RESUMO
OBJECTIVES: To evaluate the anatomic and functional outcomes of type1 tympanoplasty with endoscopic modified butterfly cartilage-perichondrium technique. METHODS: In our modification, perichondrium was elevated circumferentially till the attached part of the composite graft was approximately same size and shape of the perforation, cartilage was trimmed based on the perforation but 0.5 mm larger. Cartilage portion of the graft was placed medial to the edge of the perforation, then perichondrium was rolled out and draped on the circumferential raw surface of remaining tympanic membrane around. RESULTS: At 4 months postop, the anatomic integrity rate of the tympanic membrane perforation for small & medium sized perforation and large sized perforation group were 100 % and 94 % (p > 0.05). For the small & medium perforation group, the mean pre and 4 months postop ACs were 30 ± 8 dB and 18 ± 6.4 dB (p < 0.01). The mean pre and 4 months postop ABGs were 19 ± 11 dB and 9 ± 3 dB (p < 0.01). For the large perforation group, the mean pre and 4 months postop ACs were 43 ± 12.5 dB and 21.5 ± 7 dB (p < 0.01). The mean pre and 4 months postop ABGs were 34 ± 8.5 dB and 12.5 ± 6 dB (p < 0.01). The differences of mean 4 months postop ACs and mean 4 months postop ABGs between the two groups were not significant (p > 0.05). CONCLUSIONS: Compared to the conventional inlay butterfly cartilage tympanoplasty technique, large or marginal perforations can be sealed more securely by this modification.
Assuntos
Cartilagem , Endoscopia , Perfuração da Membrana Timpânica , Timpanoplastia , Humanos , Perfuração da Membrana Timpânica/cirurgia , Masculino , Feminino , Timpanoplastia/métodos , Endoscopia/métodos , Resultado do Tratamento , Adulto , Cartilagem/transplante , Pessoa de Meia-Idade , Adulto JovemRESUMO
Western flower thrips (WFTs), Frankliniella occidentalis (Thysanoptera, Thripidae), is one of the most serious pests that attack rose flowers. Little is known about the effect of different parts of the rose flower on nutritional contents and digestive enzyme activities in thrips. This study assessed variations in the nutritional contents and digestive enzyme activities in the second-instar larvae and adults WFTs fed on 3 food types (rose petals, rose flowers, and honey solution + kidney bean pods) for multiple generations. The highest contents of soluble sugar (in 10% honey solution + kidney bean pods), amino acid (in rose flowers), and protein (in rose flowers) were observed, respectively. Soluble sugar and protein contents in the second-instar larvae and adults fed on rose petals decreased in the F1 generation but increased in the F2 generation and remained at higher levels until the F7 generation. Feeding of thrips with 3 food types increased the lipid content in the F1 generation, which peaked in the F2 generation and remained high until the F7 generation. In most cases, α-amylase and trypsin activities significantly decreased in the F1 generation after feeding on rose petals and then prominently increased in the F2 generation. In contrast, chymotrypsin activity remarkably increased and peaked in the F1 generation after second-instar larvae thrips fed on rose petals. There were correlations among the contents of 3 nutrient related positively with the activities of α-amylase and trypsin in WFTs second-instar larvae and adults, respectively. Overall, variations in the nutrient properties of the 3 food types caused changes in nutrient contents and digestive enzyme activities in thrips.
Assuntos
Tisanópteros , Animais , Tripsina , Flores , Larva , Açúcares , Nutrientes , alfa-Amilases , Valor Nutritivo , DigestãoRESUMO
BACKGROUND: This study was to evaluate the effects of repetitive brief ischemia (RBI) on bone healing in patients with tibial shaft fractures. METHODS: In this prospective clinical trial, patients with tibia shaft fractures were enrolled between January 2016 and January 2021. The intermittent pneumatic compression (IPC) device was used to make RBI on the affected limb after surgical operation 24 h. The inflation pressure was the systolic pressure of patients + 50 mmHg. Patients were received 30 s inflation/30 s deflation 30 times twice a day for 4 weeks. The primary outcome was bone healing time and the secondary outcomes were the rates of delayed union and nonunion, the rates of venous thrombosis of lower limbs, Johner-Wruhs scores, Lysholm knee score, VAS scores, postoperative complications, serum BMP-2, osteocalcin (OC) and bone specific alkaline phosphatase (BS-ALP). RESULTS: A total of 32 patients were enrolled finally and all were completed with a 12 months follow-up. All the fractures were healed and the bone healing time was 3(1) months in RBI group. However, the bone healing time of control group was 4(1) and there was statistical difference between the two groups (p < 0.01). No patient with fracture delayed union, nonunion and venous thrombosis of lower limbs in RBI group. 2 patients were delayed union in the control group. In RBI group, the Lysholm knee score was 83(6) at 6 months and 100(8) at 12 months. In the control group, the score was 78(4) and 90.5(17), there was statistical difference between the two groups (p < 0.01, p = 0.014, respectively). VAS scores were postoperative 2 weeks 6(1) in RBI group and 7(0.5) in the control group, there was statistical difference between the two groups (p = 0.016). There were 2 patients with intramuscular venous thrombosis of lower extremity in control group. Besides, RBI treatment increased the serum BMP-2, OC and BS-ALP at postoperative 2 weeks and 1 month. CONCLUSIONS: RBI is a new method to accelerate bone healing in tibia shaft fracture patients and is a simple and noninvasive method. TRIAL REGISTRATION: Chinese clinical trial registry, ChiCTR-INR-17014208 . Registered 28 December 2017-Retrospectively registered.
