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BACKGROUND AND PURPOSE: Chondrosarcoma and synovial chondromatosis of the temporomandibular joint share overlapping clinical and histopathologic features. We aimed to identify CT and MR imaging features to differentiate chondrosarcoma from synovial chondromatosis of the temporomandibular joint. MATERIALS AND METHODS: The CT and MR images of 12 and 35 patients with histopathologically confirmed chondrosarcoma and synovial chondromatosis of the temporomandibular joint, respectively, were retrospectively reviewed. Imaging features including lesion size, center, enhancement, destruction/sclerosis of surrounding bone, infiltration into the tendon of the lateral pterygoid muscle, calcification, periosteal reaction, and osteophyte formation were assessed. A comparison between chondrosarcoma and synovial chondromatosis was performed with a Student t test for quantitative variables and the Fisher exact test or linear-by-linear association test for qualitative variables. Receiver operating characteristic analysis was performed to determine the diagnostic performance for differentiation of chondrosarcoma and synovial chondromatosis based on a composite score obtained by assigning 1 point for each of 9 imaging features. RESULTS: High-risk imaging features for chondrosarcoma were the following: lesion centered on the mandibular condyle, destruction of the mandibular condyle, no destruction/sclerosis of the articular eminence/glenoid fossa, infiltration into the tendon of the lateral pterygoid muscle, absent or stippled calcification, periosteal reaction, internal enhancement, and size of ≥30.5 mm. The best cutoff value to discriminate chondrosarcoma from synovial chondromatosis was the presence of any 4 of these high-risk imaging features, with an area under the curve of 0.986 and an accuracy of 95.8%. CONCLUSIONS: CT and MR imaging features can distinguish chondrosarcoma from synovial chondromatosis of the temporomandibular joint with improved diagnostic performance when a subcombination of 9 imaging features is used.
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BACKGROUND: Human epidermal growth factor receptor 2 (HER2) (ERBB2)-directed agents are standard treatments for patients with HER2-positive breast and gastric cancer. Herein, we report the results of an open-label, single-center, phase II basket trial to investigate the efficacy and safety of trastuzumab biosimilar (Samfenet®) plus treatment of physician's choice for patients with previously treated HER2-positive advanced solid tumors, along with biomarker analysis employing circulating tumor DNA (ctDNA) sequencing. METHODS: Patients with HER2-positive unresectable or metastatic non-breast, non-gastric solid tumors who failed at least one prior treatment were included in this study conducted at Asan Medical Center, Seoul, Korea. Patients received trastuzumab combined with irinotecan or gemcitabine at the treating physicians' discretion. The primary endpoint was the objective response rate as per RECIST version 1.1. Plasma samples were collected at baseline and at the time of disease progression for ctDNA analysis. RESULTS: Twenty-three patients were screened from 31 December 2019 to 17 September 2021, and 20 were enrolled in this study. Their median age was 64 years (30-84 years), and 13 patients (65.0%) were male. The most common primary tumor was hepatobiliary cancer (seven patients, 35.0%), followed by colorectal cancer (six patients, 30.0%). Among 18 patients with an available response evaluation, the objective response rate was 11.1% (95% confidence interval 3.1% to 32.8%). ERBB2 amplification was detected from ctDNA analysis of baseline plasma samples in 85% of patients (n = 17), and the ERBB2 copy number from ctDNA analysis showed a significant correlation with the results from tissue sequencing. Among 16 patients with post-progression ctDNA analysis, 7 (43.8%) developed new alterations. None of the patients discontinued the study due to adverse events. CONCLUSIONS: Trastuzumab plus irinotecan or gemcitabine was safe and feasible for patients with previously treated HER2-positive advanced solid tumors with modest efficacy outcomes, and ctDNA analysis was useful for detecting HER2 amplification.
