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1.
Med Oncol ; 40(5): 138, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37022566

RESUMO

Malignant melanoma is aggressive cancer with a high rate of local invasiveness and metastasis. Currently, the treatment options for patients with advanced-stage and metastatic oral melanoma are limited. A promising treatment option is oncolytic viral therapy. This study aimed to evaluate novel therapies for malignant melanoma using a canine model. Oral melanoma, which frequently occurs in dogs is used as a model for human melanoma, was isolated and cultured and used for the evaluation of the tumor lytic effect induced by viral infection. We constructed a recombinant Newcastle disease virus (rNDV) that promotes the extracellular release of IFNγ from the virus-infected melanoma. The expression of oncolytic and apoptosis-related genes, the immune response by lymphocytes, and IFNγ expression were evaluated in virus-infected melanoma cells. The results showed that the rate of rNDV infection varied according to the isolated melanoma cells and the oncolytic effect differed between melanoma cells owing to the infectivity of the virus. The oncolytic effect tended to be greater for the IFNγ-expressing virus than for the GFP-expressing prototype virus. Additionally, lymphocytes co-cultured with the virus showed induced expression of Th1 cytokines. Therefore, recombinant NDV expressing IFNγ is expected to induce cellular immunity and oncolytic activity. This oncolytic treatment shows promise as a therapeutic approach for melanoma treatment once evaluated using clinical samples from humans.


Assuntos
Melanoma , Neoplasias Bucais , Terapia Viral Oncolítica , Vírus Oncolíticos , Humanos , Animais , Cães , Vírus da Doença de Newcastle/genética , Melanoma/terapia , Vírus Oncolíticos/genética , Neoplasias Bucais/terapia , Terapia Viral Oncolítica/métodos , Melanoma Maligno Cutâneo
2.
Elife ; 122023 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-36852482

RESUMO

Salt taste sensation is multifaceted: NaCl at low or high concentrations is preferably or aversively perceived through distinct pathways. Cl- is thought to participate in taste sensation through an unknown mechanism. Here, we describe Cl- ion binding and the response of taste receptor type 1 (T1r), a receptor family composing sweet/umami receptors. The T1r2a/T1r3 heterodimer from the medaka fish, currently the sole T1r amenable to structural analyses, exhibited a specific Cl- binding in the vicinity of the amino-acid-binding site in the ligand-binding domain (LBD) of T1r3, which is likely conserved across species, including human T1r3. The Cl- binding induced a conformational change in T1r2a/T1r3LBD at sub- to low-mM concentrations, similar to canonical taste substances. Furthermore, oral Cl- application to mice increased impulse frequencies of taste nerves connected to T1r-expressing taste cells and promoted their behavioral preferences attenuated by a T1r-specific blocker or T1r3 knock-out. These results suggest that the Cl- evokes taste sensations by binding to T1r, thereby serving as another preferred salt taste pathway at a low concentration.


