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Air pollution, a global health concern, has been associated with adverse effects on human health. In particular, particulate matter (PM), which is a major contributor to air pollution, impacts various organ systems including the skins. In fact, PM has been suggested as a culprit for accelerating skin aging and pigmentation. In this study, using single-cell RNA sequencing, IL-24 was found to be highly upregulated among the differentially expressed genes commonly altered in keratinocytes and fibroblasts of ex vivo skins exposed to PM. It was verified that PM exposure triggered the expression of IL-24 in keratinocytes, which subsequently led to a decrease in type I procollagen expression and an increase in MMP1 expression in fibroblasts. Furthermore, long-term treatment of IL-24 induced cellular senescence in fibroblasts. Through high-throughput screening, we identified chemical compounds that inhibit the IL-24-STAT3 signaling pathway, with lovastatin being the chosen candidate. Lovastatin not only effectively reduced the expression of IL24 induced by PM in keratinocytes but also exhibited a capacity to restore the decrease in type I procollagen and the increase in MMP1 caused by IL-24 in fibroblasts. This study provides insights into the significance of IL-24, illuminating mechanisms behind PM-induced skin aging, and proposes IL-24 as a promising target to mitigate PM-associated skin aging.
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Fibroblastos , Interleucinas , Queratinócitos , Material Particulado , Envelhecimento da Pele , Envelhecimento da Pele/efeitos dos fármacos , Material Particulado/toxicidade , Interleucinas/metabolismo , Interleucinas/genética , Queratinócitos/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Humanos , Senescência Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 1 da Matriz/metabolismo , Fator de Transcrição STAT3/metabolismo , Pele/efeitos dos fármacos , Poluentes Atmosféricos/toxicidadeRESUMO
BACKGROUND: Cancer is associated with an increased risk of stroke. Tumor cells activate platelets, induce a coagulation cascade, and generate thrombin. The composition of thrombi may reflect the mechanism of thrombosis, aiding the determination of the treatment strategy. Here, we investigated the composition and expression of coagulation factors in the thrombi of patients with cancer-associated stroke. METHODS: Patients with stroke who underwent endovascular thrombectomy between September 2014 and June 2020 and whose cerebral thrombi were obtained were divided into those with cancer-associated stroke (cancer group) and propensity score-matched patients without cancer (control group), using 1:1 matching based on age and sex. Immunohistochemistry was performed of the thrombi, and the composition and expression of coagulation factors were compared between groups. RESULTS: Among the 320 patients who underwent endovascular thrombectomy and who had thrombi obtained, this study included 23 patients with cancer and 23 matched controls. In both groups, the median age was 65 years, and 12 patients (52.2%) were men. Platelet composition was significantly higher in the cancer group than in the control group (median [interquartile range], 51.3% [28.0%-61.4%] versus 9.5% [4.8%-14.0%]; P<0.001). Among coagulation factors, thrombin (26.2% [16.2%-52.7%] versus 4.5% [1.3%-7.2%]; P<0.001) and tissue factors (0.60% [0.34%-2.06%] versus 0.37% [0.22%-0.60%]; P=0.024) were higher and factor X was lower (1.25% [0.39%-3.60%] versus 2.33% [1.67%-4.48%]; P=0.034) in the cancer group. There was a positive correlation between thrombin and platelets in the cancer group (r=0.666; P=0.001) but not in the control group (r=-0.167; P=0.627). CONCLUSIONS: Cerebral thrombi in patients with cancer-associated stroke showed higher proportions of platelets, thrombin, and tissue factors, suggesting their key roles in arterial thrombosis in cancer and providing a therapeutic perspective for preventing stroke in patients with cancer-associated stroke.