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Medicamentos Biossimilares , DNA Tumoral Circulante , Neoplasias Gástricas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medicamentos Biossimilares/efeitos adversos , DNA Tumoral Circulante/genética , Gencitabina , Irinotecano , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Trastuzumab/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou maisRESUMO
AIMS: To evaluate the clinical efficacy of adding temozolomide (TMZ) to preoperative capecitabine (CAP)-based chemoradiotherapy in patients with locally advanced rectal cancer (LARC) and validate O6-methylguanine DNA methyltransferase (MGMT) methylation status as a predictive marker for TMZ combined regimens. MATERIALS AND METHODS: LARC patients with clinical stage II (cT3-4N0) or III (cTanyN+) disease were enrolled. They were stratified into unmethylated MGMT (uMGMT) and methylated MGMT (mMGMT) groups by methylation-specific polymerase chain reaction before randomisation and were then randomly assigned (1:1) to one of four treatment arms: uMGMT/CAP (arm A), uMGMT/TMZ + CAP (arm B), mMGMT/CAP (arm C) and mMGMT/TMZ + CAP (arm D). The primary end point was the pathological complete response (pCR) rate. RESULTS: Between November 2017 and July 2020, 64 patients were randomised. Slow accrual caused early study termination. After excluding four ineligible patients, 60 were included in the full analysis set. The pCR rate was 15.0% (9/60), 0%, 14.3%, 18.8% and 26.7% for the entire cohort, arms A, B, C and D, respectively (P = 0.0498 between arms A and D). The pCR rate was 9.7% in the CAP group (arms A + C), 20.7% in the TMZ + CAP group (arms B + D), 6.9% in the uMGMT group (arms A + B) and 22.6% in the mMGMT group (arms C + D). Grade 1-2 nausea or vomiting was significantly more frequent in the TMZ + CAP treatment groups (arms B + D) than in the CAP treatment groups (arms A + C, P < 0.001) with no difference in grade 3 adverse events. There were no grade 4 or 5 adverse events. CONCLUSION: The addition of TMZ to CAP-based chemoradiotherapy tended to improve pCR rates, particularly in those with mMGMT LARC. MGMT status may warrant further investigation as a predictive biomarker for chemotherapeutic agents and radiotherapy.
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Neoplasias Encefálicas , Glioblastoma , Neoplasias Retais , Humanos , Temozolomida/uso terapêutico , Capecitabina , Dacarbazina/efeitos adversos , Estudos Prospectivos , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/patologia , Quimiorradioterapia , Enzimas Reparadoras do DNA/genética , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/genética , DNA/uso terapêutico , Metilação de DNA , Neoplasias Encefálicas/terapia , Antineoplásicos Alquilantes/uso terapêuticoRESUMO
BACKGROUND: Patients with advanced sarcomas have a poor prognosis and few treatment options that improve overall survival. We assessed the efficacy and tolerability of pemetrexed and cisplatin combination therapy in patients with refractory bone and soft tissue sarcoma (STS). PATIENTS AND METHODS: Patients were included in this multicenter, phase II study (ClinicalTrials.gov identifier NCT03809637) if they progressed after receiving one or more chemotherapy regimens containing an anthracycline and/or ifosfamide. Pemetrexed was first administered intravenously, followed by cisplatin, over a cycle of 21 days, for a maximum of six cycles. The primary endpoint was a progression-free rate (PFR) at 3 months (3-month PFR). RESULTS: From January 2017 to September 2019, we enrolled 37 patients; of these, 73% had previously undergone three or more rounds of chemotherapy. Five patients (13.5%) exhibited objective responses, including two patients (2/6, 33.3%) with malignant peripheral nerve sheath tumors, one patient (1/4, 25%) with synovial sarcoma, one patient (1/4, 25%) with undifferentiated pleomorphic sarcoma, and one patient (1/4, 25%) with angiosarcoma. The median progression-free survival was 2.6 months, and the 3-month PFR was 45.9% (n = 17). None of the four patients with osteosarcoma exhibited objective responses or were progression free at 3 months. The most frequent treatment-related grade 3-4 toxicities included neutropenia (16.2%), anemia (13.5%), thrombocytopenia (13.5%), and fatigue (8.1%). Among 26 patients (70.3%) available for immunohistochemical assessments, patients in the low-excision repair cross-complementation group 1 (ERCC1) and low-thymidylate synthase expression groups showed a tendency for longer overall survival. CONCLUSIONS: Combination therapy with pemetrexed and cisplatin was associated with clinically meaningful and sustained responses among patients with advanced and refractory STS. The combination therapy met its predefined primary study endpoint.
