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BACKGROUND: Dental film mounting is an essential but time-consuming task in dental radiography, with manual methods often prone to errors. This study aims to develop a deep learning (DL) model for accurate automated classification and mounting of both intraoral and extraoral dental radiography. METHOD: The present study employed a total of 22,334 intraoral images and 1,035 extraoral images to train the model. The performance of the model was tested on an independent internal dataset and two external datasets from different institutes. Images were categorized into 32 tooth areas. The VGG-16, ResNet-18, and ResNet-101 architectures were used for pretraining, with the ResNet-101 ultimately being chosen as the final trained model. The model's performance was evaluated using metrics of accuracy, precision, recall, and F1 score. Additionally, we evaluated the influence of misalignment on the model's accuracy and time efficiency. RESULTS: The ResNet-101 model outperformed VGG-16 and ResNet-18 models, achieving the highest accuracy of 0.976, precision of 0.969, recall of 0.984, and F1-score of 0.977 (p < 0.05). For intraoral images, the overall accuracy remained consistent across both internal and external datasets, ranging from 0.963 to 0.972, without significant differences (p = 0.348). For extraoral images, the accuracy consistently achieved the highest value of 1 across all institutes. The model's accuracy decreased as the tilt angle of the X-ray film increased. The model achieved the highest accuracy of 0.981 with correctly aligned films, while the lowest accuracy of 0.937 was observed for films exhibiting severe misalignment of ± 15° (p < 0.001). The average time required for the tasks of image rotation and classification for each image was 0.17 s, which was significantly faster than that of the manual process, which required 1.2 s (p < 0.001). CONCLUSION: This study demonstrated the potential of DL-based models in automating dental film mounting with high accuracy and efficiency. The proper alignment of X-ray films is crucial for accurate classification by the model.
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Aprendizado Profundo , Humanos , Radiografia DentáriaRESUMO
Background/purpose: In Taiwan, the dental radiology has a history of more than 100 years. However, medical radiation schools or teaching hospitals have not yet established a set of standard learning content for dental radiology internship. Materials and methods: We used the observational method and dental radiology teaching survey to explore the connotation of clinical dental radiology education for medical radiation students in Taiwan. Results: There were 64 dental departments of hospitals with their own independent dental radiology departments in Taiwan in 2022. Among them, 58 (90.63%) were in the teaching hospitals. Of the 58 dental radiology departments in the teaching hospitals, 40 (68.97%) had medical radiation interns in their dental radiology departments. There was a complete set of seven training items for dental radiology internship. The mean training items in the medical centers (4.94) was significantly higher than that in the regional hospital (3.9) (P < 0.05). No matter what level of hospital, it is the most common way to implement the training mode with preclinical exercises and then clinical practice. Conclusion: In Taiwan, the current status of dental radiology teachers in the teaching hospital is indeed seriously insufficient. It is necessary to establish a standard dental radiology education system, including setting one common dental radiology subject for medical radiation students, and the relevant regulations to formulate the basic requirements of the training items and training hours for dental radiology internship. Thus, medical radiation interns can acquire the operation skills related to dental X-ray machines after completing the internship training.
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This study examined whether interventions through barrier-free home environment improvements could reduce family caregivers' care stress, improve their family functions, and increase their quality of life. This study recruited family caregivers of older people with disabilities from a long-term care management center in central Taiwan. These older people required improvements related to a barrier-free home environment. A pretest was conducted before and a post-test was conducted 2 months after the improvements. The content of the pretest and the post-test questionnaires included: demographic characteristics, Caregiver stress scale, Family functions scale, World Health Organization Quality of Life-BREF (WHOQOL-BREF) Questionnaire. This study recruited 72 family caregivers; the average age was 56.25 ± 12.99 years. The results indicated that interventions through barrier-free home environment improvements could significantly reduce the family caregivers' care stress, improve their family functions (e.g., reducing conflicts), and enhance their quality of life. Additionally, after intervention, the family cohesion of family caregivers caring for those with mild disability improved to a greater extent than did that of those caring for people with other disease severities. This study revealed that interventions involving barrier-free home environment improvements have positive effects on family caregivers.
