Colorectal Cancer (CRC) ranks third in terms of incidence and second in terms of mortality and prevalence worldwide. In relation to chemotherapy treatment, the most used drug is 5-fluorouracil (5-FU); however, the use of this drug generates various toxic effects at the systemic level. For this reason, new therapeutic strategies are currently being sought that can be used as neoadjuvant or adjuvant treatments. Recent research has shown that natural compounds, such as genistein, have chemotherapeutic and anticancer effects, but the mechanisms of action of genistein and its molecular targets in human colon cells have not been fully elucidated. The results reported in relation to non-malignant cell lines are also unclear, which does not allow evidence of the selectivity that this compound may have. Therefore, in this work, genistein was evaluated in vitro in both cancer cell lines SW480 and SW620 and in the non-malignant cell line HaCaT. The results obtained show that genistein has selectivity for the SW480 and SW620 cell lines. In addition, it inhibits cell viability and has an antiproliferative effect in a dose-dependent manner. Increased production of reactive oxygen species (ROS) was also found, suggesting an association with the cell death process through various mechanisms. Finally, the encapsulation strategy that was proposed made it possible to demonstrate that bacterial nanocellulose (BNC) is capable of protecting genistein from the acidic conditions of gastric fluid and also allows the release of the compound in the colonic fluid. This would allow genistein to act locally in the mucosa of the colon where the first stages of CRC occur.
Background/Objetives: This study standardized a chemically induced colorectal cancer (CRC) model using azoxymethane (AOM) and dextran sodium sulfate (DSS) in BALB/c mice, replicating the progression from preneoplastic lesions to adenocarcinoma observed in human colorectal carcinogenesis. Methods: The CCR-AOM/DSS model was standardized in male and female BALB/c mice. Two protocols were tested. Subsequently, the positive control group was established with nine evaluation points. Tumor progression was characterized histopathologically and corroborated by methylene blue staining and scanning electron microscopy. Results: Two cycles of 2% DSS combined with a single injection of AOM (10 mg/kg) were necessary to induce adenocarcinoma in 100% of the mice, with no significant sex-based differences in tumor development. Females showed earlier tumor susceptibility under certain protocols. Inflammatory processes played a critical role in tumorigenesis, with neutrophil infiltration and fibrosis observed. Conclusions: The findings align with previous reports, emphasizing the influence of DSS cycles, molecular weight, and mouse strain on model outcomes. This standardized model provides a reliable platform for the preclinical evaluation of novel preventive and therapeutic strategies for CRC.
Seven styrylquinolines were synthesized in this study. Two of these styrylquinolines are new and were elucidated by spectroscopic analysis. The chemopreventive potential of these compounds was evaluated against SW480 human colon adenocarcinoma cells, its metastatic derivative SW620, and normal cells (HaCaT). According to the results, compounds 3a and 3d showed antiproliferative activity in SW480 and SW620 cells, but their effect seemed to be caused by different mechanisms of action. Compound 3a induced apoptosis independent of ROS production, as evidenced by increased levels of caspase 3, and had an immunomodulatory effect, positively regulating the production of different immunological markers in malignant cell lines. In contrast, compound 3d generated a pro-oxidant response and inhibited the growth of cancer cells, probably by another type of cell death other than apoptosis. Molecular docking studies indicated that the most active compound, 3a, could efficiently bind to the proapoptotic human caspases-3 protein, a result that could provide valuable information on the biochemical mechanism for the in vitro cytotoxic response of this compound in SW620 colon carcinoma cell lines. The obtained results suggest that these compounds have chemopreventive potential against CRC, but more studies should be carried out to elucidate the molecular mechanisms of action of each of them in depth.
Background/Objectives: Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide, with its development influenced by diet, obesity, and gut microbiota (GM) alterations. This study aimed to evaluate the impact of human fecal microbiota transplantation (FMT) on the progression of CRC in a murine model. Methods: CRC was chemically induced in BALB/c mice using azoxymethane/dextran sulfate sodium (AOM/DSS). Mice were transferred with GM via FMT and divided into two experimental groups according to the microbiota source (healthy donors or CRC patients). A positive control group (AOM/DSS without FMT) and a negative control group (no CRC induction or FMT) were included. Clinical parameters, histopathological analyses, and cytokine profiling were performed. Results: Mice receiving FMT, particularly from CRC patients, exhibited increased mitotic activity, dysplasia, neoplastic proliferation, structural alterations in the colon, and more pronounced GALT hyperplasia. At the immunological level, both FMT groups (healthy and CRC-derived) showed modulation of IL-1β, IL-4, IL-6, IL-10, IL-17A, and TNF-α compared to the positive control. Conclusions: Human GM transplantation modulated the colonic microenvironment through histopathological and immunological changes, influencing CRC progression in this murine model. These findings highlight the role of GM in shaping CRC development and suggest that human-derived microbiota may significantly impact tumor dynamics.
Most fungal infections are caused by species of the Candida genus, particularly C. albicans. The increasing number of strains developing resistance to antifungals, resulting in treatment failures, underscores the urgency of finding new antifungal agents. Since many bacteria of the genus Streptomyces produce molecules that inhibit fungal growth, this work aimed to evaluate the antifungal activity of three native isolates obtained from a rhizosphere and an artisanal composting system. Based on 16S RNA gene sequences, as well as biochemical and morphological traits, we identified S. globisporus, S. bacillaris, and S. cavourensis as the species most closely related to the S1H, S40, and S41 isolates, respectively. These species have been reported to produce antifungal compounds. Theinhibition of Candida by antagonistic activity increased with longer Streptomyces incubation times, with no differences observed between Candida species. Few studies have simultaneously evaluated the inhibitory activity of Streptomyces isolates against different Candida strains. In this study, the isolates inhibited the growth of C. albicans, C. krusei, C. guilliermondii, C. glabrata, and C. lusitaniae, including strains resistant to fluconazole.
1 July 2025 in Revista Nova publicación científica en ciencias biomédicas
Introduction. The search for microorganisms producing antimicrobial compounds repre sents a strategy to address the global crisis of antibiotic resistance. Identification of bacteria of the genus Streptomyces with antagonistic activity against resistant bacteria is the initial step for the subsequent recovery of effective antibacterial metabolites for the inhibition of these resistant organisms. Objectives. Recognize promising sources to isolate filamentous bacteria able to inhibit clinical isolates, including ESBL- and KPC- producing Entero bacteriaceae and MRSA. Methods. Actinobacteria were isolated from rhizospheres and a compost system. MRSA, Escherichia coli, and Klebsiella pneumoniae clinical isolates were chosen to address antagonism tests. Antibacterial activity was recorded by a cross-streak method. Streptomyces isolates were characterized according to International Streptomyces Project and the native isolates with antimicrobial activity were identified by molecular te chniques. Results. Nine isolates of actinobacteria with activity against resistant-antibiotic bacteria were obtained, two from the avocado rhizosphere, four from a living fence and three from a composting system. Two of the isolates showed activity against all the tested antibiotic-resistant bacteria. Molecular taxonomic identification found S. jumonjinensis, S. bacillaris, S. prasinus, S. microflavus, and S. cadmiisoli as putative species for native iso lates. Conclusions. Streptomyces with antibacterial activities against ESBL and KPC-pro ducing Enterobacteria and MRSA have been isolated and the potential of rhizospheres and compost systems for obtaining antibiotic-producing bacteria was validated. Native isolates exhibited common traits for Streptomyces; although NCBI’s Blast did not show a resolution to identification, EzBioCloud 16S-based identification was able to accurately detect the identity of the isolates down to the species level.