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The host immunologic response to a specific material is a critical aspect when considering it for clinical implementation. Collagen and gelatin extracted from marine sources have been proposed as biomaterials for tissue engineering applications, but there is a lack of information in the literature about their immunogenicity. In this work, we evaluated the immune response to collagen and/or gelatin from blue shark and codfish, previously extracted and characterized. After endotoxin evaluation, bone marrow-derived macrophages were exposed to the materials and a panel of pro- and anti-inflammatory cytokines were evaluated both for protein quantification and gene expression. Then, the impact of those materials in the host was evaluated through peritoneal injection in C57BL/6 mice. The results suggested shark collagen as the less immunogenic material, inducing low expression of pro-inflammatory cytokines as well as inducible nitric oxide synthase (encoded by Nos2) and high expression of Arginase 1 (encoded by Arg1). Although shark gelatin appeared to be the material with higher pro-inflammatory expression, it also presents a high expression of IL-10 (anti-inflammatory cytokine) and Arginase (both markers for M2-like macrophages). When injected in the peritoneal cavity of mice, our materials demonstrated a transient recruitment of neutrophil, being almost non-existent after 24 hours of injection. Based on these findings, the studied collagenous materials can be considered interesting biomaterial candidates for regenerative medicine as they may induce an activation of the M2-like macrophage population, which is involved in suppressing the inflammatory processes promoting tissue remodeling. Marine-origin biomaterials are emerging in the biomedical arena, namely the ones based in marine-derived collagen/gelatin proposed as cell templates for tissue regeneration. Nevertheless, although the major cause of implant rejection in clinical practice is the host's negative immune response, there is a lack of information in the literature about the immunological impact of these marine collagenous materials. This work aims to contribute with knowledge about the immunologic response to collagen/gelatin extracted from blue shark and codfish skins. The results demonstrated that despite some differences observed, all the materials can induce a macrophage phenotype related with anti-inflammation resolution and then act as immuno-modulators and anti-inflammatory inducible materials. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract In recent years, we have witnessed a significant increase in the amount of studies using Mesenchymal Stem Cells (MSCs) for cancer therapy, mostly as vectors for drug or gene delivery strategies. This is because of their intrinsic capacity of homing into tumor niches. However, the interactions between MSCs themselves and tumor cells is not fully understood, with contradictory results frequently being observed regarding their effects on cancer cell invasion and proliferation. This poses an important question of safety in respect to the application of these cells. The source of the MSC population used, as well as the type of cancer cells under study might strongly influence this interaction. Moreover, differences in isolation protocols, culture media compositions, time of culture and conditioned media collection, or even timing and mode of MSCs administration to in vivo models of cancer may also affect the interaction MSC-tumor cells. In this review, we drive our focus into malignant brain tumors, particularly gliomas, one of the deadliest forms of cancer. Moreover, we look with some detail into different studies using MSCs as a treatment for brain tumors and compare them, highlighting the main deviations and similarities among them. Highlights • The migration capacity of MSCs towards glioma cells and the factors and molecules associated to this mechanism are described. • The interaction between naive MSCs and glioma cells is characterized by comparing different studies. • The MSCs secretome effects on glioma cells are reviewed and factors/molecules responsible for those effects are highlighted. • A brief consideration on the needs of protocols standardization in MSCs-glioma research is provided. [ABSTRACT FROM AUTHOR]

Due to their complex structure and traditional low-intensity management, Portuguese oak woodland rangelands known as montados are often considered high nature value (HNV) farming systems, and as such, they may be deemed eligible for subsidies and incentives by governmental and nongovernmental agencies. Too little is known about how the HNV concept might be applied to conserve complex silvopastoral systems. These systems, due to their structural and functional complexity at multiple scales, tend to support high levels of biodiversity. Montados are in sharp decline as a result of the rapid specialization of land management that, through simplification, undermines multifunctionality. Understanding how changes in management influence these systems and their biodiversity is needed for prioritizing conservation efforts and for ensuring they remain HNV systems. On the basis of a field survey in 58 plots distributed among 29 paddocks on 17 farms, we conducted an integrated analysis of the relationship between grazing intensity and biodiversity in montados of similar biophysical and structural characteristics. Data on management were obtained through interviews, and biodiversity data (vegetation, macrofungi, birds, herpetofauna) were obtained through specific field protocols. Additional spatial data, such as soil characteristics, slope, land cover, and linear landscape elements, were also analyzed. The results show no overall biodiversity variation as a result of different management practices. However, different groups of species react differently to specific management practices, and within a pasture, grazing impacts are heterogenous. In low grazing intensity plots, macrofungi species richness was found to be higher, while bird species richness was lower. Using tree regeneration as proxy for montado sustainability, results show less tree regeneration in areas with higher forage quality and more intense grazing. Pathways for future progress are proposed, including creating areas within a paddock that attract grazing away from where regeneration is desired. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is a highly aggressive malignant brain tumor currently without an effective treatment. Inspired by the recent advances in cell membrane biomimetic nanocarriers and by the key role of macrophages in GBM pathology, we developed macrophage membrane liposomes (MML) for GBM targeting. For the first time, it was assessed the role of macrophage polarization states in the effectiveness of these drug delivery systems. Interestingly, we observed that MML derived from M2 macrophages (M2 MML) presents higher uptake and increased delivery of the anticarcinogenic drug doxorubicin compared to M1 macrophage-derived nanocarriers (M1 MML) and control liposomes (CL). Moreover, the lowest uptake by macrophages of MML reveals promising immune escaping properties. Notably, M2 macrophages unveiled a higher expression of integrin CD49d, a crucial protein involved in the bilateral communication of macrophages with tumor cells. Therefore, our findings suggest the potential of using M2 macrophage membranes to develop novel nanocarriers targeting GBM. Cell Membranes isolated from distinct macrophage polarization states (classically activated – M1 and alternatively activated – M2), were used as biological material to synthesize macrophage membrane liposomes (MML). The developed biomimetic nanocarriers successfully delivered anticarcinogenic drugs and impaired the growth and proliferation of glioblastoma cells. [Display omitted] [ABSTRACT FROM AUTHOR]

