RESUMO

Arthritis, defined as a chronic inflammation often accompanied by swelling of one or more joints, encompasses more than 100 conditions that affect the joints, tissues around them as well as other connective tissues. This condition causes severe discomfort compromising the quality of life drastically, and thereby inflicts severe financial and social impact on the people affected. The incidence rate of arthritis is increasing all around the globe including the United States every year. In general, osteoarthritis (OA) affects more people in comparison to rheumatoid arthritis (RA). In the USA itself, more than 14 million people are affected by OA in comparison to 1.4 million people suffering from RA. In both conditions, elevated levels of proinflammatory cytokines have been recorded, this incidence generally precedes the cartilage degradation observed in the patients. The use of mesenchymal stem cells (MSCs) has proven to be a safe and efficient therapeutic option for treating many inflammation-rooted pathological conditions. Evidence suggests that MSCs down-regulate the effects of proinflammatory cytokines including tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1B, IL-2, and IL-17, and help restore the functions of immune cells. In addition, these cells promote the polarization of M2 phenotype macrophages, thus contributing to the suppression of the inflammatory process and consequentially to cartilage regeneration. Preclinical and clinical trials have proven the safety and effectiveness of this therapy, supported by the fact that these do not provoke any host immune response, and their influence on the cytokine profiles. An attempt to survey the results of stem cell therapy for treating arthritis has been carried out in this review.

RESUMO

Osteoarthritis (OA) is the most common degenerative joint disease. Mesenchymal stromal cells (MSC) are promising cell-based therapy for OA. However, there is still a need for additional randomized, dose-dependent studies to determine the optimal dose and tissue source of MSC for improved clinical outcomes. Here, we performed a dose-dependant evaluation of umbilical cord (UC)-derived MSC (Celllistem) in a murine model and in knee OA patients. For the preclinical study, a classical dose (200.000 cells) and a lower dose (50.000 cells) of Cellistem were intra-articularly injected into the mice knee joints. The results showed a dose efficacy response effect of Cellistem associated with a decreased inflammatory and degenerative response according to the Pritzker OARSI score. Following the same approach, the dose-escalation phase I clinical trial design included 3 sequential cohorts: low-dose group (2 × 106 cells), medium-dose group (20 × 106), and high-dose group (80 × 106). All the doses were safe, and no serious adverse events were reported. Nonetheless, 100% of the patients injected with the high-dose experienced injection-related swelling in the knee joint. According to WOMAC total outcomes, patients treated with all doses reported significant improvements in pain and function compared with baseline after 3 and 6 months. However, the improvements were higher in patients treated with both medium and low dose as compared to high dose. Therefore, our data demonstrate that the intra-articular injection of different doses of Cellistem is both safe and efficient, making it an interesting therapeutic alternative to treat mild and symptomatic knee OA patients. Trial registration ClinicalTrials.gov NCT03810521.

Assuntos

Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Osteoartrite do Joelho , Animais , Humanos , Camundongos , Injeções Intra-Articulares , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Transplante de Células-Tronco Mesenquimais/métodos , Osteoartrite do Joelho/terapia , Resultado do Tratamento , Cordão Umbilical

RESUMO

Dopamine (DA) and dopamine agonists (DA-Ag) have shown antiangiogenic potential through the vascular endothelial growth factor (VEGF) pathway. They inhibit VEGF and VEGF receptor 2 (VEGFR 2) functions through the dopamine receptor D2 (D2R), preventing important angiogenesis-related processes such as proliferation, migration, and vascular permeability. However, few studies have demonstrated the antiangiogenic mechanism and efficacy of DA and DA-Ag in diseases such as cancer, endometriosis, and osteoarthritis (OA). Therefore, the objective of this review was to describe the mechanisms of the antiangiogenic action of the DA-D2R/VEGF-VEGFR 2 system and to compile related findings from experimental studies and clinical trials on cancer, endometriosis, and OA. Advanced searches were performed in PubMed, Web of Science, SciFinder, ProQuest, EBSCO, Scopus, Science Direct, Google Scholar, PubChem, NCBI Bookshelf, DrugBank, livertox, and Clinical Trials. Articles explaining the antiangiogenic effect of DA and DA-Ag in research articles, meta-analyses, books, reviews, databases, and clinical trials were considered. DA and DA-Ag have an antiangiogenic effect that could reinforce the treatment of diseases that do not yet have a fully curative treatment, such as cancer, endometriosis, and OA. In addition, DA and DA-Ag could present advantages over other angiogenic inhibitors, such as monoclonal antibodies.