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Neoplasias , Acidente Vascular Cerebral , Trombose , Masculino , Humanos , Idoso , Feminino , Trombina , Trombose/patologia , Acidente Vascular Cerebral/terapia , Trombectomia/efeitos adversos , Neoplasias/complicaçõesRESUMO
BACKGROUND: We aimed to develop and validate machine learning models to diagnose patients with ischemic stroke with cancer through the analysis of histopathologic images of thrombi obtained during endovascular thrombectomy. METHODS: This was a retrospective study using a prospective multicenter registry which enrolled consecutive patients with acute ischemic stroke from South Korea who underwent endovascular thrombectomy. This study included patients admitted between July 1, 2017 and December 31, 2021 from 6 academic university hospitals. Whole-slide scanning was performed for immunohistochemically stained thrombi. Machine learning models were developed using transfer learning with image slices as input to classify patients into 2 groups: cancer group or other determined cause group. The models were developed and internally validated using thrombi from patients of the primary center, and external validation was conducted in 5 centers. The model was also applied to patients with hidden cancer who were diagnosed with cancer within 1 month of their index stroke. RESULTS: The study included 70 561 images from 182 patients in both internal and external datasets (119 patients in internal and 63 in external). Machine learning models were developed for each immunohistochemical staining using antibodies against platelets, fibrin, and erythrocytes. The platelet model demonstrated consistently high accuracy in classifying patients with cancer, with area under the receiver operating characteristic curve of 0.986 (95% CI, 0.983-0.989) during training, 0.954 (95% CI, 0.937-0.972) during internal validation, and 0.949 (95% CI, 0.891-1.000) during external validation. When applied to patients with occult cancer, the model accurately predicted the presence of cancer with high probabilities ranging from 88.5% to 99.2%. CONCLUSIONS: Machine learning models may be used for prediction of cancer as the underlying cause or detection of occult cancer, using platelet-stained immunohistochemical slide images of thrombi obtained during endovascular thrombectomy.
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AVC Isquêmico , Neoplasias , Acidente Vascular Cerebral , Trombose , Humanos , Estudos Retrospectivos , Estudos Prospectivos , AVC Isquêmico/complicações , Acidente Vascular Cerebral/etiologia , Trombectomia/métodos , Trombose/patologia , Aprendizado de Máquina , Neoplasias/complicaçõesRESUMO
Continuous consumption of high-calorie meals causes lipid accumulation in the liver and liver damage, leading to non-alcoholic fatty liver disease (NAFLD). A case study of the hepatic lipid accumulation model is needed to identify the mechanisms underlying lipid metabolism in the liver. In this study, the prevention mechanism of lipid accumulation in the liver of Enterococcus faecalis 2001 (EF-2001) was extended using FL83B cells (FL83Bs) and high-fat diet (HFD)-induced hepatic steatosis. EF-2001 treatment inhibited the oleic acid (OA) lipid accumulation in FL83B liver cells. Furthermore, we performed lipid reduction analysis to confirm the underlying mechanism of lipolysis. The results showed that EF-2001 downregulated proteins and upregulated AMP-activated protein kinase (AMPK) phosphorylation in the sterol regulatory element-binding protein 1c (SREBP-1c) and AMPK signaling pathways, respectively. The effect of EF-2001 on OA-induced hepatic lipid accumulation in FL83Bs enhanced the phosphorylation of acetyl-CoA carboxylase and reduced the levels of lipid accumulation proteins SREBP-1c and fatty acid synthase. EF-2001 treatment increased the levels of adipose triglyceride lipase and monoacylglycerol during lipase enzyme activation, which, when increased, contributed to increased liver lipolysis. In conclusion, EF-2001 inhibits OA-induced FL83B hepatic lipid accumulation and HFD-induced hepatic steatosis in rats through the AMPK signaling pathway.
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Lipólise , Hepatopatia Gordurosa não Alcoólica , Ratos , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Dieta Hiperlipídica , Enterococcus faecalis/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Temperatura Alta , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Metabolismo dos Lipídeos , Transdução de Sinais , Lipídeos/farmacologiaRESUMO
In this study, we aimed to develop natural and/or functional materials with antioxidant and anti-inflammatory effects. We obtained extracts from natural plants through an oil and hot-water extraction process and prepared an extract composite of an effective unsaturated fatty acid complex (EUFOC). Furthermore, the antioxidant effect of the extract complex was evaluated, and the anti-inflammatory effect was explored by assessing its inhibitory effect on nitric oxide production through its HA-promoting effect. We conducted a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay to evaluate the cell viability of the EUFOC, and the results showed that EUFOC was not cytotoxic at the test concentrations. In addition, it showed no endogenous cytotoxicity in HaCaT (human keratinocyte) cells. The EUFOC showed excellent 1,1-diphenyl-2-picrylhydrazyl- and superoxide-scavenging abilities. Moreover, it exerted an inhibitory effect on NO production at concentrations that did not inhibit cell viability. The secretion of all the cytokines was increased by lipopolysaccharide (LPS) treatment; however, this was inhibited by the EUFOC in a concentration-dependent manner. In addition, hyaluronic acid content was markedly increased by the EUFOC in a dose-dependent manner. These results suggest that the EUFOC has excellent anti-inflammatory and antioxidant properties, and hence, it can be used as a functional material in various fields.