Assuntos
Fixação Intramedular de Fraturas , Fraturas da Tíbia , Consolidação da Fratura , Humanos , Isquemia/etiologia , Estudos Prospectivos , Tíbia/diagnóstico por imagem , Tíbia/cirurgia , Fraturas da Tíbia/diagnóstico por imagem , Fraturas da Tíbia/cirurgia , Resultado do TratamentoRESUMO
Foveal structure that is specified by the thickness, depth and the overall shape of the fovea is a promising tool to qualify and quantify retinal pathology in Parkinson's disease. To determine the model variable that is best suited for discriminating Parkinson's disease eyes from those of healthy controls and to assess correlations between impaired contrast sensitivity and foveal shape we characterized the fovea in 48 Parkinson's disease patients and 45 control subjects by optical coherence tomography (OCT). The model quantifies structural changes in the fovea of Parkinson's disease patients that are correlated with a decline in contrast sensitivity. Retinal foveal remodeling may serve as a parameter for vision deficits in Parkinson's disease. Whether foveal remodeling reflects dopaminergic driven pathology or rather both dopaminergic and non-dopaminergic pathology has to be investigated in longitudinal studies.
Assuntos
Sensibilidades de Contraste , Doença de Parkinson , Fóvea Central/diagnóstico por imagem , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Retina/diagnóstico por imagem , Tomografia de Coerência ÓpticaRESUMO
Evidence has demonstrated that the microRNA (miR) may play a significant role in the development of congenital heart disease (CHD). Here, we explore the mechanism of microRNA-592 (miR-592) in heart development and CHD with the involvement of KCTD10 and Notch signaling pathway in a CHD mouse model. Cardiac tissues were extracted from CHD and normal mice. Immunohistochemistry staining was performed to detect positive expression rate of KCTD10. A series of inhibitor, activators, and siRNAs was introduced to verified regulatory functions for miR-592 governing KCTD10 in CHD. Furthermore, the effect of miR-592 on cell proliferation and apoptosis was also investigated. Downregulated positive rate of KCTD10 was observed in CHD mice. Downregulation of miR-592 would upregulate expression of KCTD10 and inhibit the activation of Notch signaling pathway, thus promote cell proliferation. This study demonstrates that downregulation of miR-592 prevents CHD and hypoplastic heart by inhibition of the Notch signaling pathway via negatively binding to KCTD10.
Assuntos
Cardiopatias Congênitas/prevenção & controle , MicroRNAs/metabolismo , Miocárdio/metabolismo , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Receptores Notch/metabolismo , Regiões 3' não Traduzidas , Animais , Apoptose , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Sítios de Ligação , Proliferação de Células , Células Cultivadas , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/metabolismo , Cardiopatias Congênitas/patologia , Proteína Jagged-1/genética , Proteína Jagged-1/metabolismo , Masculino , Camundongos , MicroRNAs/genética , Miocárdio/patologia , Canais de Potássio de Abertura Dependente da Tensão da Membrana/genética , Receptores Notch/genética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Transdução de Sinais , Fatores de Transcrição HES-1/genética , Fatores de Transcrição HES-1/metabolismoRESUMO
A meta-analysis of 14 studies (16 cohorts) incorporating 1751 participants was performed to evaluate the correlation between baseline neutrophil-to-lymphocyte ratio (NLR) and outcome of immune checkpoint inhibitors (ICI). The pooled hazard ratio (HR) suggested elevated pretreatment NLR was associated with poor OS (HR: 2.61, 95% confidence intervals (CI): 1.77-3.86, p < 0.00001) and PFS (HR: 1.74, 95% CI: 1.34-2.27, p < 0.0001). Stratified analyses on tumor types, ICI agents, the cutoff value of NLR and study regions exhibited the similar outcomes. This study demonstrated that elevated NLR was a predictor of poor OS and PFS for ICI.
