Jenningssalling6644

When tumor cells are killed by targeted therapy, radiotherapy, or chemotherapy, they trigger their primary tumor by releasing pro-inflammatory cytokines. Microenvironmental interactions can also promote tumor heterogeneity and development. In this line, several immune cells within the tumor microenvironment, including macrophages, dendritic cells, regulatory T-cells, and CD8+ and CD4+ T cells, are involved in the clearance of apoptotic tumor cells through a process called efferocytosis. Although the efficiency of apoptotic tumor cell efferocytosis is positive under physiological conditions, there are controversies regarding its usefulness in treatment-induced apoptotic tumor cells (ATCs). Efferocytosis can show the limitation of cytotoxic treatments, such as chemotherapy and radiotherapy. Since cytotoxic treatments lead to extensive cell mortality, efferocytosis, and macrophage polarization toward an M2 phenotype, the immune response may get involved in tumor recurrence and metastasis. Tumor cells can use the anti-inflammatory effect of apoptotic tumor cell efferocytosis to induce an immunosuppressive condition that is tumor-tolerant. Since M2 polarization and efferocytosis are tumor-promoting processes, the receptors on macrophages act as potential targets for cancer therapy. Moreover, researchers have shown that efferocytosis-related molecules/pathways are potential targets for cancer therapy. These include phosphatidylserine and calreticulin, Tyro3, Axl, and Mer tyrosine kinase (MerTK), receptors of tyrosine kinase, indoleamine-2,3-dioxygenase 1, annexin V, CD47, TGF-β, IL-10, and macrophage phenotype switch are combined with conventional therapy, which can be more effective in cancer treatment. Thus, we set out to investigate the advantages and disadvantages of efferocytosis in treatment-induced apoptotic tumor cells.Several terpenoids were isolated from Ganoderma colossum with potential chemotherapeutic properties against different solid tumor cells. Herein, we further assessed the potential chemomodulatory effects of colossolactone-G to gemcitabine (GCB) and 5-fluorouracil (5-FU) against colorectal cancer cells. Colossolactone-G induced moderate cell killing effects against both HT-29 and HCT-116 cells, with IC50's of 90.5 ± 1.7 µM and 22.3 ± 3.9 µM, respectively. Equitoxic combination demonstrated a synergistic effect between colossolactone-G and GCB, or 5-FU with combination indices ranging from 0.22 to 0.67. Both GCB and 5-FU induced moderate cell cycle arrest at G0/G1-phase and S-phase. Despite colossolactone-G's lack of influence on cell cycle distribution, it significantly potentiated GCB- and 5-FU-induced cell cycle arrest. Similarly, colossolactone-G treatment alone did not induce pronounced apoptosis in both cell lines. However, 5-FU and GCB induced significant apoptosis which was further potentiated via combination with colossolactone-G. Furthermore, colossolactone-G significantly increased autophagic cell death response in both HCT-116 and HT-29 cells and potentiated 5-FU- and GCB-induced autophagic cell death. The influence of colossolactone-G alone or in combination with GCB or 5-FU on the apoptosis and autophagy were confirmed by qPCR analysis for the expression of several key apoptosis and autophagy genes such as, TRAIL, TP53INP1, BNIP3, hp62, ATG5, ATG7, Lamp2A and the golden standard for autophagy (LC3-II). In conclusion, a synergistic effect in terms of anticancer properties was observed when colossolactone-G was combined with 5-FU and GCB, where it influenced both apoptosis and autophagic cell death mechanisms.The present article reviews and compares the immunomodulatory activities of Crocus sativus (C. sativus) and Nigella sativa (N. sativa) and their main bioactive compounds. Immunomodulatory effects of these plants, especially with respect to Th1 and Th2 cytokines, are discussed based on relevant articles, books, and conference papers published in English until the end of April 2020, that were retrieved from Web of Science, PubMed, Scopus and Google Scholar databases. C. Delanzomib sativus and its constituents increase immunoglobulin (Ig-)G, interleukin 2 (IL)-2, interferon gamma (IFN-γ), and IFN-γ/IL-4 ratio, but decreased IgM, IL-10 and IL-4 secretion. N. sativa extract and thymoquinone reduce the levels of IL-2, -4, -10, and -12, while enhance IFN-γ and serum IgG1 and 2a. The reviewed articles indicate that C. sativus and N. sativa and their constituents could be potentially considered promising treatments for disorders associated with immune-dysregulation such as asthma and cancer.The cytoskeleton is a supramolecular structure consisting of interacting protein networks that support cell dynamics in essential processes such as migration and division, as well as in responses to stress. Fast cytoskeletal remodeling is achieved with the participation of regulatory proteins and posttranslational modifications (PTMs). Redox-related PTMs are emerging as critical players in cytoskeletal regulation. Here we used a cellular model of mild nitroxidative stress in which a peroxynitrite donor induced transient changes in the organization of three key cytoskeletal proteins, i.e., vimentin, actin and tubulin. Nitroxidative stress-induced reconfiguration of intermediate filaments, microtubules and actin structures were further correlated with their PTM profiles and dynamics of the PTM landscape. Using high-resolution mass spectrometry, 62 different PTMs were identified and relatively quantified in vimentin, actin and tubulin, including 12 enzymatic, 13 oxidative and 2 nitric oxide-derived modifications as well as 35 modifications by carbonylated lipid peroxidation products, thus evidencing the occurrence of a chain reaction with formation of numerous reactive species and activation of multiple signaling pathways. Our results unveil the presence of certain modifications under basal conditions and their modulation in response to stress in a target-, residue- and reactive species-dependent manner. Thus, some modifications accumulated during the experiment whereas others varied transiently. Moreover, we identified protein PTM "hot spots", such as the single cysteine residue of vimentin, which was detected in seven modified forms, thus, supporting its role in PTM crosstalk and redox sensing. Finally, identification of novel PTMs in these proteins paves the way for unveiling new cytoskeleton regulatory mechanisms.