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1.
Artigo em Inglês | MEDLINE | ID: mdl-38561175

RESUMO

Chest wall reconstruction is challenging due to the complex shape and large defect size. The three-dimensional printing technology enables the fabrication of customized implants, and 3D-printed pure-titanium could provide superior mechanical properties to conventional materials. The aim of this study was to evaluate long-term outcomes of patients undergoing chest wall reconstruction with a 3D-printed pure-titanium implant. Between August 2018 and May 2021, 5 patients underwent surgery due to sternal metastasis (n = 3), postoperative sternal wound infection (n = 1) and deformity (n = 1). The customized implant was designed and constructed based on the size and shape of the chest wall defect measured on computed tomography. All patients demonstrated uneventful recovery without complications during the hospital course. During the median follow-up of 20 months, 1 patient underwent revision surgery due to implant breakage, and 1 removed the implant due to trauma-related chest wall infection. One patient died from cancer progression, while 3 patients are alive without any implant-related complications. Chest wall reconstruction using a 3D-printed pure-titanium implant could be a novel alternative for patients with various conditions affecting the sternum and ribs.

2.
Microorganisms ; 10(12)2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36557739

RESUMO

Alcoholic liver disease (ALD), caused by excessive alcohol consumption, leads to high mortality. We investigated the hepatoprotective effect of Levilactobacillus brevis MG5311 in C57BL/6 mice with liver injuries induced by chronic ethanol plus binge feeding. L. brevis MG5311 was administered orally at a dose of 1 × 109 CFU/mouse once daily for 32 days. L. brevis MG5311 administration significantly reduced serum ALT, AST, and triglyceride (TG) levels in ethanol-fed mice. L. brevis MG5311 also decreased malondialdehyde levels and increased glutathione peroxidase (GPx) activity in liver tissues. In addition, hepatic TG content and histopathological scores were significantly reduced. L. brevis MG5311 increased the protein expression of SIRT1, PPARα, SOD1, CAT, and GPx 1/2 in liver tissue, while inhibiting CYP2E1 and SREBP-1c. These results indicated that L. brevis MG5311 alleviated ethanol-induced liver injury by inhibiting hepatic oxidative stress and promoting lipid metabolism. Therefore, L. brevis MG5311 may be a useful probiotic candidate for ameliorating or preventing ALD.

3.
Sci Rep ; 12(1): 19897, 2022 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-36400819

RESUMO

The use of cellular structures has led to unprecedented outcomes in various fields involving optical and mechanical cloaking, negative thermal expansion, and a negative Poisson's ratio. The unique characteristics of periodic cellular structures primarily originate from the interconnectivity, periodicity, and unique design of the unit cells. However, the periodicity often induces unfavorable mechanical behaviors such as a "post-yielding collapse", and the mechanical performance is often limited by the design of the unit cells. Therefore, we propose a novel structure called a meta grain structure (MGS), which is inspired by a polycrystalline structure, to enhance flexibility in design and mechanical reliability. A total of 138 different MGSs were built and tested numerically, and the correlations between the design parameters (e.g., the relative density) and mechanical properties of the MGSs were rigorously analyzed. A systematic design methodology was developed to obtain the optimal design of the MGS with the target Young's modulus. This methodology makes it possible to build a unique structure that offers various design options and overcomes the current limitations of cellular structures. Furthermore, a systematic inverse design methodology makes it possible to produce an MGS that satisfies the required mechanical performance.


Assuntos
Materiais Biocompatíveis , Porosidade , Materiais Biocompatíveis/química , Reprodutibilidade dos Testes , Módulo de Elasticidade
4.
Food Sci Biotechnol ; 31(13): 1667-1678, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36312999

RESUMO

A Box-Behnken Design (BBD) was employed to optimize the extraction of antioxidants from Ruby S apple peel by ultrasound-assisted extraction (UAE). The effect of extraction temperature (20-40 °C), extraction time (15-45 min), and ethanol concentration (50-90%) in water on extraction yield, total phenol content (TPC), total flavonoid content (TFC), and DPPH radical scavenging activity of Ruby S peel extracts (RPEs) were investigated. The optimized extraction conditions that maximized extraction yield, TPC, TFC, and DPPH radical scavenging ability, were temperature 20 °C, extraction time 25.30 min, and ethanol concentration 50%. The validity of designed model was verified, and experimental values obtained under optimum conditions concurred with predicted values. Hyperoside, isoquercitrin, and phloridzin, were among the major flavonoids extracted. Our findings demonstrate the suitability of UAE and RSM for the optimization of Ruby S peel extraction and suggest the potential use of RPEs as bioactive functional materials.