Humans perceive taste when proteins called taste receptors on the surface of the tongue are activated by molecules of food. These receptors turn on nerve cells that send signals the brain can read as sweet, sour, salty, bitter, or umami, depending on which receptor was activated. Most animals with backbones share the same five types of taste receptors. In food, salty flavors are usually the result of adding table salt, which has two components: a sodium ion and chloride ion. The main taste receptors that signal to the brain that a food is salty become activated when they bind to the sodium ion. However, some studies have shown that salt is also perceived as sweet when eaten in minuscule amounts. It is poorly understood why this happens, but it is possible that the chloride half of salt drives the sweet taste. In 2017, scientists worked out the structure of a taste receptor from a fish, that is equivalent to the sweet receptor in humans. Curiously, one part of this receptor, known as T1r2a/T1r3LBD, was bound to a chloride ion. This prompted Atsumi, Yasumatsu et al. to think about the 'sweet' taste of salt, leading them to take a closer look at T1r2a/T1r3LBD and whether chloride could indeed activate it. Atsumi, Yasumatsu et al. used structural biology techniques to examine T1r2a/T1r3LBD and found evidence that the receptor might be binding chloride. Further biophysical experiments confirmed that chloride does indeed bind to the receptor, and that it also causes it to change shape. Usually, changes in shape are hallmarks of receptor activation, suggesting that chloride may activate T1r2a/T1r3LBD. Next, Atsumi, Yasumatsu et al. checked whether chloride could stimulate the neurons that signal when food tastes sweet, by using an approach known as electrophysiology to measure the activity of these neurons in mice. The results showed that the neurons became active when a solution containing small amounts of chloride was placed on the mouse's tongue. This activity went away when a compound that can block the receptor's activity was delivered alongside the chloride. Additionally, when mice were given a choice of plain water or water containing chloride, they seemed to prefer the latter. This confirmed that mice recognized the sweetness of chloride via the activation of sweet taste receptors and neurons. Based on these findings, Atsumi, Yasumatsu et al. propose that small amounts of salt may taste sweet because the chloride ions in the salt activate sweet taste receptors and their linked neurons. Their results also suggest that animals sense salt in many ways, likely because balanced salt levels are essential for the body to work properly. Future experiments on human taste receptors may reveal how these pathways help assess salt levels in humans.


Assuntos
Papilas Gustativas , Paladar , Animais , Humanos , Camundongos , Cloretos , Ligantes , Cloreto de Sódio , Cloreto de Sódio na Dieta , Espaço Extracelular/metabolismo
4.
Skin Res Technol ; 29(1): e13231, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36437544

RESUMO

BACKGROUND: Skin characteristics show great variation from person to person and are affected by multiple factors, including genetic, environmental, and physical factors, but details of the involvement and contributions of these factors remain unclear. OBJECTIVES: We aimed to characterize genetic, environmental, and physical factors affecting 16 skin features by developing models to predict personal skin characteristics. METHODS: We analyzed the associations of skin phenotypes with genetic, environmental, and physical features in 1472 Japanese females aged 20-80 years. We focused on 16 skin characteristics, including melanin, brightness/lightness, yellowness, pigmented spots, wrinkles, resilience, moisture, barrier function, texture, and sebum amount. As genetic factors, we selected 74 single-nucleotide polymorphisms of genes related to skin color, vitamin level, hormones, circulation, extracellular matrix (ECM) components and ECM-degrading enzymes, inflammation, and antioxidants. Histories of ultraviolet (UV) exposure and smoking as environmental factors and age, height, and weight as physical factors were acquired by means of a questionnaire. RESULTS: A linear association with age was prominent for increase in the area of crow's feet, increase in number of pigmented spots, decrease in forehead sebum, and increase in VISIA wrinkle parameters. Associations were analyzed by constructing linear regression models for skin feature changes and logistic regression models to predict whether subjects show lower or higher skin measurement values in the same age groups. Multiple genetic factors, history of UV exposure and smoking, and body mass index were statistically selected for each skin characteristic. The most important association found for skin spots, such as lentigines and wrinkles, was adolescent sun exposure. CONCLUSION: Genetic, environmental, and physical factors associated with interindividual differences of the selected skin features were identified. The developed models should be useful to predict the skin characteristics of individuals and their age-related changes.


Assuntos
Transtornos da Pigmentação , Envelhecimento da Pele , Feminino , Humanos , População do Leste Asiático , Pele , Envelhecimento da Pele/genética , Pigmentação da Pele/genética , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais
5.
CEN Case Rep ; 12(1): 84-90, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35927545