Assuntos

Endometriose , Neoplasias , Osteoartrite , Feminino , Humanos , Agonistas de Dopamina/farmacologia , Dopamina/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Endometriose/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Neoplasias/metabolismo , Adjuvantes Imunológicos/uso terapêutico , Osteoartrite/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo

RESUMO

Osteoarthritis (OA) affects nearly 240 million people worldwide. Knee OA is the most common type of arthritis, especially in older adults. Physicians measure the severity of knee OA according to the Kellgren and Lawrence (KL) scale through visual inspection of X-ray or MR images. We propose a semi-automatic CADx model based on Deep Siamese convolutional neural networks and a fine-tuned ResNet-34 to simultaneously detect OA lesions in the two knees according to the KL scale. The training was done using a public dataset, whereas the validations were performed with a private dataset. Some problems of the imbalanced dataset were solved using transfer learning. The model results average of the multi-class accuracy is 61%, presenting better performance results for classifying classes KL-0, KL-3, and KL-4 than KL-1 and KL-2. The classification results were compared and validated using the classification of experienced radiologists.

RESUMO

Abstract This study aimed to investigate the acute effects of oleic acid (OA) on glucose homeostasis in mice fed a standard chow diet (SCD) and a high-fructose, high-fat diet (HFrHFD); moreover, the role of free fatty acid receptor 1 (FFAR1) was evaluated. The mice in the two groups were further divided into three subgroups as follows: control, OA (40 mg/kg), and OA + GW1100 (0.4 mg/kg, selective FFAR1 blocker). After a 16-week feeding period, the mice received the drugs via intraperitoneal (i.p.) injection followed by an i.p. glucose tolerance test (IPGTT) 30 min later. After 3 days, the mice received the same drugs to examine the effects of the drugs on the hepatic levels of phosphatidylinositol-4,5-bisphosphate (PIP2) and diacylglycerol (DAG). OA in the SCD-fed mice significantly increased the blood glucose level (48%, P < 0.001) after 30 min of glucose load compared to that in the control group, but did not affect the levels of PIP2 and DAG. Pre-injection with GW1100 significantly decreased the area under the curve of the IPGTT (28%, P < 0.05) in the SCD group compared to that in the SCD + OA group. OA reduced the blood glucose level (35%, P < 0.001) after 120 min of glucose load in the HFrHFD-fed mice; in addition, it increased hepatic PIP2 (160%, P < 0.01) and decreased hepatic DAG (60%, P < 0.001) levels. Pre-injection with GW1100 blocked the effects of OA on hepatic PIP2 and DAG without affecting the glucose tolerance. In conclusion, OA acutely impaired the glucose tolerance in the SCD-fed mice by acting on FFAR1 but did not improve it in the HFrHFD-fed mice.

RESUMO

Diarrhetic shellfish poisoning (DSP) is a syndrome caused by the intake of shellfish contaminated with a group of lipophilic and thermostable toxins, which consists of okadaic acid (OA), dinophysistoxin-1 (DTX-1) and dinophysistoxin-2 (DTX-2). These toxins are potent protein Ser/Thr phosphatase inhibitors, mainly type 1 protein phosphatase (PP1) and type 2A protein phosphatase (PP2A). Different effects have been reported at the cellular, molecular and genetic levels. In this study, changes in cell survival and cell mobility induced by OA, DTX-1 and DTX-2 were determined in epithelial cell lines of the colon and colon cancer. The cell viability results showed that tumoral cell lines were more resistant to toxins than the nontumoral cell line. The results of the functional assays for testing cell migration, evaluation of cell death and the expression of proteins associated with cell adhesion showed a dual effect of toxins since in the nontumoral cell line, a greater induction of cell death, presumably by anoikis, was detected. In the tumoral cell lines, there was an induction of a more aggressive phenotype characterized by increased resistance to toxins, increased migration and increased FAK activation. In tumoral cell lines of colon cancer, OA, DTX-1/DTX-2 induce a more aggressive phenotype.

