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A marked decrease in human cancers, including breast cancer, bone cancer, and cervical cancer, has been linked to the consumption of vegetable and fruit, and the corresponding chemoprotective effect has been associated with the presence of several active molecules, such as kaempferol. Kaempferol is a major flavonoid aglycone found in many natural products, such as beans, bee pollen, broccoli, cabbage, capers, cauliflower, chia seeds, chives, cumin, moringa leaves, endive, fennel, and garlic. Kaempferol displays several pharmacological properties, among them antimicrobial, anti-inflammatory, antioxidant, antitumor, cardioprotective, neuroprotective, and antidiabetic activities, and is being applied in cancer chemotherapy. Specifically, kaempferol-rich food has been linked to a decrease in the risk of developing some types of cancers, including skin, liver, and colon. The mechanisms of action include apoptosis, cell cycle arrest at the G2/M phase, downregulation of epithelial-mesenchymal transition (EMT)-related markers, and phosphoinositide 3-kinase/protein kinase B signaling pathways. In this sense, this article reviews data from experimental studies that investigated the links between kaempferol and kaempferol-rich food intake and cancer prevention. Even though growing evidence supports the use of kaempferol for cancer prevention, further preclinical and clinical investigations using kaempferol or kaempferol-rich foods are of pivotal importance before any public health recommendation or formulation using kaempferol.

One of the most remarkable findings in the immunology and neuroscience fields was the discovery of the bidirectional interaction between the immune and the central nervous systems. This interplay is tightly regulated to maintain homeostasis in physiological conditions. Disruption in this interplay has been suggested to be associated with several neuropsychiatric disorders. Most studies addressing the impact of an immune system disruption on behavioral alterations focus on acute pro-inflammatory responses. However, chronic infections are highly prevalent and associated with an altered cytokine milieu that persists over time. Studies addressing the potential effect of mycobacterial infections on mood behavior originated discordant results and this relationship needs to be further addressed. To increase our understanding on the effect of chronic infections on the central nervous system, we evaluated the role of Mycobacterium avium infection. A model of peripheral chronic infection with M. avium in female from three mouse strains (Balb/c, C57BL/6, and CD-1) was used. The effect of the infection was evaluated in the cytokine expression profile (spleen and hippocampus), hippocampal cell proliferation, neuronal plasticity, serum corticosterone production and mood behavior. The results show that M. avium peripheral chronic infection induces alterations not just in the peripheral immune system but also in the central nervous system, namely in the hippocampus. Interestingly, the cytokine expression profile alterations vary between mouse strains, and are not accompanied by hippocampal cell proliferation or neuronal plasticity changes. Accordingly, no differences were observed in locomotor, anxious and depressive-like behaviors, in any of the mouse strains used. We conclude that the M. avium 2447 infection-induced alterations in the cytokine expression profile, both in the periphery and the hippocampus, are insufficient to alter hippocampal plasticity and behavior.

Cell-based approaches have emerged as a promising therapy to achieve successful vascularization in tissue engineering. Since fibroblasts activation and migration is required for physiological events relying on angiogenesis, we hypothesize herein that different fibroblasts exhibit distinct capacity to promote capillary-like structures assembly, by mature and progenitor endothelial cells (ECs). Outgrowth endothelial cells (OECs) were isolated from human umbilical cord blood samples and characterized by immunofluorescence and imaging flow cytometry for endothelial markers. Coculture systems were established using either human umbilical vein ECs (HUVECs) or OECs with fibroblasts, being evaluated at 7, 14, and 21 days of culture. Two types of human dermal fibroblasts (HDF) were used, namely neonatal human foreskin fibroblasts-1 (HFF-1) and juvenile HDF. OECs expressed EC markers and formed capillary-like structures. HFF-1 exhibited higher expression of transglutaminase-2, while HDF exhibited a higher expression of α-smooth muscle actin (α-SMA) and podoplanin, which were not observed for HFF-1. Formation of capillary-like structures was only observed in cocultures with HDF and not with HFF-1. No significant differences were found between HDF and OECs or HUVECs cocultures. These findings suggest that HDF is a preferential cell source for promoting vascularization, either using mature or progenitor ECs, probably due to their higher expression of α-SMA and podoplanin, and increased synthesis of extracellular matrix. This work opens new research possibilities regarding the use of specific fibroblast populations cocultured with ECs, as efficient partners for vascular development in regenerative medicine strategies.

Background and objectives: The incidence of cutaneous melanoma has been increasing. Melanoma is an aggressive form of skin cancer irresponsive to radiation and chemotherapy, rendering this cancer a disease with poor prognosis: In order to surpass some of the limitations addressed to melanoma treatment, alternatives like vitamins have been investigated. In the present study, we address this relationship and investigate the possible role of vitamin A. Materials and Methods: We perform a co-culture assay using a macrophage cell model and RAW 264.7 from mouse, and also a murine melanoma cell line B16-F10. Macrophages were stimulated with both Escherichia coli lipopolysaccharides (LPS) as control, and also with LPS plus vitamin A. Results: Using B16-F10 and RAW 264.7 cell lines, we were able to demonstrate that low concentrations of vitamin A increase cytotoxic activity of macrophages, whereas higher concentrations have the opposite effect. Conclusion: These findings can constitute a new point of view related to immunostimulation by nutrients, which may be considered one major preventive strategy by enhancing the natural defense system of the body.