RESUMO

Exacerbations or de novo autoimmune/autoinflammatory disease have been reported after COVID-19 vaccination. A young male presented with cutaneous IgA vasculitis with glomerular hematuria, diarrhea and pericarditis following his second COVID-19 mRNA vaccination. He also showed positivity for proteinase 3 anti-neutrophil cytoplasmic antibody (PR3-ANCA) and anti-cardiolipin antibody. Skin biopsy was compatible to IgA vasculitis. His purpura subsided and hematuria spontaneously disappeared. Treatment with anti-inflammatory medications and prednisolone resolved the pericarditis. He had a history of persistent diarrhea, and colonic biopsies showed possible ulcerative colitis without vasculitis. Kidney biopsy after prednisolone therapy revealed minor glomerular abnormalities without any immune reactants and did not show vasculitis. After prednisolone treatment, PR3-ANCA decreased in a medium degree despite of improvement of symptoms and inflammatory data, suggesting that his PR3-ANCA may be associated with ulcerative colitis. The cause of the transient glomerular hematuria was unclear, however, it might be caused by focal glomerular active lesions (glomerular vasculitis) due to vaccine-induced IgA vasculitis with nephritis. This case highlights that COVID-19 mRNA vaccination can activate multiple autoimmune/autoinflammatory systems. The conditions might help us better understand the mutual mechanisms of the relevant disorders.


Assuntos
COVID-19 , Colite Ulcerativa , Vasculite por IgA , Pericardite , Vasculite , Humanos , Masculino , Hematúria/etiologia , Anticorpos Anticitoplasma de Neutrófilos , Vacinas contra COVID-19/efeitos adversos , Vasculite/diagnóstico , Vasculite/etiologia , Mieloblastina , Prednisolona/uso terapêutico , Diarreia , Vacinação , RNA Mensageiro
7.
Sci Rep ; 11(1): 1666, 2021 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462315

RESUMO

Autophagy is a cellular degradation system contributing to homeostasis of tissue stem cells including haematopoietic stem cells (HSCs). It plays pleiotropic roles in HSC characteristics throughout life, but its stage-specific roles in HSC self-renewal are unclear. To investigate the effects of Atg5 deletion on stage-specific HSC functions, we compared the repopulating capacity of HSCs in Atg5f/f;Vavi-cre mice from postnatal day (P) 0-7 weeks of age. Interestingly, Atg5 deficiency led to no remarkable abnormality in the HSC self-renewal capacity at P0, but significant defects at P7, followed by severe defects. Induction of Atg5 deletion at P5 by tamoxifen administration to Atg5f/f;Rosa26-Cre-ERT2 mice resulted in normal haematopoiesis, including the HSC population, until around 1 year, suggesting that Atg5 in the early neonatal period was critical for haematopoiesis in adults. Mitochondrial oxidative stress was increased by Atg5 loss in neonatal HSC/progenitor cells. Although p62 had accumulated in immature bone marrow cells of Atg5f/f;Vavi-cre mice, p62 deletion did not restore defective HSC functions, indicating that Atg5-dependent haematopoietic regulation in the developmental period was independent of p62. This study proposes a critical role of autophagy in HSC protection against harsh environments in the early neonatal stage, which is essential for healthy long-term haematopoiesis.


Assuntos
Proteína 5 Relacionada à Autofagia/metabolismo , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Proteína Sequestossoma-1/metabolismo , Animais , Animais Recém-Nascidos , Autofagia/fisiologia , Proteína 5 Relacionada à Autofagia/genética , Modelos Animais de Doenças , Feminino , Células-Tronco Hematopoéticas/patologia , Masculino , Camundongos , Camundongos Knockout , Estresse Oxidativo/fisiologia
8.
Asian J Anesthesiol ; 58(1): 14-23, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33081430

