A comprehensive review of chemokine CXC17 (VCC1) in cancer, infection, and inflammation.

A crucial component of the immune system are chemokiness. Chemokine's dysregulation has been linked to a number of pathological diseases. Recently, CXCL17, a chemokine belonging to the CXC subfamily, was identified. With regard to a number of physiological conditions and disorders, CXCL17 either has homeostatic or pathogenic effects. Some research suggests that CXCL17 is an orphan ligand, despite the fact that G protein-coupled receptor (GPR) 35 has been suggested as a possible receptor for CXCL17. Since CXCL17 is primarily secreted by mucosal epithelia, such as those in the digestive and respiratory tracts, under physiological circumstances, this chemokine is referred to as a mucosal chemokine. Macrophages and monocytes are the cells that express GPR35 and hence react to CXCL17. In homeostatic conditions, this chemokine has anti-inflammatory, antibacterial, and chemotactic properties. CXCL17 promotes angiogenesis, metastasis, and cell proliferation in pathologic circumstances like malignancies. However, other studies suggest that CXCL17 may have anti-tumor properties. Additionally, studies have shown that CXCL17 may have a role in conditions such as idiopathic pulmonary fibrosis, multiple sclerosis, asthma, and systemic sclerosis. Additionally, deregulation of CXCL17 in some diseases may serve as a biomarker for diagnosis and prognosis. Clarifying the underlying mechanism of CXCL17's activity in homeostatic and pathological situations may thus increase our understanding of its role and hold promise for the development of novel treatment strategies.

Designing new nanoliposomal formulations and evaluating their effects on myeloid-derived suppressor cells and regulatory T cells in a colon cancer model aiming to develop an efficient delivery system for cancer treatment; an in vitro and in vivo study.

Regulfatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) are common immunosuppressive cells in the tumor microenvironment. These cells, through various mechanisms, inhibit antitumor immune responses and impede effective therapies. Therefore, designing an efficient protocol for inducing immune surveillance in tumors is highly recommended. Recently, nanoliposomes have provided broad-spectrum and state-of-the-art vehicles to deliver antigens or immune system compartments in immunotherapies. It has been shown that different lipids in the structure of liposomes and various liposomal formulations can affect immune responses in the tumor microenvironment. This study was aimed to evaluate the effects of four different liposomal formulations on MDSCs and Tregs in C26 tumor-bearing mice. To this end, after preparing liposomes, they were injected into tumor-inoculated mice and analyzed MDSC and Treg population and functions in spleen and tumor tissues. Results showed that 1,2-dioleoyl-3-trimethylammonium propane (DOTAP)-containing liposomes reduced MDSC population and activity in the spleen, but not tumor, compared with other groups significantly (p < 0.05 and p < 0.01, respectively). Moreover, DOTAP-containing liposomes reduced the expression of S100A8 and arginase-1 genes in splenic MDSCs (p < 0.05). In conclusion, we provided evidence that DOTAP-containing liposomes contributed to stimulating immune responses and provided a situation to inhibit immunosuppression in the tumor microenvironment.

Interleukin-25: New perspective and state-of-the-art in cancer prognosis and treatment approaches.

Cancer is a leading cause of death which imposes a substantial financial burden. Among the several mechanisms involved in cancer progression, imbalance of immune cell-derived factors such as cytokines and chemokines plays a central role. IL-25, as a member of the IL-17 cytokine subfamily, exerts a paradoxical role in cancer, including tumor supportive and tumor suppressive. Hence, we have tried to clarify the role of IL-25 and its receptor in tumor progression and cancer prognosis. It has been confirmed that IL-25 exerts a tumor-suppressive role through inducing infiltration of eosinophils and B cells into the tumor microenvironment and activating the apoptotic pathways. In contrast, the tumor-supportive function has been implemented by activating inflammatory cascades, promoting cell cycle, and inducing type-2 immune responses. Since IL-25 has been dysregulated in tumor tissues and this dysregulation is involved in cancer development, its examination can be used as a tumor diagnostic and prognostic biomarker. Moreover, IL-25-based therapeutic approaches have shown promising results in cancer inhibition. In cancers in which IL-25 has a tumor-suppressive function, employing IL-25-enhancing approaches, such as Virulizin® and dihydrobenzofuran administration, has potentially inhibited tumor cell growth. On the other hand, in the case of IL-25-dependent tumor progression, using IL-25 blocking methods, including anti-IL-25 antibodies, might be a complementary approach to the other anticancer agent. Collectively, it is hoped, IL-25 might be a promising target in cancer treatment.

Topical application of curcumin regulates the angiogenesis in diabetic-impaired cutaneous wound.

