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Previously, studies have shown that leukemic cells exhibit elevated glycolytic metabolism and oxidative phosphorylation in comparison to hematopoietic stem cells. These metabolic processes play a crucial role in the growth and survival of leukemic cells. Due to the metabolic plasticity of tumor cells, the use of natural products has been proposed as a therapeutic alternative due to their ability to attack several targets in tumor cells, including those that could modulate metabolism. In this study, the potential of Petiveria alliacea to modulate the metabolism of K562 cell lysates was evaluated by non-targeted metabolomics. Initially, in vitro findings showed that P. alliacea reduces K562 cell proliferation; subsequently, alterations were observed in the endometabolome of cell lysates treated with the extract, mainly in glycolytic, phosphorylative, lipid, and amino acid metabolism. Finally, in vitro assays were performed, confirming that P. Alliacea extract decreased the oxygen consumption rate and intracellular ATP. These results suggest that the anti-tumor activity of the aqueous extract on the K562 cell line is attributed to the decrease in metabolites related to cell proliferation and/or growth, such as nucleotides and nucleosides, leading to cell cycle arrest. Our results provide a preliminary part of the mechanism for the anti-tumor and antiproliferative effects of P. alliacea on cancer.

Natural products obtained from Petiveria alliacea (Anamu-SC) and Caesalpinia spinosa (P2Et) have been used for cancer treatment, but the mechanisms by which they exert their antitumor activity appear to be different. In the present work, we show that the Anamu-SC extract reduces tumor growth in the 4T1 murine mammary carcinoma model but not in the B16-F10 melanoma model, unlike the standardized P2Et extract. Both extracts decreased the levels of interleukin-10 (IL-10) in the B16-F10 model, but only P2Et increased the levels of tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ). Likewise, co-treatment of P2Et and doxorubicin (Dox) significantly reduced tumor size by 70% compared to the control group, but co-treatment of Anamu-SC with Dox had no additive effect. Analysis of intratumoral immune infiltrates showed that Anamu-SC decreased CD4+ T cell frequency more than P2Et but increased CD8+ T cell frequency more significantly. Both extracts reduced intratumoral monocytic myeloid-derived suppressor-like cell (M-MDSC-LC) migration, but the effect was lost when co-treated with doxorubicin. The use of P2Et alone or in co-treatment with Anamu-SC reduced the frequency of regulatory T cells and increased the CD8+/Treg ratio. In addition, Anamu-SC reduced glucose consumption in tumor cells, but this apparently has no effect on IFNγ- and TNFα-producing T cells, although it did reduce the frequency of IL-2-producing T cells. The efficacy of these herbal preparations is increasingly clear, as is the specificity conditioned by tumor heterogeneity as well as the different chemical complexity of each preparation. Although these results contribute to the understanding of specificity and its future benefits, they also underline the fact that the development of each of these standardized extracts called polymolecular drugs must follow a rigorous path to elucidate their biological activity.

The main limits of current antitumor therapies are chemoresistance, relapses, and toxicity that impair patient quality of life. Therefore, the discovery of therapeutic alternatives, such as adjuvants to conventional therapy that modulate the intracellular oxidation state or the immune response, remains a challenge. Owing to traditional medicine, several uses of plants are known, indicating a promising antitumor and immunomodulatory effect. We evaluated the effect of ethanolic extract of T. usneoides in vitro and in vivo in models of 4T1 breast cancer and B16-F10 melanoma. In vitro evaluations with both cell lines showed that the extract has cytotoxic activity and induces apoptotic cell death. However, its effect on ROS production and glucose uptake was opposite. In vivo, only in the 4T1 model, a significant decrease in tumor size was found in animals treated with the extract, accompanied by an increase in dendritic cells and activated CD8 + T cells, and a decrease in myeloid-derived suppressor-like cells (MDSC-LC) and Tregs in the tumor microenvironment. These results suggest that T. usneoides extract antagonistically regulates tumor metabolism of 4T1 vs. B16-F10, impacting the tumor microenvironment and effective antitumor immune response, leading to a reduction in 4T1 tumor size but not on B16-F10.