RESUMO

OBJECTIVE: We sometimes encounter cases with unexpected increase in intraoperative urine output during tympanoplasty. However, no previous study has evaluated whether intraoperative urine output during tympanoplasty is higher than that during other surgeries. Thus, this study aimed to evaluate the association between tympanoplasty and intraoperative urine output. METHODS: This single-center retrospective cohort study was conducted by assessing the records of patients who underwent tympanoplasty, sinus surgery, or thyroidectomy under general anesthesia between April 2013 and March 2017. We defined intraoperative polyuria as a urine output rate of ≥ 2.5 mL/kg/h. The factors associated with high urine output were investigated using multivariable analysis. The influence of tympanoplasty on intraoperative urine output was evaluated after propensity score matching that excluded confounding factors, except the surgical procedure. RESULTS: Intraoperative polyuria occurred in 48 of 173 patients (27.7%) who underwent tympanoplasty. Multivariable analysis revealed that tympanoplasty (p = 0.001), operative time of ≥ 3 h (p = 0.010), and fluid infusion volume of ≥ 5 mL/kg/h (p = 0.029) were risk factors for polyuria. Among the study patients, 100 who underwent tympanoplasty (tympanoplasty group) and 100 who underwent sinus surgery or thyroidectomy (control group) were matched by propensity score analysis. The intraoperative urine output rate was significantly higher in the tympanoplasty group than in the control group (1.2 [0.51-2.20] mL/kg/h vs. 0.70 [0.32-1.60] mL/kg/h, p = 0.010). CONCLUSION: Our findings indicate that intraoperative urine output is higher during tympanoplasty than that during other otologic surgeries.


Assuntos
Timpanoplastia , Humanos , Duração da Cirurgia , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco
9.
Commun Chem ; 3(1): 183, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36703437

RESUMO

Metabolic syndrome is associated with obesity, hypertension, and dyslipidemia, and increased cardiovascular risk. Therefore, quick and accurate measurements of specific metabolites are critical for diagnosis; however, detection methods are limited. Here we describe the synthesis of pillar[n]arenes to target 1-methylnicotinamide (1-MNA), which is one metabolite of vitamin B3 (nicotinamide) produced by the cancer-associated nicotinamide N-methyltransferase (NNMT). We found that water-soluble pillar[5]arene (P5A) forms host-guest complexes with both 1-MNA and nicotinamide, and water-soluble pillar[6]arene (P6A) selectively binds to 1-MNA at the micromolar level. P6A can be used as a "turn-off sensor" by photoinduced electron transfer (detection limit is 4.38 × 10-6 M). In our cell-free reaction, P6A is used to quantitatively monitor the activity of NNMT. Moreover, studies using NNMT-deficient mice reveal that P6A exclusively binds to 1-MNA in crude urinary samples. Our findings demonstrate that P6A can be used as a biosensor to quantify 1-MNA in crude biological samples.

10.
PLoS One ; 14(10): e0218909, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31584955

RESUMO

Taste receptor type 1 (T1r) is responsible for the perception of essential nutrients, such as sugars and amino acids, and evoking sweet and umami (savory) taste sensations. T1r receptors recognize many of the taste substances at their extracellular ligand-binding domains (LBDs). In order to detect a wide array of taste substances in the environment, T1r receptors often possess broad ligand specificities. However, the entire ranges of chemical spaces and their binding characteristics to any T1rLBDs have not been extensively analyzed. In this study, we exploited the differential scanning fluorimetry (DSF) to medaka T1r2a/T1r3LBD, a current sole T1rLBD heterodimer amenable for recombinant preparation, and analyzed their thermal stabilization by adding various amino acids. The assay showed that the agonist amino acids induced thermal stabilization and shifted the melting temperatures (Tm) of the protein. An agreement between the DSF results and the previous biophysical assay was observed, suggesting that DSF can detect ligand binding at the orthosteric-binding site in T1r2a/T1r3LBD. The assay further demonstrated that most of the tested l-amino acids, but no d-amino acid, induced Tm shifts of T1r2a/T1r3LBD, indicating the broad l-amino acid specificities of the proteins probably with several different manners of recognition. The Tm shifts by each amino acid also showed a fair correlation with the responses exhibited by the full-length receptor, verifying the broad amino-acid binding profiles at the orthosteric site in LBD observed by DSF.