5.
Int J Mol Sci ; 23(17)2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36077182

RESUMO

Paraprobiotics, inactivated microbial cells, regulate immune system and exhibit antioxidant and anti-inflammatory activities in patients with weakened immunity or the elderly. This study evaluated the anti-tumor effects of heat-killed Bifidobacterium and Lactobacillus on human gastric cancer MKN1 cells in vitro and in vivo in xenograft animal models. First, cytotoxicity and apoptosis in MKN1 cells of 11 different heat-killed Bifidobacterium or Lactobacillus strains were examined using the MTT assay or flow cytometry, respectively. Then, BALB/c nude mice xenograft animal models were implanted with human gastric cancer MKN1 cells and orally administered a selected single or a mixture of heat-killed bacterial strains to investigate their inhibitory effect on tumor growth. In addition, the expression of p-Akt, p53, Bax, Bak, cleaved caspase-9, -3, and PARP in the tumor tissues was analyzed using Western blotting assay or immunohistochemistry staining. The results show that heat-killed B. bifidum MG731 (MG731), L. reuteri MG5346 (MG5346), and L. rhamnosus MG5200 (MG5200) induced relatively greater apoptosis than other strains in MKN1 cells. Oral administration of a single dose or a mixture of MG731, MG5346, or MG5200 significantly delayed tumor growth, and MG731 had the most effective anti-tumor effect in the xenograft model. Protein expression of p-Akt, p53, Bax, cleaved caspase-3 and -9, and PARP in tumors derived from the xenograft model correlated with the results of the immunohistochemistry staining.


Assuntos
Bifidobacterium bifidum , Neoplasias Gástricas , Idoso , Animais , Apoptose , Bifidobacterium bifidum/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Xenoenxertos , Temperatura Alta , Humanos , Camundongos , Camundongos Nus , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína X Associada a bcl-2/metabolismo
6.
Eur J Pharmacol ; 923: 174938, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35381263

RESUMO

Kurarinone (KR), a naturally occurring flavonoid in Sophora flavescens Aiton and a traditional herbal medicine, reportedly has anti-cancer activity against various cancer types both in vitro and in vivo. However, the cellular mechanism of KR remains unknown. Therefore, we aimed to elucidate the mechanism of cell cycle arrest induced by KR in human colorectal cancer cells. KR not only reduced cell proliferation but also induced G0/G1 arrest of colorectal cancer cell lines. The results of western blotting analysis showed that KR reduced the protein levels of cyclin D1/D3 and CDK4/6 by downregulating signaling proteins such as K-RAS, c-MYC, and p-extracellular signal-regulated kinase. Additionally, KR arrested the cell cycle in the G0/G1 phase in a p53-independent manner, and decreased the protein level of K-RAS by proteasomal degradation dependent on WDR76, an E3 ubiquitin ligase. From these results, we propose that KR could be a potent anti-cancer agent, acting through the degradation of K-RAS dependent on WDR76, regardless of the p53 status.


Assuntos
Proteínas de Ciclo Celular , Neoplasias Colorretais , Proteínas de Ligação a DNA , Flavonoides , Apoptose , Ciclo Celular , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , Proteínas de Ligação a DNA/metabolismo , Flavonoides/farmacologia , Pontos de Checagem da Fase G1 do Ciclo Celular , Humanos , Proteínas Proto-Oncogênicas p21(ras) , Proteína Supressora de Tumor p53/metabolismo
7.
Microorganisms ; 10(3)2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35336106

