treatment of gout disease. In order to easily and quickly identify potent inhibitors in complex matrix, we developed a complementary strategy based on an HPLC method and an Effect Directed Assay (EDA) method combining HPTLC and biochemical assays. The HPLC method, capable of determining compounds exhibiting interactions with the enzyme, could be an efficient strategy for evaluating potent enzyme inhibitors in a complex mixture. This strategy could be applied for quantitative assays using LC/MS experiments.

Background: Some Bupleurum species, such as the Bupleurum chinense DC. or the Bupleurum scorzonerifolium Willd have been extensively studied (especially their roots) for the treatment of inflammation. In contrast, only compounds extracted from the aerial parts of Bupleurum rotundifolium have been studied and showed anti-inflammatory or antiproliferative activities. This study was conducted to investigate the antioxidant, anti-inflammatory, and immunomodulatory effects of Bupleurum rotundifolium roots. Methods: To tackle the various aspects of inflammation, we studied in vitro a methanolic extract from the roots of Bupleurum rotundifolium on peripheral blood mononuclear cells (PBMCs), polymorphonuclear neutrophils (PMNs), and the monocytic cells THP-1. Its antioxidant capacities and iron-chelating activity were assessed. The extract was tested on THP-1 differentiation, reactive oxygen species (ROS) production by leukocytes, neutrophils chemotaxis, cytokines, PGE2 production, and NF-κB activation in PBMCs. Results: The extract showed a decreased ROS production in stimulated cells. It increased PBMC chemokine secretion and up-regulated the differentiation of THP-1 monocytes into macrophage-like cells, indicating a potential interest of the extract in the resolution of acute inflammation. In addition, the analysis of cytokine production suggests that Bupleurum rotundifolium has immunomodulatory properties. Conclusions: Cytokines secretion, especially IL-1β and IL-12p70, provided us with a set of indicators suggesting that the extract might be able to drive the polarization of macrophages and lymphocytes toward a Th2 anti-inflammatory profile in excessive inflammation.

Inflammation is a vital protective response to threats, but it can turn harmful if chronic and uncontrolled. Key elements involve pro-inflammatory cells and signaling pathways, including the secretion of pro-inflammatory cytokines, NF-κB, reactive oxygen species (ROS) production, and the activation of the NLRP3 inflammasome. Ampelopsis grossedentata, or vine tea, contains dihydromyricetin (DHM) and myricetin, which are known for their various health benefits, including anti-inflammatory properties. Therefore, the aim of this study is to assess the impact of an extract of A. grossedentata leaves (50 µg/mL) on inflammation factors such as inflammasome, pro-inflammatory pathways, and macrophage polarization, as well as its antioxidant properties, with a view to combating the development of low-grade inflammation. Ampelopsis grossedentata extract (APG) significantly decreased ROS production and the secretion of pro-inflammatory cytokines (IFNγ, IL-12, IL-2, and IL-17a) in human leukocytes. In addition, APG reduced LPS/IFNγ -induced M1-like macrophage polarization, resulting in a significant decrease in the expression of the pro-inflammatory cytokines TNF-α and IL-6, along with a decrease in the percentage of M1 macrophages and an increase in M0 macrophages. Simultaneously, a significant decrease in NF-κB p65 phosphorylation and in the expression of inflammasome genes (NLRP3, IL-1β and Caspase 1) was observed. The results suggest that Ampelopsis grossedentata could be a promising option for managing inflammation-related chronic diseases. Further research is needed to optimize dosage and administration methods.