Assuntos

Carcinógenos/toxicidade , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/patologia , Ácido Okadáico/análogos & derivados , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quinase 1 de Adesão Focal/genética , Humanos , Concentração Inibidora 50 , Ácido Okadáico/toxicidade , Proteína Fosfatase 2/antagonistas & inibidores

RESUMO

Osteoarthritis (OA) pain has been proposed to be a mixed pain state, because in some patients, central nervous system factors are superimposed upon the more traditional peripheral factors. In addition, a considerable amount of preclinical and clinical evidence has shown that, accompanying the central neuroplasticity changes and partially driven by a peripheral nociceptive input, a real neuropathic component occurs that are particularly linked to disease severity and progression. Hence, innovative strategies targeting neuroprotection and particularly neuroinflammation to prevent and treat OA pain could be introduced. Mangiferin (MG) is a glucosylxanthone that is broadly distributed in higher plants, such as Mangifera indica L. Previous studies have documented its analgesic, anti-inflammatory, antioxidant, neuroprotective, and immunomodulatory properties. In this paper, we propose its potential utility as a multitargeted compound for mixed OA pain, even in the context of multimodal pharmacotherapy. This hypothesis is supported by three main aspects: the cumulus of preclinical evidence around this xanthone, some preliminary clinical results using formulations containing MG in clinical musculoskeletal or neuropathic pain, and by speculations regarding its possible mechanism of action according to recent advances in OA pain knowledge.

Assuntos

Analgésicos/uso terapêutico , Mangifera/química , Neuralgia/tratamento farmacológico , Osteoartrite/complicações , Xantonas/uso terapêutico , Humanos , Hiperalgesia/etiologia , Neuralgia/etiologia , Neuralgia/prevenção & controle , Neuroproteção/efeitos dos fármacos

RESUMO

We used a goat as a live incubator, along with associated nonsurgical embryo transfer techniques, to perform ex situ (in vivo) maturation of bovine oocytes. Immature bovine cumulus-oocyte complexes (COCs) aspirated from 3-8 mm follicles from slaughterhouse ovaries were randomly split into two groups for in vitro (IVM; n = 38) and ex situ maturation (ESM; n = 40). IVM was performed for a period of 24 h at 38.5 ºC and with 5% CO2 in the air of maximum humidity. For ESM, a presynchronized nulliparous goat (12 months old) received 40 immature COCs in the uterine horn apiece, via the transcervical route. After 24 h the structures were retrieved through uterine flushing. Analyses of nuclear maturation and lipid quantification were performed on oocytes from both groups. Fluorescent intensity was compared using the Student’s t-test. Forty-seven percent of the structures were recovered after uterine flushing (19/40). The nuclear maturation rate was 94.5% (18/19) and 81.6% (31/38) for the ESM and IVM groups, respectively. In vitro-matured COCs contained more lipid droplets, expressed as a higher amount (p < 0.05) of emitted fluorescent light than ex situ-matured COCs (858 ± 73 vs. 550 ± 64 arbitrary fluorescence units, respectively). This is the first report to associate nonsurgical embryo transfer techniques and a goat as a live incubator for the maturation of bovine oocytes. We

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Utilizamos uma cabra como incubadora viva, juntamente com técnicas de transferência de embriões não cirúrgicas associadas, para realizar a maturação ex situ (in vivo) de oócitos bovinos. Os complexos cumulus-oócitos bovinos (COCs), aspirados de folículos de 3-8 mm de ovários de abatedouro foram aleatoriamente divididos em dois grupos para maturação in vitro (IVM; n = 38) e ex situ (ESM; n = 40). A MIV foi realizada por um período de 24 h no meio TCM-199, a 38,5 ºC, e com 5% de CO2 em umidade máxima. Para o ESM, uma cabra nulípara pré-sincronizada (12 meses de idade) recebeu 40 COCs imaturos no ápice do corno uterino, por via transcervical. Após 24 h as estruturas foram recuperadas através de lavagem uterina. Análises de maturação nuclear e quantificação de lipídios foram realizadas em oócitos de ambos os grupos. A intensidade de fluorescente foi comparada usando o teste t de Student. Quarenta e sete por cento das estruturas foram recuperadas após lavagem uterina (19/40). A taxa de maturação nuclear foi de 94,5% (18/19) e 81,6% (31/38) para os grupos ESM e IVM, respectivamente. Os COCs maturados in vitro continham mais gotículas lipídicas, expressos como uma quantidade maior (p < 0,05) da luz fluorescente emitida do que os COCs ex situ (858 ± 73 vs 550 ± 64 unidades de fluorescência arbitrárias, respectivamente). Este é o primeiro relató