RESUMO

In this study, we examined the anti-tumor effects of heat-killed Bifidobacterium and Lactobacillus strains on human colorectal carcinoma RKO cells in in vitro and in vivo xenograft models. First, the cytotoxic and apoptotic effects of 11 different strains were examined using an MTT assay and flow cytometry, respectively. Then, xenograft BALB/c nude mice were implanted with RKO cells and orally administered with single or mixed heat-killed bacterial strains to examine their inhibitory effects on tumor growth. Additionally, the levels of cleaved caspase-9, -3, and -7 and PARP in tumor tissues were analyzed using Western blotting or immunohistochemistry staining. The results showed that RKO cells were highly susceptible to heat-killed B. bifidum MG731 and L. reuteri MG5346 and that L. casei MG4584 induced apoptosis to a greater extent than other strains. The oral administration of individual MG731, MG5346, or MG4584 significantly delayed tumor growth, and mixtures of MG5346 and MG4584 or MG731, MG5346, and MG4584 synergistically inhibited the tumor growth in the xenograft model. The expression of cleaved caspase-3, -7, and -9 and PARP in the tumor tissues was increased in Western blotting, and the expression of cleaved caspase-3 and PARP in immunohistochemistry staining was also increased. Therefore, we suggest that the use of the combination of MG5346 and MG4584 as parabiotics could effectively inhibit the growth of colorectal cancer.

8.
Microorganisms ; 10(2)2022 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-35208925

RESUMO

The present study investigated the anti-bacterial vaginitis (BV) effects of a mixture of five lactobacilli strains (LM5), containing equal amounts of Ligilactobacillus salivarius MG242, Limosilactobacillus fermentum MG901, Lactiplantibacillus plantarum MG989, Lacticaseibacillus paracasei MG4272, and Lacticaseibacillus rhamnosus MG4288), in HeLa cells and Gardnerella vaginalis (GV)-infected BV mice. All strains produced lactic acid and hydrogen peroxide, and were resistant to nonoxynol-9. LM5 significantly inhibited GV growth by 80%, exhibited good adhesion to HeLa cells, and significantly inhibited GV adhesion to these cells. In GV-infected mice, LM5 administered orally at 5 × 109 CFU/mouse significantly inhibited GV proliferation in the vaginal tract and significantly reduced myeloperoxidase activity, pro-inflammatory cytokine (TNF-α, IL-1ß, and IL-6) levels, and nitric oxide levels in vaginal tissue lysates. Histopathological analysis of vaginal tissues revealed that LM5 markedly suppressed the exfoliation of vaginal epithelial cells. Overall, these results suggest that LM5 might alleviate BV by direct antibacterial and antagonistic activity in vaginal tissues of GV-infected mice.

9.
Food Nutr Res ; 652021.
Artigo em Inglês | MEDLINE | ID: mdl-34776827

RESUMO

BACKGROUND: Excessive consumption of dietary fat is closely related to obesity, diabetes, insulin resistance, cardiovascular disease, hypertension, and non-alcoholic fatty liver disease. Recently, probiotics have been highly proposed as biotherapeutic to treat and prevent diseases. Previously, there are studies that demonstrated the beneficial effects of probiotics against metabolic disorders, including obesity and diabetes. OBJECTIVE: We investigated the anti-obesity effect and mechanism of action of four human-derived lactic acid bacterial (LAB) strains (Lacticaseibacillus rhamnosus MG4502, Lactobacillus gasseri MG4524, Limosilactobacillus reuteri MG5149, and Weissella cibaria MG5285) in high-fat diet (HFD)-induced obese mice. DESIGN: Obesity was induced in mice over 8 weeks, with a 60% HFD. The four human-derived LAB strains (2 × 108 CFU/mouse) were orally administered to male C57BL/6J mice once daily for 8 weeks. Body weight, liver and adipose tissue (AT) weights, glucose tolerance, and serum biochemistry profiles were determined. After collecting the tissues, histopathological and Western blot analyses were conducted. RESULTS: Administration of these LAB strains resulted in decreased body weight, liver and AT weights, and glucose tolerance. Serum biochemistry profiles, including triglyceride (TG), total cholesterol, low-density lipoprotein cholesterol, and leptin, pro-inflammatory cytokines, improved. Hepatic steatosis and TG levels in liver tissue were significantly reduced. In addition, the size of adipocytes in epididymal tissue was significantly reduced. In epididymal tissues, Limosilactobacillus reuteri MG5149 and Weissella cibaria MG5285 groups showed a significantly reduced expression of lipogenic proteins, including peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α, fatty acid synthase (FAS), and adipocyte-protein 2. In addition, sterol regulatory element-binding protein 1-c and its downstream protein FAS in the liver tissue were significantly decreased. These strains attenuated fat accumulation in the liver and AT by upregulating the phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase in HFD-fed mice. CONCLUSION: We suggest that L. reuteri MG5149 and W. cibaria MG5285 could be used as potential probiotic candidates to prevent obesity.

