The primary purpose of the study, presented in this article, was to obtain a composite cement material intended for osteanagenesis. The β-tricalcium phosphate powder (β-TCP, β-Ca3(PO4)2) was obtained by the liquid-phase method. Setting and hardening of the cement system were achieved by adding calcium sulfate hemihydrate (CSH, CaSO4·1/2H2O). An aqueous solution of polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), and a PVA/PVP mixture were used as a polymer component. The methods of capillary viscometry and Fourier-transform infrared spectroscopy (FTIR) revealed the formation of intermolecular hydrogen bonds between polymer components, which determines the good miscibility of polymers. The physicochemical properties of the synthesized materials were characterized by X-ray diffraction (XRD) and FTIR methods, and the added amount of polymers does not significantly influence the processes of phase formation and crystallization of the system. The size of crystallites CSD remained in the range of 32–36 nm, regardless of the ratio of polymer components. The influence of the composition of composites on their solubility was investigated. In view of the lower solubility of pure β-TCP, as compared to calcium sulfate dihydrate (CSD, CaSO4·2H2O), the solubility of composite materials is determined to a greater degree by the CSD solubility. Complexometric titration showed that the interaction between PVA and PVP impeded the diffusion of calcium ions, and at a ratio of PVA to PVP of 1/1, the smallest exit of calcium ions from the system is observed. The cytotoxicity analysis results allowed us to establish the fact that the viability of human macrophages in the presence of the samples varied from 80% to 125% as compared to the control.
Colorectal cancer is the third most common cancer worldwide, making lymph node recovery critical for treatment decisions and prognosis. Within the colorectal tumor microenvironment, the metabolic programming of tumor-associated macrophages (TAMs) can drive both pro- and anti-tumor responses, yet the specific glycolytic pathways governing their pro-metastatic conversion present promising therapeutic targets. This study investigated the role of glycolysis activating enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) in mediating TAMs metabolic polarization, and its potential as a therapeutic target. PFKFB3 expression was found to be predominant in TAMs in CRC tumor samples. Lipidomic analysis performed by HPLC-MS/MS revealed that PFKFB3 inhibition altered glycerophospholipid metabolism (p = 6.13 × 10−10), and shifted TAMs toward sphingolipid-mediated immunosuppressive metabolism. PFKFB3 activity was associated with a specific reduction in asparagine availability, potentially pointing to a targeted reprogramming of amino acid metabolism supporting distinct TAM functions under conditions of intra-tumoral metabolic stress. These findings highlight PFKFB3 as an essential regulator of TAMs pro-tumoral metabolism in CRC, particularly in colon cancer.
Nowadays, due to the increasing number of diseases and injuries related to bone tissue, there is an acute problem of creating a material that could be incorporated into the bone tissue structure and contribute to accelerated bone regeneration. Such materials can be represented by a polymeric matrix that holds the material in the bone and an inorganic component that can be incorporated into the bone structure and promote accelerated bone regeneration. Therefore, in this work we investigated polyvinyl alcohol-based composite cryogels containing an in situ deposited inorganic filler, hydroxyapatite. The freezing temperature was varied during the synthesis process. The composition of the components was determined by infrared spectroscopy and the phase composition by X-ray phase analysis, from which it was found that the main phase of the composite is hydroxyapatite and that the particle size decreases with increasing freezing temperature. The elemental composition of the surface is dominated by carbon, oxygen, phosphorus and calcium; no impurities of other elements not typical for polyvinyl alcohol/ hydroxyapatite cryogels were found. Higher mechanical properties and melting points were observed at −15 °C. Cryogenic treatment parameters did not affect cell viability; however, cell viability was above 80% in all samples.
Immunotherapy is a promising treatment strategy for treating colorectal cancer (CRC). Despite significant advances in this field, resistance and low efficacy of immunotherapy remain a principal problem. One of the most important factors affecting the response to immunotherapy is the tumor microenvironment (TME). Among the components of the TME, tumor-associated macrophages (TAMs) are key immune cells involved in cancer progression by stimulating tumor cell proliferation, angiogenesis, epithelial-mesenchymal transition, metastasis, and tumor immune evasion. This review presents currently investigated combination therapy based on the immune checkpoint inhibitors and inhibitors of diverse components of the TME, including TAMs, that can potentially increase the effectiveness of CRC treatment. Therapeutic efficacy, together with the functional activity of TAMs, is estimated in multiple preclinical data obtained with diverse in vitro and in vivo models. Ongoing clinical trials demonstrated the association of treatment effectiveness with TAM phenotypes and functions.
Colorectal cancer is the third most common cancer worldwide, making lymph node re-covery critical for treatment decisions and prognosis. Within the colorectal tumor mi-croenvironment, the metabolic programming of tumor-associated macrophages (TAMs) can drive both pro- and anti-tumor responses, yet the specific glycolytic pathways gov-erning their pro-metastatic conversion present promising therapeutic targets. This study investigated the role of glycolysis activating enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) in mediating TAM metabolic polarization, and its potential as a therapeutic target. PFKFB3 expression was found to be predominant in tumor-associated macrophages in CRC human tumor sam-ples. Lipidomic analysis performed by HPLC-MS/MS revealed that PFKFB3 inhibition altered glycerophospholipid metabolism (p=6.13E-10), and shifted TAMs toward sphingolipid-mediated immunosuppressive metabolism. PFKFB3 activity was associated with a specific reduction in asparagine availability, potentially pointing to a targeted reprogramming of amino acid metabolism supporting distinct macrophage functions under conditions of intra-tumoral metabolic stress. These findings highlight PFKFB3 as an essential metabolic regulator of TAMs pro-tumoral activity in CRC, particularly in colon cancer.