RESUMO

BACKGROUND AIMS: Fourier Transform Infrared Micro-spectroscopy (FTIRM) is an emerging tool that obtains images with biochemical information of samples that are too small to be chemically analyzed by conventional Fourier transform infrared (FTIR) spectroscopy techniques. So, the central objective of this project was to study the biochemical similarity between articular and cultured chondrocytes by chemometric analysis from FTIRM. METHODS: Nine samples of knee articular cartilage were obtained; each sample was divided into two fragments, one portion was used for FTIRM characterization in situ, and from another part, chondrocytes were obtained to be cultured (in vitro), which were subjected to an FTIRM to characterize their biomolecular components. The FTIRM spectra were normalized, and the second derivative was calculated. From these data, principal component analysis (PCA) and a chemometric comparison between in situ and cultured chondrocytes were carried out. Finally, the biochemical mapping was conducted obtaining micro-FTIR imaging. RESULTS: FTIRM spectra of in situ and in vitro chondrocytes were obtained, and different biomolecules were detected, highlighting lipids, proteins, glycosaminoglycans, collagen, and aggrecan. Despite slight differences in the FTIR spectra, the PCA proved the organic similarity between in situ chondrocytes and cultured chondrocytes, which was also observed in the analysis of the ratios related to the degradation of the articular cartilage and collagen. In the same way, the ability of the FTIRM to characterize the molecular biodistribution was demonstrated. CONCLUSION: The biochemical composition and biodistribution analysis using FTIRM have been useful for comparing cultured chondrocytes and in situ chondrocytes.

RESUMO

Free fatty acids (FFAs) are an energy source, and induce activation of signal transduction pathways that mediate several biological processes. In breast cancer cells, oleic acid (OA) induces proliferation, matrix metalloproteinase-9 (MMP-9) secretion, migration and invasion. However, the signal transduction pathways that mediate migration and invasion induced by OA in breast cancer cells have not been studied in detail. We demonstrate here that FFAR1 and FFAR4 mediate migration induced by OA in MDA-MB-231 and MCF-7 breast cancer cells. Moreover, OA induces migration, invasion, AKT1 and AKT2 activation, 12-LOX secretion and an increase of NFκB-DNA binding activity in breast cancer cells. Cell migration requires FFAR1, FFAR4, EGFR, AKT and PI3K activity, whereas invasion is mediated though a PI3K/Akt-dependent pathway. Furthermore, OA promotes relocalization of paxillin to focal contacts and it requires PI3K and EGFR activity, whereas NFκB-DNA binding activity requires PI3K and AKT activity.

RESUMO

Okadaic acid group (OA-group) is a set of lipophilic toxins which are characterised by being produced by species associated with the genera Dinophysis and Prorocentrum. OA-group has been regularly detected in endemic shellfish species from the southern zone of Chile only through the mouse bioassay. The purpose of this work was to determine the variability of OA-group toxins in endemic aquatic organisms (bivalves, crabs, gastropods and fish) and to establish the relationship with the concentration of fatty acids (FAs) detected in the evaluated species. The toxicity of OA-group and the FA profiles were determined using LC-MS/MS and gas chromatography with flame-ionisation detection, respectively. In the study area, the dinoflagellate Dinophysis acuta was detected in densities ≈2000 cells ml-1 with a toxicity ≈18.3 pg OA equiv cel-1. The analysis identified OA and dinophysistoxin-1 in shellfish in a range of ≈90 to ≈225 µg OA eq kg-1, where no toxins in fish were detected. A positive relationship between the FA level and the concentration of OA-group toxins in the digestive glands of bivalves and gastropods was established, noted for high levels of saturated FAs (C14:0 and C16:0). The toxic variability of OA-group toxins determined in the different species allowed us to establish that the consumption of these vectors, regulated by non-analytical methods, can be harmful when consumed by humans, thus suggesting that the sanitary regulations for the control of OA-group in Chile should be updated.

