RESUMEN

Surgery-induced tumor growth acceleration and synchronous metastatic growth promotion have been observed for decades. Surgery-induced wound healing, orchestrated through growth factors, chemokines, and cytokines, can negatively impact patients harboring residual or metastatic disease. We provide detailed clinical evidence of this process in surgical breast, prostate, and colorectal cancer patients. Plasma samples were analyzed from 68 cancer patients who had not received treatment before surgery or adjuvant therapy until at least four weeks post-surgery. The levels of plasma cytokines, chemokines, and growth factors were simultaneously quantified and profiled using multiplexed immunoassays for eight time points sampled per patient. The immunologic processes are induced immediately after surgery in patients, characterized by a drastic short-term shift in the expression levels of pro-inflammatory and angiogenic molecules and cytokines. A rapid and significant spike in circulating plasma levels of hepatocyte growth factor (HGF), interleukin-6 (IL-6), placental growth factor (PLGF), and matrix metalloproteinase-9 (MMP-9) after surgery was noted. The rise in these molecules was concomitant with a significant drop in transforming growth factor-ß1 (TGF-ß1), platelet-derived growth factor (PDGF-AB/BB), insulin-like growth factor-1 (IGF-1), and monocyte chemoattractant protein-2 (MCP-2). If not earlier, each plasma analyte was normalized to baseline levels within 1-2 weeks after surgery, suggesting that surgical intervention alone was responsible for these effects. The effects of surgical tumor removal on disrupting the pro-inflammatory and angiogenic plasma profiles of cancer patients provide evidence for potentiating malignant progression. Our findings indicate a narrow therapeutic window of opportunity after surgery to prevent disease recurrence.

Asunto(s)

Neoplasias Colorrectales , Neoplasias de la Próstata , Masculino , Humanos , Factor de Crecimiento Placentario , Recurrencia Local de Neoplasia , Quimiocinas , Neoplasias de la Próstata/cirugía , Neoplasias Colorrectales/patología

RESUMEN

This study aimed to assess the nutritional quality of cowpea seeds (cv. Doljana - CSD) and the impact of partially replacing soybean meal with CSD, along with the supplementation of microencapsulated Lactobacillus salivarius (LS), on the growth performance, selected carcass traits, biochemical plasma profile, tibia bone quality, and microbial populations in the ceca and excreta of broiler chickens aged 1 to 35 days. A total of 432 mixed-sex Ross 308 broiler chickens, aged one day, were randomly allocated to four groups, with 108 birds in each group, further divided into 6 pens containing 18 birds each. The experimental design featured a 2 × 2 factorial arrangement, with two cowpea seed levels (CSD0 and CSD15%) and the presence or absence (Yes/No) of microencapsulated LS probiotic (0 and 1 g/kg feed). The experimental diets did not significantly influenced (p > 0.05) production performances. However, the production efficiency factor was notably higher in the CSD0 (336.8%) and CSD15 (332.2%) groups with LS compared to CSD0 (322.4%) and CSD15 (320.6%) groups without LS supplementation. Regarding carcass traits, the CSD15 group with LS supplementation exhibited higher dressing (70.69%) and liver (2.47%) percentages compared to the other groups. Plasma profile analysis revealed significant reductions (p < 0.05) in total cholesterol (from 115 mg/dL to 105 mg/dL) and triglycerides (from 54.80 mg/dL to 46.80 mg/dL) in the CSD15 group with LS supplementation compared to the CSD0 group, with or without LS supplementation. Moreover, the CSD15 group with LS had significantly higher total protein, albumin, and calcium levels and significantly lower (p < 0.05) uric acid levels compared to the CSD0 group, irrespective of LS supplementation. Tibia bone traits and minerals showed no significant effects. However, the pH exhibited a linear decrease from 6.90 in the CSD0 group without LS to 6.69 in the CSD15 group with LS supplementation. In terms of cecal microbial populations, Coliforms decreased from 7.14 CFU/g in the CSD15 group without LS to 5.48 CFU/g in the CSD15 group with LS. Significant alterations were also observed in Clostridium spp., E. coli, Enterococcus spp., and Staphylococcus spp. in the ceca and excreta of the CSD15 group with LS supplementation compared to the CSD0 group, with or without LS supplementation. Beneficial bacteria, specifically Lactobacillus spp., significantly increased in the cecal content of CSD0 (9.06 CFU/g) and CSD15 (9.01 CFU/g) groups with LS compared to CSD0 (8.41 CFU/g) and CSD15 (8.11 CFU/g) groups without LS. In summary, this study suggests that cowpea seeds can be used as a partial replacement for soybean meal in broiler chicken diets, and microencapsulated Lactobacillus salivarius can be employed as a probiotic supplement.

RESUMEN

Vascular dementia (VaD) is a pathogenetically heterogeneous neuropsychiatric syndrome, mainly characterized by cognitive impairment. Among dementias, it is second by incidence after Alzheimer's dementia (AD). VaD biomolecular bases have been poorly characterized, but vascular-linked factors affecting the CNS and its functions are generally hypothesized to perform a major role, together with cardiovascular and immunological factors. miRNAs, which perform critically important biomolecular roles within cell networks, are also found in biological fluids as circulating miRNAs (cmiRNAs). We hypothesized that differentially expressed (DE) cmiRNAs in plasma from VaD patients could be applied to diagnose VaD through liquid biopsies; these profiles also could allow to start investigating VaD molecular bases. By exploiting TaqMan Low-Density Arrays and single TaqMan assays, miR-10b*, miR29a-3p, and miR-130b-3p were discovered and validated as significantly downregulated DE cmiRNAs in VaD patients compared to unaffected controls (NCs). These miRNAs also were found to be significantly downregulated in a matched cohort of AD patients, but miR-130b-3p levels were lower in AD than in VaD. A negative correlation was detected between miR-29a and miR-130b expression and cognitive impairment in VaD and AD, respectively. Receiver operating characteristic curves demonstrated that decreased plasma levels of miR-10b*, miR29a-3p, and miR-130b-3p allow to discriminate VaD and AD patients from NCs. Furthermore, the concurrent downregulation of both miR-10b* and miR-130b-3p in VaD showed an area under the curve (AUC) of 0.789 (p < 0.0001) with 75% of sensitivity and 72% of specificity, whereas an AUC of 0.789 (p < 0.0001) with 92% of sensitivity and 81% of specificity was found for both in AD. The miRNAs profiles reported in this paper pave the way to translational applications to molecular VaD diagnosis, but they also should allow to further investigate on its molecular bases.