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Cuidadores , Qualidade de Vida , Adulto , Idoso , Ansiedade , Família , Humanos , Assistência de Longa Duração , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
Apart from numerous applications, for example in azo dye precursors, explosives, and industrial processes, the nitro group (-NO2 ) appears on countless molecules in photochemical research owing to its unique characteristics such as a strong electron-withdrawing ability and facile conversion to the reduced substituent. Although it is well known as a fluorescence quencher, fluorescent chromophores that contain the nitro group have also emerged, with 3-nitrophenothiazine being recently reported to have 100 % emission quantum yield in nonpolar solvents. The diverse characters of nitro-containing chromophores motivated us to systematically review those chromophores with nitro substituents, their associated photophysical properties, and applications. In this Review, we succinctly elaborate the advance of the fluorescent nitro chromophores in fields of intramolecular charge transfer, fluorescent probes and nonlinear properties. Special attention is paid to the rationalization of the associated emission spectroscopy, so that the readers can gain insights into the structure-photophysics relationship and hence gain insights for the strategic design of nitro chromophores.
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The weak fluorescence (quantum yield <1 % in cyclohexane) of phenothiazine (PTZ) impedes its further application. In addition, the nitro group (NO2 ) is a well-known fluorescence quencher. Interestingly, we obtained a highly fluorescent chromophore by combining these two moieties, forming 3-nitrophenothiazine (PTZ-NO2 ). For comparison, a series of PTZ derivatives bearing electron-withdrawing groups (EWGs; CN and CHO) or electron-donating groups (EDGs; OMe) at the 3-position have been designed and synthesized. The phenothiazines bearing EWGs exhibited enhanced emission compared with the parent PTZ or EDG derivatives. Computational approaches unveiled that for PTZ and PTZ-OMe, the transitions are from HOMOs dominated by π orbitals to LUMOs of mixed sulfur nonbonding-π* orbitals, and hence are partially forbidden. In contrast, the EWGs lower the energy level of the lone-pair electrons on the sulfur atom, thereby suppressing the mixing of the nonbonding orbital with the π* orbital in the LUMO, such that the allowed ππ* transition becomes dominant. This work thus demonstrates a judicious chemical design to fine-tune the transition character in PTZ analogues, with PTZ-NO2 attaining 100 % emission quantum yields in nonpolar solvent.
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With the aim of generalizing the structure-properties relationship of bending heterocyclic molecules that undergo prominent photoinduced structural planarization (PISP), a series of new dihydrodibenzo[ac]phenazine derivatives in which one nitrogen atom is replaced by oxygen (PNO), sulfur (PNS), selenium (PNSe), or dimethylmethanediyl (PNC) was strategically designed and synthesized. Compounds PNO, PNS, and PNSe have significantly nonplanar geometries in the ground state, which undergo PISP to give a planarlike conformer and hence a large emission Stokes shift. A combination of femtosecond early relaxation dynamics and computational approaches established an R*âI* (intermediate)âP* sequential kinetic pattern for PNS and PNSe, whereas PNO undergoes R*âP* one-step kinetics. The polarization ability of the substituted heteroatoms, which is in the order O
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Phenothiazine derivatives based on the 10-phenyl-10H-phenothiazine (NAS) chromophore, namely 7-phenyl-7H-benzo[c]phenothiazine (NAS-1) and 12-phenyl-12H-benzo[a]phenothiazine (NAS-2), were designed and synthesized. NAS-1 and NAS-2 are constitutional isomers with different steric strains imposed on the phenothiazine core moiety. In solution, the more-strained NAS-2 possesses a bent structure and undergoes photoinduced structural planarization (PISP). In the crystal, despite the absence of PISP, bent NAS-2 exhibits prominent excimer emission as well as emission mechanochromism, which is not observed in the planar-like NAS and NAS-1. This unconventional observation results from the bent core structure facilitating π-π stacking of the peripheral naphthalene moieties. Two-photon-coupled depth-dependent emission shows spectral differences between the surface and kernel of the NAS-2 crystal, and is believed to be a general phenomenon, at least in part, for materials exhibiting emission mechanochromism.