Assuntos

Organismos Aquáticos/química , Ácidos Graxos/análise , Toxinas Marinhas/química , Toxinas Marinhas/toxicidade , Ácido Okadáico/química , Ácido Okadáico/toxicidade , Animais , Bivalves/química , Braquiúros/química , Cromatografia Líquida , Peixes , Gastrópodes/química , Especificidade da Espécie , Espectrometria de Massas em Tandem

RESUMO

We used a goat as a live incubator, along with associated nonsurgical embryo transfer techniques, to perform ex situ (in vivo) maturation of bovine oocytes. Immature bovine cumulus-oocyte complexes (COCs) aspirated from 3-8 mm follicles from slaughterhouse ovaries were randomly split into two groups for in vitro (IVM; n = 38) and ex situ maturation (ESM; n = 40). IVM was performed for a period of 24 h at 38.5 ºC and with 5% CO2 in the air of maximum humidity. For ESM, a presynchronized nulliparous goat (12 months old) received 40 immature COCs in the uterine horn apiece, via the transcervical route. After 24 h the structures were retrieved through uterine flushing. Analyses of nuclear maturation and lipid quantification were performed on oocytes from both groups. Fluorescent intensity was compared using the Student’s t-test. Forty-seven percent of the structures were recovered after uterine flushing (19/40). The nuclear maturation rate was 94.5% (18/19) and 81.6% (31/38) for the ESM and IVM groups, respectively. In vitro-matured COCs contained more lipid droplets, expressed as a higher amount (p < 0.05) of emitted fluorescent light than ex situ-matured COCs (858 ± 73 vs. 550 ± 64 arbitrary fluorescence units, respectively). This is the first report to associate nonsurgical embryo transfer techniques and a goat as a live incubator for the maturation of bovine oocytes. We

---

Utilizamos uma cabra como incubadora viva, juntamente com técnicas de transferência de embriões não cirúrgicas associadas, para realizar a maturação ex situ (in vivo) de oócitos bovinos. Os complexos cumulus-oócitos bovinos (COCs), aspirados de folículos de 3-8 mm de ovários de abatedouro foram aleatoriamente divididos em dois grupos para maturação in vitro (IVM; n = 38) e ex situ (ESM; n = 40). A MIV foi realizada por um período de 24 h no meio TCM-199, a 38,5 ºC, e com 5% de CO2 em umidade máxima. Para o ESM, uma cabra nulípara pré-sincronizada (12 meses de idade) recebeu 40 COCs imaturos no ápice do corno uterino, por via transcervical. Após 24 h as estruturas foram recuperadas através de lavagem uterina. Análises de maturação nuclear e quantificação de lipídios foram realizadas em oócitos de ambos os grupos. A intensidade de fluorescente foi comparada usando o teste t de Student. Quarenta e sete por cento das estruturas foram recuperadas após lavagem uterina (19/40). A taxa de maturação nuclear foi de 94,5% (18/19) e 81,6% (31/38) para os grupos ESM e IVM, respectivamente. Os COCs maturados in vitro continham mais gotículas lipídicas, expressos como uma quantidade maior (p < 0,05) da luz fluorescente emitida do que os COCs ex situ (858 ± 73 vs 550 ± 64 unidades de fluorescência arbitrárias, respectivamente). Este é o primeiro relató