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Sarcoma , Neoplasias de Tecidos Moles , Cisplatino/efeitos adversos , Humanos , Ifosfamida , Pemetrexede/efeitos adversos , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológicoRESUMO
Forest restoration is a prime goal within the 2021-2030 UN "Decade of Ecosystem Resoration". As part of these activities, natural regeneration has to be promoted for biological as well as for economic reasons. For this, the processes of seed dispersal, seed predation and germination have to be understood in the original as well as in degraded vegetation formations. We used seed removal experiments to assess post-dispersal processes that influence recruitment along a gradient of forest degradation in Madagascar analyzing seeds of three animal dispersed tree species. The percentage of seeds consumed or dispersed, declined from forest (28.6%) to degraded forest (17.2%) to savanna (10.8%). Only three out of 1080 seeds were cached and remained intact during the 14-day experiment. All three seeds were cached in the forest habitat and none in the degraded forest and savanna. The low percentage of seeds removed may be due to the lack of endemic rodents caching seeds, as only introduced rats were recorded in the area. The species-poor fauna of potential secondary seed dispersers of the region and especially in the degraded areas might represent an obstacle for diverse regeneration in degraded regions of Madagascar.
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AIM: To investigate the imaging features of synovial chondromatosis of the temporomandibular joint (TMJ), which is a rare benign arthropathy with cartilaginous proliferation. MATERIALS AND METHODS: Computed tomography and magnetic resonance imaging examinations of 34 patients with histopathologically confirmed primary synovial chondromatosis of the TMJ were reviewed retrospectively. Imaging features including the lesion epicentre, destruction/sclerosis of surrounding bone, calcification, periosteal reaction, osteophyte, lesion size, and joint space dimensions were assessed. RESULTS: Thirty-one of thirty-four patients (91.2%) showed the superior joint space as the lesion epicentre. For the mandibular condyle, more than one-third of patients (14/34; 41.2%) showed no destruction, and more than half of patients (19/34; 55.9%) showed no sclerosis. Conversely, >70% of patients showed destruction and sclerosis of the articular eminence/glenoid fossa, while >80% of patients (28/34; 82.4%) presented with various calcifications, including the ring-and-arc (9/34; 26.5%) and popcorn (13/34; 38.2%) types. The mean joint space on the affected side was significantly larger than that of the unaffected side (p<0.001). More than three-fourths of patients (76.9%) experienced no interval increase in lesion size during an average of 1.6 years of follow-up. CONCLUSION: Synovial chondromatosis of the TMJ demonstrated several imaging features, including the lesion centre being located in the superior joint space, resultant articular eminence/glenoid fossa-oriented bone changes, ring-and-arc and popcorn calcification, joint space widening, and self-limiting growth. These imaging features may be helpful in differentiating synovial chondromatosis from other lesions of the TMJ.
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Condromatose Sinovial/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Articulação Temporomandibular/diagnóstico por imagem , Adulto JovemRESUMO
AIM: To identify odontogenesis-promoting compounds and examine the molecular mechanism underlying enhanced odontoblast differentiation and tooth formation. METHODOLOGY: Five different nymphaeols, nymphaeol B (NB), isonymphaeol B (INB), nymphaeol A (NA), 3'-geranyl-naringenin (GN) and nymphaeol C (NC) were isolated from the fruit of Macaranga tanarius. The cytotoxic effect of nymphaeols on human DPSCs was observed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effect of nymphaeols on odontoblast differentiation was analysed with Alizarin Red S staining and odontoblast marker expression was assessed using real-time polymerase chain reaction and Western blot analysis. The molecular mechanism was investigated with Western blot analysis. In order to examine the effect of INB on dentine formation in the developing tooth germ, INB-soaked beads were placed under the tooth bud explants in the collagen gel; thereafter, the tooth bud explant-bead complexes were implanted into the sub-renal capsules for 3 weeks. Tooth root formation was analysed using micro-computed tomography and histological analysis. Data are presented as mean ± standard error (SEM) values of three independent experiments, and results are compared using a two-tailed Student's t-test. The data were considered to have statistical significance when the P-value was less than 0.05. RESULTS: Three of the compounds, NB, INB, and GN, did not exert a cytotoxic effect on human DPSCs. However, INB was most effective in promoting the deposition of calcium minerals in vitro (P < 0.001) and induced the expression of odontogenic marker genes (P < 0.05). Moreover, this compound strongly induced the phosphorylation of mitogen-activated protein (MAP) kinases and protein kinase B (AKT) (P < 0.05). The inhibition of p38 MAP, c-Jun N-terminal kinase (JNK), and AKT substantially suppressed the INB-induced odontoblast differentiation (P < 0.001). In addition, isonymphaeol B significantly induced the formation of dentine and elongation of the tooth root in vivo (P < 0.05). CONCLUSIONS: Prenylflavonoids, including INB, exerted stimulatory effects on odontoblast differentiation and tooth root and dentine formation via the MAP kinase and AKT signalling pathways. These results suggest that nymphaeols could stimulate the repair processes for dentine defects or injuries.
