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1.
Adv Mater ; 36(4): e2307402, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37989225

RESUMO

For optimizing steady-state performance in organic electrochemical transistors (OECTs), both molecular design and structural alignment approaches must work in tandem to minimize energetic and microstructural disorders in polymeric mixed ionic-electronic conductor films. Herein, a series of poly(diketopyrrolopyrrole)s bearing various lengths of aliphatic-glycol hybrid side chains (PDPP-mEG; m = 2-5) is developed to achieve high-performance p-type OECTs. PDPP-4EG polymer with the optimized length of side chains exhibits excellent crystallinity owing to enhanced lamellar and backbone interactions. Furthermore, the improved structural ordering in PDPP-4EG films significantly decreases trap state density and energetic disorder. Consequently, PDPP-4EG-based OECT devices produce a mobility-volumetric capacitance product ([µC*]) of 702 F V-1 cm-1 s-1 and a hole mobility of 6.49 ± 0.60 cm2 V-1 s-1 . Finally, for achieving the optimal structural ordering along the OECT channel direction, a floating film transfer method is employed to reinforce the unidirectional orientation of polymer chains, leading to a substantially increased figure-of-merit [µC*] to over 800 F V-1 cm-1 s-1 . The research demonstrates the importance of side chain engineering of polymeric mixed ionic-electronic conductors in conjunction with their anisotropic microstructural optimization to maximize OECT characteristics.

2.
J Cachexia Sarcopenia Muscle ; 14(6): 2908-2915, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37964719

RESUMO

BACKGROUND: Myosteatosis and liver steatosis (LS) have been recognized as patient-derived image biomarkers that correlate with prognosis in colorectal cancer (CRC) patients. However, the significance of considering fat deposition in multiple body areas simultaneously has been underestimated. This study aimed to investigate the combined effect of myosteatosis and LS in stage I-III CRC patients. METHODS: A total of 616 stage I-III CRC patients were included in the study. Myosteatosis was assessed using skeletal muscle radiodensity (SMD), and LS was estimated by calculating the Hounsfield unit of the liver and spleen ratio (LSR). Cox proportional hazard models were utilized to evaluate disease-free survival (DFS). A combination of myosteatosis and LS was proposed, and its discriminatory performance was compared using the C-index. RESULTS: Among the 616 participants, the median (interquartile) age was 64 (55-72) years, and 240 (38.9%) were female. The median and interquartile range of LSR were determined as 1.106 (0.967-1.225). The optimal cutoff value for LSR was identified as 1.181, leading to the classification of patients into low (410, 66.5%) and high LSR (206, 33.4%) groups. Among the patients, 200 were categorized into the low SMD group, while 416 were allocated to the high SMD group. Both myosteatosis and LS were identified as independent prognostic factors in the multivariable analysis. The combination of these two variables resulted in a three-group classification: high SMD with low LSR group, high SMD with high LSR group, and low SMD group. When comparing the C-index values, the three-group classification exhibited superior discriminatory performance compared with considering myosteatosis and LS separately. CONCLUSIONS: Myosteatosis was associated with poorer survival, while the presence of LS was linked to a better prognosis in non-metastatic CRC patients. Simultaneously considering fat infiltration can serve as a more effective prognosticator in non-metastatic CRC patients.


Assuntos
Neoplasias Colorretais , Fígado Gorduroso , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Prognóstico , Músculo Esquelético/patologia , Neoplasias Colorretais/patologia , Modelos de Riscos Proporcionais , Fígado Gorduroso/complicações , Fígado Gorduroso/patologia
3.
Nat Commun ; 14(1): 7577, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38016963

RESUMO

Despite the growing interest in dynamic behaviors at the frequency domain, there exist very few studies on molecular orientation-dependent transient responses of organic mixed ionic-electronic conductors. In this research, we investigated the effect of ion injection directionality on transient electrochemical transistor behaviors by developing a model mixed conductor system. Two polymers with similar electrical, ionic, and electrochemical characteristics but distinct backbone planarities and molecular orientations were successfully synthesized by varying the co-monomer unit (2,2'-bithiophene or phenylene) in conjunction with a novel 1,4-dithienylphenylene-based monomer. The comprehensive electrochemical analysis suggests that the molecular orientation affects the length of the ion-drift pathway, which is directly correlated with ion mobility, resulting in peculiar OECT transient responses. These results provide the general insight into molecular orientation-dependent ion movement characteristics as well as high-performance device design principles with fine-tuned transient responses.