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Antioxidantes , Ácido Hialurônico , Humanos , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Óxido Nítrico/metabolismo , Anti-Inflamatórios/farmacologia , CitocinasRESUMO
South Korea has developed its first Para Report Card on physical activity (PA) for children and adolescents with disabilities. Five national surveillance databases were used to evaluate PA indicators based on the benchmarks and grading rubric provided by Active Healthy Kids Global Alliance. Report card evaluation committees were invited to grade and assess the results using strengths, weaknesses, opportunities, and threats analysis. Five indicators (overall PA, D+; organized sports and PA, D-; active transportation, D-; physical fitness, D+; and government, A+) and one additional indicator (sleep, C-) were assigned a letter grade. The other five indicators were graded as incomplete. The Para Report Card revealed a significant gap between the behavioral-indicator grades (D- to D+) and the policy-indicator grade (A+), suggesting that government strategies and investment have not yet been translated into behavioral PA among children and adolescents with disabilities.
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Pessoas com Deficiência , Comportamento Sedentário , Humanos , Criança , Adolescente , Política de Saúde , Promoção da Saúde , Exercício Físico , República da CoreiaRESUMO
[This corrects the article DOI: 10.1016/j.jesf.2022.10.014.].
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Background: With intensifying air pollutant levels and the COVID-19 pandemic, physical inactivity of South Korean children and adolescents may be threatened. Therefore, monitoring and surveillance of physical activity (PA) and relevant indicators are important for policy making pertaining to health promotion. Report Card is a third comprehensive evaluation of PA-related behaviors among and the sources of influence for South Korean children and adolescents. Purpose: To provide the outcome of the South Korea's 2022 Report Card on PA for children and adolescents. Methods: Based on a variety of sources including national surveys collected pre- and during-COVID-19 and information collected from government webpages, 11 indicators were graded by a committee of experts informed by the best available evidence. Data from during-COVID-19 were available for Overall PA, Sedentary Behavior, and Sleep and considered together in generating the overall grades. Results: Grades were assigned to behavioral indicators (Overall PA: D-; Active Transportation: B+; Sedentary Behavior: D; Sleep: F) and sources of Influence (Family and Peers: C-; School: A; Community and Environment: B-; Government: A). Organized Sport and PA, Active Play, and Physical Fitness could not be graded due to the lack of data. The results largely indicated that children and adolescents show unfavorable behavioral grades even with favorable grades observed for the sources of influence indicators. Trivial differences were observed pre- and during-pandemic for Overall PA (≥60 min of MVPA for ≥4 d/wk: 20.8% vs 19.9%) and Sleep (met age-specific recommendation: 14.1% vs 15.0%); however, a marked increase in Sedentary Behavior was observed (≤2 h/d screen time: 28.8% vs 20.1%). A stark weekday vs weekend difference was observed in sleep duration. In terms of PA related sources of influence, high accessibility to PA facilities (81.1%) and high satisfaction of neighborhood public transit (74.6%) and safety (80.7%) were well reflected in our Active Transportation grade (B+). Nonetheless, perception of green environments including outdoor air quality (44.0%), noise (39.6%) and green space (56.5%) showed lower scores, suggesting that new barriers to active lifestyles are emerging for South Korean children and adolescents. Gender differences were also observed for overall PA (≥60 min of MVPA for ≥4 d/wk: 29.1% for boys vs 11.3% for girls) and sleep (met age-specific recommendations: 17.3% for boys vs 11.4% for girls), but not for sedentary behavior (≤2 h/d screen time: 26.4% for boys and 24.9% for girls). Conclusions: Government and school policies/programs and the built environment are, in general, conducive to physically active lifestyles for South Korean children and adolescents; however, behavioural indicators received poor grades except for Active Transportation. A thorough evaluation of policies/programs at government, local, and school levels is needed to ensure that the efforts to have PA-enhancing infrastructure and systems are actually being translated into the behavior of children and adolescents in South Korea. Furthermore, improving PA surveillance, monitoring, and advocacy to ultimately establish healthy lifestyle patterns among children and adolescents is a top priority.