Assuntos
Aminoácidos/química , Proteínas de Peixes/química , Oryzias , Multimerização Proteica , Receptores Acoplados a Proteínas G/química , Animais , Sítios de Ligação
11.
Cancer Sci ; 109(8): 2497-2508, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29902340

RESUMO

Autophagy plays a critical role in tumorigenesis, but how autophagy contributes to cancer cells' responses to chemotherapeutics remains controversial. To investigate the roles of autophagy in malignant gliomas, we used CRISPR/CAS9 to knock out the ATG5 gene, which is essential for autophagosome formation, in tumor cells derived from patients with glioblastoma. While ATG5 disruption inhibited autophagy, it did not change the phenotypes of glioma cells and did not alter their sensitivity to temozolomide, an agent used for glioblastoma patient therapy. Screening of an anticancer drug library identified compounds that showed greater efficacy to ATG5-knockout glioma cells compared to control. While several selected compounds, including nigericin and salinomycin, remarkably induced autophagy, potent autophagy inducers by mTOR inhibition did not exhibit the ATG5-dependent cytoprotective effects. Nigericin in combination with ATG5 deficiency synergistically suppressed spheroid formation by glioma cells in a manner mitigated by Ca2+ chelation or CaMKK inhibition, indicating that, in combination with autophagy inhibition, calcium-mobilizing compounds contribute to efficient anticancer therapeutics. ATG5-knockout cells treated with nigericin showed increased mitochondria-derived reactive oxygen species and apoptosis compared to controls, indicating that autophagy protects glioma cells from mitochondrial reactive oxygen species-mediated damage. Finally, using a patient-derived xenograft model, we demonstrated that chloroquine, a pharmacological autophagy inhibitor, dramatically enhanced the efficacy of compounds selected in this study. Our findings propose a novel therapeutic strategy in which calcium-mobilizing compounds are combined with autophagy inhibitors to treat patients with glioblastoma.


Assuntos
Autofagia/efeitos dos fármacos , Cálcio/metabolismo , Glioma/tratamento farmacológico , Glioma/metabolismo , Animais , Apoptose/efeitos dos fármacos , Proteína 5 Relacionada à Autofagia/metabolismo , Linhagem Celular Tumoral , Cloroquina/uso terapêutico , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Feminino , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Temozolomida
12.
Biochem Biophys Res Commun ; 495(1): 1129-1135, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29175333

RESUMO

The mammalian target of rapamycin (mTOR) complex 1 (mTORC1) senses a cell's energy status and environmental levels of nutrients and growth factors. In response, mTORC1 mediates signaling that controls protein translation and cellular metabolism. Although mTORC1 plays a critical role in hematopoiesis, it remains unclear which upstream stimuli regulate mTORC1 activity in the context of hematopoietic stem cells (HSC) maintenance in vivo. In this study, we investigated the function of Rheb, a critical regulator of mTORC1 activity controlled by the PI3K-AKT-TSC axis, both in HSC maintenance in mice at steady-state and in HSC-derived hematopoiesis post-transplantation. In contrast to the severe hematopoietic dysfunction caused by Raptor deletion, which completely inactivates mTORC1, Rheb deficiency in adult mice did not show remarkable hematopoietic failure. Lack of Rheb caused abnormalities in myeloid cells but did not have impact on hematopoietic regeneration in mice subjected to injury by irradiation. As previously reported, Rheb deficiency resulted in defective HSC-derived hematopoiesis post-transplantation. However, while Raptor is essential for HSC competitiveness in vivo, Rheb is dispensable for HSC maintenance under physiological conditions, indicating that the PI3K-AKT-TSC pathway does not contribute to mTORC1 activity for sustaining HSC self-renewal activity at steady-state. Thus, the various regulatory elements that impinge upstream of mTORC1 activation pathways are differentially required for HSC homeostasis in vivo.