4.
Chem Mater ; 35(8): 3290-3299, 2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37123107

RESUMO

Emergent bioelectronic technologies are underpinned by the organic electrochemical transistor (OECT), which employs an electrolyte medium to modulate the conductivity of its organic semiconductor channel. Here we utilize postpolymerization modification (PPM) on a conjugated polymer backbone to directly introduce glycolated or anionic side chains via fluoride displacement. The resulting polymers demonstrated increased volumetric capacitances, with subdued swelling, compared to their parent polymer in p-type enhancement mode OECTs. This increase in capacitance was attributed to their modified side chain configurations enabling cationic charge compensation for thin film electrochemical oxidation, as deduced from electrochemical quartz crystal microbalance measurements. An overall improvement in OECT performance was recorded for the hybrid glycol/ionic polymer compared to the parent, owing to its low swelling and bimodal crystalline orientation as imaged by grazing-incidence wide-angle X-ray scattering, enabling its high charge mobility at 1.02 cm2·V-1·s-1. Compromised device performance was recorded for the fully glycolated derivative compared to the parent, which was linked to its limited face-on stacking, which hindered OECT charge mobility at 0.26 cm2·V-1·s-1, despite its high capacitance. These results highlight the effectiveness of anionic side chain attachment by PPM as a means of increasing the volumetric capacitance of p-type conjugated polymers for OECTs, while retaining solid-state macromolecular properties that facilitate hole transport.

5.
Clin Cosmet Investig Dermatol ; 15: 1919-1931, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36133400

RESUMO

Background: Poria cocos (PC), a fungus, has been used for more than 2000 years as a food and medicine in China. PC and its components have various pharmacological effects on the skin, including immunomodulatory activities, barrier function improvement, and anti-tumor effects. However, the effect of PC in aquaporin-3 (AQP3) expression, which is essential for epidermal water permeability barrier maintenance, was not reported. Methods: This study examined the mechanism through which the ethanol extract of the sclerotium of PC (EPC) promoted the expression of AQP3 in cultured human keratinocytes. Western blotting was used to investigate the expression of AQPs and the activation of phosphoinositide 3-kinase (PI3K)/Akt-related signaling molecules in HaCaT cells. Cells were treated with inhibitors of PI3K/Akt and mechanistic target of rapamycin (mTOR) prior to EPC treatment. Results: EPC promoted the expression of AQP3 in HaCaT cells without affecting AQP1 and AQP2 expression. Phosphorylated Akt levels were increased by EPC treatment, and the inhibition of PI3K by LY2940002 resulted in a reduction in EPC-induced AQP3 expression. Furthermore, EPC stimulated the phosphorylation of p70S6K and AktSer473, which are downstream targets of mTORC1 and mTORC2, respectively. The mTOR complex inhibitors, rapamycin and Torin 1, partially reduced EPC-induced AQP3 expression. Conclusion: These results suggest that EPC increased expression of AQP3, which is important for skin moisturization, by activating the PI3K/Akt/mTOR signaling pathway in human keratinocytes.

6.
Cancers (Basel) ; 14(1)2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-35008418

RESUMO

The flare phenomenon (FP) on bone scintigraphy after the initiation of systemic treatment seriously complicates evaluations of therapeutic response in patients with bone metastases. The aim of this study was to evaluate whether serum alkaline phosphatase (ALP) can differentiate FP from disease progression on bone scintigraphy in these patients. Breast or prostate cancer patients with bone metastases who newly underwent systemic therapy were reviewed. Pretreatment baseline and follow-up data, including age, pathologic factors, type of systemic therapy, radiologic and bone scintigraphy findings, and ALP levels, were obtained. Univariate and multivariate analyses of these factors were performed to predict FP. An increased extent and/or new lesions were found in 160 patients on follow-up bone scintigraphy after therapy. Among the 160 patients, 80 (50%) had an improvement on subsequent bone scintigraphy (BS), while subsequent scintigraphy also showed an increased uptake in 80 (50%, progression). Multiple regression analysis revealed that stable or decreased ALP was an independent predictor for FP (p < 0.0001). ALP was an independent predictor for FP on subgroup analysis for breast and prostate cancer (p = 0.001 and p = 0.0223, respectively). Results of the study suggest that ALP is a useful serologic marker to differentiate FP from disease progression on bone scintigraphy in patients with bone metastasis. Clinical interpretation for scintigraphic aggravation can be further improved by the ALP data and it may prevent fruitless changes of therapeutic modality by misdiagnosis of disease progression in cases of FP.