10.
Mar Drugs ; 19(8)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34436273

RESUMO

The anti-amnesic effect of a mixture (4:6 = phlorotannin:fucoidan from Ecklonia cava, P4F6) was evaluated on amyloid-beta peptide (Aß)-induced cognitive deficit mice. The cognitive function was examined by Y-maze, passive avoidance, and Morris water maze tests, and the intake of the mixture (P4F6) showed an ameliorating effect on Aß-induced learning and memory impairment. After the behavioral tests, superoxide dismutase (SOD) activity and thiobarbituric acid-reactive substances (TBARS) contents were confirmed in brain tissue, and in the results, the mixture (P4F6) attenuated Aß-induced oxidative stress. In addition, mitochondrial activity was evaluated by mitochondrial reactive oxygen species (ROS) content, mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) content, and mitochondria-mediated apoptotic signaling pathway, and the mixture (P4F6) enhanced mitochondrial function. Furthermore, the mixture (P4F6) effectively regulated tau hyperphosphorylation by regulating the protein kinase B (Akt) pathway, and promoted brain-derived neurotrophic factor (BDNF) in brain tissue. Moreover, in the cholinergic system, the mixture (P4F6) ameliorated acetylcholine (ACh) content by regulating acetylcholinesterase (AChE) activity and choline acetyltransferase (ChAT) expression in brain tissue. Based on these results, we suggest that this mixture of phlorotannin and fucoidan (P4F6) might be a substance for improving cognitive function by effectively regulating cognition-related molecules.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Kelp , Fármacos Neuroprotetores/administração & dosagem , Polissacarídeos/administração & dosagem , Taninos/administração & dosagem , Acetilcolina/metabolismo , Animais , Organismos Aquáticos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Colinérgicos/metabolismo , Modelos Animais de Doenças , Quimioterapia Combinada , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Mitocôndrias/metabolismo , Fármacos Neuroprotetores/farmacologia , Fitoterapia , Polissacarídeos/farmacologia , Taninos/farmacologia
11.
Foods ; 10(7)2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34359526

RESUMO

Periodontitis is one of the most common chronic inflammatory diseases. The anti-inflammatory effect of the extract from brown algae Ecklonia cava was analyzed in lipopolysaccharide (LPS)-stimulated human gingival fibroblasts (HGF-1), the most abundant cells in gingival tissue. The gene expressions of cyclooxygenase-2 and interleukin-6 were decreased by 78 and 50%, respectively, at 100 µg/mL Ecklonia cava extract (ECE) treatment. The gene expressions of matrix metalloproteases (MMP-2 and MMP-8) and chemokines (macrophage inflammatory protein 1-alpha and stromal cell-derived factor 1) were also significantly down-regulated by ECE treatment (p < 0.05). The increased reactive oxygen species (ROS) production in HGF-1 cells by LPS stimulation was decreased by 30% at 100 µg/mL ECE treatment. The mitogen-activated protein kinase pathway and the nuclear factor-kappa B (NF-κB) signal activated by ROS were suppressed by ECE in a dose-dependent manner. ECE treatment (400 mg/kg, 8 weeks) significantly improved alveolar bone resorption in the ligature-induced chronic periodontitis rat model. ECE supplementation also lowered elevated mRNA expression of the receptor activator of nuclear factor-kappa B (RANKL)/osteoprotegerin (OPG) in the gingival tissue (p < 0.05). Therefore, ECE mitigated gingival tissue destruction and bone resorption associated with chronic periodontitis condition.