Assuntos
Autorrenovação Celular/fisiologia , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/fisiologia , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Proteína Enriquecida em Homólogo de Ras do Encéfalo/metabolismo , Proteína Regulatória Associada a mTOR/metabolismo , Animais , Células Cultivadas , Camundongos , Camundongos Endogâmicos C57BL
13.
PLoS One ; 11(9): e0161704, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27598258

RESUMO

Procyanidins are the oligomeric or polymeric forms of epicatechin and catechin. In this study, we isolated and purified dimer to tetramer procyanidins from black soybean seed coat and investigated the anti-hyperglycemic effects by focusing on glucose transporter 4 (GLUT4) translocation and the underlying molecular mechanism in skeletal muscle of mice. The anti-hyperglycemic effects of procyanidins were also compared with those of monomer (-)-epicatechin (EC) and major anthocyanin, cyanidin-3-O-ß-glucoside (C3G). To investigate GLUT4 translocation and its related signaling pathways, ICR mice were orally given procyanidins, EC and C3G in water at 10 µg/kg body weight. The mice were sacrificed 60 min after the dose of polyphenols, and soleus muscle was extracted from the hind legs. The results showed that trimeric and tetrameric procyanidins activated both insulin- and AMPK-signaling pathways to induce GLUT4 translocation in muscle of ICR mice. We confirmed that procyanidins suppressed acute hyperglycemia with an oral glucose tolerance test in a dose-dependent manner. Of these beneficial effects, cinnamtannin A2, one of the tetramers, was the most effective. In conclusion, procyanidins, especially cinnamtannin A2, significantly ameliorate postprandial hyperglycemia at least in part by promoting GLUT4 translocation to the plasma membrane by activating both insulin- and AMPK-signaling pathways.


Assuntos
Proteínas Quinases Ativadas por AMP/genética , Biflavonoides/administração & dosagem , Catequina/administração & dosagem , Transportador de Glucose Tipo 4/genética , Hiperglicemia/tratamento farmacológico , Insulina/metabolismo , Proantocianidinas/administração & dosagem , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Antocianinas/administração & dosagem , Modelos Animais de Doenças , Glucose/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Glucosídeos/administração & dosagem , Humanos , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Camundongos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Transdução de Sinais/efeitos dos fármacos
14.
J Poult Sci ; 53(1): 34-39, 2016 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-32908361

RESUMO

Previously, we showed that the growth of chicks fed a diet containing 43% whole-grain paddy rice and 10% soybean oil was retarded relative to a control group fed a corn-based diet containing 6% soybean oil. However, feeding chicks with 43% whole-grain paddy rice containing 6% soybean oil resulted in normal growth. It is possible that the observed growth retardation was caused by the high soybean oil content or resulted from the combination of whole-grain paddy rice and the high level of soybean oil which was added to the diet to maintain the overall energy content. The present study was therefore carried out to identify the reasons for the observed growth retardation. Thirty-six chicks (0-day-old) were divided into six equal-sized groups that were fed one of the following six experimental diets ad libitum for 28 d: two kinds of dehulled rice-based diets containing 5% or 10% soybean oil (DS5% or DS10%), another three whole-grain paddy rice-based diets containing 10% soybean oil, corn oil, or rendering oil (WS10%, WC10%, WR10%, respectively), and a WS10% diet supplemented with vitamin B12, methionine and ethoxyquin. The body weight gain of groups fed the WS10% and WC10% diets was significantly lower than the weight gain of birds fed the DS5% diet (control). In addition, the liver of birds fed the WS10% and WC10% diet exhibited significantly higher lipid peroxidation than that of the control group. In comparison, supplementation of the WS10% diet with vitamin B12, methionine and ethoxyquin dramatically improved growth and hepatic oxidation status. These results indicate that diets combining whole-grain paddy rice and high levels of soybean and corn oil adversely affect performance, presumably via lipid peroxidation in the liver.