7.
Surgeon ; 20(3): e3-e6, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33931346

RESUMO

BACKGROUND: In most patients with severe, chronic extremity ischemic diseases, intervention or surgical treatment is often not suitable. Combination of intramuscular transplantation of autologous monocular bone marrow cells (AMBMCs) and sympathectomy (L2, 3) has been proved therapeutically beneficial. METHODS: We studied 170 patients (combined group 80, control group 90) with extremity ischemia (TAO, ASO FontaineⅡ,Ⅲ, Ⅳ) between January 2013 and September 2019. RESULTS: In contrast to pre-operation, the walking distance of patients increased significantly (from 61.34 ± 52.23 m to 156.0 ± 32.4 m, p < 0.01), and the ankle-brachial index (ABI) remarkably improved (from 0.28 ± 0.13 to 0.59 ± 0.23, p < 0.05). CONCLUSION: Combined therapy is feasible and effective for patients with peripheral arterial disease (PAD).


Assuntos
Transplante de Medula Óssea , Doença Arterial Periférica , Células da Medula Óssea , Doença Crônica , Humanos , Isquemia/cirurgia , Doença Arterial Periférica/cirurgia , Simpatectomia , Transplante Autólogo , Resultado do Tratamento
8.
Adv Mater ; 33(10): e2007550, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33538016

RESUMO

Despite the importance of carrier mobility, recent research efforts have been mainly focused on the improvement of volumetric capacitance in order to maximize the figure-of-merit, µC* (product of carrier mobility and volumetric capacitance), for high-performance organic electrochemical transistors. Herein, high-performance microfiber-based organic electrochemical transistors with unprecedentedly large µC* using highly ordered crystalline poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) microfibers with very high carrier mobilities are reported. The strain engineering via uniaxial tension is employed in combination with solvent-mediated crystallization in the course of drying coagulated fibers, resulting in the permanent preferential alignment of crystalline PEDOT:PSS domains along the fiber direction, which is verified by atomic force microscopy and transmission wide-angle X-ray scattering. The resultant strain-engineered microfibers exhibit very high carrier mobility (12.9 cm2 V-1 s-1 ) without the trade-off in volumetric capacitance (122 F cm-3 ) and hole density (5.8 × 1020  cm-3 ). Such advantageous electrical and electrochemical characteristics offer the benchmark parameter of µC* over ≈1500 F cm-1  V-1  s-1 , which is the highest metric ever reported in the literature and can be beneficial for realizing a new class of substrate-free fibrillar and/or textile bioelectronics in the configuration of electrochemical transistors and/or electrochemical ion pumps.


Assuntos
Equipamentos e Provisões Elétricas , Microtecnologia/instrumentação , Compostos Orgânicos , Anisotropia
9.
Foods ; 9(11)2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33126674

RESUMO

Producers of soy sauce are constantly making efforts to improve the sensory quality and nutritional value of their products. In this study, radishes, apples, and pears were used to prepare a distinctly flavored soy sauce, and the lactic acid bacteria, volatile compound content, and nutritional and functional qualities of the product were compared with two commercial flavored soy sauce products. Comparable physiochemical properties, antioxidant activities (in vitro and cellular), and higher prevalence of lactic acid bacteria (7.74 ± 0.55 log CFU mL-1) were observed in the prepared flavored soy sauce than in commercial flavored soy sauce. The comprehensive enzyme activity profile of the isolated lactic acid bacteria, Tetragenococcus halophilus (NCBI GenBank Accession no. MN270899), revealed the absence of any harmful enzymes such as ß-glucuronidase. Moreover, the cell-free extract of T. halophilus showed xanthine oxidase inhibitory activity (half maximal inhibitory concentration (IC50) = 0.79 mg mL-1), suggesting that the product possessed functionality against xanthine oxidase-induced oxidative stress. Additionally, the prepared flavored soy sauce had higher amounts of total free amino acids (48.68 mg mL-1) and organic acids (7.77 mg mL-1). These results suggest that radishes, apples, and pears at a defined ratio are suitable for the large scale production of a flavored soy sauce with improved nutritional and functional qualities.