Commercially pure (c.p.) titanium grade IV with a bimodal microstructure is a promising material for biomedical implants. The influence of the processing parameters on the physical, microstructural, and mechanical properties was investigated. The bimodal microstructure was achieved from the blends of powder particles with different sizes, while the porous structure was obtained using the space-holder technique (50 vol.% of ammonium bicarbonate). Mechanically milled powders (10 and 20 h) were mixed in 50 wt.% or 75 wt.% with c.p. titanium. Four different mixtures of powders were precompacted via uniaxial cold pressing at 400 MPa. Then, the specimens were sintered at 750 °C via hot pressing in an argon gas atmosphere. The presence of a bimodal microstructure, comprised of small-grain regions separated by coarse-grain ones, was confirmed by optical and scanning electron microscopies. The samples with a bimodal microstructure exhibited an increase in the porosity compared with the commercially available pure Ti. In addition, the hardness was increased while the Young's modulus was decreased in the specimens with 75 wt.% of the milled powders (20 h).

In the last decade, titanium metal matrix composites (TMCs) have received considerable attention thanks to their interesting properties as a consequence of the clear interface between the matrix and the reinforcing phases formed. In this work, TMCs with 30 vol % of B₄C are consolidated by hot pressing. This technique is a powder metallurgy rapid process. Incorporation of the intermetallic to the matrix, 20 vol % (Ti-Al), is also evaluated. Here, the reinforcing phases formed by the reaction between the titanium matrix and the ceramic particles, as well as the intermetallic addition, promote substantial variations to the microstructure and to the properties of the fabricated composites. The influences of the starting materials and the consolidation temperature (900 °C and 1000 °C) are investigated. By X-ray diffraction, scanning and transmission electron microscopy analysis, the in-situ-formed phases in the matrix and the residual ceramic particles were studied. Furthermore, mechanical properties are studied through tensile and bending tests in addition to other properties, such as Young's modulus, hardness, and densification of the composites. The results show the significant effect of temperature on the microstructure and on the mechanical properties from the same starting powder. Moreover, the Ti-Al addition causes variation in the interface between the reinforcement and the matrix, thereby affecting the behaviour of the TMCs produced at the same temperature., Competing Interests: The authors declare no conflict of interest.

In this work, a study of the influence of the starting materials and the processing time used to develop W/Cu alloys is carried out. Regarding powder metallurgy as a promising fabrication route, the difficulties in producing W/Cu alloys motivated us to investigate the influential factors on the final properties of the most industrially demanding alloys: 85-W/15-Cu, 80-W/20-Cu, and 75-W/25-Cu alloys. Two different tungsten powders with large variation among their particle size-fine (W f ) and coarse (W c ) powders-were used for the preparation of W/Cu alloys. Three weight ratios of fine and coarse (W f :W c ) tungsten particles were analyzed. These powders were labelled as "tungsten bimodal powders". The powder blends were consolidated by rapid sinter pressing (RSP) at 900 °C and 150 MPa, and were thus sintered and compacted simultaneously. The elemental powders and W/Cu alloys were studied by optical microscopy (OM) and scanning electron microscopy (SEM). Thermal conductivity, hardness, and densification were measured. Results showed that the synthesis of W/Cu using bimodal tungsten powders significantly affects the final alloy properties. The higher the tungsten content, the more noticeable the effect of the bimodal powder. The best bimodal W powder was the blend with 10 wt % of fine tungsten particles (10-W f :90-W c ). These specimens present good values of densification and hardness, and higher values of thermal conductivity than other bimodal mixtures.

This research is focused on the influence of processing temperature on titanium matrix composites reinforced through Ti, Al, and B₄C reactions. In order to investigate the effect of Ti-Al based intermetallic compounds on the properties of the composites, aluminum powder was incorporated into the starting materials. In this way, in situ Ti x Al y were expected to form as well as TiB and TiC. The specimens were fabricated by the powder metallurgy technique known as inductive hot pressing (iHP), using a temperature range between 900 °C and 1400 °C, at 40 MPa for 5 min. Raising the inductive hot pressing temperature may affect the microstructure and properties of the composites. Consequently, the variations of the reinforcing phases were investigated. X-ray diffraction, microstructural analysis, and mechanical properties (Young's modulus and hardness) of the specimens were carried out to evaluate and determine the significant influence of the processing temperature on the behavior of the composites.