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Scoparone (SCOP), an active and efficient coumarin compound derived from Artemisia capillaris Thunb, has been used as a traditional Chinese herbal medicine. Herein, we investigated the effects of SCOP on the osteogenic processes using MC3T3-E1 pre-osteoblasts in in vitro cell systems. SCOP (C11 H10 O4 , > 99.17%) was purified and identified from A. capillaries. SCOP (0.1 to 100 µM concentrations) did not have cytotoxic effects in pre-osteoblasts; however, it promoted alkaline phosphatase (ALP) staining and activity, and mineralized nodule formation under early and late osteogenic induction. SCOP elevated osteogenic signals through the bone morphogenetic protein 2 (BMP2)-Smad1/5/8 pathway, leading to the increased expression of runt-related transcription factor 2 (RUNX2) with its target protein, matrix metallopeptidase 13 (MMP13). SCOP also induced the non-canonical BMP2-MAPKs pathway, but not the Wnt3a-ß-catenin pathway. Moreover, SCOP promoted autophagy, migration and adhesion under the osteogenic induction. Overall, the findings of this study demonstrated that SCOP has osteogenic effects associated with cell differentiation, adhesion, migration, autophagy and mineralization.
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Subunidade alfa 1 de Fator de Ligação ao Core , Osteogênese , Autofagia , Proteína Morfogenética Óssea 2/metabolismo , Diferenciação Celular , Linhagem Celular , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Cumarínicos/farmacologia , Osteoblastos/metabolismoRESUMO
BMP2 is clinically used as an ectopic bone inducer and plays a significant role in bone development, formation, and diseases. Chitinase 3-like 1 protein (Chi3L1) is found in the skeletal system. However, Chi3L1-mediated bone metabolism and aging-related bone erosion via BMP2 signaling have not yet been demonstrated. Herein, Chi3L1 increased BMP2-induced osteoblast differentiation in mesenchymal precursor cells and human primary osteoblasts. Chi3L1KO(-/-) showed abnormal bone development, and primary osteoblasts isolated from Chi3L1KO(-/-) exhibited impaired osteoblast differentiation and maturation. Chi3L1 also potentiated BMP2 signaling and RUNX2 expression in primary osteoblasts. Chi3L1 interacted with BMPRIa, which increased the surface expression of BMPRIa and promoted BMP2 signaling to induce osteoblast differentiation. Chi3L1KO(-/-) mice showed bone formation reduced with a decrease in RUNX2 expression in calvarial defects. Chi3L1KO(-/-) mice exhibited aging-related osteoporotic bone loss with decreases in the levels of RUNX2 and OPG, while serum PYD level and osteoclast number increased. Chi3L1 increased OPG via non-canonical BMP2 signaling in osteoblasts, which suppressed osteoclastogenesis in BMMs. Furthermore, ROC analysis showed that serum Chi3L1 level clinically decreased in osteoporosis patients. Our findings demonstrate that Chi3L1 promotes bone formation, suppresses osteoclastogenesis, and prevents aging-related osteoporosis.
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Quitinases , Osteoporose , Animais , Biomarcadores/metabolismo , Diferenciação Celular , Proteína 1 Semelhante à Quitinase-3/genética , Proteína 1 Semelhante à Quitinase-3/metabolismo , Quitinases/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Humanos , Camundongos , Osteoblastos/metabolismo , Osteogênese , Osteoporose/tratamento farmacológico , Osteoporose/metabolismoRESUMO
Heart rate variability (HRV) is closely related to changes in the autonomic nervous system (ANS) associated with stress and pain. In this study, we investigated whether HRV could be used to assess cancer pain in mice with peritoneal metastases. At 12 days after cancer induction, positive indicators of pain such as physiological characteristics, appearance, posture, and activity were observed, and time- and frequency-domain HRV parameters such as mean R-R interval, square root of the mean squared differences of successive R-R intervals, and percentage of successive R-R interval differences greater than 5 ms, low frequency (LF), high frequency (HF), and ratio of LF and HF power, were found to be significantly decreased. These parameters returned to normal after analgesic administration. Our results indicate that overall ANS activity was decreased by cancer pain and that HRV could be a useful tool for assessing pain.
