RESUMO
Objective: This study aimed to explore the relationship between maternal plasma lipoxin A4 (LXA4) levels during the second trimester of pregnancy and certain proinflammatory molecules, such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α), as well as the antiangiogenic factor vascular endothelial growth factor receptor 1 (VEGFR-1), in conjunction with obesity among pregnant women. Materials and Methods: A total of 30 pregnant women with obesity were compared with 30 pregnant women of normal weight, matched for both age and gestational week. Plasma samples were collected from all participants between the 18th and 28th weeks of pregnancy. The levels of LXA4, VEGFR-1, IL-6, and TNF-α were quantified using enzyme-linked immunosorbent assay. Results: Plasma levels of LXA4 were notably lower in pregnant women with obesity, whereas levels of TNF-α and VEGFR1 were significantly higher (p=0.041, p<0.001, and p<0.001, respectively). There was no significant difference in IL-6 levels between groups (p=0.072). The binary logistic regression model revealed significant associations between obesity and the examined inflammatory mediators. Specifically, the results demonstrated that higher levels of LXA4 were linked to a reduced obesity risk, with each unit increase corresponding to a 0.926-fold decrease in the likelihood of obesity. Conversely, elevated levels of TNF-α and VEGFR1 were associated with an increased risk of obesity. Conclusion: The study concluded that increased body mass index during pregnancy affects the levels of plasma lipoxin, cytokines, and angiogenesis-related factors. Although the exact mechanisms remain unclear, the observed changes suggest a disruption in the metabolic systems of women with obesity, which may influence physiological changes during pregnancy and lead to obesity-related pathological conditions.
RESUMO
Cancer has the second-highest mortality rate worldwide after cardiovascular disease. In addition, breast and cervical cancer are two of the leading causes of cancer-related deaths among women. The tumor microenvironment, which consists of fibroblasts, immune cells, cells that form blood vessels, and proteins, is a therapeutic target for cancer therapy. As part of the cellular microenvironment, glycosaminoglycan chondroitin sulfate is associated with various aspects of tumor progression and metastasis depending on the sulfate pattern of chondroitin sulfate. This study evaluated the roles of Microbial Chondroitin Sulfate (CS) and Commercial CS in tumor growth and metastasis comparatively using MDA-MB-231 metastatic breast cancer cells, HeLa cervical cancer cells, and normal fibroblasts. In addition, the role of CS types in wound healing was also assessed comparatively. Microbial CS was more cytotoxic in MDA-MB-231 cells than HeLa compared to Commercial CS. Although both CS reduced cell viability in normal cells, the selective index of Microbial CS in MDA-MB-213 cells was higher than its commercial counterpart. In addition, the role of CS types in wound healing was also assessed comparatively. Both types of CS decreased the cell migration in MDA-MB-231 cancer cells, but HeLa cells were more sensitive to Microbial CS than Commercial CS to heal the wound. The wound healing of NIH3T3 cells after Microbial CS was similarly high to the healing after Commercial CS. This preliminary study shows that microbial CS produced by biotechnological methods from a recombinant source created by our team can be an effective therapeutic agent in various types of cancer.
Assuntos
Antineoplásicos , Neoplasias do Colo do Útero , Camundongos , Animais , Feminino , Humanos , Sulfatos de Condroitina/farmacologia , Sulfatos de Condroitina/uso terapêutico , Células HeLa , Neoplasias do Colo do Útero/tratamento farmacológico , Células NIH 3T3 , Cicatrização , Microambiente TumoralRESUMO
Chondroitin synthesis was performed using the recombinant Escherichia coli(C2987) strain created by transforming the plasmid pETM6-PACF-vgb, which carries the genes responsible for chondroitin synthesis, kfoA, kfoC, kfoF, and the Vitreoscilla hemoglobin gene (vgb). Then, Microbial chondroitin sulfate (MCS)'s antioxidant, anticholinesterase, and antibacterial activity were compared with commercial chondroitin sulfate (CCS). The antioxidant studies revealed that the MCS and CCS samples could be potential targets for scavenging radicals and cupric ion reduction. MCS demonstrated better antioxidant properties in the ABTS assay with the IC50 value of 0.66â mg than CCS. MCS showed 2.5-fold for DPPH and almost 5-fold for ABTSâ + (with a value of 3.85â mg/mL) better activity than the CCS. However, the compounds were not active for cholinesterase enzyme inhibitions. In the antibacterial assay, the Minimum inhibitory concentration (MIC) values of MCS against S. aureus, E. aerogenes, E. coli, P. aeruginosa, and K. pneumoniae (0.12, 0.18, 0.12, 0.18, and 0.18â g/mL, respectively) were found to be greater than that of CCS (0.42, 0.48, 0.36, 0.36, and 0.36â g/mL, respectively). This study demonstrates that MCS is a potent pharmacological agent due to its physicochemical properties, and its usability as a therapeutic-preventive agent will shed light on future studies.
RESUMO
Chondroitin sulfate (CS) is an important biomedical product. CS is the basic structural component of the mammalian extracellular matrix and is widely used in many applications in the fields of medicine, veterinary medicine, pharmaceuticals and cosmetics. For CS production, mainly animal sources are used. However, in today's conditions, due to various risks and artificial synthesis, there has been an increase in alternative sources of production methods for CS, instead of using animal resources. In this study as a powerful alternative microbial production of CS has been targeted. By using recombinant E. coli strains to integrate VHb /vgb+ and kfo+ systems, the aim was to obtain high purity CS from reliable biotechnological processes. Plasmid pUC8:15 bearing the vgb gene region, and plasmid pETM6-PACF carrying the kfoA, kfoC and kfoF genes responsible for chondroitin synthesis, were transferred to E. coli bacteria. Microbial CS was obtained by adding sulfate groups to chondroitin acquired after the treatments. The results were confirmed by HPLC and NMR analyses. The product, compared to its counterparts, was found to be an effective drug, potentially with a low molecular weight value.