Particulate fillers are often used to enhance the properties of soft materials; polymer composites often contain nanometer-sized particles to improve reinforcement, for example. The rationale for using nanometer-sized particles remains unclear, however, and classical micromechanical models cannot account for a scale dependent reinforcement. The systems studied here reveal that the reinforcement increases with decreasing filler size. A new relation is proposed, based only on the particle size, volume fraction, and relative moduli of filler and matrix, that describes the experimental results for reinforcement of both filled rubbers and a model system. [ABSTRACT FROM AUTHOR]

Scarce data are available regarding the molecular mechanisms implicated in paclitaxel resistance. There is controversial data about β-tubulin mutations role in paclitaxel resistance. We have conducted this trial to address the influence of β-tubulin mutations in paclitaxel resistance in advanced non-small cell lung cancer (NSCLC). A group of 15 patients were biopsied and diagnosed of stages IIIB and IV NSCLC. Tumor specimens were used for DNA isolation and exon 4 of HM40 β-tubulin isotype was amplified and automatically sequenced, using both intronic and exonic primers. Next, the chemotherapy schedule consisted of weekly paclitaxel (100 or 150 mg/m2×6) followed 2 weeks later by cisplatin 100 mg/m2 on day 1, gemcitabine 1000 mg/m2 on days 1 and 14, and vinorelbine 25 mg/m2 on days 1 and 14, every 28 days. Using exonic primers, gene sequence alterations were found in 13/15 (87%) patients, including transitions (codons 180 and 182) and one silent transversion (codon 195). Also, three transversions (codons 231, 234, and 235) were found in all patients and controls. All alterations disappeared when sequenced with intronic primers. Our results suggest that point mutations demonstrated with exonic primers but not with intronic ones are probably due to β-tubulin pseudogenes present in advanced NSCLC specimens. Even so, when these β-tubulin pseudogenes are found there is a clear relation with clinical response. Although these changes could be relevant in paclitaxel resistance, this observation must be proven in future clinical trials to resolve “the tubulin dilemma”. [Copyright &y& Elsevier]

Introduction In blunt abdominal trauma, lesions of the small bowell and mesentery are often underdiagnosed; although unusual, they represent the third most injured organ, with increasing morbidity and mortality. Presentation of case The authors present the case of a 68 years old male, admitted to the emergency department after being hit by a bale of straw, weighing around 300 kg, in the abdomen. After successful ressuscitation, a CT scan was performed, suggesting hemoperitoneum because of vascular lesion of the right colon bleeding. An exploratory laparotomy was performed, confirming the presence of blood in the abdominal cavity and identifying jejunal perforation, an apparently innocent hematoma of the small bowel mesentery (beside the bowel wall) distally to the first lesion and a laceration of the sigmoid serosa; a segmental jejunal resection and suture of the colon serosa were performed. In the early post-operative period, an enteric discharge was noticed, mandating surgical reexploration; a previously unnoticed bowel perforation, in the mesenteric border where the hematoma was identified, justified an additional enterectomy, after what the patients recovery progressed uneventfully. Discussion In this case, a sudden increase in abdominal pressure could explain that missed rupture of the mesenteric border of t he jejunum, also causing the mesenteric hematoma, or, in spite of that, a state of low perfusion could have lead to total wall ischemia of an already irrigation compromised segment. Only noted after surgical exploration, despite prior evaluation with a computed tomography. Small bowell and mesenteric injuries are potentially missed due to decreased exploratory laparotomies for blunt abdominal trauma. Conclusion Although uncommon, small bowel and mesenteric injuries are associated with high morbidity and mortality. High clinical suspicion is essential for an early diagnosis [ABSTRACT FROM AUTHOR]

A fundamental issue in understanding how energy balance is accomplished involves comprehending how changes in intake affect subsequent intake. This was investigated in free-living humans by reanalyzing the data previously collected from 733 adults who were paid to maintain a 7-d diary of everything they ate and when they ate it. Food energy intake during a day was found to only mildly affect intake on the subsequent day (mean r = -0.07, P < 0.001), but was more strongly negatively related to intake occurring on the second (mean r = -0.18, P < 0.001) and third day (mean r = -0.10, P < 0.001) afterward. Each macronutrient was shown to have a maximal negative relationship with subsequent intake of that same macronutrient, with 2-d lag mean autocorrelations equal to -0.11, P < 0.001 for carbohydrate, equal to -0.18, P < 0.001 for fat, and equal to -0.13, P < 0.001 for protein. These effects on daily intake were found to result from separate negative feedback effects on meal size and frequency. The results suggest that intake affects subsequent intake by persistently setting a long-term bias that, integrated over time, produces a net shift in intake. [ABSTRACT FROM AUTHOR]