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INTRODUCTION: Transglutaminase 2 (TG2), a protein crosslinking enzyme with multiple biochemical functions, has been connected to various inflammatory processes. In this study, the involvement of TG2 in monosodium urate (MSU) crystal-induced inflammation was studied. METHODS: Immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) were performed to detect TG2 expression in synovial fluid mononuclear cells (SFMCs) and synovial tissue from patients with gouty arthritis. MSU crystal-exposed RAW264.7 mouse macrophages were analyzed for interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), transforming growth factor ß1 (TGF-ß1) and TG2 expression by RT-PCR and enzyme-linked immunosorbent assay (ELISA). TG2 small interfering (si)-RNA-mediated silencing and overexpression in RAW264.7 cells were used to evaluate the involvement of TG2 in resolving MSU crystal-induced inflammation. The role of metastatic tumor antigen 1 (MTA1), a master chromatin modifier, was investigated by MTA1 si-RNA-mediated knockdown. In addition, the inflammatory responses were followed in wild type and TG2 null mice after being challenged with MSU crystals in an in vivo peritonitis model. RESULTS: TG2 expression was up-regulated in the synovium tissue and SFMCs from patients with gouty arthritis. The levels of MTA1, TG2, TGF-ß1, IL-1ß and TNF-α mRNAs were consistently increased in MSU crystal-stimulated RAW264.7 cells. si-MTA1 impaired the basal, as well as the MSU crystal-induced expression of TG2 and TGF-ß1, but increased that of IL-1ß and TNF-α. TG2 overexpression dramatically suppressed MSU crystal-induced IL-1ß and TNF-α, but significantly enhanced the TGF-ß1 production. Neutralizing TGF-ß antibodies or inhibition of the crosslinking activity of TG2 attenuated these effects. On the contrary, loss of TG2 resulted in a reduced TGF-ß, but in an increased IL-1ß and TNF-α production in MSU crystal-stimulated RAW264.7 cells and mouse embryonic fibroblasts (MEFs). MSU crystal-stimulated IL-1ß production was Janus kinase 2 (JAK2)-signaling dependent and TG2-induced TGF-ß suppressed the activity of it. Finally, TG2-deficient mice exhibited hyper inflammatory responses after being challenged with MSU crystals in an in vivo peritonitis model. CONCLUSIONS: These findings reveal an inherent regulatory role of the MTA1-TG2 pathway in the self-limitation of MSU crystal-induced inflammation via positively regulating the levels of active TGF-ß1 in macrophages that opposes the MSU crystal-induced JAK2-dependent pro-inflammatory cytokine formation.
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Artrite Gotosa/metabolismo , Proteínas de Ligação ao GTP/biossíntese , Histona Desacetilases/biossíntese , Proteínas Repressoras/biossíntese , Fator de Crescimento Transformador beta1/biossíntese , Transglutaminases/biossíntese , Regulação para Cima/fisiologia , Ácido Úrico/toxicidade , Animais , Artrite Gotosa/patologia , Linhagem Celular , Humanos , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 2 Glutamina gama-Glutamiltransferase , Transativadores , Regulação para Cima/efeitos dos fármacosRESUMO
Prolactin is the key hormone to stimulate milk synthesis in mammary epithelial cells. It signals through the Jak2-Stat5 pathway to induce the expression of ß-casein, a milk protein which is often used as a marker for mammary differentiation. Here we examined the effect of pyrrolidine dithiocarbamate (PDTC) on prolactin signaling. Our results show that PDTC downregulates prolactin receptor levels, and inhibits prolactin-induced Stat5 tyrosine phosphorylation and ß-casein expression. This is not due to its inhibitory action on NF-κB since application of another NF-κB inhibitor, BAY 11-7082, and overexpression of I-κBα super-repressor do not lead to the same results. Instead, the pro-oxidant activity of PDTC is involved as inclusion of the antioxidant N-acetylcysteine restores prolactin signaling. PDTC triggers great extents of activation of ERK and JNK in mammary epithelial cells. These do not cause suppression of prolactin signaling but confer serine phosphorylation of insulin receptor substrate-1, thereby perturbing insulin signal propagation. As insulin facilitates optimal ß-casein expression, blocking insulin signaling by PDTC might pose additional impediment to ß-casein expression. Our results thus imply that lactation will be compromised when the cellular redox balance is dysregulated, such as during mastitis.