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Dor do Câncer , Neoplasias Peritoneais , Animais , Sistema Nervoso Autônomo , Frequência Cardíaca/fisiologia , CamundongosRESUMO
Triterpenes are a diverse group of natural compounds found in plants. Soyasapogenol B (SoyB) from Arachis hypogaea (peanut) has various pharmacological properties. This study aimed to elucidate the pharmacological properties and mechanisms of SoyB in bone-forming cells. In the present study, 1-20 µM of SoyB showed no cell proliferation effects, whereas 30-100 µM of SoyB increased cell proliferation in MC3T3-E1 cells. Next, osteoblast differentiation was analyzed, and it was found that SoyB enhanced ALP staining and activity and bone mineralization. SoyB also induced RUNX2 expression in the nucleus with the increased phosphorylation of Smad1/5/8 and JNK2 during osteoblast differentiation. In addition, SoyB-mediated osteoblast differentiation was not associated with autophagy and necroptosis. Furthermore, SoyB increased the rate of cell migration and adhesion with the upregulation of MMP13 levels during osteoblast differentiation. The findings of this study provide new evidence that SoyB possesses biological effects in bone-forming cells and suggest a potentially beneficial role for peanut-based foods.
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Arachis , Triterpenos , Autofagia , Diferenciação Celular , Linhagem Celular , Necroptose , Ácido Oleanólico/análogos & derivados , Osteoblastos/metabolismo , Saponinas , Triterpenos/metabolismo , Triterpenos/farmacologiaRESUMO
Minoxidil is the most widely used treatment for hair growth, but has been associated with several side effects. In this study, we investigated the effects of heat-killed Enterococcus faecalis EF-2001 on hair loss prevention and regrowth using human dermal papilla cells and male C57BL/6 mice. To examine the effects of EF-2001, we used minoxidil as the positive control. In the in vitro experiments, EF-2001 treatment (75-500 µg/mL) led to the proliferation of human dermal papilla cells in a concentration-dependent manner. In the in vivo experiment, the topical application of 200 µL EF-2001 on the dorsal surface of C57BL/6 male mice led to hair growth. Changes in hair regrowth were examined by visual comparison and hematoxylin and eosin staining of skin sections. We also determined the expression levels of marker genes (Wnt) and growth factors (fibroblast growth factor, insulin growth factor 1, and vascular endothelial growth factor) in the skin tissues of the back of each mouse using a quantitative polymerase chain reaction. EF-2001 accelerated the progression of hair regrowth in mice and promoted hair-follicle conversion from telogen to anagen, likely by increasing the expression levels of growth factors and marker genes.
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Enterococcus faecalis , Minoxidil , Animais , Proliferação de Células , Cabelo , Temperatura Alta , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Minoxidil/farmacologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/farmacologiaRESUMO
Stem cells have received attention in various diseases, such as inflammatory, cancer, and bone diseases. Mesenchymal stem cells (MSCs) are multipotent stem cells that are critical for forming and repairing bone tissues. Herein, we isolated calycosin-7-O-ß-glucoside (Caly) from the roots of Astragalus membranaceus, which is one of the most famous medicinal herbs, and investigated the osteogenic activities of Caly in MSCs. Caly did not affect cytotoxicity against MSCs, whereas Caly enhanced cell migration during the osteogenesis of MSCs. Caly increased the expression and enzymatic activities of ALP and the formation of mineralized nodules during the osteogenesis of MSCs. The osteogenesis and bone-forming activities of Caly are mediated by bone morphogenetic protein 2 (BMP2), phospho-Smad1/5/8, Wnt3a, phospho-GSK3ß, and phospho-AKT, inducing the expression of runt-related transcription factor 2 (RUNX2). In addition, Caly-mediated osteogenesis and RUNX2 expression were attenuated by noggin and wortmannin. Moreover, the effects were validated in pre-osteoblasts committed to the osteoblast lineages from MSCs. Overall, our results provide novel evidence that Caly stimulates osteoblast lineage commitment of MSCs by triggering RUNX2 expression, suggesting Caly as a potential anabolic drug to prevent bone diseases.