Diabetic wound characterizes with a delayed repair as a result of the lack of neoangiogenesis and the excess of inflammation. Natural products such as curcumin have shown great promises in their regulatory potentials on inflammation and angiogenesis. However, natural agents have several shortages in their bioavailability and stability when used in vivo. In this study, we have evaluated the efficacy of a topical formulation of curcumin in the enhancement of diabetic wound repair. Streptozocin-induced diabetic mice were wounded, and cream of curcumin (1%) was applied topically to wounds twice daily for different treatment periods. Inflammation, neoangiogenesis, and re-epithelialization were evaluated in each experimental group. Wounds of animals treated with curcumin showed an enhanced neoangiogenesis. Application of topical curcumin also increased the expression level of RelA as the main subunit of the nuclear factor-κB (NF-κB) signalling pathway. However, no significant effects on macrophage polarization and re-epithelialization were observed in the curcumin-treated animals. Our study using a higher concentration of curcumin in the form of a topical cream further confirmed the efficacy of curcumin as an angiogenesis-promoting agent; however, it also conveyed uncertainty over the claimed regulatory effects of curcumin on inflammation. SIGNIFICANCE OF THE STUDY: Diabetes results in several complications such as impaired cutaneous wound repair. Excess of inflammation and lack of angiogenesis are among the main causes of delayed healing in diabetes. Curcumin is famous for its anti-inflammatory properties. However, when in the body curcumin has shown to have a limited benefit unless in high-dosage consumes. This is because of its poor absorption from digestive system and its bioavailability. In this study, we have used a topical formulation of curcumin at a relatively high concentration to enhance the healing of a diabetic wound in an animal model of diabetes. We also have studied different cellular and molecular mechanisms by which curcumin may help the wound repair. Our results re-emphasize the proangiogenic potential of curcumin in diabetic wound environment.

Interactive anticancer effect of nanomicellar curcumin and galbanic acid combination therapy with some common chemotherapeutics in colon carcinoma cells.

OBJECTIVE: In the current investigation, we aimed to study the combined cytotoxicity of curcumin, as a nanomicellar formulation, and galbanic acid (Gal), dissolved in DMSO against the murine C26 and human Caco-2 colon carcinoma cells. Further, curcumin potential for cisplatin and doxorubicin (Dox) co-therapy was studied. MATERIALS AND METHODS: The combined cytotoxic effect of these phytochemicals at varying dose ratios were examined using the MTT colorimetric assay. Moreover, the time-dependent toxicity of curcumin, cisplatin, Dox, and pegylated liposomal Dox (Doxil) was determined. The interactive anti-proliferative behavior of these compounds was examined using the CompuSyn software. RESULTS: Nanomicellar curcumin showed considerable cytotoxicity in C26 cells 24 hr post-treatment. Co-treatment of cells with curcumin nanomicelles: Gal had a synergistic effect in C26 (at 10:1 molar ratio), and Caco-2 (at 1:5 molar ratio) cell lines in cell cultures. Nanomicellar curcumin showed strong and mild synergistic inhibitory effects in C26 cells when co-administered with Doxil and cisplatin, respectively. CONCLUSION: Curcumin nanomicelles and Gal had a synergistic effect in C26 and Caco-2 cell lines. It is speculated that nanomicellar curcumin shows synergistic cancer cell killing if administered 24-hr post-injection of Doxil and cisplatin.

A study on the role of cholesterol and phosphatidylcholine in various features of liposomal doxorubicin: From liposomal preparation to therapy.

The lipid membrane composition defines the physical and pharmacological characteristics of liposomal drugs, and it can be tailored to meet the desired drug delivery needs. The current study is aimed to provide a sharper understanding of the lipid composition effect on doxorubicin (DOX) delivery kinetics, using cholesterol and phosphatidylcholine lipids (PCs) with different acyl chains in liposomal DOX formulations. The PCs were distearoyl (DSPC), dipalmitoyl (DPPC), dimyristoyl (DMPC) and egg-derived PC (EPC), either alone or in combination with cholesterol. Several characteristics were monitored, including DOX loading capacity of liposomes, DOX release in phosphate buffered saline (PBS), PBS/human plasma including buffy coat and human blood, cell uptake, as well as in vivo distribution and therapeutic effects in BALB/c mice bearing C26 colon carcinoma. Addition of cholesterol to liposomal formulation enhanced the particle size stability of the liposomes and the DOX-to-lipid ratio. EPC-liposomes and EPC/Cholesterol-liposomes showed few distinctive features. Overall, cholesterol decreased DOX release from the liposomes, and longer saturated fatty acyl chains in PC decreased DOX release and side-effects and increased the anti-tumor effects of liposomal DOX.