10.
Am J Chin Med ; 48(4): 987-1003, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32431181

RESUMO

Our previous report revealed that Gardenia jasminoides (GJ) has protective effects against acute pancreatitis. So, we examined whether aqueous extract of GJ has anti-inflammation and antifibrotic effects even against cerulein-induced chronic pancreatitis (CP). CP was induced in mice by an intraperitoneal injection of a stable cholecystokinin (CCK) analogue, cerulein, six times a day, four days per week for three weeks. GJ extract (0.1 or 1[Formula: see text]g/kg) or saline (control group) were intraperitoneally injected 1[Formula: see text]h before first cerulein injection. After three weeks of stimulation, the pancreas was harvested for the examination of several fibrotic parameters. In addition, pancreatic stellate cells (PSCs) were isolated using gradient methods to examine the antifibrogenic effects of GJ. In the cerulein-induced CP mice, the histological features of the pancreas showed severe tissue damage such as enlarged interstitial spaces, inflammatory cell infiltrate and glandular atrophy, and tissue fibrosis. However, treatment of GJ reduced the severity of CP such as pancreatic edema and inflammatory cell infiltration. Furthermore, treatment of GJ increased pancreatic acinar cell survival, and reduced pancreatic fibrosis and activation of PSC in vivo and in vitro. In addition, GJ treatment inhibited the activation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase (ERK) in the PSCs. These results suggest that GJ attenuated the severity of CP and the pancreatic fibrosis by inhibiting JNK and ERK activation during CP.


Assuntos
Ceruletídeo/efeitos adversos , Gardenia/química , Pancreatite Crônica/tratamento farmacológico , Pancreatite Crônica/prevenção & controle , Fitoterapia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Animais , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Fibrose , Injeções Intraperitoneais , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Pâncreas/patologia , Células Estreladas do Pâncreas/patologia , Pancreatite Crônica/induzido quimicamente , Pancreatite Crônica/patologia , Extratos Vegetais/isolamento & purificação
11.
Mol Med Rep ; 21(1): 258-266, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31746359

RESUMO

The major role of inner medullary collecting duct (IMCD) cells is to maintain water and sodium homeostasis. In addition to the major role, it also participates in the protection of renal and systemic inflammation. Although IMCD cells could take part in renal and systemic inflammation, investigations on renal inflammation in IMCD cells have rarely been reported. Although berberine (BBR) has been reported to show diverse pharmacological effects, its anti­inflammatory and protective effects on IMCD cells have not been studied. Therefore, in the present study, we examined the anti­inflammatory and protective effects of BBR in mouse IMCD­3 (mIMCD­3) cells against lipopolysaccharide (LPS). An MTT assay was carried out to investigate the toxicity of BBR on mIMCD­3 cells. Reverse transcription quantitative­PCR and western blotting were performed to analysis pro­inflammatory molecules and cytokines. Mechanisms of BBR were examined by western blotting and immunocytochemistry. According to previous studies, pro­inflammatory molecules, such as inducible nitric oxide synthase and cyclooxygenase­2, and pro­inflammatory cytokines, such as interleukin (IL)­1ß, IL­6 and tumor necrosis factor­α are increased in LPS­exposed mIMCD­3 cells. However, the production of these pro­inflammatory molecules is significantly inhibited by treatment with BBR. In addition, BBR inhibited translocation of nuclear factor (NF)­κB p65 from the cytosol to the nucleus, and degradation of inhibitory κ­Bα in LPS­exposed mIMCD­3 cells. In conclusion, BBR could inhibit renal inflammatory responses via inhibition of NF­κB signaling and ultimately contribute to amelioration of renal injury during systemic inflammation.


Assuntos
Berberina/farmacologia , Inflamação/tratamento farmacológico , Rim/efeitos dos fármacos , Fator de Transcrição RelA/genética , Animais , Linhagem Celular , Ciclo-Oxigenase 2/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/induzido quimicamente , Inflamação/patologia , Interleucina-1beta/genética , Interleucina-6/genética , Rim/patologia , Lipopolissacarídeos/toxicidade , Camundongos , NF-kappa B/genética , Óxido Nítrico Sintase/genética , Transdução de Sinais/efeitos dos fármacos
12.
Mol Immunol ; 114: 620-628, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31542607