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Calcificação Fisiológica/efeitos dos fármacos , Glucosídeos/farmacologia , Isoflavonas/farmacologia , Osteogênese/efeitos dos fármacos , Animais , Astragalus propinquus/metabolismo , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Proteína Morfogenética Óssea 2/metabolismo , Calcificação Fisiológica/fisiologia , Diferenciação Celular/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Glucosídeos/isolamento & purificação , Glucosídeos/metabolismo , Humanos , Isoflavonas/isolamento & purificação , Isoflavonas/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/fisiologia , Camundongos , Células NIH 3T3 , Osteoblastos/metabolismo , Osteogênese/fisiologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologiaRESUMO
The histological features of thrombus in stroke patients with cancer are not well known. Using immunohistochemical staining of thrombi retrieved during mechanical thrombectomy in stroke patients, thrombus compositions were compared between 16 patients with active cancer, 16 patients with inactive cancer, and 16 patients without any history of cancer. The active cancer group showed higher platelet and lower erythrocyte fractions than the inactive cancer or the control group. Four patients with vegetation showed very high platelet and low erythrocyte fractions. Patients with cryptogenic etiology in the active cancer group showed a similar pattern to those with vegetation. These findings may aid the determination of treatment strategies in cancer-associated stroke. ANN NEUROL 2019.
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Trombose Intracraniana/sangue , Trombose Intracraniana/diagnóstico por imagem , Neoplasias/sangue , Neoplasias/diagnóstico por imagem , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Eritrócitos/metabolismo , Feminino , Humanos , Trombose Intracraniana/cirurgia , Masculino , Pessoa de Meia-Idade , Neoplasias/cirurgia , Estudos Prospectivos , Acidente Vascular Cerebral/cirurgia , Trombectomia/tendências , Trombose/sangue , Trombose/diagnóstico por imagem , Trombose/cirurgiaRESUMO
The disruption of the blood-brain barrier influences the degree of brain damage and prognosis in cerebral ischemia or other brain diseases accompanied by inflammation. Vascular endothelial growth factor (VEGF) released during brain ischemia or inflammation has been implicated in the breakdown of the blood-brain barrier by increasing endothelial permeability. Saxatilin, a disintegrin-containing RGD motif, has been reported to disaggregate platelets via interactions with platelet integrins and to have a thrombolysis effect. Additionally, the Fc-saxatilin fusion protein reduces vascular leakage in cerebral ischemia in mice. In this study, we show that Fc-saxatilin prevents VEGF-induced permeability in human brain microvascular endothelial cells (HBMECs). The activation of Src and Fak, downstream signaling proteins of VEGF in the induction of endothelial permeability, was inhibited by Fc-saxatilin in HBMECs. The downregulation of a tight junction protein, claudin-5, at the protein and mRNA levels by VEGF was recovered by Fc-saxatilin. Our findings suggest that Fc-saxatilin attenuates VEGF-induced endothelial permeability via the regulation of downstream signaling, and this may contribute to its protective effect against vascular leakage in the ischemic brain.
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Encéfalo/irrigação sanguínea , Permeabilidade Capilar/efeitos dos fármacos , Claudina-5/metabolismo , Desintegrinas/farmacologia , Células Endoteliais/efeitos dos fármacos , Microvasos/efeitos dos fármacos , Proteínas Recombinantes de Fusão/farmacologia , Junções Íntimas/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/farmacologia , Células Cultivadas , Claudina-5/genética , Células Endoteliais/metabolismo , Ativação Enzimática , Quinase 1 de Adesão Focal/metabolismo , Humanos , Microvasos/metabolismo , Transdução de Sinais , Junções Íntimas/metabolismo , Quinases da Família src/metabolismoRESUMO
Osseointegration is important in osteopenia and osteoporosis patients due to their low bone densities. Gold nanoparticles (GNPs) are greatly beneficial materials as osteogenic agents. The aim of this study is to investigate osseointegration between bones and double layers of GNP-immobilized titanium (Ti) implants. The physicochemical properties of the Ti surface were evaluated by scanning electron microscopy, by atomic force microscopy, by means of the contact angle using water drops, and by x-ray photoelectron spectroscopy. Osteogenic differentiation of human bone-marrow-derived mesenchymal stem cells was analyzed and showed the higher values in double layers of GNP (GNP2) groups. In addition, we performed an in vivo study using hydroxyapatite (HA) and GNP2 spine pedicle screws in ovariectomized (OVX) and SHAM rabbits. Osseointegration parameters also showed higher values in GNP2 than in HA groups. These findings suggest that implants with double layers of GNPs can be a useful alternative in osteoporotic patients.