RESUMO

We used a goat as a live incubator, along with associated nonsurgical embryo transfer techniques, to perform ex situ (in vivo) maturation of bovine oocytes. Immature bovine cumulus-oocyte complexes (COCs) aspirated from 3-8 mm follicles from slaughterhouse ovaries were randomly split into two groups for in vitro (IVM; n = 38) and ex situ maturation (ESM; n = 40). IVM was performed for a period of 24 h at 38.5 ºC and with 5% CO2 in the air of maximum humidity. For ESM, a presynchronized nulliparous goat (12 months old) received 40 immature COCs in the uterine horn apiece, via the transcervical route. After 24 h the structures were retrieved through uterine flushing. Analyses of nuclear maturation and lipid quantification were performed on oocytes from both groups. Fluorescent intensity was compared using the Student’s t-test. Forty-seven percent of the structures were recovered after uterine flushing (19/40). The nuclear maturation rate was 94.5% (18/19) and 81.6% (31/38) for the ESM and IVM groups, respectively. In vitro-matured COCs contained more lipid droplets, expressed as a higher amount (p < 0.05) of emitted fluorescent light than ex situ-matured COCs (858 ± 73 vs. 550 ± 64 arbitrary fluorescence units, respectively). This is the first report to associate nonsurgical embryo transfer techniques and a goat as a live incubator for the maturation of bovine oocytes. We

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Utilizamos uma cabra como incubadora viva, juntamente com técnicas de transferência de embriões não cirúrgicas associadas, para realizar a maturação ex situ (in vivo) de oócitos bovinos. Os complexos cumulus-oócitos bovinos (COCs), aspirados de folículos de 3-8 mm de ovários de abatedouro foram aleatoriamente divididos em dois grupos para maturação in vitro (IVM; n = 38) e ex situ (ESM; n = 40). A MIV foi realizada por um período de 24 h no meio TCM-199, a 38,5 ºC, e com 5% de CO2 em umidade máxima. Para o ESM, uma cabra nulípara pré-sincronizada (12 meses de idade) recebeu 40 COCs imaturos no ápice do corno uterino, por via transcervical. Após 24 h as estruturas foram recuperadas através de lavagem uterina. Análises de maturação nuclear e quantificação de lipídios foram realizadas em oócitos de ambos os grupos. A intensidade de fluorescente foi comparada usando o teste t de Student. Quarenta e sete por cento das estruturas foram recuperadas após lavagem uterina (19/40). A taxa de maturação nuclear foi de 94,5% (18/19) e 81,6% (31/38) para os grupos ESM e IVM, respectivamente. Os COCs maturados in vitro continham mais gotículas lipídicas, expressos como uma quantidade maior (p < 0,05) da luz fluorescente emitida do que os COCs ex situ (858 ± 73 vs 550 ± 64 unidades de fluorescência arbitrárias, respectivamente). Este é o primeiro relató

RESUMO

Pathological α-synuclein (α-syn) overexpression and iron (Fe)-induced oxidative stress (OS) are involved in the death of dopaminergic neurons in Parkinson's disease (PD). We have previously characterized the role of triacylglycerol (TAG) formation in the neuronal response to Fe-induced OS. In this work we characterize the role of the α-syn variant A53T during Fe-induced injury and investigate whether lipid metabolism has implications for neuronal fate. To this end, we used the N27 dopaminergic neuronal cell line either untransfected (UT) or stably transfected with pcDNA3 vector (as a transfection control) or pcDNA-A53T-α-syn (A53T α-syn). The overexpression of A53T α-syn triggered an increase in TAG content mainly due to the activation of Acyl-CoA synthetase. Since fatty acid (FA) ß-oxidation and phospholipid content did not change in A53T α-syn cells, the unique consequence of the increase in FA-CoA derivatives was their acylation in TAG moieties. Control cells exposed to Fe-induced injury displayed increased OS markers and TAG content. Intriguingly, Fe exposure in A53T α-syn cells promoted a decrease in OS markers accompanied by α-syn aggregation and elevated TAG content. We report here new evidence of a differential role played by A53T α-syn in neuronal lipid metabolism as related to the neuronal response to OS.