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Diferenciação Celular/efeitos dos fármacos , Euphorbiaceae/química , Flavonoides/farmacologia , Odontoblastos/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Células Cultivadas , Polpa Dentária/citologia , Humanos , Proteínas Quinases Ativadas por Mitógeno , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Raiz Dentária , Microtomografia por Raio-XRESUMO
AIM: To investigate the imaging features of chondrosarcoma of the temporomandibular joint (TMJ) and review the literature. MATERIALS AND METHODS: Computed tomography (CT), magnetic resonance imaging (MRI), and integrated positron-emission tomography (PET)/CT images of nine patients with histopathologically confirmed chondrosarcoma of the TMJ were reviewed retrospectively. Imaging features regarding the direction of lesion growth, bone destruction, infiltration into the tendon of the lateral pterygoid muscle (LPM) in the pterygoid fovea, enhancement pattern, calcification, periosteal reaction, markedly hyperintense T2 signal area, and qualitative PET signal intensity were evaluated. RESULTS: Seven of nine patients (77.8%) presented with lesion growth that was outward from the medulla of the mandibular condyle. Infiltration into the tendon of LPM in the pterygoid fovea was observed in all cases, and 77.8% (7/9) of them demonstrated >50% infiltration. All the lesions showed a mixed peripheral and internal enhancement, and revealed a markedly hyperintense T2 signal intensity area, which showed no enhancement. Although five of nine cases demonstrated higher FDG uptake compared with that of the liver, the other four cases showed less FDG uptake than that of the liver. CONCLUSION: Chondrosarcoma of the TMJ demonstrated several imaging features, including outward growth from the mandibular condyle, resultant infiltration into the tendon of LPM in the pterygoid fovea, various patterns of internal enhancement, and a markedly hyperintense T2 signal intensity area. These imaging features may be helpful to differentiate chondrosarcoma from other lesions of the TMJ.
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Condrossarcoma/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Articulação Temporomandibular/diagnóstico por imagem , Adolescente , Adulto , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Músculos Pterigoides/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
The embryoid body test (EBT) is a developmental toxicity test method that measures the size of embryoid bodies (EBs) and the viability of mouse embryonic stem cells (mESCs) and fibroblasts (3T3 cells). The previous pre-validation study confirmed the high accuracy (above 80%) of EBT using 26 coded test chemicals. This second-phase validation study assessed the inter-laboratory reproducibility (5 chemicals in common) and predictive capacity (10 chemicals in each laboratory) test using the coded test chemicals at three laboratories. For the prediction model, the accuracy is increased when more data is accumulated. Therefore, we updated the prediction model and analyzed the results of the second year with the newly created-prediction model. Statistical analysis of the inter-laboratory reproducibility test results indicated that accuracy, sensitivity, and specificity were 87%, 78%, and 100%, respectively. The results of the statistical analysis of the predictive capacity test showed an accuracy of 80%, sensitivity of 78%, and specificity of 81%. In conclusion, the EBT can accurately classify various embryotoxicants within a short period and with relatively little effort. Therefore, EBT can be used as a good way to test developmental toxicity.