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Acetilcisteína/farmacologia , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Prolactina/metabolismo , Pirrolidinas/antagonistas & inibidores , Pirrolidinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Tiocarbamatos/antagonistas & inibidores , Tiocarbamatos/farmacologia , Animais , Caseínas/genética , Bovinos , Células Epiteliais/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Insulina/metabolismo , Proteínas Substratos do Receptor de Insulina/química , Proteínas Substratos do Receptor de Insulina/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Glândulas Mamárias Animais/citologia , Camundongos , NF-kappa B/antagonistas & inibidores , Fosforilação/efeitos dos fármacos , Gravidez , Serina/metabolismoRESUMO
Clearance of apoptotic cells, termed "efferocytosis", is the mechanism required to prevent secondary necrosis and release of proinflammatory cytokines. Defective efferocytosis is cumulatively regarded as one of mechanisms in the development of autoimmune and chronic inflammatory diseases. Our previous finding showed that ethanolic extract from Glycine tomentella Hayata (GTH) can enhance mouse macrophage RAW264.7 efferocytosis (clearance of apoptotic cells). We have demonstrated that the major components of GTH are daidzein, catechin, epicatechin and naringin. Here, we explore the potential of each component in modulating efferocytic capability. For this, RAW264.7 cells were cultured with CFDA-stained apoptotic cells and assayed by flow cytometry. We found that daidzein is the main component of GTH, and it can enhance RAW264.7 efferocytosis dose-dependently. Moreover, the enhancive effect of daidzein on macrophage efferocytic capability is accompanied by increased transglutaminase 2 (TG2) at both mRNA and protein levels. TG2 knockdown attenuated daidzein increased macrophage efferocytic capability. After treatment with daidzein, increased phosphorylation was observed in Erk, but not in p38 and JNK. Finally, we report that after daidzein treatment, Rac1 activity was markedly increased and the mitochondrial membrane potential was decreased, which may contribute to efferocytosis. Taken together, these data suggest that enhancement of macrophage efferocytic capability by daidzein treatment was mainly through up-regulation of TG2 expression and Rac1 activity. Daidzein may have the therapeutical potential in the treatment of inflammatory diseases.
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Proteínas de Ligação ao GTP/metabolismo , Isoflavonas/farmacologia , Fagocitose/efeitos dos fármacos , Transglutaminases/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo , Animais , Linhagem Celular , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Fosforilação/efeitos dos fármacos , Proteína 2 Glutamina gama-Glutamiltransferase , Regulação para Cima/efeitos dos fármacosRESUMO
In mammary epithelial cells (MECs), prolactin-induced signaling and gene expression requires integrin-mediated cell adhesion to basement membrane (BM). In the absence of proper cell-BM interactions, for example, culturing cells on collagen-coated plastic dishes, signal propagation is substantially impaired. Here we demonstrate that the RhoA-Rok-myosin II pathway accounts for the ineffectiveness of prolactin signaling in MECs cultured on collagen I. Under these culture conditions, the RhoA pathway is activated, leading to downregulation of prolactin receptor expression and reduced prolactin signaling. Enforced activation of RhoA in MECs cultured on BM suppresses prolactin receptor levels, and prevents prolactin-induced Stat5 tyrosine phosphorylation and ß-casein expression. Overexpression of dominant negative RhoA in MECs cultured on collagen I, or inhibiting Rok activity, increases prolactin receptor expression, and enhances prolactin signaling. In addition, inhibition of myosin II ATPase activity by blebbistatin also exerts a beneficial effect on prolactin receptor expression and prolactin signaling, suggesting that tension exerted by the collagen substratum, in collaboration with the RhoA-Rok-myosin II pathway, contributes to the failure of prolactin signaling. Furthermore, MECs cultured on laminin-coated plastic have similar morphology and response to prolactin as those cultured on collagen I. They display high levels of RhoA activity and are inefficient in prolactin signaling, stressing the importance of matrix stiffness in signal transduction. Our results reveal that RhoA has a central role in determining the fate decisions of MECs in response to cell-matrix interactions.
