Omega-3 polyunsaturated fatty acids (PUFAs) are considered immunonutrients and are commonly used in the nutritional therapy of cancer patients due to their ample biological effects. Omega-3 PUFAs ...play essential roles in cell signaling and in the cell structure and fluidity of membranes. They participate in the resolution of inflammation and have anti-inflammatory and antinociceptive effects. Additionally, they can act as agonists of G protein-coupled receptors, namely, GPR40/FFA1 and GPR120/FFA4. Cancer patients undergo complications, such as anorexia-cachexia syndrome, pain, depression, and paraneoplastic syndromes. Interestingly, the 2017 European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines for cancer patients only discuss the use of omega-3 PUFAs for cancer-cachexia treatment, leaving aside other cancer-related complications that could potentially be managed by omega-3 PUFA supplementation. This critical review aimed to discuss the effects and the possible underlying mechanisms of omega-3 PUFA supplementation in cancer-related complications. Data compilation in this critical review indicates that further investigation is still required to assess the factual benefits of omega-3 PUFA supplementation in cancer-associated illnesses. Nevertheless, preclinical evidence reveals that omega-3 PUFAs and their metabolites might modulate pivotal pathways underlying complications secondary to cancer, indicating that this is a promising field of knowledge to be explored.
This study further investigated the mechanisms underlying the rat model of tooth pulp inflammatory pain elicited by complete Freund's adjuvant (CFA), in comparison to other pulpitis models. Pulps of ...the left maxillary first molars were accessed. In the CFA group, the pulps were exposed, and CFA application was followed by dental sealing. In the open group, the pulps were left exposed to the oral cavity. For the closed group, the pulps were exposed, and the teeth were immediately sealed. Naïve rats were used as negative controls. Several parameters were evaluated at 1, 2, 3 and 8 days. There was no statistical significant difference among the groups when body weight variation, food or water consumption were compared. Analysis of serum cytokines (IL-1β, TNF or IL-6) or differential blood cell counts did not reveal any evidence of systemic inflammation. The CFA group displayed a significant reduction in the locomotor activity (at 1 and 3 days), associated with an increased activation of satellite glial cells in the ipsilateral trigeminal ganglion (TG; for up to 8 days). Amygdala astrocyte activation was unaffected in any experimental groups. We provide novel evidence indicating that CFA-induced pulp inflammation impaired the locomotor activity, with persistent activation of ipsilateral TG satellite cells surrounding sensory neurons, without any evidence of systemic inflammation or amygdala astrogliosis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Individuals with dentofacial deformities often display a low quality of life (QoL) through biological mechanisms that remain unraveled. In this case–control study, the salivary levels of ...cytokines, glutamate, and kynurenine metabolites were assessed in patients undergoing orthognathic surgery (OS), while correlating these parameters with QoL and psychological symptoms. Thirty-six patients were enrolled in control (under orthodontic treatment) and test (undergoing OS) groups, matched by age and sex. The QoL was assessed through the World Health Organization Quality of Life BREF (WHOQOL-BREF) and the Orthognathic Quality of Life Questionnaire (OQLQ). The psychological symptoms were evaluated by the Satisfaction with Life Scale, the Rosenberg Self-Esteem Scale (RSES), and the Depression, Anxiety, and Stress Scale-21 (DASS-21). The salivary levels of IL-1β, IL-6, IL-10, glutamate, and kynurenine metabolites were evaluated. The OQLQ demonstrated increased QoL scores in the test group, regarding social aspects, facial esthetics, and function domains, without significant differences in respect to the other surveys. These patients displayed higher IL-1β and glutamate levels; conversely, the kynurenine metabolites were unaltered. The glutamate levels positively correlated with the OQLQ function scores. The data brings novel evidence about the psychobiological features of patients with dentofacial deformities, showing salivary variations of inflammatory biomarkers in these individuals.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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Pharmaconutrition is an area of current interest, especially concerning the advances in the pharmacology of nutrient-sensing receptors, as have been accomplished in the last 20 years. ...The family of free fatty acid (FFA) receptors is composed of four members, sequentially named as FFA1 to FFA4, which are activated by the short to long-chain fatty acids. The affinity of the FFA1 and FFA4 receptors for the omega-3 polyunsaturated fatty acids prompted pre-clinical and clinical investigations regarding their involvement in metabolic diseases. The main studies have been focused on the receptors’ expression analyses, the featuring of knockout mice, and the assessment of selective synthetic ligands. These clearly have indicated a relevant role for FFA1 and FFA4 in the peripheral and central circuits for the regulation of energetic metabolism. This review article aimed to discuss the relevance of the FFA1 and FFA4 receptors in appetite-related complications, mainly related to obesity, cancer cachexia, and anorexia in the elderly, emphasizing whether their pharmacological modulation might be useful for the management of these disorders.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Purpose
After extraction, dental alveolus filling aims to reduce bone loss and maintain the alveolus volume during patient rehabilitation. Boric acid (BA) is a boron-derived compound with osteogenic ...properties and an interesting candidate for alveoli filling. This study aims to investigate the osteogenic capacity of the local application of BA in dental socket preservation.