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Alternativas aos Testes com Animais/métodos , Corpos Embrioides/patologia , Células-Tronco Embrionárias Murinas/patologia , Testes de Toxicidade/métodos , Alternativas aos Testes com Animais/normas , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Corpos Embrioides/efeitos dos fármacos , Camundongos , Células-Tronco Embrionárias Murinas/efeitos dos fármacos , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos TestesRESUMO
BACKGROUND AND PURPOSE: After endovascular coiling of intracranial aneurysms, round dark parenchymal lesions believed to be particulate metal are sometimes encountered in MR imaging studies of the brain. We used SWI to assess the frequency of such occurrences, in addition to exploring likely causes and clinical implications. MATERIALS AND METHODS: We reviewed 700 MR imaging studies performed between September 2018 and March 2019 at our institution as follow-up monitoring of coiled intracranial aneurysms. Any sizeable (>5 mm) rounded dark-signal lesions encountered were presumed to be metallic. The magnitudes and locations of such lesions were recorded. In patients with these lesions, pertinent procedural documentation was screened for devices used, including coils, microcatheters, microguidewires, and stents. Medical records were also examined to determine whether any related symptoms ensued. RESULTS: Twenty patients (2.8%) exhibited a total of 25 lesions on SWI. Diameters ranged from 5 to 11 mm (median, 8 mm). All except 2 lesions were located in brain regions downstream from aneurysms, but all lesions occupied vascular territories of vessels used to place guiding catheters. Other than the Synchro 14, which was routinely deployed, no device was regularly used in patients with SWI-detectable lesions; and none of the affected patients developed focal neurologic symptoms as a consequence. CONCLUSIONS: Although the origins remain unclear, distal embolization of particulate metal distal to coiled cerebral aneurysms is occasionally observed on follow-up MR imaging studies. Such lesions, however, seem to have no apparent clinical impact.
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Prótese Vascular/efeitos adversos , Aneurisma Intracraniano/cirurgia , Embolia Intracraniana/diagnóstico por imagem , Embolia Intracraniana/etiologia , Imageamento por Ressonância Magnética/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Procedimentos Endovasculares/instrumentação , Procedimentos Endovasculares/métodos , Feminino , Seguimentos , Humanos , Masculino , Metais , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Despite improved survival of patients with lupus nephritis (LN), some require kidney transplantation because of progression to end-stage renal disease (ESRD). However, the transplant outcomes of these patients and other recipients have not been thoroughly compared. METHODS: In total, 1848 Korean kidney recipients who underwent transplantation from 1998 to 2017 at two tertiary referral centers were evaluated retrospectively. Among them, 28 recipients with LN, and 50 control recipients matched by age, sex, and donor type, were compared with respect to graft and patient survival. We pooled our data with 17 previous cohort studies in which the graft survival of recipients with LN was described in detail. RESULTS: During the median follow-up period of 9.5 years (maximum 21 years), graft failure (GF) occurred in 10.7% and 16.0% of LN and control recipients, respectively. No differences were found in the rates of GF and death-censored graft failure or patient survival between the two groups. The risks of acute T cell-mediated and antibody-mediated rejection were also similar between the two groups. The pooled analysis showed similar 1- and 5-year graft survival rates between LN and control recipients. CONCLUSIONS: Kidney transplantation is an acceptable option in patients with concurrent LN and ESRD.
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Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Nefrite Lúpica/cirurgia , Adulto , Progressão da Doença , Feminino , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/mortalidade , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/mortalidade , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Complicações Pós-Operatórias/epidemiologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND AND AIM: Effects of whole egg consumption on cardiovascular diseases (CVD) risk in the middle-aged and older population remain unclear due to inconsistent findings from observational and randomized controlled trials (RCTs). This meta-analysis aimed to assess the impacts of whole egg and egg category (whole eggs versus egg substitutes) intake quantity on CVD risk factors from systematically searched RCTs. Egg substitutes were hypothesized to have minimal effects of the blood lipid and lipoprotein profile as they are void of dietary cholesterol. METHODS AND RESULTS: As many as 434 studies identified from PubMed, Cochrane Library, CINAHL and Medline (Ovid) databases were screened and data were extracted from 8 selected RCTs. Quality of the selected studies were assessed and the overall effect sizes of weighted mean differences (WMD) were calculated using a random effects model. Non-differential effects in blood pressures, lipids and lipoproteins were observed when >4 whole eggs/week compared to ≤4 whole eggs/week were consumed. Intake of >4 whole eggs/week compared to equivalent amounts of egg substitutes caused greater elevations in blood total cholesterol (WMD: 0.198 mmol/L; 95% CIs: 0.056, 0.339), HDL cholesterol (WMD: 0.068 mmol/L; 95% CIs: 0.006, 0.130) and LDL cholesterol (WMD: 0.171 mmol/L; 95% CIs: 0.028, 0.315) but did not differentially affect triglycerides concentration. CONCLUSION: Overall, the results support the notion that quantity of whole egg intake does not affect CVD risk factors and consuming egg substitutes may also be beneficial compared to whole eggs on lowering CVD risk in the middle-aged and older population.