15.
J Craniofac Surg ; 25(2): 648-51, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24621714

RESUMO

Nasal dermoid sinus cysts (NDSCs) are rare congenital malformations derived from ectodermal and mesodermal tissues. There are numerous reports on surgical approaches for extirpation of NDSCs with intracranial extension. Here we describe the "stepped caudal exposure" approach, a technique that minimizes the risk for bacterial infection of the central nervous system from the nasal space. This procedure involves a stepwise osteotomy of the frontal and nasal bones that permits sufficient exposure to allow complete extirpation of NDSCs; it was used successfully to treat a 20-month-old boy with NDSC extending into the intracranial space and an infectious abscess. After NDSC extirpation and debridement of the abscess, the anterior skull base was reconstructed with bone grafts placed on both the intracranial and intranasal sides of the widened foramen cecum. Thereafter, each graft was covered by frontal pericranial flaps for blood supply. These modified surgical techniques may enhance the safety of surgical removal of NDSC, particularly in cases accompanied by infectious lesions such as abscesses.


Assuntos
Cisto Dermoide/cirurgia , Neoplasias Nasais/cirurgia , Transplante Ósseo , Osso Frontal/cirurgia , Humanos , Lactente , Masculino , Osso Nasal/cirurgia , Osteotomia/métodos , Retalhos Cirúrgicos/patologia , Resultado do Tratamento
16.
J Paediatr Child Health ; 50(1): 51-6, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24134830

RESUMO

AIM: This study aims to examine the influence of formula milk promotion via the media from Thailand to Lao People's Democratic Republic (PDR), where a cultural and linguistic proximity are shared. METHODS: A cross-sectional study was conducted through a structured questionnaire survey and focus group discussion (FGD) with mothers who had children under 2 years of age and lived in Vientiane Capital, Lao PDR. Multivariate logistic regression models were constructed for quantitative data analysis. Content analysis was used for qualitative data analysis. RESULTS: Among infants aged 6-23 months, exclusive breastfeeding (EBF) rate for 6 months was 16.1% (n = 106/658). Among infants aged 0-5 months, 17.6% (n = 61/346) was exclusively breastfed at the time of survey (24 h recall). Of 1022 mothers, 89.9% reported frequent exposure to the Thai media's promotion of formula milk through TV commercials and 79.1% identified TV commercial as influential for them to develop a positive attitude towards the use of formula milk. In multivariate logistic regression analyses, mothers who reported a positive attitude towards Thai TV commercial on the formula use (n = 449) were approximately 75% less likely to practice EBF for 6 months than those who reported a negative attitude (n = 64). FGD further revealed that the participants tend to believe in the information in TV commercial for formula milk. CONCLUSION: The promotion of formula milk via media from Thailand negatively affects breastfeeding mothers in Lao PDR. Cross-border impacts of promoting formula milk should be addressed globally.


Assuntos
Publicidade , Fórmulas Infantis , Mães , Adulto , Idoso , Atitude , Aleitamento Materno/estatística & dados numéricos , Estudos Transversais , Feminino , Humanos , Lactente , Laos , Modelos Logísticos , Masculino , Meios de Comunicação de Massa , Pessoa de Meia-Idade , Inquéritos e Questionários , Tailândia
17.
Cranio ; 31(4): 260-9, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24308099

RESUMO

The purpose of this study was to test the null hypothesis that molar movement during gum chewing in children with primary dentition is as smooth as in adults. Twenty-two healthy children with primary dentition and 23 healthy adult females participated in this study. Mandibular movement during gum chewing was recorded using an optoelectronic analysis system with six degrees-of-freedom at 100 Hz, and 10 cycles were selected for analysis. Normalized jerk cost (NJC) at the incisors and working and balancing molars were calculated in each phase (i.e., opening, closing and occlusal level phases) for each chewing cycle. The NJC of the working side molar in children was larger than in adults in both the opening and occlusal phases. Inter-individual variances of the NJC in each phase in children and adults were smaller than corresponding intra-individual variances, except for the NJC during the occlusal phase of adults for the working and balancing side molars. The inter- and intra-individual variances of the NJC during the closing phase were the smallest in each phase for both children and adults. This indicates that the jaw movements of children with primary dentition are more variable, less smooth, and faster than that of adults.


