Chemokine 12 (CXCL12), also known as stromal cell derived factor-1 (SDF-1) and a member of the CXC chemokine subfamily, is ubiquitously expressed in many tissues and cell types. It interacts specifically with the ligand for the transmembrane G protein-coupled receptors CXCR4 and CXCR7. The CXCL12/CXCR4 axis takes part in a series of physiological, biochemical, and pathological process, such as inflammation and leukocyte trafficking, cancer-induced bone pain, and postsurgical pain, and also is a key factor in the cross-talking between tumor cells and their microenvironment. Aberrant overexpression of CXCR4 is critical for tumor survival, proliferation, angiogenesis, homing and metastasis. In this review, we summarized the role of CXCL12/CXCR4 in cancer, CXCR4 inhibitors under clinical study, and natural product CXCR4 antagonists. In conclusion, the CXCL12/CXCR4 signaling is important for tumor development and targeting the pathway might represent an effective approach to developing novel therapy in cancer treatment.
Animals ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Biological Products ; chemistry ; pharmacology ; Chemokine CXCL12 ; genetics ; metabolism ; Humans ; Molecular Targeted Therapy ; Neoplasms ; drug therapy ; genetics ; metabolism ; Receptors, CXCR4 ; antagonists & inhibitors ; genetics ; metabolism

This study aims to develop a method to detect bovine multi-cytokines based on flow cytometry. Previously we have prepared and screened monoclonal antibodies against bovine cytokines IFN-γ, IL-2, TNF-α, IP-10 and MCP-1. These bovine cytokine monoclonal antibodies were fluorescently labeled, and the combination of antibody and cell surface molecules were used to develop the method for detecting bovine multi-cytokines. Subsequently, the developed method was used to determine the cytokine expression profile of Mycobacterium bovis BCG infected bovine peripheral blood mononuclear cells in vitro, and evaluate the cytokine expression level of peripheral blood CD4⁺ T cells of tuberculosis-positive cattle. The bovine multi-cytokine flow cytometry detection method can effectively determine the cytokine expression of BCG-infected bovine peripheral blood T lymphocytes. Among them, the expression levels of IFN-γ, IL-2, and TNF-α continue to increase after 40 hours of infection, while the expression levels of IP-10 and MCP-1 decreased. The combined detection of IFN-γ, IL-2, and TNF-α on CD4⁺ T lymphocytes in peripheral blood of cattle can effectively distinguish tuberculosis-positive and tuberculosis-negative samples. This method may facilitate evaluating the level of cellular immune response after bovine pathogen infection and vaccine injection.
Cattle ; Animals ; Cytokines ; BCG Vaccine/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-2 ; Flow Cytometry/methods* ; Chemokine CXCL10/metabolism* ; Leukocytes, Mononuclear ; CD4-Positive T-Lymphocytes/metabolism* ; Tuberculosis ; Antibodies, Monoclonal/metabolism*

Objective: To compare the effect on the flow conditions of adhesives and the retention force of restorations among different cement-retained methods of implant-supported fixed prostheses. Methods: Four common cement-retained methods were selected, including the occlusal hole for screw access (OH), the lingual hole for adhesives overflow (LH), the resin replica for titanium abutment (RR), and the traditional cement-retained method (the control group). The adhesive used in this study was resin-modified glass ionomer cement. The two-dimensional analysis models of computational fluid dynamics (CFD) were established. The flow conditions of adhesives in the adhesion process was analyzed by the CFD analysis. The internal filling ratio and the amount of neck overflow of adhesives below the edge of the prosthesis were calculated. Ten zirconia prostheses in each group were processed and cemented. The retention force was examined by mechanical tensile experiments in vitro. Results: The CFD analysis showed the internal filling ratio of adhesives from high to low was the LH group, the OH group, the RR group and the control group. The amount of neck overflow of adhesives below the edge of the prosthesis from less to more was the RR group, the OH group, the LH group and the control group. The retention force was (240.7±33.9) N in the control group, (278.2±59.1) N in the OH group, (292.9±47.9) N in the LH group, and (262.8±59.4) N in the RR group. There was a statistically significant difference in the retention force between the LH group and the control group (P=0.029). There was no significant difference among the other groups (P>0.05). Conclusions The modified cement-retained methods can effectively reduce the amount of neck overflow of adhesives, and improve the filling condition of adhesive in the adhesive clearance to ensure the retention force of the prostheses. Clinically, the appropriate modified cement-retained method should be selected according to the three-dimensional position of the implant and the position of prosthetic margin.