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Pressão Sanguínea , Doenças Cardiovasculares/epidemiologia , Colesterol na Dieta/administração & dosagem , Ovos , Lipídeos/sangue , Lipoproteínas/sangue , Valor Nutritivo , Fatores Etários , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Colesterol na Dieta/efeitos adversos , Ovos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Recomendações Nutricionais , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND AND OBJECTIVE: Phelligridin D is a hispidin analogue from the mushroom Phellinus baumii that is widely used as a food source in East Asia. This study tested phelligridin D for the anti-inflammatory effect and mechanism in lipopolysaccharide (LPS)-induced human periodontal ligament cells (HPDLCs). The objective of this study was to clarify whether the anti-inflammatory function of phelligridin D affects periodontal regeneration for supporting the HPDLCs of teeth. MATERIAL AND METHODS: Primary HPDLCs were isolated from healthy teeth and then cultured. The anti-inflammatory function, mechanism and differentiation molecules were verified with reactive oxygen species generation and western blot analysis in LPS-induced HPDLCs. RESULTS: HPDLCs showed increased inflammatory molecules (intracellular adhesion molecule-1 and vascular cell adhesion molecule-1) and decreased osteogenic proteins (bone morphogenetic protein-7, Osterix and runt-related transcription factor 2) by LPS treatment. Phelligridin D decreased inflammatory molecules and increased osteogenic molecules via downregulation of the extracellular signal-regulated kinase and c-jun N-terminal kinases pathway among the mitogen-activated protein kinase, followed by blocking of nuclear factor kappa-B translocation from cytosol to nucleus. In addition, phelligridin D showed antioxidant properties by reducing reactive oxygen species activity. Finally, the anti-inflammatory and antioxidant function of phelligridin D promoted the periodontal differentiation of HPDLCs. CONCLUSION: These results suggest that phelligridin D supports teeth on the alveolar bone against outside stress, and may be used as an anti-inflammatory compound for the prevention of periodontitis or periodontal regenerative related disease.
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Anti-Inflamatórios , Diferenciação Celular/efeitos dos fármacos , Lipopolissacarídeos/efeitos adversos , Ligamento Periodontal/efeitos dos fármacos , Ligamento Periodontal/fisiologia , Pironas/farmacologia , Regeneração/efeitos dos fármacos , Agaricales/química , Proteína Morfogenética Óssea 7/metabolismo , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Ligamento Periodontal/citologia , Ligamento Periodontal/metabolismo , Periodontite/prevenção & controle , Pironas/isolamento & purificação , Fator de Transcrição Sp7/metabolismo , Estimulação Química , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
The role of astrocytes in brain plasticity has not been extensively studied compared with that of neurons. Here we adopted integrative translational and reverse-translational approaches to explore the role of an astrocyte-specific major water channel in the brain, aquaporin-4 (AQP4), in brain plasticity and learning. We initially identified the most prevalent genetic variant of AQP4 (single nucleotide polymorphism of rs162008 with C or T variation, which has a minor allele frequency of 0.21) from a human database (n=60 706) and examined its functionality in modulating the expression level of AQP4 in an in vitro luciferase reporter assay. In the following experiments, AQP4 knock-down in mice not only impaired hippocampal volumetric plasticity after exposure to enriched environment but also caused loss of long-term potentiation after theta-burst stimulation. In humans, there was a cross-sectional association of rs162008 with gray matter (GM) volume variation in cortices, including the vicinity of the Perisylvian heteromodal language area (Sample 1, n=650). GM volume variation in these brain regions was positively associated with the semantic verbal fluency. In a prospective follow-up study (Sample 2, n=45), the effects of an intensive 5-week foreign language (English) learning experience on regional GM volume increase were modulated by this AQP4 variant, which was also associated with verbal learning capacity change. We then delineated in mice mechanisms that included AQP4-dependent transient astrocytic volume changes and astrocytic structural elaboration. We believe our study provides the first integrative evidence for a gliogenetic basis that involves AQP4, underlying language-associated brain plasticity.