RESUMO

Acute pancreatitis (AP) is a severe inflammatory condition of the pancreas, with no specific treatment available. We have previously reported that Nardostachys jatamansi (NJ) ameliorates cerulein-induced AP. However, the specific compound responsible for this inhibitory effect has not been identified. Therefore, in the present study, we focused on a single compound, 8α-hydroxypinoresinol (HP), from NJ. The aim of this study was to determine the effect of HP on the development of pancreatitis in mice and to explore the underlying mechanism(s). AP was induced by the injection of cerulein (50 µg/kg/h) for 6 h. HP (0.5, 5 or 10 mg/kg, i.p.) was administered 1 h prior to and 1, 3 or 5 h after the first cerulein injection, with vehicle- and DMSO-treated groups as controls. Blood samples were collected to determine serum levels of amylase, lipase, and cytokines. The pancreas was removed for morphological examination, myeloperoxidase (MPO) assays, cytokine assays, and assessment of nuclear factor (NF)-κB activation. The lungs were removed for morphological examination and MPO assays. Administration of HP dramatically improved pancreatic damage and pancreatitis-associated lung damage and also reduced amylase and lipase activities in serum. Moreover, administration of HP reduced the production of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 in the pancreas and serum during AP. In addition, the administration of HP inhibited degradation of inhibitory κ-Bα (Iκ-Bα), NF-κB p65 translocation into nucleus and NF-κB binding activity in the pancreas. Our results suggest that HP exerted therapeutic effects on pancreatitis and these beneficial effects may be due to the inhibition of NF-κB activation.


Assuntos
Ceruletídeo/farmacologia , Furanos/farmacologia , Lignanas/farmacologia , Nardostachys/química , Pâncreas/efeitos dos fármacos , Pancreatite/induzido quimicamente , Pancreatite/tratamento farmacológico , Fator de Necrose Tumoral alfa/metabolismo , Animais , Citocinas/metabolismo , Feminino , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Pâncreas/metabolismo , Pancreatite/metabolismo , Transdução de Sinais/efeitos dos fármacos
13.
Mol Med Rep ; 20(4): 3709-3718, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485676

RESUMO

Chronic pancreatitis (CP) is characterized by recurrent pancreatic injury, resulting in inflammation and fibrosis. Currently, there are no drugs for the treatment of pancreatic fibrosis associated with CP. Piperine, a natural alkaloid found in black pepper, has been reported to show anti­inflammatory, anti­oxidative, and antitumor activities. Although piperine exhibits numerous properties in regards to the regulation of diverse diseases, the effects of piperine on CP have not been established. To investigate the effects of piperine on CP in vivo, we induced CP in mice through the repetitive administration of cerulein (50 µg/kg) six times at 1­h intervals, 5 times per week, for a total of 3 weeks. In the pre­treatment groups, piperine (1, 5, or 10 mg/kg) or corn oil were administrated orally at 1 h before the first cerulein injection, once a day, 5 times a week, for a total of 3 weeks. In the post­treatment groups, piperine (10 mg/kg) or corn oil was administered orally at 1 or 2 week after the first cerulein injection. Pancreases were collected for histological analysis. In addition, pancreatic stellate cells (PSCs) were isolated to examine the anti­fibrogenic effects and regulatory mechanisms of piperine. Piperine treatment significantly inhibited histological damage in the pancreas, increased the pancreatic acinar cell survival, reduced collagen deposition and reduced pro­inflammatory cytokines and chemokines. In addition, piperine treatment reduced the expression of fibrotic mediators, such as α­smooth muscle actin (α­SMA), collagen, and fibronectin 1 in the pancreas and PSCs. Moreover, piperine treatment reduced the production of transforming growth factor (TGF)­ß in the pancreas and PSCs. Furthermore, piperine treatment inhibited TGF­ß­induced pSMAD2/3 activation but not pSMAD1/5 in the PSCs. These findings suggest that piperine treatment ameliorates pancreatic fibrosis by inhibiting TGF­ß/SMAD2/3 signaling during CP.