12.
Chembiochem ; 22(24): 3425-3430, 2021 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-34263972

RESUMO

A novel autophagy inhibitor, autophazole (Atz), which promoted cancer cell death via caspase activation, is described. This compound was identified from cell-based high-content screening of an imidazole library. The results showed that Atz was internalized into lysosomes of cells where it induced lysosomal membrane permeabilization (LMP). This process generated nonfunctional autolysosomes, thereby inhibiting autophagy. In addition, Atz was found to promote LMP-mediated apoptosis. Specifically, LMP induced by Atz caused release of cathepsins from lysosomes into the cytosol. Cathepsins in the cytosol cleaved Bid to generate tBid, which subsequently activated Bax to induce mitochondrial outer membrane permeabilization (MOMP). This event led to cancer cell death via caspase activation. Overall, the findings suggest that Atz will serve as a new chemical probe in efforts aimed at gaining a better understanding of the autophagic process.


Assuntos
Antineoplásicos/farmacologia , Bibliotecas de Moléculas Pequenas/farmacologia , Antineoplásicos/química , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Estrutura Molecular , Bibliotecas de Moléculas Pequenas/química
13.
Curr Microbiol ; 78(8): 3181-3191, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34213618

RESUMO

Diabetes, a chronic metabolic disorder, is characterized by persistent hyperglycemia. This study aimed to evaluate the hypoglycemic and antioxidant activities of lactic acid bacteria strains isolated from humans and food products and investigate the probiotic properties of the selected four strains. The hypoglycemic activity of the isolated strains was examined by evaluating the α-glucosidase and α-amylase inhibitory activities. The antioxidant activity was measured using the DPPH, ABTS, and FRAP assays. Four strains (Lactiplantibacillus plantarum MG4229, MG4296, MG5025, and Lacticaseibacillus paracasei MG5012) exhibited potent α-glucosidase inhibitory (>75%) and α-amylase inhibitory (>85%) activities, which were comparable to those of acarbose (>50%; 1000 µg/mL). Similarly, the radical scavenging and antioxidant activities of the four strains were comparable to those of ascorbic acid (50 µg/mL). Additionally, the probiotic properties of the four selected strains were examined based on acid and bile salt tolerance, auto-aggregation ability, and antibiotic resistance. The four strains were resistant to pH 2 (>50% of survivability) and 0.5% bile salt (>80% of survivability). Therefore, we suggest that the selected strains with hypoglycemic, antioxidant, probiotic properties can potentially prevent diabetes.


Assuntos
Lactobacillales , Probióticos , Antioxidantes , Humanos , Hipoglicemiantes/farmacologia , alfa-Amilases
14.
Inorg Chem ; 60(15): 10857-10872, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34286969

RESUMO

Herein, we report a comprehensive coordination study of the previously reported ligands cyclam, CB-cyclam, TMC, DMC, and CB-DMC and of their C-functional analogues, cyclam-E, CB-cyclam-E, TMC-E, DMC-E, and CB-DMC-E. This group of ligands includes cyclam, cross-bridged cyclams, their di- or tetramethylated derivatives, and the analogues bearing an additional hydroxyethyl group on one ß-N position of the ring. The Cu(II) and Zn(II) complexes of these macrocycles have been highlighted previously for the biological interest, but the details of their structures in the solid state and in solution remained largely unexplored. In particular, we analyzed the impact that adding noncoordinating N-methyl and C-hydroxyethyl functionalities has in the structures of the complexes. All the Cu(II) and Zn(II) complexes were synthesized and investigated using single crystal X-ray diffraction and NMR, electronic absorption, and EPR spectroscopies, along with DFT studies. Dissociation kinetics experiments in acidic conditions and electrochemical studies were also performed. Special attention was paid to analyze the different configurations present in solution and in the solid state, as well as the impact of the C-appended hydroxyethyl group on the coordination behavior. Various ratios of the trans-I, trans-III, and cis-V configurations have been observed depending on the degree of N-methylation and the presence of the ethylene cross-bridge.