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Glândulas Mamárias Animais/metabolismo , Miosina Tipo II/metabolismo , Prolactina/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo , Quinases Associadas a rho/metabolismo , Animais , Sequência de Bases , Adesão Celular , Diferenciação Celular , Células Cultivadas , Microambiente Celular , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Matriz Extracelular/metabolismo , Feminino , Regulação da Expressão Gênica , Glândulas Mamárias Animais/citologia , Glândulas Mamárias Animais/efeitos dos fármacos , Camundongos , Miosina Tipo II/antagonistas & inibidores , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores da Prolactina/genética , Receptores da Prolactina/metabolismo , Transdução de Sinais , Proteínas rac de Ligação ao GTP/metabolismo , Quinases Associadas a rho/antagonistas & inibidores , Proteína rhoA de Ligação ao GTPRESUMO
BACKGROUND: To assess the effects of Glycine tomentella Hayata (GTH), a traditional herbal medicine for treatment of rheumatic diseases on the expression of the proinflammatory cytokines and on the clearance of apoptotic cells by macrophages. METHODS: RAW264.7 cells were cultured with lipopolysaccharide (LPS) in the presence or absence of ethanol extract of GTH. The expression of proinflammatory cytokines IL-1ß, IL-6, and TNF-α, and inducible nitric oxide synthase (iNOS) and transglutaminase 2 (TG2) were assayed by reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Matrix metalloproteinase (MMP)-2 and MMP-9 were assayed by gelatin zymography. For detecting uptake of apoptotic cells, RAW264.7 cells were cultured with carboxyfluorescein diacetate (CFDA)-stained apoptotic cells and assayed by flow cytometry. RESULTS: The major components of GTH analyzed by high-performance liquid chromatography (HPLC) chromatogram were daidzein (42.5%), epicatechin (28.8%), and naringin (9.4%).GTH treatment inhibited the expression of proinflammatory cytokines IL-1ß, IL-6 and MMP-9 but did not affect the expression of TNF-α and iNOS. GTH significantly enhanced the expression of TG2 and the clearance of apoptotic cells by RAW264.7 macrophages. CONCLUSIONS: GTH inhibits proinflammatory cytokine secretion and MMP-9 activity, enhances apoptotic cell uptake and up-regulates TG2 expression. Our data show that GTH might have beneficial effects on rheumatic diseases.
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Apoptose , Glicina , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Macrófagos , Inibidores de Metaloproteinases de Matriz , Extratos Vegetais/farmacologia , Animais , Linhagem Celular , Proteínas de Ligação ao GTP/metabolismo , Glicina/química , Glicina/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/química , Proteína 2 Glutamina gama-Glutamiltransferase , Transglutaminases/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: Acute pyelonephritis is a common infectious disease in children and can result in permanent renal damage. Interleukin-6 (IL-6) is an important mediator of inflammation in response to bacterial infection. This study investigated the potential relationship between acute-phase IL-6 and subsequent renal scarring in children with a first time febrile acute pyelonephritis. MATERIAL AND METHODS: In total, 79 children (age range 1-120 months) with a first time febrile urinary tract infection (UTI) were included. The diagnosis of acute pyelonephritis was confirmed by (99m)Tc-dimercaptosuccinic acid (DMSA) renal scan. Serum and urine samples were collected for IL-6 measurement by enzyme-linked immunosorbent assay before antibiotic treatment for the infection. RESULTS: The 79 children were divided into acute pyelonephritis (n=45) and lower UTI (n=34) groups according to the findings of DMSA scans. The initial serum and urine IL-6 levels of children with acute pyelonephritis were significantly higher compared with lower UTI (p < 0.001). Renal scarring was detected at the follow-up DMSA scans in 15 (34.1%) of the 44 children with acute pyelonephritis. Both serum and urine IL-6 levels during the acute phase of pyelonephritis were significantly higher in children with renal scarring than in those without (p=0.005 and p = 0.002). The median age of children with renal scarring was significantly lower than those without (p=0.034). Multiple regression analysis showed that higher initial serum and urine IL-6 levels and a younger age were associated with renal scarring. CONCLUSION: These results demonstrate that in younger children with a first time febrile acute pyelonephritis, elevations of the acute-phase serum and urine IL-6 levels were correlated with an increased risk of subsequent renal scarring.