Assuntos
Alcaloides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Benzodioxóis/uso terapêutico , Pancreatite Crônica/tratamento farmacológico , Piperidinas/uso terapêutico , Alcamidas Poli-Insaturadas/uso terapêutico , Proteínas Smad/imunologia , Fator de Crescimento Transformador beta/imunologia , Animais , Modelos Animais de Doenças , Feminino , Fibrose , Camundongos , Camundongos Endogâmicos C57BL , Pâncreas/efeitos dos fármacos , Pâncreas/imunologia , Pâncreas/patologia , Pancreatite Crônica/imunologia , Pancreatite Crônica/patologia , Transdução de Sinais/efeitos dos fármacos
15.
Int Immunopharmacol ; 69: 225-234, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30738992

RESUMO

Heme oxygenase-1 (HO-1) has an anti-inflammatory action in acute pancreatitis (AP). However, its mechanism of action and natural compounds/drugs to induce HO-1 in pancreas are not well understood. In this study, we investigated the regulatory mechanisms of HO-1 during AP using desoxo-narchinol-A (DN), the natural compound inducing HO-1 in the pancreas. Female C57/BL6 Mice were intraperitoneally injected with supramaximal concentrations of cerulein (50 µg/kg) hourly for 6 h to induce AP. DMSO or DN was administered intraperitoneally, then mice were sacrificed 6 h after the final cerulein injection. Administration of DN increased pancreatic HO-1 expression through activation of activating protein-1, mediated by mitogen-activated protein kinases. Furthermore, DN treatment reduced the pancreatic weight-to-body weight ratio as well as production of digestive enzymes and pro-inflammatory cytokines. Inhibition of HO-1 by tin protoporphyrin IX abolished the protective effects of DN on pancreatic damage. Additionally, DN treatment inhibited neutrophil infiltration into the pancreas via regulation of chemokine (C-X-C motif) ligand 2 (CXCL2) by HO-1. Our results suggest that DN is an effective inducer of HO-1 in the pancreas, and that HO-1 regulates neutrophil infiltration in AP via CXCL2 inhibition.


Assuntos
Quimiocina CXCL2/metabolismo , Heme Oxigenase-1/metabolismo , Neutrófilos/fisiologia , Pâncreas/metabolismo , Pancreatite/metabolismo , Doença Aguda , Amilases/sangue , Animais , Ceruletídeo/administração & dosagem , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Naftóis/metabolismo , Infiltração de Neutrófilos , Pâncreas/patologia , Pancreatite/patologia
16.
Int Immunopharmacol ; 69: 169-177, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30716587

RESUMO

Inflammasomes promote the production of pro-inflammatory cytokines, such as interleukin (IL)-1ß and IL-18, which are the representative mediators of inflammation. Abnormal activation of inflammasomes leads to the development of inflammatory diseases such as acute pancreatitis (AP). In this study, we demonstrate the inhibitory effects of a new natural compound fraxinellone on inflammasome formation and examine the role of inflammasomes in a mouse model of AP. AP was induced with hourly intraperitoneal injections of supramaximal concentrations of the stable cholecystokinin analogue cerulein (50 µg/kg) for 6 h. Mice were sacrificed 6 h after the final cerulein injection. Blood and pancreas samples were obtained for further experiments. Intraperitoneal injection of fraxinellone significantly inhibited the pancreatic activation of multiple inflammasome molecules such as NACHT, LRR and PYD domains-containing protein 3 (NLRP3), PY-CARD, caspase-1, IL-18, and IL-1ß during AP. In addition, fraxinellone treatment inhibited pancreatic injury, elevation in serum amylase and lipase activities, and infiltration of inflammatory cells such as neutrophils and macrophages but had no effect on pancreatic edema. To investigate whether inflammasome activation leads to the infiltration of inflammatory cells, we used parthenolide, a well-known natural inhibitor, and IL-1 receptor antagonist mice. The inhibition of inflammasome activation by pharmacological/or genetic modification restricted the infiltration of inflammatory cells, but not edema, consistent with the results observed with fraxinellone. Taken together, our study highlights fraxinellone as a natural inhibitor of inflammasomes and that inflammasome inhibition may lead to the suppression of inflammatory cells during AP.


Assuntos
Anti-Inflamatórios/uso terapêutico , Benzofuranos/uso terapêutico , Inflamassomos/metabolismo , Inflamação/tratamento farmacológico , Macrófagos/imunologia , Neutrófilos/imunologia , Pancreatite/tratamento farmacológico , Doença Aguda , Animais , Movimento Celular/efeitos dos fármacos , Ceruletídeo/administração & dosagem , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
17.
Food Res Int ; 109: 614-625, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29803491

RESUMO

Three refined and four unrefined branded commercial sugars available in Korea were investigated in terms of pH, soluble solids, moisture, ash content, turbidity, color values, microbial profile, reducing power, 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activities, cellular antioxidant activity, and total phytoconstituent (i.e. phenolic, flavonoid, mineral, sucrose, glucose, and fructose) contents using standard analytical protocols such as high-performance liquid chromatography, gas chromatography-flame ionization detector/mass spectrometry, and inductively coupled plasma atomic emission spectroscopy. All tested physicochemical parameters were within the recommended standard levels. Significantly high nutritional and antioxidant properties were observed for the unrefined sugars, especially AUNO® sugar, whereas a high sucrose content was detected for the refined sugars. Hence, this study revealed that the degree of purification affects the nutritional values and antioxidant potentials of sugars. The present findings also indicate that unrefined sugars can be used as sweeteners in sugar-based cuisine to obtain nutritional and antioxidant-rich foodstuff.