15.
Microorganisms ; 9(6)2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34070604

RESUMO

The purpose of this study was to evaluate the capacity of Lactiplantibacillus plantarum MG4296 (MG4296) and Lacticaseibacillus paracasei MG5012 (MG5012) on insulin resistance (IR) and diabetes-related metabolic changes in palmitic acid (PA)-induced HepG2 cells and high-fat diet-induced mice. In vitro, cell-free extracts of MG4296 and MG5012 alleviated IR by increasing glucose uptake and glycogen content in PA-induced insulin-resistant HepG2 cells. In vivo, MG4296 and MG5012 supplementation markedly decreased body weight and glucose tolerance. Administration of both strains also improved serum glucose, glycated hemoglobin, insulin, triglyceride, LDL/HDL ratio, and homeostatic model assessment of IR (HOMA-IR). Histopathological analysis of liver tissue demonstrated a significant reduction in lipid accumulation and glycogen content. Moreover, MG4296 and MG5012 treatment enhanced phosphoinositide-3 kinase (PI3K)/protein kinase B (Akt) expression in the liver. Overall, MG4296 and MG5012 could prevent HFD-induced glucose tolerance and hyperglycemia by improving IR. Therefore, L. plantarum MG4296 and L. paracasei MG5012 could be useful as new probiotics candidates to improve T2DM.

16.
J Microbiol Biotechnol ; 31(4): 584-591, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33782218

RESUMO

Marine algae (seaweed) encompass numerous groups of multicellular organisms with various shapes, sizes, and colors, and serve as important sources of natural bioactive substances. The brown alga Ecklonia cava Kjellman, an edible seaweed, contains many bioactives such as phlorotannins and fucoidans. Here, we evaluated the antioxidative, neuroprotective, and anti-apoptotic effects of E. cava extract (ECE), E. cava phlorotannin-rich extract (ECPE), and the phlorotannin dieckol on neuronal PC-12 cells. The antioxidant capacities of ECPE and ECE were 1,711.5 and 1,050.4 mg vitamin C equivalents/g in the ABTS assay and 704.0 and 474.6 mg vitamin C equivalents/g in the DPPH assay, respectively. The dieckol content of ECPE (58.99 mg/g) was approximately 60% higher than that of ECE (36.97 mg/g). Treatment of PC-12 cells with ECPE and ECE increased cell viability in a dose-dependent manner. Intracellular oxidative stress in PC-12 cells due to ECPE and ECE decreased dose-independently by up to 63% and 47%, respectively, compared with the stress control (323%). ECPE reduced the production of the pro-apoptotic proteins Bax and caspase-3 more effectively than ECE. Early and late apoptosis in PC-12 cells were more effectively decreased by ECPE than ECE treatments. From the results obtained in this study, we concluded that ECPE, which is rich in phlorotannins, including the marker compound dieckol, may be applied to the development of functional materials for improving cognition and memory.


Assuntos
Apoptose/efeitos dos fármacos , Benzofuranos/farmacologia , Produtos Biológicos/farmacologia , Neurônios/efeitos dos fármacos , Phaeophyceae/química , Animais , Antioxidantes/farmacologia , Caspase 3 , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Ratos , Alga Marinha , Proteína X Associada a bcl-2
17.
ACS Chem Biol ; 16(2): 360-370, 2021 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-33517652

RESUMO

Autophagy plays an important role in maintaining tumor cell progression and survival in response to metabolic stress. Thus, the regulation of autophagy can be used as a strategy for anticancer therapy. Here, we report dutomycin (DTM) as a novel autophagy enhancer that eventually induces apoptosis due to excessive autophagy. Also, human serine protease inhibitor B6 (SERPINB6) was identified as a target protein of DTM, and its novel function which is involved in autophagy was studied for the first time. We show that DTM directly binds SERPINB6 and then activates intracellular serine proteases, resulting in autophagy induction. Inhibitory effects of DTM on the function of SERPINB6 were confirmed through enzyme- and cell-based approaches, and SERPINB6 was validated as a target protein using siRNA-mediated knockdown and an overexpression test. In a zebrafish xenograft model, DTM showed a significant decrease in tumor area. Furthermore, the present findings will be expected to contribute to the expansion of novel basic knowledge about the correlation of cancer and autophagy by promoting active further research on SERPINB6, which was not previously considered the subject of cancer biology.