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Interleucina-6/sangue , Interleucina-6/urina , Rim/patologia , Pielonefrite/sangue , Pielonefrite/urina , Doença Aguda , Quelantes , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Succímero , Refluxo Vesicoureteral/sangue , Refluxo Vesicoureteral/urinaRESUMO
AIM: Acute pyelonephritis is a common infectious disease in children and can result in permanent renal damage. Interleukin (IL)-1beta is an important inflammatory mediator that appears early during bacterial infection. This prospective study examined urine IL-1beta levels in children with acute pyelonephritis documented by (99m)Tc-dimercaptosuccinic acid (DMSA) scan, and also evaluated whether this cytokine correlated with renal scarring. METHODS: A total of 75 children aged 1-121 months with a diagnosis of first-time febrile urinary tract infection (UTI) were studied. The following inflammatory markers were assessed: fever, white blood cell (WBC), neutrophil, C-reactive protein (CRP) and urine IL-1beta. Urine samples were collected for IL-1beta measurement by enzyme-linked immunosorbent assay before and after antibiotic treatment of the infection. Follow-up DMSA scan was performed at 6-12 months after the acute pyelonephritis to detect renal scarring. Twenty children with other febrile illnesses served as non-renal febrile controls. RESULTS: The 75 children were divided into acute pyelonephritis (n = 41) and lower UTI (n = 34) groups according to the findings of DMSA scans. Fever, WBC count, neutrophil count and CRP were significantly higher in the children with acute pyelonephritis than in those with lower UTI (all P < 0.001). The initial urine IL-1beta levels of children with acute pyelonephritis were significantly higher when compared with lower UTI and non-renal febrile controls (P < 0.001). Urine IL-1beta in children with acute pyelonephritis was positively correlated with fever, CRP, WBC, neutrophil and leucocyturia. Renal scarring was found in 12 (29.3%) of the 41 children with acute pyelonephritis. The mean age was significantly lower in the children with renal scarring compared with those without (P < 0.05). CONCLUSION: These results have shown that urine IL-1beta level may serve as a useful marker for the early detection of acute pyelonephritis in febrile children. Young children are at a risk of the development of renal scarring following acute pyelonephritis.
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Cicatriz/etiologia , Cicatriz/urina , Interleucina-1beta/urina , Pielonefrite/complicações , Pielonefrite/urina , Doença Aguda , Envelhecimento , Biomarcadores/metabolismo , Criança , Pré-Escolar , Cicatriz/diagnóstico , Creatinina/urina , Feminino , Humanos , Lactente , Recém-Nascido , Inflamação/metabolismo , Masculino , Estudos Prospectivos , Pielonefrite/diagnóstico , Compostos Radiofarmacêuticos , Ácido Dimercaptossuccínico Tecnécio Tc 99m , Ultrassonografia , Infecções Urinárias/diagnóstico , Infecções Urinárias/urina , Refluxo Vesicoureteral/complicações , Refluxo Vesicoureteral/urinaRESUMO
Bone marrow and intestinal damage limits the efficacy of radiotherapy for cancer and can result in death if the whole body is exposed to too high a dose, as might be the case in a nuclear accident or terrorist incident. Identification of an effective nontoxic biological radioprotector is therefore a matter of some urgency. In this study, we show that an orally administered hot-water extract from a Chinese herbal medicine, Cordyceps sinensis (CS), protects mice from bone marrow and intestinal injuries after total-body irradiation (TBI). CS increased the median time to death from 13 to 20 days after 8 Gy TBI and from 9 to 18 days after 10 Gy TBI. Although CS-treated mice receiving 10 Gy TBI survived intestinal injury, most died from bone marrow failure, as shown by severe marrow hypoplasia in mice dying between 18 and 24 days. At lower TBI doses of 5.5 and 6.5 Gy, CS protected against bone marrow death, an effect that was confirmed by the finding that white blood cell counts recovered more rapidly. In vitro, CS reduced the levels of free radical species (ROS) within cells, and this is one likely mechanism for the radioprotective effects of CS, although probably not the only one.