Assuntos
Antioxidantes/química , Açúcares da Dieta/química , Valor Nutritivo , Edulcorantes/química , Bactérias/isolamento & purificação , Cor , Análise de Alimentos/métodos , Manipulação de Alimentos/métodos , Microbiologia de Alimentos/métodos , Concentração de Íons de Hidrogênio , Solubilidade , Água/análise
18.
Pancreas ; 46(8): 1046-1055, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28797013

RESUMO

OBJECTIVES: We set out to examine whether berberine (BBR) might affect the severity of pancreatitis and pancreatitis-associated lung injury in choline-deficient ethionine-supplemented (CDE) diet-induced severe acute pancreatitis. METHODS: Severe acute pancreatitis was induced by feeding a CDE diet for 3 days. Berberine was administered intraperitoneally during CDE diet. Mice were killed on days 1, 2, and 3 after the onset of CDE diet. The severity of pancreatitis was assessed by evaluating changes to the pancreas and lung and survival rate. Blood, pancreas, and lung were harvested for further examination. Furthermore, the regulating mechanisms of BBR were evaluated on the pancreas. RESULTS: Administration of BBR significantly inhibited histological damage to the pancreas and lung and decreased serum level of amylase and lipase, myeloperoxidase activity, cytokine production, and the mortality rate. Furthermore, administration of BBR inhibited activation of nuclear factor kappa B, c-Jun N-terminal kinases, and p38 in the pancreas during CDE diet. CONCLUSIONS: These findings suggest that BBR attenuates the severity of pancreatitis by inhibiting activation of nuclear factor kappa B, c-Jun N-terminal kinase, and p38 and that BBR could be used as a beneficial agent to regulate AP.


Assuntos
Berberina/farmacologia , Lesão Pulmonar/prevenção & controle , Pulmão/efeitos dos fármacos , Pâncreas/efeitos dos fármacos , Pancreatite Necrosante Aguda/prevenção & controle , Amilases/sangue , Animais , Colina/isolamento & purificação , Dieta/efeitos adversos , Etionina/administração & dosagem , Feminino , Lipase/sangue , Pulmão/metabolismo , Pulmão/patologia , Lesão Pulmonar/mortalidade , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Pâncreas/metabolismo , Pâncreas/patologia , Pancreatite Necrosante Aguda/etiologia , Pancreatite Necrosante Aguda/mortalidade , Fitoterapia/métodos , Taxa de Sobrevida
20.
Enzyme Microb Technol ; 104: 56-68, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28648181

RESUMO

A quantitative carbapenemase assay was developed using laser desorption/ionization mass spectrometry (LDI-MS) based on a parylene-matrix chip. As a first step, the reproducibility (spot-to-spot, shot-to-shot, and day-to-day) of LDI-MS based on a parylene-matrix chip and the quantification ranges for four carbapenem antibiotics (doripenem, ertapenem, imipenem, and meropenem) were determined. A carbapenem-susceptibility test was performed using the four carbapenems and 51 bacterial strains that displayed (1) carbapenem resistance with carbapenemase, (2) carbapenem resistance without carbapenemase, or (3) carbapenem susceptibility. The susceptibility test results showed that LDI-MS based on a parylene-matrix chip was more sensitive and selective for detecting the carbapenemase reaction than conventional MALDI-TOF MS based on a 2,5-dihydroxybenzoic acid matrix.


Assuntos
Proteínas de Bactérias/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , beta-Lactamases/análise , Bactérias/efeitos dos fármacos , Bactérias/enzimologia , Carbapenêmicos/metabolismo , Carbapenêmicos/farmacologia , Gentisatos , Testes de Sensibilidade Microbiana , Polímeros , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/estatística & dados numéricos , Xilenos , Resistência beta-Lactâmica
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