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Aquaporina 4/metabolismo , Astrócitos/citologia , Desenvolvimento da Linguagem , Aprendizagem/fisiologia , Neuroglia/citologia , Plasticidade Neuronal/fisiologia , Adulto , Animais , Aquaporina 4/biossíntese , Aquaporina 4/genética , Astrócitos/metabolismo , Encéfalo/metabolismo , Estudos Transversais , Modelos Animais de Doenças , Feminino , Seguimentos , Frequência do Gene , Substância Cinzenta/citologia , Substância Cinzenta/metabolismo , Hipocampo/metabolismo , Humanos , Masculino , Camundongos , Camundongos Knockout , Neuroglia/metabolismo , Neurônios/metabolismo , Polimorfismo de Nucleotídeo Único , Estudos ProspectivosRESUMO
AIM: To examine the properties of Schisandrin C as an anti-inflammatory and antioxidant compound, and whether its characteristics promote mitochondrial biogenesis in human dental pulp cells (HDPCs). METHODOLOGY: HDPCs were extracted from fresh third molars and cultured for experiments. Reactive oxidative stress (ROS) and nitric oxide (NO) formation were analysed by a Muse cell analyser. Western blotting and gelatin zymography were used to identify the presence of antioxidants, as well as anti-inflammatory and mitochondrial biogenesis with specific antibody. An unpaired Student's t-test was used for statistical analysis. RESULTS: Schisandrin C inhibited lipopolysaccharide-stimulated inflammatory molecules; interleukin 1 beta, tumour necrosis factor alpha, intracellular adhesion molecule-1, vascular cell adhesion molecule-1, matrix metalloproteinase-2 and -9, NO production, ROS formation, nuclear factor kappa B translocation (P < 0.05) through the mitogen-activated protein kinase pathway. Schisandrin C increased the expression of superoxide dismutase enzymes as well as haem oxygenase-1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha through the phosphorylated-protein kinase B (p-Akt) and nuclear factor erythroid 2-related factor-2 pathways (P < 0.05). The anti-inflammatory and antioxidant properties of Schisandrin C promoted mitochondrial biogenesis. CONCLUSIONS: Schisandrin C has the potential to reduce inflammation and oxidation and to promote mitochondrial biogenesis. Therefore, Schisandrin C may be considered for use as an anti-inflammatory compound for oral inflammation through mitochondrial biogenesis.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Polpa Dentária/citologia , Polpa Dentária/efeitos dos fármacos , Lignanas/farmacologia , Biogênese de Organelas , Compostos Policíclicos/farmacologia , Ciclo-Octanos/farmacologia , Gelatina , Heme Oxigenase (Desciclizante)/metabolismo , Humanos , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos/efeitos adversos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Mitocôndrias/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Fatores de Transcrição/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Adipose tissue is now appreciated as the pivotal regulator of metabolic and endocrine functions. Subcutaneous (SC) fat, in contrast to visceral fat, may protect against metabolic syndrome and systemic inflammation. We demonstrated that chronic as well as acute ultraviolet (UV) irradiation to the skin induces loss of underlying SC fat. UV-irradiated SC fat may produce chemokines or cytokines that modulate lipid homeostasis and secretion of adipokines. OBJECTIVES: To elucidate UV-induced specific adipochemokines implicated in UV-induced modulation of SC fat. METHODS: Primary cultured adipocytes were treated with conditioned medium from UV- or sham-irradiated skin cells. Young and older healthy participants provided SC fat from sun-exposed and sun-protected skin. Sun-protected skin from other participants was irradiated with UV. Differentially expressed adipochemokines were screened by cytokine array, and confirmed in vitro and in vivo. The functions of select adipochemokines involved in lipid metabolism were examined via short interfering RNA-mediated knockdown of cognate receptors. RESULTS: Specific adipochemokines, including C-X-C motif chemokine (CXCL) family members such as CXCL5/ENA-78, and C-C motif chemokine (CCL) family members such as CCL20/MIP-3α and CCL5/RANTES, were greatly induced in SC fat by UV exposure. They could impair triglyceride synthesis via downregulation of lipogenic enzymes and sterol regulatory element-binding protein-1 through their respective cognate receptors, CXC chemokine receptor type (CXC-R)2, C-C chemokine receptor type (CCR)-6, and CCR-5. In addition, UV irradiation induced infiltration of adipose tissue macrophages responsible for the secretion of several chemokines into SC fat. CONCLUSIONS: These UV-induced adipochemokines may be implicated in the reduction of lipogenesis in SC fat, leading to impairment of fat homeostasis and associated comorbidities such as obesity.