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Doenças da Medula Óssea/prevenção & controle , Cordyceps/química , Medicamentos de Ervas Chinesas/administração & dosagem , Enteropatias/prevenção & controle , Lesões por Radiação/patologia , Lesões por Radiação/prevenção & controle , Tolerância a Radiação/efeitos dos fármacos , Animais , Doenças da Medula Óssea/etiologia , Doenças da Medula Óssea/patologia , Enteropatias/etiologia , Enteropatias/patologia , Camundongos , Camundongos Endogâmicos C57BL , Proteção Radiológica/métodos , Taxa de SobrevidaRESUMO
Urinary tract infection (UTI) is a common clinical disorder in younger infants and children and may result in permanent renal damage. The inflammatory cytokines interleukin (IL)-6 and IL-8 play an important role in response to bacterial infection. This prospective study investigated the association between serum and urine IL-6 and IL-8 levels and acute pyelonephritis confirmed by (99m)Tc-dimercaptosuccinic acid (DMSA) scan. A total of 78 children aged 1-121 months with a diagnosis of first-time febrile UTI were included. The following inflammatory markers were assessed: fever; white blood cells count (WBC); C-reactive protein (CRP); and serum and urine IL-6 and IL-8. The patients were divided into the acute pyelonephritis group (n=42) and the lower UTI group (n=36) according to the results of DMSA scan. Fever, WBC and CRP levels were significantly higher in children with acute pyelonephritis than in those with lower UTI (all p <0.001). Significantly, higher initial serum and urine IL-6 and IL-8 levels were found in children with acute pyelonephritis than in those with lower UTI (all p <0.001). Serum and urine IL-6 in children with acute pyelonephritis were positively correlated with fever, CRP and leucocyturia. These results indicate that both serum and urine IL-6 and IL-8 levels, particularly IL-6, are useful diagnostic tools for early recognition of acute pyelonephritis in febrile children.
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Interleucina-6/sangue , Interleucina-6/urina , Interleucina-8/sangue , Interleucina-8/urina , Pielonefrite/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pielonefrite/sangue , Pielonefrite/diagnóstico , Pielonefrite/urina , Refluxo Vesicoureteral/sangue , Refluxo Vesicoureteral/diagnóstico , Refluxo Vesicoureteral/imunologia , Refluxo Vesicoureteral/urinaRESUMO
Human parvovirus B19 has been found in various tissues in addition to erythroid lineage cells, and non-structural protein (NS1) is reported to induce cytotoxicity and apoptosis in erythroid lineage cells, but the mechanism in non-permissive cells is still unclear. To address this issue, we have constructed the NS1 gene in a cytomegalovirus episomal vector, pEGFP-C1 and transfected it into monkey epithelial cells, COS-7. EGFP-NS1 expression in transfected cells was monitored and assessed by fluorescence microscopy, RT-PCR and Western blot. The flow cytometric analysis showed that the NS1-transfected cells were arrested at G1 phase by paclitaxel treatment and there was increased apoptosis. The expression of p53, an important molecule in apoptosis and cell cycle regulation, and its downstream cell cycle kinase inhibitors p16(INK4) and p21(WAF1/CIP1) were up-regulated in the NS1-transfected cells. Also, increased expression of the pro-apoptotic Bcl-2 members Bax, Bad and activation of caspase 3 and caspase 9, but not the activation of caspase 8 or Fas were detected in the NS1-transfected cells. p53-induced Bax expression and subsequent activation of caspase 9 is probably the apoptotic pathway in NS1-transfected cells since activation of the caspase 9 was suppressed by the p53 inhibitor and apoptosis was significantly inhibited by the caspase 9 inhibitor. Our results suggest that the cell death of the NS1-transfected cells is associated with mitochondria related apoptosis. These findings might provide alternative information for further study and characterization of B19 NS1 protein in B19 non-permissive cells.