Assuntos
Antraciclinas/uso terapêutico , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Serpinas/metabolismo , Animais , Antraciclinas/metabolismo , Antraciclinas/farmacologia , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Células HeLa , Humanos , Serina Proteases/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Peixe-Zebra
18.
Pharm Res ; 38(1): 15-26, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33449249

RESUMO

PURPOSE: Azelaic acid (AzA) is a dicarboxylic acid naturally occurring in various grains having anti-inflammatory and anti-oxidation properties. Recently, AzA is shown to reduce high-fat diet-induced adiposity in animals. However, its physiological role in lipid metabolism and aging in various environmental stresses is unknown. METHODS AND RESULTS: Using C. elegans as an invertebrate animal model, we demonstrate that AzA suppresses fat accumulation with no effect on lifespan at normal temperatures. Moreover, AzA promotes lifespan at low temperatures by elevation of unsaturated long-chain fatty acids and expression of genes in fatty acid desaturation. We further find that genes encoding fatty acid desaturases such as fat-1, fat-5, fat-6, and fat-7 are crucial for the lifespan-extending effect of AzA at low temperature. CONCLUSIONS: Taken together, our results suggest that AzA promotes adaption to low temperature in C. elegans via shifting fatty acid profile to unsaturated long-chain fatty acids.


Assuntos
Aclimatação/efeitos dos fármacos , Temperatura Baixa/efeitos adversos , Ácidos Dicarboxílicos/administração & dosagem , Longevidade/efeitos dos fármacos , Animais , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Dessaturases/metabolismo , Ácidos Graxos Insaturados/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Modelos Animais
19.
Pharmaceutics ; 12(12)2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33352912

RESUMO

Studies on ethanol-induced stress and acetaldehyde toxicity are actively being conducted, owing to an increase in alcohol consumption in modern society. In this study, ent-peniciherqueinone (EPQ) isolated from a Hawaiian volcanic soil-associated fungus Penicillium herquei FT729 was found to reduce the acetaldehyde-induced cytotoxicity and oxidative stress in PC12 cells. EPQ increased cell viability in the presence of acetaldehyde-induced cytotoxicity in PC12 cells. In addition, EPQ reduced cellular reactive oxygen species (ROS) levels and restored acetaldehyde-mediated disruption of mitochondrial membrane potential. Western blot analyses revealed that EPQ treatment increased protein levels of ROS-scavenging heme oxygenase-1 and superoxide dismutase, as well as the levels of aldehyde dehydrogenase (ALDH) 1, ALDH2, and ALDH3, under acetaldehyde-induced cellular stress. Finally, EPQ reduced acetaldehyde-induced phosphorylation of p38 and c-Jun N-terminal kinase, which are associated with ROS-induced oxidative stress. Therefore, our results demonstrated that EPQ prevents cellular oxidative stress caused by acetaldehyde and functions as a potent agent to suppress hangover symptoms and alcohol-related stress.

20.
Food Sci Biotechnol ; 29(11): 1519-1530, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33088601

RESUMO

In this study, the anti-oxidative and neuro-protective effects of ethanolic extracts of the dried roots of Allium hookeri were investigated. Total phenolic contents and total flavonoid contents of A. hookeri extract depended on the ethanol concentrations used (50, 70 and 95%). In order to evaluate radical scavenging activity, DPPH and ABTS radical scavenging assays and ferric reducing powers were evaluated. The results showed the 95% ethanol extract of A. hookeri (95AH) had higher phenolic and flavonoid contents, and greater radical scavenging activities than 50 or 70% ethanol extracts of A. hookeri. The neuro-protective effects of 95AH were evaluated using H2O2-treated PC12 neuronal cells. Treatment of 95AH increased cell viability and superoxide dismutase and glutathione peroxidase activities, reduced lactate dehydrogenate release, reduced reactive oxygen species production, and increased Bcl-2/Bax ratio. HPLC revealed 95AH was rich in phenolics, especially catechin. These results demonstrate 95AH has substantial anti-oxidative and neuro-protective effects against H2O2-induced oxidative stress.

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