Assuntos

Ferro/toxicidade , Neurônios/metabolismo , alfa-Sinucleína/metabolismo , Animais , Linhagem Celular , Sobrevivência Celular/genética , Gotículas Lipídicas/metabolismo , Mutação , Neurônios/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transfecção/métodos , Triglicerídeos/metabolismo , alfa-Sinucleína/genética

RESUMO

In the title compound, C12H12N2O4, the di-hydro-pyrrole ring is almost planar (r.m.s. deviation = 0.0049 Å) and is nearly coplanar with the adjacent C2O2 residue [dihedral angle = 4.56 (9)°], which links to the 4-nitro-benzene substituent [dihedral angle = 4.58 (8)°]. The mol-ecule is concave, with the outer rings lying to the same side of the central C2O2 residue and being inclined to each other [dihedral angle = 8.30 (7)°]. In the crystal, supra-molecular layers parallel to (10-5) are sustained by nitro-benzene-C-H⋯O(carbon-yl) and pyrrole-C-H⋯O(nitro) inter-actions. The layers are connected into a three-dimensional architecture by π(pyrrole)-π(nitro-benzene) stacking [inter-centroid separation = 3.7414 (10) Å] and nitro-O⋯π(pyrrole) inter-actions.

RESUMO

The present study aimed to evaluate the effect of the adjuvant use of resveratrol with meloxicam on the clinical scores of knee OA patients. This was a double-blind placebo-controlled randomised trial involving 100 patients with knee osteoarthritis performed at the Shar Teaching Hospital, Sulaimani General Hospital and Specialised Rheumatology Center, Sulaimani City from December 2016 to September 2017. The efficacy of the treatment was evaluated by measuring the changes from baseline in the KOOS score, WOMAC index, and VAS-100 score after 90 days of treatment. Resveratrol significantly improves the knee OA pain and associated symptoms compared with placebo, and both clinical scores were found to be eligible for following treatment outcomes. In conclusion, resveratrol, when used in combination with meloxicam, improves pain and symptom scores in patients with mild-to-moderate knee OA compared with placebo. The intervention with a dietary supplement may significantly impact the pain and overall quality of life in patients with knee OA.

Assuntos

Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Método Duplo-Cego , Resultado do Tratamento , Osteoartrite do Joelho/tratamento farmacológico , Resveratrol/análise , Meloxicam/análise

RESUMO

The study assesses the effects of carbon dioxide capture and storage (CCS) leaks and ocean acidification (OA) on the metal bioavailability and reproduction of the mytilid Perna perna. In laboratory-scale experiments, CCS leakage scenarios (pH 7.0, 6.5, 6.0) and one OA (pH 7.6) scenario were tested using metal-contaminated sediment elutriates and seawater from Santos Bay. The OA treatment did not have an effect on fertilisation, while significant effects were observed in larval-development bioassays where only 16 to 27 % of larva developed normally. In treatments that simulated CO2 leaks, when compared with control, fertilisation success gradually decreased and no larva developed to the D-shaped stage. A fall in pH increased the bioavailability of metals to marine mussels. Larva shell size was significantly affected by both elutriates when compared with seawater; moreover, a significant difference occurred at pH 6.5 between elutriates in the fertilisation bioassay.

Assuntos

Dióxido de Carbono/análise , Sequestro de Carbono , Metais/análise , Perna (Organismo)/efeitos dos fármacos , Água do Mar/química , Poluentes Químicos da Água/análise , Animais , Disponibilidade Biológica , Fertilidade/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Larva/metabolismo , Metais/toxicidade , Oceanos e Mares , Perna (Organismo)/crescimento & desenvolvimento , Perna (Organismo)/metabolismo , Testes de Toxicidade , Poluentes Químicos da Água/toxicidade

RESUMO

Procyanidins are highly hydroxylated polymers known as antioxidant compounds, thereby exhibiting beneficial effects. These compounds are protective agents against oxidative stress and the damage induced by free radicals in membranes and nucleic acids. This paper describes a study of the conformational space of (4α→6″, 2α→O→1″)-phenylflavan substituted with R'=R=OH as part of a larger study of similar structures with different substitutions. The relationships between aqueous solution-vacuum variations of some properties were studied, as well as the stabilization and reactivity of (4α→6″, 2α→O→1″)-phenylflavan substituted with R'=R=H, R'=H, R=OH, R'=R=OH, and (+)-catechin. The variations in geometric parameters and electronic properties due to conformational changes, as well as the effects of substituents and polar solvents, were evaluated and analyzed. Bader's theory of atoms in molecules was applied to characterize intramolecular interactions, along with a natural bond orbital analysis for each conformer described. The molecular electrostatic potential was rationalized by charge delocalization mechanisms and interatomic intramolecular interactions, relating them to the structural changes and topological properties of the electron charge density. Molecular polarizability and permanent electric dipole moment values were estimated. The results show the importance of a knowledge of the conformational space, and values for each conformer. Based on our previous results, we showed the existence of electron charge delocalization mechanisms acting cooperatively as "delocalization routes", showing interactions between different rings not even sharing the same plane. These "delocalization routes" were more effective for (4α→6″, 2α→O→1″)-phenylflavan substituted with R'=R=OH than for (+)-catechin, and are proposed as adding insight into the structure-antioxidant activity relationship of flavans.