Nanomaterials offer a broad spectrum of applications in biomedicine. The shapes of gold nanoparticles could modulate tumor cell behavior. Spherical (AuNPsp), stars (AuNPst) and rods (AuNPr) shapes of polyethylene glycol coated-gold nanoparticles (AuNPs-PEG) were synthesized. Metabolic activity, cellular proliferation, and reactive oxygen species (ROS) were measured and the impact of AuNPs-PEG in metabolic enzymes function was evaluated by RT-qPCR in PC3, DU145, and LNCaP prostate cancer cells. All AuNPs were internalized, and the different morphologies of AuNPs showed to be an essential modulator of metabolic activity. For PC3 and DU145, the metabolic activity of AuNPs was found to rank in the following order from lowest to highest: AuNPsp-PEG, AuNPst-PEG, and AuNPr-PEG. Regarding LNCaP cells, the AuNPst-PEG were less toxic, followed by AuNPsp-PEG and AuNPr-PEG, but it seems not to be dose-dependent. The proliferation was lower in AuNPr-PEG in PC3 and DU145 cells but was stimulated around 10% in most conditions (0.001–0.1 mM) in LNCaP cells (not statistically significant). For 1 mM, LNCaP cells showed a significant decrease in proliferation only for AuNPr-PEG. The outcomes of the current study demonstrated that different AuNPs conformations influence cell behavior, and the correct size and shape must be chosen considering its final application in the field of nanomedicine.

More than 50% of all prostate cancer (PCa) patients are treated by radiotherapy (RT). Radioresistance and cancer recurrence are two consequences of the therapy and are related to dose heterogeneity and non-selectivity between normal and tumoral cells. Gold nanoparticles (AuNPs) could be used as potential radiosensitizers to overcome these therapeutic limitations of RT. This study assessed the biological interaction of different morphologies of AuNPs with ionizing radiation (IR) in PCa cells. To achieve that aim, three different amine-pegylated AuNPs were synthesized with distinct sizes and shapes (spherical, AuNPsp-PEG, star, AuNPst-PEG, and rods, AuNPr-PEG) and viability, injury and colony assays were used to analyze their biological effect on PCa cells (PC3, DU145, and LNCaP) when submitted to the accumulative fraction of RT. The combinatory effect of AuNPs with IR decreased cell viability and increased apoptosis compared to cells treated only with IR or untreated cells. Additionally, our results showed an increase in the sensitization enhancement ratio by cells treated with AuNPs and IR, and this effect is cell line dependent. Our findings support that the design of AuNPs modulated their cellular behavior and suggested that AuNPs could improve the RT efficacy in PCa cells.

Regeneration is the process of regrowth of an injured/missing tissue/organ from the residual tissue. One outstanding example is the regeneration of tail in lizards in which they can completely regenerate without the formation of scaring or fibrotic tissue. This study presents an analysis of the main differences between a mature regenerated tail and the original tail of the lizard Podarcis bocagei by comparing histological biomarkers for support structures, morphology and pigmentation, vasculature and energy storage. Matured regenerated and original tails were studied with different histological staining’s and immunohistochemistry to highlight the various tissue components. We found differences in the morphological features scalation pattern and pigmentation, as well as in the support structures: muscle organization, collagen and calcification. Vasculature was remodeled. Energy storage was restored with regeneration maintaining therefore the main metabolic function. We demonstrate that the regenerated tail does not lose its main functions like locomotion and energy metabolism. The present findings may open a new window of research with implications in regenerative medicine.

Adrenocortical tumors (ACT) are common adrenal tumors. The majority of ACTs are non-functioning and benign, while adrenocortical carcinomas (ACC) are rare, usually very aggressive and often metastasized when first diagnosed. Our aim was to assess whether blood and lymph vessel density within ACTs correlate with the malignancy character or tumor functionality. For that, the microvascular distribution was evaluated by immunohistochemistry staining with D2–40 antibody, for lymph vessels and CD-31 antibody, for blood vessels, in ACCs ( n  = 15), adenomas with Cushing syndrome ( n  = 9) and non-functioning adenomas ( n  = 10). The percentage of stained area was quantified by computerized morphometric analysis. D2–40 expression was significantly lower in ACC as compared to adenomas with Cushing syndrome ( p  < 0.01) and correlated positively with the expression of the steroidogenic acute regulatory protein (StAR) (R 2  = 0.553, p  < 0.001). CD31 expression was found to be significantly higher in ACC as compared to adenomas with Cushing syndrome ( p  < 0.05). Our results show that angiogenesis is increased in ACC, suggesting that this phenomenon may have an important role in ACT biological behavior, while lymph vascular density seems to be more closely related to the tumor functional status than malignancy.

Chronic wounds are one of the most frequent complications that are associated with diabetes mellitus. The overproduction of reactive oxygen species (ROS) is a key factor in the delayed healing of a chronic wound. In the present work, we develop a novel in situ-forming silk sericin-based hydrogel (SSH) that is produced by a simple methodology using horseradish peroxidase (HRP) crosslinking as an advanced dressing for wound healing. The antioxidant and angiogenic effects were assessed in vitro and in vivo after in situ application using an excisional wound-healing model in a genetically-induced diabetic db/db mice and though the chick embryo choriollantoic membrane (CAM) assay, respectively. Wounds in diabetic db/db mice that were treated with SSH closed with reduced granulation tissue, decreased wound edge distance, and wound thickness, when compared to Tegaderm, a dressing that is commonly used in the clinic. The hydrogel also promoted a deposition of collagen fibers with smaller diameter which may have had a boost effect in re-epithelialization. SSH treatment slightly induced two important endogenous antioxidant defenses, superoxide dismutase and catalase. A CAM assay made it possible to observe that SSH led to an increase in the number of newly formed vessels without inducing an inflammatory reaction. The present hydrogel may result in a multi-purpose technology with angiogenic, antioxidant, and anti-inflammatory properties, while advancing efficient and organized tissue regeneration.