Assuntos
Goma de Mascar , Mandíbula/fisiologia , Mastigação/fisiologia , Dente Molar/fisiologia , Dente Decíduo/fisiologia , Pré-Escolar , Feminino , Humanos , Modelos Lineares , Masculino , Movimento , Adulto Jovem
18.
Mol Cell ; 52(6): 794-804, 2013 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-24268578

RESUMO

Autophagy is a cellular self-catabolic process wherein organelles, macromolecules, and invading microbes are sequestered in autophagosomes that fuse with lysosomes. In this study, we uncover the role of nitric oxide (NO) as a signaling molecule for autophagy induction via its downstream mediator, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP). We found that 8-nitro-cGMP-induced autophagy is mediated by Lys63-linked polyubiquitination and that endogenous 8-nitro-cGMP promotes autophagic exclusion of invading group A Streptococcus (GAS) from cells. 8-nitro-cGMP can modify Cys residues by S-guanylation of proteins. We showed that intracellular GAS is modified with S-guanylation extensively in autophagosomes-like vacuoles, suggesting the role of S-guanylation as a marker for selective autophagic degradation. This finding is supported by the fact that S-guanylated bacteria were selectively marked with polyubiquitin, a known molecular tag for selective transport to autophagosomes. These results collectively indicate that 8-nitro-cGMP plays a crucial role in cytoprotection during bacterial infections or inflammations via autophagy upregulation.


Assuntos
Autofagia , GMP Cíclico/análogos & derivados , Imunidade Inata , Macrófagos/metabolismo , Streptococcus pyogenes/metabolismo , Animais , Proteína 5 Relacionada à Autofagia , Proteínas de Bactérias/metabolismo , GMP Cíclico/metabolismo , Células HeLa , Humanos , Interferon gama/farmacologia , Lipopolissacarídeos/farmacologia , Proteínas Luminescentes/biossíntese , Proteínas Luminescentes/genética , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/microbiologia , Camundongos , Camundongos Knockout , Proteínas Associadas aos Microtúbulos/deficiência , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Óxido Nítrico/metabolismo , Poliubiquitina/metabolismo , Transporte Proteico , Transdução de Sinais , Streptococcus pyogenes/imunologia , Streptococcus pyogenes/patogenicidade , Fatores de Tempo , Transfecção , Ubiquitinação
19.
Food Chem ; 141(3): 2507-12, 2013 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-23870988

RESUMO

Proanthocyanidin oligomers (dimers to tetramers) were isolated from black soybean seed coats, using Sephadex LH-20 column chromatography and reversed-phase preparative HPLC. The isolated oligomers consisted of only (-)-epicatechin units, which were linked through either 4ß→8 or 4ß→6 (B-type) bonds. Procyanidin B2, procyanidin C1, and cinnamtannin A2 were identified as the main compounds of the proanthocyanidin dimers, trimers, and tetramers, respectively.


Assuntos
Glycine max/química , Extratos Vegetais/química , Proantocianidinas/química , Sementes/química , Conformação Molecular , Extratos Vegetais/isolamento & purificação , Proantocianidinas/isolamento & purificação
20.
Chembiochem ; 14(9): 1068-71, 2013 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-23703929

RESUMO

Seeing is believing: S-guanylation is a novel key mechanism by which signal transduction under oxidative stress is regulated. A chemical probe whose fluorescent intensity increases after the reaction with proteinous cysteine (S-guanylation) is described. The use of this probe revealed that S-guanylation products localized in lysosomes.


Assuntos
Corantes Fluorescentes/química , Guanina/química , Óxido Nítrico/química , Animais , Azidas/química , Linhagem Celular , Cumarínicos/química , Cisteína/química , Guanina/metabolismo , Humanos , Imuno-Histoquímica , Lisossomos/metabolismo , Camundongos , Microscopia de Fluorescência
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