Assuntos
Adipócitos/metabolismo , Adipocinas/efeitos da radiação , Quimiocinas/efeitos da radiação , Gordura Subcutânea/metabolismo , Raios Ultravioleta , Adipocinas/biossíntese , Adulto , Idoso , Quimiocina CCL20/efeitos da radiação , Quimiocina CCL5/efeitos da radiação , Quimiocina CXCL5/efeitos da radiação , Quimiocinas/biossíntese , Feminino , Técnicas de Silenciamento de Genes , Humanos , Lipogênese/efeitos da radiação , Macrófagos/efeitos da radiação , Masculino , Interferência de RNA/efeitos da radiação , Receptores de Quimiocinas/antagonistas & inibidores , Receptores de Quimiocinas/efeitos da radiação , Triglicerídeos/biossíntese , Regulação para Cima/efeitos da radiaçãoRESUMO
BACKGROUND AND PURPOSE: The effect of delayed transit time is the main source of error in the quantitative measurement of CBF in arterial spin-labeling. In the present study, we evaluated the usefulness of the transit time-corrected CBF and arterial transit time delay from multiple postlabeling delays arterial spin-labeling compared with basal/acetazolamide stress technetium Tc99m-hexamethylpropylene amineoxime (Tc99m-HMPAO) SPECT in predicting impairment in the cerebrovascular reserve. MATERIALS AND METHODS: Transit time-corrected CBF maps and arterial transit time maps were acquired in 30 consecutive patients with unilateral ICA or MCA steno-occlusive disease (severe stenosis or occlusion). Internal carotid artery territory-based ROIs were applied to both perfusion maps. Additionally, impairment in the cerebrovascular reserve was evaluated according to both qualitative and quantitative analyses of the ROIs on basal/acetazolamide stress Tc99m-HMPAO SPECT using a previously described method. The area under the receiver operating characteristic curve was used to evaluate the diagnostic accuracy of arterial spin-labeling in depicting impairment of the cerebrovascular reserve. The correlation between arterial spin-labeling and cerebrovascular reserve was evaluated. RESULTS: The affected hemisphere had a decreased transit time-corrected CBF and increased arterial transit time compared with the corresponding values of the contralateral normal hemisphere, which were statistically significant (P < .001). The percentage change of transit time-corrected CBF and the percentage change of arterial transit time were independently differentiating variables (P < .001) for predicting cerebrovascular reserve impairment. The correlation coefficient between the arterial transit time and cerebrovascular reserve index ratio was -0.511. CONCLUSIONS: Our results demonstrate that the transit time-corrected CBF and arterial transit time based on arterial spin-labeling perfusion MR imaging can predict cerebrovascular reserve impairment.
Assuntos
Encéfalo/irrigação sanguínea , Doenças Arteriais Cerebrais/diagnóstico por imagem , Circulação Cerebrovascular , Imageamento por Ressonância Magnética/métodos , Imagem de Perfusão/métodos , Idoso , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Marcadores de Spin , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
BACKGROUND: This prospective, randomised, controlled study was performed to evaluate the usefulness of the McGrath VL compared with Macintosh laryngoscopy in children with expected normal airway during endotracheal intubation, by comparing the time to intubation and difficulty of intubation. METHODS: Eighty-four patients aged 1-10 years who underwent endotracheal intubation for elective surgery were randomly assigned to the McGrath group (n = 42) or the Macintosh group (n = 42). Anaesthesia was induced with 2.5-3.0 mg/kg of propofol and sevoflurane 5-8 vol%. Orotracheal intubation was performed 2 min after injection of rocuronium 0.6 mg/kg with McGrath VL or Macintosh laryngoscope; the primary outcome was the time to intubation. The Cormack and Lehane glottic grade, intubation difficulty score (IDS), and success rate on intubation were assessed. Haemodynamic changes were also recorded. RESULTS: As the primary outcome, median time to intubation [interquartile range] did not differ between the McGrath group and the Macintosh group (25.0 [22.8-28.3] s vs. 26.0 [24.0-29.0] s, P = 0.301). The incidence of grade I glottic view was significantly higher in the McGrath group than in the Macintosh group (95% vs. 74%, P = 0.013). Median IDS was lower in the McGrath group than in the Macintosh group (0 [0-0] vs. 0 [0-1], P = 0.018). There were no significant differences in success rate on intubation or haemodynamics between the two groups. CONCLUSIONS: McGrath VL provides better laryngeal views and lower IDS but similar intubation times and success rates compared with the Macintosh laryngoscope in children with normal airway.