Methods
Thirty-two male Wistar rats were submitted to upper right incisor extraction and randomly divided into four groups (
n
= 8): control group (no intervention), BA (8 mg/kg) socket filling, bone graft (Cerabone®, Botiss, Germany), and BA + bone graft socket filling. Animals were euthanized 28 days after dental extraction. MicroCT and histological analysis were performed to evaluate the newly formed bone on the dental alveolus.
Results
MicroCT analysis demonstrated that bone volume fraction (BV/TV), bone surface (BS), bone surface/bone volume ratio (BS/BV), bone surface density (BS/TV), trabecular thickness (Tb.Th), total bone porosity (Po-tot), and total volume of pore space (Po.V(tot)) from BA and BA + bone graft rats were significantly different from the control group. Histological evaluation displayed a delayed bone repair in BA rats, with the presence of connective tissue and inflammatory infiltrate. However, the BA + bone graft group demonstrated histological aspects like the bone graft animals, with less organized osteoblasts, suggesting inferior bone repair.
Conclusion
Osteogenic capacity did not depend on the BA local application after 28 days of dental extraction. The presence of inflammation in the BA group can represent toxicity induced by the substance dosage used.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•Environmental enrichment (EE) did not alter CFA-induced hypernociception.•Peripherally, EE reduced the acute edema formation and inflammatory scores.•At the central level, EE prevented the microglia ...activation in pre-frontal cortex.•Finally, EE potentiated the hippocampal BDNF expression.
This study analyzed whether environmental enrichment (EE) modulates the nociceptive and inflammatory responses in the mouse model of arthritis induced by Complete Freund’s Adjuvant (CFA). Ninety male mice (C57BL/6-JUnib, 4-weeks-old; 20–25 g) were distributed into EE and standard (SE) groups. For EE, mice were kept in bigger cages using an alternation of materials to chew (wood and paper), for nesting (cotton), to use as hiding places (plastic tunnels), and for voluntary exercise (wheel running). Arthritis was induced by an injection of CFA (50 μL) into the right hind paw or saline solution in the control group. Separate groups received the anti-inflammatory drug dexamethasone (0.5 mg/kg; every 48 h). Inflammatory and pain measurements were performed from 1 to 35 days after CFA administration. EE per se reduced the acute paw edema formation and arthritis scores. The serum levels of tumor necrosis factor (TNF) were undetectable in any experimental groups. EE diminished the immunopositivity for the microglia marker IBA1 in the pre-frontal cortex, with slight changes for hippocampal GFAP-positive activated astrocytes. Finally, EE induced a marked increment of brain-derived nerve factor (BDNF) expression in the hippocampus, an effect that was fully prevented by dexamethasone. These data bring novel evidence on the peripheral and central effects of EE in a mouse arthritis model.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
We have previously demonstrated that fructose supplementation (FS), given in a scheme used for inducing metabolic syndrome (MS), elicited pain relief in the nitroglycerin (NTG)-elicited rat migraine ...model. Herein, we evaluated whether FS could reestablish the impaired metabolic pathways in NTG-injected rats.
Male Wistar rats (N = 40) were divided into two groups for receiving 10 % FS or tap water. After 45 days, they were subdivided into NTG-injected (10 mg/kg; 15 days) or controls. After the fourth NTG injection, 18F-fluorodeoxyglucose (18F FDG) micro-PET scanning was accomplished. The day after, euthanasia was performed, and blood was collected for glycemia and LDH analysis. The levels of energy molecules, TBARS, PGC-1α, and MCTS1 were evaluated in the brain cortices. The activated satellite glial cells (SGC) were assessed in the trigeminal ganglion (TG).
There were no variations of glycemia or LDH serum levels. NTG-injected rats showed a significant increase in glucose uptake in the hypothalamus (HT) vs. NTG-free rats. The FS-NTG group showed increased metabolism in the superior colliculus (SC) vs. the NTG group. Moreover, the glucose uptake was amplified in the inferior colliculus (IC) of the FS-NTG vs. FS group. The cortical inosine levels were significantly higher in FS-NTG rats vs. NTG or FS groups, with no changes in TBARS or MCTS1 levels, despite a minor decrease of PGC1-α contents in the FS+NTG group. Finally, there was a significant increase of activated SGC around TG in the FS-NTG rats.
We provide novel evidence linking nutrition and metabolism with migraine.
