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1.
J Craniofac Surg ; 34(4): 1185-1190, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-36727990

RESUMO

BACKGROUND: Enophthalmos is one of the most distressing complications of blowout orbital fractures. Although several studies have been conducted on the topic of indications of early surgical correction, none have been performed using a set of measurable parameters. METHODS: The study quantitatively examined orbital fracture areas (OFA) and volumes (OFV) retrospectively of 242 patients with isolated medial orbital wall fractures that were treated conservatively during a 12-year period (from 2009 to 2021). Three plastic surgeons measured enophthalmos >6 months after trauma. The correlations between parameters and enophthalmos in the study cohort were analyzed. In addition, patients treated operatively, and nonoperatively were compared with assess the suitability of the predictive model. RESULTS: Significant correlations were observed between several parameters and late enophthalmos. Total 2.59 cm 2 of OFA (ie, OFA >2.59 cm 2 ) or 1.45 cm 3 of OFV (ie, OFV >1.45 cm 3 ) corresponds to 2 mm of enophthalmos. Multiple regression analysis revealed the following coefficients: -0.208 is a constant ( P <0.001), with 0.695 and 0.372 for OFA and OFV, respectively ( P <0.001 for both OFA and OFV). CONCLUSIONS: The study shows that enophthalmos can be more accurately predicted when OFA and OFV are simultaneously considered in patients with isolated medial wall fractures. Finally, an algorithm and a "blowout fracture coordinate plane" was proposed to aid treatment decision-making in isolated medial wall fractures.


Assuntos
Enoftalmia , Fraturas Orbitárias , Humanos , Enoftalmia/cirurgia , Enoftalmia/complicações , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/efeitos adversos , Órbita/cirurgia , Fraturas Orbitárias/complicações , Fraturas Orbitárias/diagnóstico por imagem , Fraturas Orbitárias/cirurgia
2.
Molecules ; 26(15)2021 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-34361637

RESUMO

Ganoderma lucidum extract is a potent traditional remedy for curing various ailments. Drying is the most important postharvest step during the processing of Ganoderma lucidum. The drying process mainly involves heat (36 h at 60 °C) and freeze-drying (36 h at -80 °C). We investigated the effects of different postharvest drying protocols on the metabolites profiling of Ganoderma lucidum using GC-MS, followed by an investigation of the anti-neuroinflammatory potential in LPS-treated BV2 microglial cells. A total of 109 primary metabolites were detected from heat and freeze-dried samples. Primary metabolite profiling showed higher levels of amino acids (17.4%) and monosaccharides (8.8%) in the heat-dried extracts, whereas high levels of organic acids (64.1%) were present in the freeze-dried samples. The enzymatic activity, such as ATP-citrate synthase, pyruvate kinase, glyceraldehyde-3-phosphatase dehydrogenase, glutamine synthase, fructose-bisphosphate aldolase, and D-3-phosphoglycerate dehydrogenase, related to the reverse tricarboxylic acid cycle were significantly high in the heat-dried samples. We also observed a decreased phosphorylation level of the MAP kinase (Erk1/2, p38, and JNK) and NF-κB subunit p65 in the heat-dried samples of the BV2 microglia cells. The current study suggests that heat drying improves the production of ganoderic acids by the upregulation of TCA-related pathways, which, in turn, gives a significant reduction in the inflammatory response of LPS-induced BV2 cells. This may be attributed to the inhibition of NF-κB and MAP kinase signaling pathways in cells treated with heat-dried extracts.


Assuntos
Anti-Inflamatórios , Antineoplásicos Fitogênicos , Neoplasias/tratamento farmacológico , Reishi/química , Metabolismo Secundário , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Dessecação , Camundongos , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia
3.
BMC Complement Med Ther ; 24(1): 217, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844985

RESUMO

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory condition characterized by the accumulation of reactive oxygen species and the expression of inflammatory factors. Regarding its anti-atopic activity, numerous traditional medicinal materials and secondary metabolic products play pivotal roles in modulating the associated mechanisms. METHODS: This study aimed to utilize Salvia miltiorrhiza Bunge (SMB) as an anti-AD source. In-vitro activity assessments and qualitative and quantitative analyses using UPLC-TQ-MS/MS and HPLC-DAD were conducted in two cultivars ('Dasan' and 'Kosan'). Statistical analysis indicated that the profiles of their secondary metabolites contribute significantly to their pharmacological properties. Consequently, bio-guided fractionation was undertaken to figure out the distinct roles of the secondary metabolites present in SMB. RESULTS: Comparative study of two cultivars indicated that 'Dasan', having higher salvianolic acid A and B, exhibited stronger antioxidant and anti-inflammatory activities. Meanwhile, 'Kosan', containing higher tanshinones, showed higher alleviating activities on anti-AD related genes in mRNA levels. Additionally, performed bio-guided fractionation re-confirmed that the hydrophilic compounds of SMB can prevent AD by inhibiting accumulation of ROS and suppressing inflammatory factors and the lipophilic components can directly inhibit AD. CONCLUSIONS: SMB was revealed as a good source for anti-AD activity. Several bioactive compounds were identified from the UPLC-TQ-MS/MS and different compounds content was linked to biological activities. Characterization of these compounds may be helpful to understand differential role of secondary metabolites from SMB on alleviation of AD.


Assuntos
Anti-Inflamatórios , Dermatite Atópica , Extratos Vegetais , Salvia miltiorrhiza , Salvia miltiorrhiza/química , Dermatite Atópica/tratamento farmacológico , Extratos Vegetais/farmacologia , Humanos , Anti-Inflamatórios/farmacologia , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo
4.
J Plast Surg Hand Surg ; 57(1-6): 46-53, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36260732

RESUMO

Background: There is still no consensus on managing zone II level partial flexor tendon lacerations, and the management of zone II partial flexor tendon injuries is controversial. No reliable large cohort studies or metaanalysis papers on partial flexor tendon laceration management are available in PubMed or Embase.Methods: We searched PubMed, Embase, Cochrane Library, Insight, Scopus, and Web of Science databases for primary research articles investigating outcomes of patients with partial flexor tendon injuries. The initial search was limited to human studies that were published from 1970-2021 and indexed as randomized controlled or clinical trials or observational, cross-sectional, or cohort studies. We used statistical package R version 4.1.2 for this meta-analysis.Results: The Standardised mean difference (SMD) of the common effects model was 2.020 (95% CI; 1.583-2.457; P < 0.0001), indicating that the results of conservative treatment without surgical intervention are similar to surgical intervention or better in some articles. The SMD of the random effect model was 7.093 (95% CI; 1.090-13.096; P < 0.0206), indicating the same result. Higgins' I2 value was 97.6%, indicating serious heterogeneity.Conclusions: In this first meta-analysis on flexor zone II conservative treatment, five papers with publication bias were analyzed. It is meaningful to verify the result of conservative treatment statistically. Even though this is a heterogeneous paper, conservative treatment seems to have a lot of benefits for the patient, including offering a fairly solid longterm prognosis with very few complications.


Assuntos
Lacerações , Traumatismos dos Tendões , Humanos , Lacerações/cirurgia , Tratamento Conservador , Estudos Transversais , Traumatismos dos Tendões/cirurgia , Tendões/cirurgia
5.
Antioxidants (Basel) ; 12(11)2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-38001762

RESUMO

The Lamiaceae family is widely recognized for its production of essential oils and phenolic compounds that have promising value as pharmaceutical materials. However, the impact of environmental conditions and different harvest stages on the phytochemical composition of Lamiaceae plants remains poorly understood. This study aimed to investigate the effects of harvest time on the phytochemical composition, including rosmarinic acid (RA) and volatile organic compounds (VOCs), of four Lamiaceae plants-Korean mint (AR), lemon balm (MO), opal basil (OBP), and sage (SO)-and was conducted under an environment-controlled system. Although all four plants had RA as the dominant compound, its distribution varied by species. The flowered plants, including AR and OBP, exhibited a rapid increase of RA during the transition from the vegetative stage to the reproductive stage. In contrast, non-flowered groups, including MO and SO, showed a steady increase in the content of total phenolics and RA. The main components of VOCs also differed depending on the plant, with characteristic fragrance compounds identified for each one (AR: estragole; MO: (Z)-neral and geranial; OBP: methyl eugenol, eugenol, and linalool; and SO: (Z)-thujone, camphor, and humulene). The total VOCs content was highest on the 60th day after transplanting regardless of the species, while the trends of total phenolics, RA content, and antioxidant activities were different depending on whether plant species flowered during the cultivation cycle. There was a steady increase in species that had not flowered, and the highest content and activity of the flowering period were confirmed in the flowering plant species.

6.
Front Plant Sci ; 14: 1124827, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37025137

RESUMO

The metabolome of strawberries at harvest determines their storage capacity. Therefore, dynamics of volatile production during storage of strawberry cultivated under diverse drainage ratios, T1 (12.0%), T2 (25.3%), T3 (36.4%), and T4 (56.5%), were evaluated. Among the various non-target VOCs analysis, there were some groups including aldehydes, esters, and furans occupied over 5% with exhibiting high coefficient of determination (R2 ) following the days after storage (DAS). Aldehydes content decreased over the storage period, while the esters (methyl butanoate, methyl hexanoate, ethyl hexanoate, and benzyl acetate) and furanones (furaneol and mesifuran) were increased as representing aroma compounds in strawberry ripening. Even on the same day, it was investigated that the release of VOCs linked to fruit decay was delayed in the groups (T1 and T2) that were given relatively little water compared to T3 and T4. The hexanal and ethyl hexanoate as an over-ripened signal showed a rapid increase from 4 DAS to 5 DAS in T3 and T4, respectively, while T1 and T2 showed significant increase from 5 DAS to 6 DAS. Relatively slower over-ripening tendency of T1 and T2 was supported by changes of firmness, total soluble solid content, anthocyanin content, and antioxidant activity during storage. T1 and T2 showed higher antioxidant activity at the harvest time and lower anthocyanin accumulation than T3 and T4. The present study elucidated that the preharvest drainage changes during cultivation was involved in fruit quality during strawberry storage. Besides, volatilomics analysis depicted that T2 as an optimal ratio, could delay the occurrence of stress and senescence, and guaranteed the strawberry yield. In conclusion, this study provided evidence that the practical application of drainage ratios could improve horticultural product quality even with low water use and VOCs might be considered an early indicator for strawberry fruit shelf-life.

7.
Plast Reconstr Surg ; 152(1): 45-54, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-36728206

RESUMO

BACKGROUND: Silicone implant augmentation rhinoplasty along with various tip plasties are commonly performed in Asian patients, but a revision rhinoplasty is frequently required because of various problems. Secondary rhinoplasties are often performed using silicone, dermofat, costal cartilage block, or diced rib cartilage, but often result in unsatisfactory outcomes. This study assessed the surgical outcomes and complications of cross-linked acellular dermal matrix (ADM) as an alternative biological substitute for silicone implant in secondary rhinoplasty. METHODS: The authors prospectively studied 56 patients with a minimum follow-up of 1 year among 104 patients who underwent secondary rhinoplasty in their clinic between January of 2015 and December of 2018. Silicone implant, capsule, and scar tissue removal; dorsal augmentation with ADM; and tip plasty using autogenous cartilage were performed for all of them. The results were assessed using the modified Rhinoplasty Outcome Evaluation, consisting of a 10-item questionnaire completed preoperatively, 6 months postoperatively, and over 1 year postoperatively. RESULT: One infection and three cases of excessive resorption were noted, with no other major complications. The mean modified Rhinoplasty Outcome Evaluation score was 31.7 on preoperative evaluation, 77.3 at 6 months postoperatively, and 81.4 at 1 year postoperatively (mean difference, 45.6 and 49.7, respectively; P < 0.001). CONCLUSIONS: Various problems that occur after primary rhinoplasty using silicone implants can be resolved successfully with secondary rhinoplasty by dorsal augmentation using the cross-linked human ADM along with various nasal tip work using autogenous cartilage. Surgical outcome showed favorable resolution of contracture deformities, a low infection rate, firm fixation of the implant, good skin texture/thickness of the skin/soft-tissue envelope, and gain of desired height and dorsal line. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.


Assuntos
Derme Acelular , Rinoplastia , Humanos , Rinoplastia/efeitos adversos , Rinoplastia/métodos , Nariz/cirurgia , Próteses e Implantes/efeitos adversos , Silicones , Estudos Retrospectivos
8.
Nutrients ; 15(17)2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37686810

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver diseases and encompasses non-alcoholic steatosis, steatohepatitis, and fibrosis. Sanguisorba officinalis L. (SO) roots have traditionally been used for their antioxidant properties and have beneficial effects on metabolic disorders, including diabetes and obesity. However, its effects on hepatic steatosis and fibrosis remain unclear. In this study, we explored the effects of a 95% ethanolic SO extract (SOEE) on NAFLD and fibrosis in vivo and in vitro. The SOEE was orally administered to C57BL/6J mice fed a choline-deficient, L-amino-acid-defined, high-fat diet for 10 weeks. The SOEE inhibited hepatic steatosis by modulating hepatic malondialdehyde levels and the expression of oxidative stress-associated genes, regulating fatty-acid-oxidation-related genes, and inhibiting the expression of genes that are responsible for fibrosis. The SOEE suppressed the deposition of extracellular matrix hydroxyproline and mRNA expression of fibrosis-associated genes. The SOEE decreased the expression of fibrosis-related genes in vitro by inhibiting SMAD2/3 phosphorylation. Furthermore, the SOEE restored the gut microbial diversity and modulated specific bacterial genera associated with NAFLD and fibrosis. This study suggests that SOEE might be the potential candidate for inhibiting hepatic steatosis and fibrosis by modulating oxidative stress, fatty acid oxidation, and gut microbiota composition.


Assuntos
Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Sanguisorba , Animais , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Estresse Oxidativo , Fibrose , Cirrose Hepática/tratamento farmacológico , Ácidos Graxos
9.
Arch Plast Surg ; 50(6): 541-549, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38143837

RESUMO

Background Despite its many advantages, prepectoral breast reconstruction also carries the risk of implant rippling. The recent introduction of partial superior implant coverage using a pectoralis muscle slip in prepectoral direct-to-implant (DTI) breast reconstruction has shown the potential to minimize upper pole rippling. The purpose of this study was to identify factors associated with rippling and the effectiveness of our surgical technique. Methods In total, 156 patients (186 breasts) who underwent prepectoral DTI breast reconstruction between August 2019 and March 2021 were identified retrospectively. Patient data were analyzed from medical records. Univariable and multivariable logistic analyses were performed to contextualize the risks associated with rippling deformity relative to demographic characteristics and other clinical factors. Retrospective propensity-matched analysis was performed to identify the relationship between rippling deformity and the reconstruction method. Results Patients with body mass index (BMI; odds ratio [OR], 0.736; p < 0.001), those with a postoperative chemotherapy history (OR, 0.324; p = 0.027) and those who received breast reconstruction via the superior coverage technique (OR, 0.2; p = 0.004), were less likely to develop rippling deformity. The median follow-up period was 64.9 weeks, and there were no significant differences between patients in types of mastectomy, implant, or acellular dermal matrix. Patients who underwent superior coverage technique-based reconstruction showed significantly reduced rippling (OR, 0.083; p = 0.017) Conclusion Patients with higher BMI and prior postoperative chemotherapy were less likely to develop rippling deformity. The superior coverage technique can be effective in minimizing upper pole rippling.

10.
Tissue Eng Regen Med ; 20(4): 607-619, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37017922

RESUMO

BACKGROUND: Breast cancer patients suffer from lowered quality of life (QoL) after surgery. Breast conservancy surgery (BCS) such as partial mastectomy is being practiced and studied as an alternative to solve this problem. This study confirmed breast tissue reconstruction in a pig model by fabricating a 3-dimensional (3D) printed Polycaprolactone spherical scaffold (PCL ball) to fit the tissue resected after partial mastectomy. METHODS: A 3D printed Polycaprolactone spherical scaffold with a structure that can help adipose tissue regeneration was produced using computer-aided design (CAD). A physical property test was conducted for optimization. In order to enhance biocompatibility, collagen coating was applied and a comparative study was conducted for 3 months in a partial mastectomy pig model. RESULTS: In order to identify adipose tissue and fibroglandular tissue, which mainly constitute breast tissue, the degree of adipose tissue and collagen regeneration was confirmed in a pig model after 3 months. As a result, it was confirmed that a lot of adipose tissue was regenerated in the PCL ball, whereas more collagen was regenerated in the collagen-coated Polycaprolactone spherical scaffold (PCL-COL ball). In addition, as a result of confirming the expression levels of TNF-a and IL-6, it was confirmed that PCL ball showed higher levels than PCL-COL ball. CONCLUSION: Through this study, we were able to confirm the regeneration of adipose tissue through a 3-dimensional structure in a pig model. Studies were conducted on medium and large-sized animal models for the final purpose of clinical use and reconstruction of human breast tissue, and the possibility was confirmed.


Assuntos
Neoplasias da Mama , Alicerces Teciduais , Humanos , Animais , Suínos , Feminino , Alicerces Teciduais/química , Qualidade de Vida , Mastectomia Segmentar , Mastectomia , Colágeno/química
11.
Antioxidants (Basel) ; 10(12)2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34943055

RESUMO

The presence of nutritional and health-benefiting compounds has increased awareness of orphan leafy vegetables such as Cleome gynandra (CG), whose phytochemicals vary among accessions and organs during growth. This study investigated the polyphenol accumulation and antioxidant activities (AOA) of eight CG accessions from the vegetative stage to the seed set stage. Plants were separated into leaves and stem (LS), flowers, and silique organs, and extracts were analyzed for total phenolic content (TPC), total flavonoid content (TFC), rutin and astragalin content, and AOA using 2,2-diphenyl-1-picrylhydrazyl-hydrate (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS). There were significant interaction effects of growth stages and accessions that contributed to changes in compounds content and AOA. TPC accumulated in plant generative parts, whereas flavonoids accumulated in young plant organs. HPLC profiling revealed that rutin was the most abundant compound in all organs, with flowers having the highest levels, while astragalin was only found in flowers. Silique extracts, particularly accession KF-14, recorded the highest TPC, which corresponded to the strongest radical scavenging activity in ABTS and DPPH assays and a strong linear correlation. The germplasm contained accessions with significantly different and varying levels of bioactive compounds and AOA. These findings potentiate the exploitation of CG organs such as siliques for AOA, flowers for rutin and astragalin, and young shoots for flavonoids. Moreover, the significant accumulation of the compounds in particular accessions of the germplasms suggest that such superior accessions may be useful candidates in genetic breeding programs to improve CG vegetable.

12.
Antioxidants (Basel) ; 10(8)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34439431

RESUMO

The effect of salt treatment on Brassica carinata (BC) microgreens grown under different light wavelengths on glucosinolates (GLs) and phenolic compounds were evaluated. Quantifiable GLs were identified using ultra-high performance-quadrupole time of flight mass spectrometry. Extracts' ability to activate antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)) was evaluated on human colorectal carcinoma cells (HCT116). Furthermore, BC compounds' ability to activate expression of nuclear transcription factor-erythroid 2 related factor (Nrf2) and heme-oxygenase-1 (HO-1) proteins was examined using specific antibodies on HCT116 cells. Sinigrin (SIN) was the abundant GLs of the six compounds identified and its content together with total aliphatic GLs increased in saline conditions. Fluorescent (FL) and blue plus red (B1R1) lights were identified as stable cultivation conditions for microgreens, promoting biomass and glucobrassicin contents, whereas other identified individual and total indole GLs behaved differently in saline and non-saline environments. Blue light-emitting diodes and FL light in saline treatments mostly enhanced SIN, phenolics and antioxidant activities. The increased SOD and CAT activities render the BC microgreens suitable for lowering oxidative stress. Additionally, activation of Nrf2, and HO-1 protein expression by the GLs rich extracts, demonstrate their potential to treat and prevent oxidative stress and inflammatory disorders. Therefore, effective salt treatments and light exposure to BC microgreens present an opportunity for targeted regulation of growth and accumulation of bioactive metabolites.

13.
Food Chem ; 335: 127645, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32738537

RESUMO

The dried Ganoderma lucidum (GL) has been widely used for its pharmacological properties and bioactive ganoderic acids (GAs). Herein, extraction procedures combining ultra-sonication and heating were optimized using response surface methodology based on four variables (antioxidant activity, anti-diabetic activity, total GAs content, and total polysaccharide content) and principal component analysis. The extraction of freeze-dried GL at temperatures between 64.2 and 70 °C for 1.2 h maximized the antioxidant activity and GA content, whereas the polysaccharide content and anti-diabetic activity were maximized by extraction between 66.8 and 70 °C for more than 2.8 h. Heat-dried GL extracted at 50 °C for 3 h provided the greatest anti-inflammatory activity against HaCaT cells by suppressing the response to inflammation related cytokines at mRNA levels. These results suggest that extraction conditions might be a limiting factor for target-oriented investigations, and optimized extraction methods may improve the potential effect and quality of harvested GL products.


Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Fracionamento Químico/métodos , Hipoglicemiantes/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Reishi/química , Triterpenos/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Linhagem Celular , Fracionamento Químico/instrumentação , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Triterpenos/química , Triterpenos/farmacologia
14.
Anat Cell Biol ; 44(1): 60-8, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21519550

RESUMO

Corticotropin-releasing factor (CRF) is a peptide involved in the activation of the hypothalamic-pituitary-adrenal (HPA) axis. CRF is distributed not only along the HPA axis but also throughout pain-relevant anatomical sites. CRF elicits potent antinociception at the three main levels of pain transmissions: namely, the brain, spinal cord, and peripheral sensory neurons. The widespread distribution of CRF receptors 1 and 2 in the brain offers several targets wherein CRF could alter pain, some of which may be independent of the HPA axis. In this study, we assessed the expression of CRF and its receptors, CRF receptor type (CRFR)1 and CRFR2, in the spinal dorsal horn and dorsal root ganglion (DRG) in a rat model of neuropathic pain induced by spinal nerve injury (SNI). CRF was expressed in a few DRG neurons and primary afferent fibers in the dorsal horns of naїve rats, and the CRF-positive neurons in DRG and fibers in the spinal dorsal horn were found to have increased after SNI. CRFR1 was not expressed in DRG or the dorsal horn and CRFR2 was expressed weakly in the small neurons in DRG in the naїve rats. After SNI, CRFR1 was expressed in the activated microglia in the ipsilateral dorsal horn, and immunoreaction for CRFR2 was increased in the contralateral DRG following SNI. Consequently, it has been suggested that the increased expression of CRF and CRFR2 in DRG neurons and primary afferent fibers in dorsal horn, and CRFR1 in the activated microglia, may be involved in the mediation of stress responses as well as in microglial activation in the neuropathic pain state following SNI.

15.
Br J Pharmacol ; 163(8): 1653-65, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21039417

RESUMO

BACKGROUND AND PURPOSE Sauchinone, an antioxidant lignan, protects hepatocytes from iron-induced toxicity. This study investigated the protective effects of sauchinone against acetaminophen (APAP)-induced toxicity in the liver and the role of nuclear factor erythroid-2-related factor-2 (Nrf2) in this effect. EXPERIMENTAL APPROACH Blood biochemistry and histopathology were assessed in mice treated with APAP or APAP + sauchinone. The levels of mRNA and protein were measured using real-time PCR assays and immunoblottings. KEY RESULTS Sauchinone ameliorated liver injury caused by a high dose of APAP. This effect was prevented by a deficiency of Nrf2. Sauchinone treatment induced modifier subunit of glutamate-cysteine ligase, NAD(P)H:quinone oxidoreductase-1 (NQO1) and heat shock protein 32 in the liver, which was abolished by Nrf2 deficiency. In a hepatocyte model, sauchinone activated Nrf2, as evidenced by the increased nuclear accumulation of Nrf2, the induction of NQO1-antioxidant response element reporter gene, and glutamate-cysteine ligase and NQO1 protein induction, which contributed to the restoration of hepatic glutathione content. Consistently, treatment of sauchinone enhanced Nrf2 phosphorylation with a reciprocal decrease in its interaction with Kelch-like ECH-associated protein-1. Intriguingly, sauchinone activated protein kinase C-δ (PKCδ), which led to Nrf2 phosphorylation. In addition, it increased the inhibitory phosphorylation of glycogen synthase kinase-3ß (GSK3ß), derepressing Nrf2 activity, which was supported by the reversal of sauchinone's activation of Nrf2 by an activated mutant of GSK3ß. Moreover, phosphorylation of GSK3ß by sauchinone depended on PKCδ activation. CONCLUSION AND IMPLICATIONS Our results demonstrate that sauchinone protects the liver from APAP-induced toxicity by activating Nrf2, and this effect is mediated by PKCδ activation, which induces inhibitory phosphorylation of GSK3ß.


Assuntos
Acetaminofen/toxicidade , Analgésicos não Narcóticos/toxicidade , Antioxidantes/farmacologia , Benzopiranos/farmacologia , Dioxóis/farmacologia , Fígado/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/fisiologia , Animais , Antioxidantes/química , Antioxidantes/metabolismo , Benzopiranos/química , Benzopiranos/metabolismo , Dioxóis/química , Dioxóis/metabolismo , Glutationa/análise , Quinase 3 da Glicogênio Sintase/genética , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Células Hep G2 , Humanos , Lignanas/química , Lignanas/metabolismo , Lignanas/farmacologia , Fígado/lesões , Fígado/metabolismo , Fígado/patologia , Complexo Principal de Histocompatibilidade/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fitoterapia , Preparações de Plantas/química , Preparações de Plantas/metabolismo , Preparações de Plantas/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/metabolismo , Substâncias Protetoras/farmacologia , Proteína Quinase C-delta/genética , Proteína Quinase C-delta/metabolismo , Proteínas/genética , Proteínas/metabolismo , Saururaceae , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Proteínas de Transporte Vesicular
16.
Free Radic Biol Med ; 49(11): 1722-34, 2010 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-20840863

RESUMO

Isoliquiritigenin (ILQ), a flavonoid obtained from Glycyrrhizae species, has an antioxidant effect. This study investigated the potential of ILQ for inhibiting liver X receptor-α (LXRα)-mediated lipogenesis and steatosis in hepatocytes and its underlying molecular basis. Treatment with ILQ antagonized the ability of an LXRα agonist (T0901317) to activate sterol regulatory element binding protein-1c (SREBP-1c), thereby repressing transcription of fatty acid synthase, acetyl-CoA carboxylase, ATP-binding cassette transporter-A1, and stearoyl-CoA desaturase-1. ILQ treatment inhibited activating phosphorylation of JNK1 elicited by palmitate or TNFα. JNK1, but not JNK2, increased LXRα phosphorylation at serine residues, promoting LXRα activation. The ability of ILQ to inhibit JNK1 downstream of ASK1-MKK7 led to the repression of T0901317-inducible LXRα and SREBP-1c activation. In mice fed a high-fat diet, ILQ treatment inhibited hepatic steatosis, as shown by a decrease in fat accumulation and repression of lipogenic genes. The results of blood biochemistry and histopathology confirmed attenuation of high-fat diet-induced liver injury by ILQ. Moreover, ILQ inhibited oxidative stress, as indicated by decreases in thiobarbituric acid-reactive substance formation, iNOS and COX2 induction, and nitrotyrosinylation. Our results demonstrate that ILQ has the ability to repress LXRα-dependent hepatic steatosis through JNK1 inhibition and protect hepatocytes from oxidative injury inflicted by fat accumulation.


Assuntos
Chalconas/uso terapêutico , Fígado Gorduroso/prevenção & controle , Proteína Quinase 8 Ativada por Mitógeno/antagonistas & inibidores , Receptores Nucleares Órfãos/antagonistas & inibidores , Inibidores de Proteínas Quinases/uso terapêutico , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Células Cultivadas , Chalconas/isolamento & purificação , Chalconas/farmacologia , Avaliação Pré-Clínica de Medicamentos , Fígado Gorduroso/metabolismo , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Glycyrrhiza/química , Células Hep G2 , Humanos , Lipogênese/efeitos dos fármacos , Lipogênese/genética , Receptores X do Fígado , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Biológicos , Receptores Nucleares Órfãos/metabolismo , Receptores Nucleares Órfãos/fisiologia , Inibidores de Proteínas Quinases/isolamento & purificação , Inibidores de Proteínas Quinases/farmacologia , Transcrição Gênica/efeitos dos fármacos
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