RESUMO

The aim of this study was to investigate the effects of trans-fatty acids (TFA) on liver and serum TAG regulation in mice fed diets containing different proportions of n-3, n-6 and n-9 unsaturated fatty acids (UFA) from olive (O), maize (C) or rapeseed (R) oils partially substituted or not with TFA (Ot, Ct and Rt, respectively). Male CF1 mice were fed (30 d) one of these diets. The effects of the partial substitution (1 %, w/w) of different UFA with TFA on the activity and expression of hepatic enzymes involved in lipogenesis and fatty acids oxidation were evaluated, as well as their transcription factor expressions. Some of the mechanisms involved in the serum TAG regulation, hepatic VLDL rich in TAG (VLDL-TAG) secretion rate and lipoprotein lipase (LPL) activity were assessed. In liver, TFA induced an increase in TAG content in the Ot and Rt groups, and this effect was associated with an imbalance between lipogenesis and ß-oxidation. In the Ot group, exacerbated lipogenesis may be one of the mechanisms responsible for the liver steatosis induced by TFA, whereas in Rt it has been related to a decreased ß-oxidation, compared with their respective controls. The enhanced hepatic VLDL-TAG secretion in the Ot and Rt groups was compensated with a differential removal of TAG by LPL enzyme in extrahepatic tissues, leading to unchanged serum TAG levels. In brief, the effects of low levels of TFA on liver and serum TAG regulation in mice depend on the dietary proportions of n-3, n-6 and n-9 UFA.

Assuntos

Dieta Hiperlipídica/efeitos adversos , Gorduras Insaturadas na Dieta/metabolismo , Óleos de Plantas/metabolismo , Ácidos Graxos trans/farmacologia , Triglicerídeos/metabolismo , Animais , Óleo de Milho/química , Óleo de Milho/metabolismo , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-6/administração & dosagem , Ácidos Graxos Ômega-6/metabolismo , Fígado Gorduroso/metabolismo , Leucotrienos/metabolismo , Lipogênese , Lipase Lipoproteica/metabolismo , Lipoproteínas VLDL/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Azeite de Oliva/química , Azeite de Oliva/metabolismo , Oxirredução , Óleos de Plantas/química , Óleo de Brassica napus , Triglicerídeos/biossíntese

RESUMO

BACKGROUND: In acute lung injury (ALI), rupture of the alveolar-capillary barrier determines the protein-rich fluid influx into alveolar spaces. Previous studies have reported that methylene blue (MB) attenuates such injuries. This investigation was carried out to study the MB effects in pulmonary capillary permeability. METHODS: Wistar rats were divided into five groups: (I) Sham: saline bolus; (II) MB, MB infusion for 2 h; (III) oleic acid (OA), OA bolus; (IV) MB/OA, MB infusion for 2 h, and at 5 min after from the beginning, concurrently with an OA bolus; and (V) OA/MB, OA bolus, and after 2 h, MB infusion for 2 h. After 4 h, blood, bronchoalveolar lavage (BAL), and lung tissue were collected from all groups for analysis of plasma and tissue nitric oxide, calculation of the wet weight to dry weight ratio (WW/DW), and histological examination of lung tissue. Statistical analysis was performed using nonparametric test. RESULTS: Although favourable trends have been observed for permeability improvement parameters (WW/WD and protein), the results were not statistically significant. However, histological analysis of lung tissue showed reduced lesion areas in both pre- and post-treatment groups. CONCLUSIONS: The data collected using this experimental model was favourable only through macroscopic and histological analysis. These observations are valid for both MB infusions before or after induction of ALI.