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Durapatita/química , Ouro/química , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Nanopartículas Metálicas/química , Osseointegração/efeitos dos fármacos , Titânio/química , Titânio/farmacologia , Fosfatase Alcalina/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Nanopartículas Metálicas/ultraestrutura , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Coelhos , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Exosomes are nanosized vesicles (30-140 nm) of endocytic origin that play important roles in regenerative medicine. They are derived from cell membranes during endocytic internalization and stabilize in biological fluids such as blood and synovia. Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative disease, which, in addition to chronic pain, is characterized by progressive cartilage breakdown, condylar bone remodeling, and synovitis. However, traditional clinical treatments have limited symptom- and structure-modifying effects to restore damaged cartilage and other TMJ tissues. This is due to the limited self-healing capacity of condylar cartilage. Recently, stem-cell-derived exosomes have been studied as an alternative therapeutic approach to tissue repair and regeneration. It is known that trophic regulation of mesenchymal stem cells (MSCs) has anti-inflammatory and immunomodulatory effects under pathological conditions, and research on MSC-derived exosomes is rapidly accumulating. MSC-derived exosomes mimic the major therapeutic effects of MSCs. They affect the activity of immune effector cells and possess multilineage differentiation potential, including chondrogenic and osteogenic differentiation. Furthermore, exosomes are capable of regenerating cartilage or osseous compartments and restoring injured tissues and can treat dysfunction and pain caused by TMJ OA. In this review, we looked at the uniqueness of TMJ, the pathogenesis of TMJ OA, and the potential role of MSC-derived exosomes for TMJ cartilage and bone regeneration.
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Exossomos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Osteoartrite/metabolismo , Regeneração , Medicina Regenerativa/métodos , Articulação Temporomandibular/metabolismo , Animais , Humanos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Osteoartrite/fisiopatologia , Osteogênese , Articulação Temporomandibular/patologia , Articulação Temporomandibular/fisiopatologiaRESUMO
BACKGROUND: Lactic acid fermentation has been widely used to improve the nutritional and functional properties of food products. Cherry silverberry (Elaeagnus multiflora Thunb.) is considered as an invasive plant species with known medicinal and functional properties. In this study, improvement of the biological activity and health benefits of cherry silverberry fruit through lactic acid fermentation was investigated. RESULTS: Extracts of cherry silverberry fruits fermented by pure cultures of Lactobacillus plantarum KCTC 33131 and L. casei KCTC 13086 exhibited favorable physicochemical properties and enhanced phytochemical content, antioxidant properties (DPPH radical scavenging activity, reducing power, superoxide dismutase-like property and hydrogen peroxide scavenging activity) and α-glucosidase and tyrosinase enzyme inhibitory activity as compared with unfermented fruits. Despite a decrease in the specific phenolic acid contents among the fermented samples, the cherry silverberry fruit fermented by mixed cultures of L. plantarum and L. casei contained superior total polyphenols (3.78 ± 0.22 mg GAE g-1 ) and total (0.66 ± 0.12 mg QE g-1 ) and individual flavonoid contents in comparison with fruits fermented by single cultures and unfermented ones. Multivariate analysis also showed strong association among total phytochemical contents and biological activities. CONCLUSIONS: This work has elucidated the effect of fermentation with L. plantarum KCTC 33131 and L. casei KCTC 13086 on the improvement of the physicochemical properties and biological activity of cherry silverberry fruit. It also revealed the potential application of fermented cherry silverberry in the production of food materials beneficial for health. © 2020 Society of Chemical Industry.
Assuntos
Elaeagnaceae/microbiologia , Lactobacillus plantarum/metabolismo , Compostos Fitoquímicos/metabolismo , Antioxidantes/química , Antioxidantes/metabolismo , Elaeagnaceae/química , Elaeagnaceae/metabolismo , Fermentação , Alimentos Fermentados/análise , Alimentos Fermentados/microbiologia , Frutas/química , Frutas/metabolismo , Frutas/microbiologia , Lactobacillus plantarum/classificação , Compostos Fitoquímicos/química , Polifenóis/química , Polifenóis/metabolismoRESUMO
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