•Fructose modulated brain glucose uptake in nitroglycerin-treated rats.•It also increased cortical inosine levels.•Fructose led to the activation of trigeminal satellite glial cells (SGC).•Fructose helps to recuperate brain homeostasis in nitroglycerin-injected rats.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Young tropical forests have higher relative plant densities of potentially nodulating Leguminosae species than old forests, but comparisons of their proportions of effective N-fixing plants and ...amounts of fixed N are scarce. We determined leaf N stocks derived from symbiotic biological N fixation in woody legumes of young and old forests under the following five edaphoclimatic conditions, in Northeastern Brazil: (1) humid lowland coastal; (2) humid montane; (3) subhumid high fertility soil; (4) semiarid high fertility soil; and (5) semiarid montane low fertility soil. N amounts derived from fixation and stocked in the leaves were estimated using the
15
N natural abundance technique. Fixed N stocks in the leaves were low in both young and old forests of the nutrient-poor semiarid montane forests (< 0.3 kg ha
−1
) due to the low relative densities of nodulating legume plants (15 and 10 pl ha
−1
, respectively), despite most individuals of the nodulating species fixing N. The relative density of nodulating species in the four other sites was higher in the young (148 to 635) than in the old forests (42 to 327 pl ha
−1
), as was the density of effectively fixing plants (96 to 265 vs. 9 to 140 pl ha
−1
). Leaf N stocks were also higher in the young than in the old forests, especially in the coastal humid forest (15.6 vs. 3.2 kg ha
−1
), except in the humid montane site (2.4 vs. 6.2 kg ha
−1
), due to the large N-fixing legume leaf biomass of the old forest. N fixation seems to provide an ecological advantage over non N-fixing plants in young tropical forests, usually growing on N poor soils, but not in semiarid forests growing on soils which are poor in other nutrients, like P, in which fixation is very low. However, the advantage of N-fixing legumes may also be related to other environmental variables and fixation continues to play a role in old forests.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Free fatty acid (FFA) receptors FFA1 and FFA4 are omega-3 molecular targets in metabolic diseases; however, their function in cancer cachexia remains unraveled. We assessed the role of FFA1 and FFA4 ...receptors in the mouse model of cachexia induced by Lewis lung carcinoma (LLC) cell implantation. Naturally occurring ligands such as α-linolenic acid (ALA) and docosahexaenoic acid (DHA), the synthetic FFA1/FFA4 agonists GW9508 and TUG891, or the selective FFA1 GW1100 or FFA4 AH7614 antagonists were tested. FFA1 and FFA4 expression and other cachexia-related parameters were evaluated. GW9508 and TUG891 decreased tumor weight in LLC-bearing mice. Regarding cachexia-related end points, ALA, DHA, and the preferential FFA1 agonist GW9508 rescued body weight loss. Skeletal muscle mass was reestablished by ALA treatment, but this was not reflected in the fiber cross-sectional areas (CSA) measurement. Otherwise, TUG891, GW1100, or AH7614 reduced the muscle fiber CSA. Treatments with ALA, GW9508, GW1100, or AH7614 restored white adipose tissue (WAT) depletion. As for inflammatory outcomes, ALA improved anemia, whereas GW9508 reduced splenomegaly. Concerning behavioral impairments, ALA and GW9508 rescued locomotor activity, whereas ALA improved motor coordination. Additionally, DHA improved grip strength. Notably, GW9508 restored abnormal brain glucose metabolism in different brain regions. The GW9508 treatment increased leptin levels, without altering uncoupling protein-1 downregulation in visceral fat. LLC-cachectic mice displayed FFA1 upregulation in subcutaneous fat, but not in visceral fat or gastrocnemius muscle, whereas FFA4 was unaltered. Overall, the present study shed new light on FFA1 and FFA4 receptors' role in metabolic disorders, indicating FFA1 receptor agonism as a promising strategy in mitigating cancer cachexia.
Alveolitis occurs after dental extraction without blood clot formation, leading to an inflammatory process and bacterial contamination. Boric acid (BA) demonstrates anti-inflammatory, antimicrobial, ...and osteogenic properties. This study aims to evaluate the possible antimicrobial effects and bone repair of BA in a rat model of alveolitis (dry socket).
33 male Wistar rats were submitted to the extraction of the upper right incisor and dry socket induction. They were first divided into two groups: dry socket (n = 17) and dry socket + 0.75 % BA (n = 16). Samples for the microbiological analysis were collected immediately after dental extraction, at the detection of clinical alveolitis, 7, and 14 days after BA application. For microCT and histological analysis, samples from euthanized rats were used in 14 and 28 days after alveolitis detection.
Higher bacterial counts were found in 4–5 days after alveolitis induction, compared to the baseline in both experimental groups, decreasing significantly after 7 and 14 days of treatment with BA (P < 0.05). The microCT evaluation displayed increased bone volume, bone volume fraction, trabecular thickness, and bone mineral density in a time-dependent manner, regardless of BA treatment. On the other hand, the number of trabeculae and total bone porosity decreased over the 28 days of the experiment in the dry-socket group and both groups, respectively (P < 0.05). Histological analysis did not differ on bone repair in both experimental groups.
This was the first report investigating the effects of BA in a rat model of alveolitis regarding microbiological and bone repair aspects. The BA local application decreased the total aerobic and facultative bacteria counts and does not seem to benefit the bone repair after alveolitis development. This study paves the way for more studies involving alveolitis and different BA applications.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP