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1.
Int J Mol Sci ; 24(6)2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36982669

RESUMO

Obese psoriatic patients experience higher disease severity and exhibit poorer treatment responses and clinical outcomes. It has been proposed that proinflammatory cytokines produced by adipose tissue exacerbate psoriasis; however, the role of obesity in psoriasis remains unclear. This study aimed to elucidate the role of obesity in the pathogenesis of psoriasis, focusing on immunological changes. To induce obesity, mice were fed a high-fat diet for 20 weeks. We then applied imiquimod to the skin on a mouse's back for seven consecutive days to induce psoriasis and scored lesion severity every day for seven days. Cytokine levels in serum and the Th17 cell population in the spleen and draining lymph nodes were studied to identify immunological differences. The clinical severity was more remarkable, and histologically the epidermis was also significantly thicker in the obese group. Increased levels of IL-6 and TNF-α were observed in serum after psoriasis. They were elevated to a greater degree, with greater expansion of the functional Th17 cell population in the obese group. It is concluded that obesity could exacerbate psoriasis through mechanisms that involve elevated proinflammatory cytokine secretion and an expanded Th17 cell population.


Assuntos
Interleucina-6 , Psoríase , Camundongos , Animais , Imiquimode/efeitos adversos , Interleucina-6/efeitos adversos , Células Th17 , Camundongos Endogâmicos C57BL , Psoríase/tratamento farmacológico , Pele/patologia , Citocinas/uso terapêutico , Obesidade/etiologia , Obesidade/patologia , Biomarcadores , Modelos Animais de Doenças
2.
Theor Appl Genet ; 135(6): 1923-1937, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35357525

RESUMO

KEY MESSAGE: Unstable Restorer-of-fertility (Rfu), conferring unstable fertility restoration in the pepper CGMS system, was delimited to a genomic region near Rf and is syntenic to the PPR-like gene-rich region in tomato. The use of cytoplasmic-genic male sterility (CGMS) systems greatly increases the efficiency of hybrid seed production. Although marker development and candidate gene isolation have been performed for the Restorer-of-fertility (Rf) gene in pepper (Capsicum annuum L.), the broad use of CGMS systems has been hampered by the instability of fertility restoration among pepper accessions, especially sweet peppers, due to the widespread presence of the Unstable Restorer-of-fertility (Rfu) locus. Therefore, to investigate the genetic factors controlling unstable fertility restoration in sweet peppers, we developed a segregation population (BC4F5) from crosses using a male-sterile line and an Rfu-containing line. Segregation did not significantly deviate from a 3:1 ratio for unstable fertility restoration to sterility, indicating single dominant locus control for unstable fertility restoration in this population. Genetic mapping delimited the Rfu locus to a 398 kb genomic region on chromosome 6, which is close to but different from the previously identified Rf-containing region. The Rfu-containing region harbors a pentatricopeptide repeat (PPR) gene, along with 10 other candidate genes. In addition, this region is syntenic to the genomic region containing the largest number of Rf-like PPR genes in tomato. Therefore, the dynamic evolution of PPR genes might be responsible for both the restoration and instability of fertility in pepper. During genetic mapping, we developed various molecular markers, including one that co-segregated with Rfu. These markers showed higher accuracy for genotyping than previously developed markers, pointing to their possible use in marker-assisted breeding of sweet peppers.


Assuntos
Capsicum , Capsicum/genética , Fertilidade/genética , Genes de Plantas , Genômica , Melhoramento Vegetal , Infertilidade das Plantas/genética
3.
Br J Anaesth ; 126(3): 692-699, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33341226

RESUMO

BACKGROUND: The purpose of this study was to investigate the effectiveness and safety between electroacupuncture (EA) combined with usual care (UC) and UC alone for pain reduction and functional improvement in patients with non-acute low back pain (LBP) after back surgery. METHODS: In this multicentre, randomised, assessor-blinded active-controlled trial, 108 participants were equally randomised to either the EA with UC or the UC alone. Participants in the EA with UC group received EA treatment and UC treatment twice a week for 4 weeks; those allocated to the UC group received only UC. The primary outcome was the VAS pain intensity score. The secondary outcomes were functional improvement (Oswestry Disability Index [ODI]) and the quality of life (EuroQol-5-dimension questionnaire [EQ-5D]). The outcomes were measured at Week 5. RESULTS: Significant reductions were observed in the VAS (mean difference [MD] -8.15; P=0.0311) and ODI scores (MD -3.98; P=0.0460) between two groups after 4 weeks of treatment. No meaningful differences were found in the EQ-5D scores and incidence of adverse events (AEs) between the groups. The reported AEs did not have a causal relationship with EA treatment. CONCLUSIONS: The results showed that EA with UC treatment was more effective than UC alone and relatively safe in patients with non-acute LBP after back surgery. EA with UC treatment may be considered as an effective, integrated, conservative treatment for patients with non-acute LBP after back surgery. CLINICAL TRIAL REGISTRATION: KCT0001939.


Assuntos
Terapia por Estimulação Elétrica/métodos , Eletroacupuntura/métodos , Dor Lombar/terapia , Manejo da Dor/métodos , Fusão Vertebral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Resultado do Tratamento
4.
Nanomedicine ; 32: 102329, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33181275

RESUMO

We used antioxidant-containing nanoparticles (NPs) to treat acute hearing loss. Alpha-lipoic acid (ALA) served as the antioxidant; we employed Pluronic F127 to fabricate NPs. In vitro, ALA-NPs protected cells of the organ of Corti in HEI-OC1 mice, triggering nuclear translocation of NRF2 and increases in the levels of antioxidant proteins, including Nrf2, HO-1, SOD-1, and SOD-2. In vivo, the hearing of mice that received ALA-NP injections into the middle ear cavity was better preserved after induction of ototoxicity than in control animals. The cochlear Nrf2 level increased in test mice, indicating that the ALA-NPs protected hearing via the antioxidant mechanism observed in vitro. ALA-NPs effectively protected against acute hearing loss by activating the Nrf2/HO-1 pathway.


Assuntos
Perda Auditiva/tratamento farmacológico , Nanopartículas/química , Poloxâmero/química , Ácido Tióctico/administração & dosagem , Ácido Tióctico/uso terapêutico , Membrana Timpânica/patologia , Animais , Antioxidantes/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Modelos Animais de Doenças , Perda Auditiva/patologia , Masculino , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Nanopartículas/ultraestrutura , Ácido Tióctico/farmacologia
5.
Int J Mol Sci ; 21(10)2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32438631

RESUMO

Cilastatin is a specific inhibitor of renal dehydrodipeptidase-1. We investigated whether cilastatin preconditioning attenuates renal ischemia-reperfusion (IR) injury via hypoxia inducible factor-1α (HIF-1α) activation. Human proximal tubular cell line (HK-2) was exposed to ischemia, and male C57BL/6 mice were subjected to bilateral kidney ischemia and reperfusion. The effects of cilastatin preconditioning were investigated both in vitro and in vivo. In HK-2 cells, cilastatin upregulated HIF-1α expression in a time- and dose-dependent manner. Cilastatin enhanced HIF-1α translation via the phosphorylation of Akt and mTOR was followed by the upregulation of erythropoietin (EPO) and vascular endothelial growth factor (VEGF). Cilastatin did not affect the expressions of PHD and VHL. However, HIF-1α ubiquitination was significantly decreased after cilastatin treatment. Cilastatin prevented the IR-induced cell death. These cilastatin effects were reversed by co-treatment of HIF-1α inhibitor or HIF-1α small interfering RNA. Similarly, HIF-1α expression and its upstream and downstream signaling were significantly enhanced in cilastatin-treated kidney. In mouse kidney with IR injury, cilastatin treatment decreased HIF-1α ubiquitination independent of PHD and VHL expression. Serum creatinine level and tubular necrosis, and apoptosis were reduced in cilastatin-treated kidney with IR injury, and co-treatment of cilastatin with an HIF-1α inhibitor reversed these effects. Thus, cilastatin preconditioning attenuated renal IR injury via HIF-1α activation.


Assuntos
Cilastatina/farmacologia , Precondicionamento Isquêmico , Rim/patologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Indazóis/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Substâncias Protetoras/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Ubiquitinação/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
6.
Clin Otolaryngol ; 44(6): 997-1003, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31468673

RESUMO

OBJECTIVES: The aim of the current study was to investigate the effectiveness and clinical feasibility of Biyeom-go for the treatment of nasal symptoms associated with rhinitis. DESIGN: Prospective observational study. SETTING: This study was conducted at the Woosuk Korean Medicine Medical Center in South Korea. PARTICIPANTS: Fifty-eight patients with rhinitis participated in this study. All patients received Biyeom-go treatment >3 times daily for a total of 4 weeks. MAIN OUTCOME MEASURES: The primary outcome was the total nasal symptom score. Mini-rhinoconjunctivitis quality of life questionnaire, nasal endoscopy index, total serum immunoglobulin E levels and immunologic factors in nasal lavage fluid were also measured. RESULTS: Biyeom-go administration was associated with significant improvements in total nasal symptoms scores (P < .0001) and mini-rhinoconjunctivitis quality of life questionnaire scores (P < .0001) in a time-dependent manner. The nasal endoscopy index also significantly improved at weeks 2 (P = .0049), 3 (P < .0001) and 4 (P = .0001) after Biyeom-go treatment. Significantly, increased interleukin-2 levels (P = .005) and decreased interleukin-8, chemokine (C-C motif) ligand (CCL) 5, chemokine (C-X-C motif) ligand (CXCL) 9, CCL2 and CXCL10 levels were observed in the nasal lavage fluid. CONCLUSIONS: The present findings suggest that Biyeom-go may be beneficial for the management of rhinitis symptoms and rhinitis-associated quality of life. Further well-designed randomised controlled trials are needed to evaluate the effectiveness of Biyeom-go for rhinitis.


Assuntos
Antialérgicos/uso terapêutico , Fitoterapia , Extratos Vegetais , Rinite/complicações , Rinite/terapia , Administração Intranasal , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sprays Nasais , Pomadas , Estudos Prospectivos , Adulto Jovem
7.
Exp Eye Res ; 134: 53-62, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25795054

RESUMO

Experimental autoimmune uveoretinitis (EAU) is an autoimmune disease that models human uveitis. Caffeic acid phenethyl ester (CAPE), a phenolic compound isolated from propolis, possesses anti-inflammatory and immunomodulatory properties. CAPE demonstrates therapeutic potential in several animal disease models through its ability to inhibit NF-κB activity. To evaluate these therapeutic effects in EAU, we administered CAPE in a model of EAU that develops after immunization with interphotoreceptor retinal-binding protein (IRBP) in B10.RIII and C57BL/6 mice. Importantly, we found that CAPE lessened the severity of EAU symptoms in both mouse strains. Notably, treated mice exhibited a decrease in the ocular infiltration of immune cell populations into the retina; reduced TNF-α, IL-6, and IFN-γ serum levels: and inhibited TNF-α mRNA expression in retinal tissues. Although CAPE failed to inhibit IRBP-specific T cell proliferation, it was sufficient to suppress cytokine, chemokine, and IRBP-specific antibody production. In addition, retinal tissues isolated from CAPE-treated EAU mice revealed a decrease in NF-κB p65 and phospho-IκBα. The data identify CAPE as a potential therapeutic agent for autoimmune uveitis that acts by inhibiting cellular infiltration into the retina, reducing the levels of pro-inflammatory cytokines, chemokine, and IRBP-specific antibody and blocking NF-κB pathway activation.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Ácidos Cafeicos/uso terapêutico , Modelos Animais de Doenças , NF-kappa B/antagonistas & inibidores , Álcool Feniletílico/análogos & derivados , Retinite/tratamento farmacológico , Uveíte/tratamento farmacológico , Animais , Doenças Autoimunes/metabolismo , Doenças Autoimunes/patologia , Western Blotting , Proteínas do Olho/imunologia , Citometria de Fluxo , Imunoglobulina G/sangue , Interferon gama/sangue , Interleucina-6/metabolismo , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Álcool Feniletílico/uso terapêutico , RNA Mensageiro/metabolismo , Retinite/metabolismo , Retinite/patologia , Proteínas de Ligação ao Retinol/imunologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Uveíte/metabolismo , Uveíte/patologia
8.
Hepatogastroenterology ; 62(137): 34-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25911863

RESUMO

BACKGROUND/AIMS: Robotic surgery is increasingly used for rectal cancer. We compared the short- and long-term outcomes between robotic- and laparoscopic-assisted resection for rectal cancer. METHODOLOGY: A retrospective chart review was performed between 2006 and 2010. RESULTS: Seventeen robotic and 61 laparoscopic surgeries were performed consecutively. Median follow-up time was 58.2 months. No operation was converted to open surgery. No difference was observed between the groups for types of operations, diverting ileostomy rate, operation time, blood loss, and postoperative hospital stay, tumor diameter, distal margin, circumferential margin, tumor stage, differentiation, lymphovascular, or perineural invasion. However, the number of harvested lymph nodes was higher in the robot than that in the laparoscopy group (p = 0.017). Overall morbidity and reoperation rates were similar between the groups. The 5-yr overall and disease-free survival rates of all patients were 82.5% and 81.3%, respectively. The 5-yr overall and disease-free survival rates of the robotic and the laparoscopy groups were 94.1% and 79.7% (p = 0.241), and 94.1% and 77.9% (p = 0.159), respectively. CONCLUSIONS: Robot-assisted resection for rectal cancer resulted in harvesting more lymph nodes without increasing morbidity and showed a comparable survival rate, compared with those of laparoscopy.


Assuntos
Laparoscopia/métodos , Neoplasias Retais/cirurgia , Robótica , Cirurgia Assistida por Computador , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Laparoscopia/efeitos adversos , Laparoscopia/mortalidade , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Estudos Retrospectivos , Fatores de Risco , Cirurgia Assistida por Computador/efeitos adversos , Cirurgia Assistida por Computador/mortalidade , Fatores de Tempo , Resultado do Tratamento
10.
J Phys Ther Sci ; 26(6): 909-10, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25013294

RESUMO

[Purpose] The purpose of this study was to compare the activity of the shoulder and trunk muscles in two push-up positions: standard push-ups and push-ups with the trunk flexed. [Subjects] Fifteen young adult males participated in the study. [Methods] This study measured the clavicular and sternocostal portions of the pectoralis major, the serratus anterior, and the rectus abdominis during push-ups under the two conditions. [Results] The activity of the sternocostal portion of the pectoralis major and that of the rectus abdominis were significantly greater under Condition 1 than under Condition 2. The activity of the clavicular portion of the pectoralis major and that of the serratus anterior were significantly greater under Condition 2 compared with Condition 1. [Conclusion] These results indicate that exercises can selectively activate muscle parts under different clinical situations.

11.
Medicine (Baltimore) ; 103(20): e38226, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38758869

RESUMO

Interstitial lung disease (ILD) encompasses a heterogeneous group of more than 200 diffuse parenchymal lung diseases with various clinical courses. Disease progression is one of the most important prognostic factors, and, the definition of progressive pulmonary fibrosis (PPF) has recently been established. This study aimed to estimate the prevalence, risk factors, and prognosis of PPF among patients with non-idiopathic pulmonary fibrosis (IPF) in real-world practice. A total of 215 patients were retrospectively analyzed between January 2010 and June 2023 at the Haeundae Paik Hospital in the Republic of Korea. According to the criteria proposed in 2022 by Raghu et al, PPF defined as a condition that satisfies 2 or more of the following in the past year: worsening of respiratory symptoms, physiological evidence of disease progression, and radiological evidence of disease progression. The median age of the subjects was 67 years and 63.7% were female. A total of 40% was diagnosed with PPF and connective tissue disease-associated ILD (52.3%) was the most common type, followed by nonspecific interstitial pneumonitis (NSIP) (25.6%) and cryptogenic organizing pneumonitis (16.3%). In multivariate logistic regression for predicting PPF, both the use of steroids and immunosuppressants (OR: 2.57, 95% CI: 1.41-4.67, P = .002) and home oxygen use (OR: 25.17, 95% CI: 3.21-197.24, P = .002) were independent risk factors. During the follow-up period, the mortality rate was significantly higher in the PPF group than in the non-PPF group (24.4% vs 2.3%, P < .001). In the survival analysis using the Cox proportional hazard regression model, disease progression, older age and lower forced vital capacity (FVC) were independent risk factors for mortality. Our study demonstrated that the prevalence of PPF was 40%. Concomitant therapy of steroids with an immunosuppressants and home oxygen use are risk factors for PPF. PPF itself was significantly associated with high mortality rates. Risk factors for mortality were disease progression, older age, and lower FVC.


Assuntos
Progressão da Doença , Humanos , Feminino , Masculino , Estudos Retrospectivos , Idoso , Prevalência , República da Coreia/epidemiologia , Prognóstico , Pessoa de Meia-Idade , Fatores de Risco , Fibrose Pulmonar/epidemiologia , Fibrose Pulmonar/mortalidade , Doenças Pulmonares Intersticiais/epidemiologia , Doenças Pulmonares Intersticiais/mortalidade , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/fisiopatologia , Imunossupressores/uso terapêutico
12.
Antibiotics (Basel) ; 13(3)2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38534693

RESUMO

Colistimethate sodium (CMS) nebulization is associated with reduced systemic toxicity compared to intravenous injection, with potentially enhanced clinical efficacy. This study aimed to assess the pharmacokinetic (PK) properties of colistin during low-dose CMS nebulization in patients with ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii. A nonlinear mixed-effects modeling approach was applied to develop population PK models for colistin in both epithelial lining fluid (ELF) and plasma. Twenty patients participated, and 80 ELF and 100 plasma samples were used for model development. Median colistin concentrations measured in ELF were 614-fold, 408-fold, and 250-fold higher than in plasma at 1, 3, and 5 h, respectively. Time courses in both ELF and plasma were best described by a one-compartment model with a Weibull absorption process. When the final model was simulated, the maximum free concentration and area under the free colistin concentration-time curve at steady state over 24 h in the plasma were approximately 1/90 and 1/50 of the corresponding values in ELF at steady state, respectively. For an A. baumannii MIC of 1 mg/L, inhaling 75 mg of CMS at 6 h intervals was deemed appropriate, with dose adjustments needed for MICs exceeding 2 mg/L. Using a nebulizer for CMS resulted in a notably higher exposure of colistin in the ELF than plasma, indicating the potential of nebulization to reduce systemic toxicity while effectively treating VAP.

13.
J Med Chem ; 67(12): 10490-10507, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38845345

RESUMO

Building on the preceding structural analysis and a structure-activity relationship (SAR) of 8-aryl-2-hexynyl nucleoside hA2AAR antagonist 2a, we strategically inverted C2/C8 substituents and eliminated the ribose moiety. These modifications aimed to mitigate potential steric interactions between ribose and adenosine receptors. The SAR findings indicated that such inversions significantly modulated hA3AR binding affinities depending on the type of ribose, whereas removal of ribose altered the functional efficacy via hA2AAR. Among the synthesized derivatives, 2-aryl-8-hexynyl adenine 4a demonstrated the highest selectivity for hA2AAR (Ki,hA2A = 5.0 ± 0.5 nM, Ki,hA3/Ki,hA2A = 86) and effectively blocked cAMP production and restored IL-2 secretion in PBMCs. Favorable pharmacokinetic properties and a notable enhancement of anticancer effects in combination with an mAb immune checkpoint blockade were observed upon oral administration of 4a. These findings establish 4a as a viable immune-oncology therapeutic candidate.


Assuntos
Adenina , Antagonistas do Receptor A2 de Adenosina , Nucleosídeos , Receptor A2A de Adenosina , Ribose , Humanos , Relação Estrutura-Atividade , Animais , Adenina/farmacologia , Adenina/química , Adenina/análogos & derivados , Antagonistas do Receptor A2 de Adenosina/farmacologia , Antagonistas do Receptor A2 de Adenosina/química , Antagonistas do Receptor A2 de Adenosina/síntese química , Nucleosídeos/química , Nucleosídeos/farmacologia , Nucleosídeos/síntese química , Ribose/química , Ribose/metabolismo , Receptor A2A de Adenosina/metabolismo , Camundongos , Estrutura Molecular , Ratos , Feminino , Linhagem Celular Tumoral
14.
Gastroenterology ; 143(5): 1341-1351, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22841785

RESUMO

BACKGROUND & AIMS: The TOR signaling pathway regulator-like (TIPRL) protein, the mammalian ortholog of yeast TIP41, was identified in an expression profiling screen for factors that regulate human liver carcinogenesis. We investigated the role of human TIPRL protein in hepatocellular carcinoma (HCC). METHODS: We measured the level of TIPRL in HCC and adjacent nontumor tissues from patients. We used small interfering RNAs and zebrafish to study the function of TIPRL. We used annexin V propidium iodide staining and immunoblot analyses to measure apoptosis and activation of apoptotic signaling pathways. We used confocal microscopy, coimmunoprecipitation, and glutathione-S transferase pull-down analyses to determine interactions among mitogen-activated protein kinase kinase 7 (MKK7 or MAP2K7), TIPRL, and the protein phosphatase type 2A (PP2Ac). We studied the effects of TIPRL in tumor xenografts in mice. RESULTS: Levels of TIPRL were higher in HCC tissues and cell lines than nontumor tissues and primary hepatocytes. Knockdown of tiprl expression in zebrafish led to large amounts of apoptosis throughout the embryos. Incubation of HCC cells, but not primary human hepatocytes, with small interfering RNA against TIPRL (siTIPRL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) caused prolonged activation (phosphorylation) of MKK7 and c-Jun N-terminal kinase (JNK) and led to apoptosis, indicated by cleavage of procaspase-8,-3 and of poly-(adenosine diphosphate-ribose) polymerase. TIPRL bound to MKK7 and PP2Ac and promoted the interaction between MKK7 and PP2Ac. In mice, injection of HCC xenograft tumors with siTIPRL and TRAIL led to tumor apoptosis and regression. CONCLUSIONS: TIPRL is highly up-regulated in human HCC samples and cell lines, compared with noncancerous liver tissues. TIPRL prevents prolonged activation of MKK7 and JNK and TRAIL-induced apoptosis by mediating the interaction between MKK7 and PP2Ac.


Assuntos
Carcinoma Hepatocelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Neoplasias Hepáticas/metabolismo , MAP Quinase Quinase 7/metabolismo , Animais , Apoptose , Carcinoma Hepatocelular/genética , Feminino , Técnicas de Silenciamento de Genes , Células Hep G2 , Hepatócitos/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Fígado/metabolismo , Neoplasias Hepáticas/genética , Camundongos , Camundongos Nus , Transplante de Neoplasias , Proteína Fosfatase 2/metabolismo , RNA Mensageiro/metabolismo , RNA Interferente Pequeno , Transdução de Sinais , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Regulação para Cima , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Peixe-Zebra/metabolismo
15.
Biochem Biophys Res Commun ; 441(2): 438-46, 2013 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-24369900

RESUMO

Human lymphoblastoid cell line (LCL) has been used as an in vitro cell model in genetic and pharmacogenomic studies, as well as a good model for studying gene expression regulatory machinery using integrated genomic analyses. In this study, we aimed to identify biological networks of LCL immortalization from transcriptomic profiles of microRNAs and their target genes in LCLs. We first selected differentially expressed genes (DEGs) and microRNAs (DEmiRs) between early passage LCLs (eLCLs) and terminally differentiated late passage LCLs (tLCLs). The in silico and correlation analysis of these DEGs and DEmiRs revealed that 1098 DEG-DEmiR pairs were found to be positively (n=591 pairs) or negatively (n=507 pairs) correlated with each other. More than 41% of DEGs are possibly regulated by miRNAs in LCL immortalizations. The target DEGs of DEmiRs were enriched for cellular functions associated with apoptosis, immune response, cell death, JAK-STAT cascade and lymphocyte activation while non-miRNA target DEGs were over-represented for basic cell metabolisms. The target DEGs correlated negatively with miR-548a-3p and miR-219-5p were significantly associated with protein kinase cascade, and the lymphocyte proliferation and apoptosis, respectively. In addition, the miR-106a and miR-424 clusters located in the X chromosome were enriched in DEmiR-mRNA pairs for LCL immortalization. In this study, the integrated transcriptomic analysis of LCLs could identify functional networks of biologically active microRNAs and their target genes involved in LCL immortalization.


Assuntos
Linhagem Celular Transformada , Regulação Leucêmica da Expressão Gênica , Redes Reguladoras de Genes , MicroRNAs/metabolismo , Cromossomos Humanos X/genética , Inibidor de Quinase Dependente de Ciclina p21/genética , Humanos , MicroRNAs/genética , RNA Mensageiro/genética , Transcriptoma
16.
BMC Cancer ; 13: 166, 2013 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-23537343

RESUMO

BACKGROUND: Cancer stem cells (CSCs) are notorious for their capacity of tumor progression, metastasis or resistance to chemo-radiotherapy. However, the undisputed role of cancer stem marker, CD133, in colorectal cancers (CRCs) is not clear yet. METHODS: We assessed 271 surgically-resected stage II and III primary CRCs with (171) and without (100) adjuvant therapy after surgery. CD133 expression was analyzed by immunohistochemical (IHC) staining and real-time RT-PCR. CD133 promoter methylation was quantified by pyrosequencing. RESULTS: The CD133 IHC expression was significantly correlated with mRNA expression (p=0.0257) and inversely correlated with the promoter methylation (p=0.0001). CD133 was expressed more frequently in rectal cancer (p=0.0035), and in moderately differentiated tumors (p=0.0378). In survival analysis, CD133 expression was not significantly correlated with overall survival (OS) (p=0.9689) as well as disease-free survival (DFS) (p=0.2103). However, CD133+ tumors were significantly associated with better OS in patients with adjuvant therapy compared to those without adjuvant therapy (p<0.0001, HR 0.125, 95% CI 0.052-0.299). But the patients with CD133- tumors did not show any significant difference of survival according to adjuvant therapy (p=0.055, HR 0.500, 95% CI 0.247-1.015). CONCLUSIONS: In stage II and III CRCs, CD133 IHC expression may signify the benefit for adjuvant therapy although it is not an independent prognostic factor.


Assuntos
Antígenos CD/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Glicoproteínas/metabolismo , Peptídeos/metabolismo , Antígeno AC133 , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/genética , Quimioterapia Adjuvante , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Metilação de DNA , Feminino , Expressão Gênica , Glicoproteínas/genética , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Peptídeos/genética , Prognóstico , Regiões Promotoras Genéticas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Estudos Retrospectivos
17.
BMC Complement Altern Med ; 13: 179, 2013 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-23866691

RESUMO

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that results from a progressive loss of motor neurons. Familial ALS (fALS) is caused by missense mutations in Cu, Zn-superoxide dismutase 1 (SOD1) that frequently result in the accumulation of mutant protein aggregates that are associated with impairments in the ubiquitin-proteasome system (UPS). UPS impairment has been implicated in many neurological disorders. Bee venom (BV) extracted from honey bees has been used as a traditional medicine for treating inflammatory diseases and has been shown to attenuate the neuroinflammatory events that occur in a symptomatic ALS animal model. METHODS: NSC34 cells were transiently transfected with a WT or G85R hSOD1-GFP construct for 24 hrs and then stimulated with 2.5 µg/ml BV for 24 hrs. To determine whether a SOD1 mutation affects UPS function in NSC34 cells, we examined proteasome activity and performed western blotting and immunofluorescence using specific antibodies, such as anti-misfolded SOD1, anti-ubiquitin, anti-GRP78, anti-LC3, and anti-ISG15 antibodies. RESULTS: We found that GFP-hSOD1G85R overexpression induced SOD1 inclusions and reduced proteasome activity compared with the overexpression of GFP alone in NSC34 motor neuronal cells. In addition, we also observed that BV treatment restored proteasome activity and reduced the accumulation of ubiquitinated and misfolded SOD1 in GFP-hSOD1G85R-overexpressing NSC34 motor neuronal cells. However, BV treatment did not activate the autophagic pathway in these cells. CONCLUSION: Our findings suggest that BV may rescue the impairment of the UPS in ALS models.


Assuntos
Esclerose Lateral Amiotrófica/metabolismo , Venenos de Abelha/farmacologia , Abelhas , Neurônios Motores/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Superóxido Dismutase/metabolismo , Ubiquitina/metabolismo , Esclerose Lateral Amiotrófica/tratamento farmacológico , Animais , Apiterapia , Autofagia , Chaperona BiP do Retículo Endoplasmático , Humanos , Camundongos , Neurônios Motores/metabolismo , Mutação , Superóxido Dismutase/genética , Superóxido Dismutase-1 , Transfecção
18.
BMC Complement Altern Med ; 13: 59, 2013 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-23497032

RESUMO

BACKGROUND: The treatment of knee osteoarthritis, which is a major cause of disability among the elderly, is typically selected from multidisciplinary options, including complementary and alternative medicine. Moxibustion has been used in the treatment of knee osteoarthritis in Korea to reduce pain and improve physical activity. However, there is no sufficient evidence of its effectiveness, and it cannot therefore be widely recommended for treating knee osteoarthritis. We designed a randomised controlled clinical trial to evaluate the effectiveness, safety, cost-effectiveness, and qualitative characteristics of moxibustion treatment of knee osteoarthritis compared to usual care. METHODS/DESIGNS: This is a protocol for a multicentre, pragmatic, randomised, assessor-blinded, controlled, parallel-group study. A total of 212 participants will be assigned to the moxibustion group (n = 106) and the usual care group (n = 106) at 4 clinical research centres. The participants assigned to the moxibustion group will receive moxibustion treatment of the affected knee(s) at 6 standard acupuncture points (ST36, ST35, ST34, SP9, Ex-LE04, and SP10) 3 times per week for 4 weeks (a total of 12 sessions). Participants in the usual care group will not receive moxibustion treatment during the study period. Follow-up will be performed on the 5th and 13th weeks after random allocation. Both groups will be allowed to use any type of treatment, including surgery, conventional medication, physical treatment, acupuncture, herbal medicine, over-the-counter drugs, and other active treatments. Educational material that explains knee osteoarthritis, the current management options, and self-exercise will be provided to each group. The global scale of the Korean Western Ontario and McMaster Osteoarthritis Index (K-WOMAC) will be the primary outcome measurement used in this study. Other subscales (pain, stiffness, and function) of the K-WOMAC, the Short-Form 36v2 Health Survey, the Beck Depression Inventory, the Physical Function test, Patient Global Assessment, and the Pain Numerical Rating Scale will be used as outcome variables to evaluate the effectiveness of moxibustion. Safety will be assessed at every visit. In addition, an economic evaluation and a qualitative study will be conducted as a mixed-methods approach. DISCUSSION: This trial may contribute to developing evidence for the effectiveness and safety of moxibustion for treating knee osteoarthritis. TRIAL REGISTRATION NUMBER: KCT0000130.


Assuntos
Pontos de Acupuntura , Articulação do Joelho , Joelho , Moxibustão , Osteoartrite do Joelho/terapia , Avaliação da Deficiência , Humanos , Osteoartrite do Joelho/complicações , Avaliação de Resultados em Cuidados de Saúde , Dor , Medição da Dor , Projetos de Pesquisa , Índice de Gravidade de Doença , Método Simples-Cego
19.
Surg Today ; 43(1): 62-6, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22391977

RESUMO

PURPOSE: Varicose vein incompetence in the legs is very prevalent in the Korean population. New technologies and improvements in established methods have changed the treatment of varicose veins. Transilluminated powered phlebectomy is an alternative surgical technique that combines endoscopic powered vein resection and ablation of superficial varicosities with tumescent anesthesia and irrigated illumination. The present study sought to determine the clinical efficacy and safety of transilluminated powered phlebectomy from clinical data. METHOD: Four hundred and forty-seven limbs in 299 patients (157 male, 142 female; mean age 50.6 years) with varicose veins were treated with transilluminated powered phlebectomy over a 7-year period. The patients were followed for 1 year postoperatively. The analyzed data included sex, age, body mass index, operative time (from skin incision to the application of elastic bandages on the legs for compression purposes), and postoperative complications. RESULTS: The mean operative time was 87.2 min for both limbs and 57.3 min for single limbs. The median number of incisions was five. Postoperative complications included an episode of cellulitis in 10 patients (2.2%), wound abscess in two patients (0.4%), hematoma in 15 patients (3.4%), residual veins in five patients (1.1%), cutaneous nerve damage in 10 patients (2.2%), and seroma in 13 patients (2.9%). No skin perforation and deep venous thrombosis were observed at the 1-year follow-up. CONCLUSION: Transilluminated powered phlebectomy is an effective and safe method for the excision of varicosities.


Assuntos
Transiluminação/métodos , Varizes/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
20.
Artigo em Inglês | MEDLINE | ID: mdl-36901170

RESUMO

As the treatment of nonspecific chronic cough with conventional medications that treat cough according to the cause is limited, Maekmundong-tang (comprising Liriopis seu Ophiopogonis Tuber, Pinelliae Tuber, Oryzae Semen, Zizyphi Fructus, Ginseng Radix, and Glycyrrhizae Radix et Rhizoma) has been used empirically in the clinical setting of East Asian traditional medicine. This study is the first to explore the feasibility, preliminary effect, safety, and cost-effectiveness of Maekmundong-tang for nonspecific chronic cough. This study protocol is that of a double-blind, randomized, active-controlled, parallel-group clinical trial for comparing Maekmundong-tang with Saengmaek-san (comprising Liriopis seu Ophiopogonis Tuber, Ginseng Radix, and Schisandrae Fructus), a Korean national health insurance-covered herbal medicine for cough. A total of 30 nonspecific chronic cough patients will participate and receive the assigned herbal medicine for 6 weeks, and clinical parameters will be assessed at weeks 0 (baseline), 3 (midterm assessment), 6 (primary endpoint), 9, and 24 (follow-up). Study feasibility outcomes, including recruitment, adherence, and completion rates, will be assessed. Preliminary effects on cough severity, frequency, and quality of life will be evaluated using outcome measures, such as the Cough Symptom Score, Cough Visual Analog Scale, and the Leicester Cough Questionnaire. Adverse events and laboratory tests will be monitored for safety evaluation, and exploratory economic evaluations will be conducted. The results will provide evidence of Maekmundong-tang in the treatment of nonspecific chronic cough.


Assuntos
Medicamentos de Ervas Chinesas , Plantas Medicinais , Humanos , Tosse/etiologia , Qualidade de Vida , Medicamentos de Ervas Chinesas/efeitos adversos , Extratos Vegetais/uso terapêutico , Método Duplo-Cego , Doença Crônica , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto
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