Assuntos
Antineoplásicos/imunologia , Antineoplásicos/uso terapêutico , Linfócitos/imunologia , Neutrófilos/imunologia , Feminino , Humanos , Imunoterapia/métodos , Contagem de Linfócitos , Linfócitos/efeitos dos fármacos , Masculino , Neutrófilos/efeitos dos fármacos , PrognósticoRESUMO
BACKGROUND: Invasive candidiasis (IC) is the most common invasive fungal infection. The epidemiology of IC in hospitalized patients has been widely investigated in many metropolitan cities; however, little information from medium and small cities is known. METHODS: A 5-year retrospective study was carried out to analyze the prevalence, species distribution, antifungal susceptibility, risk factors and mortality of inpatients with invasive Candida infection in a regional tertiary teaching hospital in Southwest China. RESULTS: A total of 243 inpatients with invasive Candida infection during the five-year study period were identified, with a mean annual incidence of 0.41 cases per 1000 admissions and a 30-day mortality rate of 12.3%. The species distributions of Candida albicans, Candida glabrata, Candida tropicalis, Candida krusei, Candida parapsilosis and other Candida species was 45.3, 30.0, 15.2, 4.9, 2.1 and 2.5%, respectively. The total resistance rates of fluconazole (FCA), itraconazole (ITR) and voriconazole (VRC) were 18.6, 23.1 and 18.5%, respectively. Respiratory dysfunction, pulmonary infection, cardiovascular disease, chronic/acute renal failure, mechanical ventilation, abdominal surgery, intensive care in adults, septic shock and IC due to C. albicans were associated with 30-day mortality (P < 0.05) according to the univariate analyses. Respiratory dysfunction [odds ratio (OR), 9.80; 95% confidence interval (CI), 3.24-29.63; P < 0.001] and IC due to C. albicans (OR, 3.35; 95% CI, 1.13-9.92; P = 0.029) were the independent predictors of 30-day mortality. CONCLUSIONS: This report shows that the incidence and mortality rates are lower and that the resistance rates to azoles are higher in medium and small cities than in large cities and that the species distributions and risk factors in medium and small cities are different from those in large cities in China. It is necessary to conduct epidemiological surveillance in medium and small cities to provide reference data for the surveillance of inpatients with IC infections.
Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candidíase Invasiva/diagnóstico , Adolescente , Adulto , Idoso , Candida/isolamento & purificação , Candida/fisiologia , Candidíase Invasiva/epidemiologia , Candidíase Invasiva/mortalidade , China/epidemiologia , Feminino , Hospitais de Ensino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Adulto JovemRESUMO
The aim of the current study was to investigate and discuss the function of ANKRD33 gene in the pathogenesis of gastric adenocarcinoma. The marked up-regulated expression of ANKRD33 gene in gastric adenocarcinoma tissues compared to normal tissues was found by bioinformatics analysis. Kaplan-Meier analysis revealed that high expression of ANKRD33 is correlated with lower overall survival of gastric adenocarcinoma patients. The results of qPCR revealed that mRNA expression level of ANKRD33 was dramatically higher in AGS, SGC7901, and BGC823 cell lines than that in the GES1 cells. Knockdown of ANKRD33 remarkably inhibited the viability, invasion, and migration of AGS and BGC823 cells. Furthermore, the ratio of p-AKT/AKT and p-mTOR/mTOR was significantly decreased in AGS cells which transfected with si- ANKRD33. All the above results illustrated that ANKRD33 would act as a tumor forwarder in gastric adenocarcinoma development and have a high potential to be a marker molecule in the diagnosis and treatment of gastric tumors.
Assuntos
Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Repressoras/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Adenocarcinoma/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Inativação Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/metabolismo , Prognóstico , Proteínas Repressoras/deficiência , Transdução de Sinais/genética , Neoplasias Gástricas/patologiaRESUMO
Some lipoxygenase (LOX) isoenzymes can co-oxidize carotenoids. Carotenoids are collectors of light energy for photosynthesis and can protect plants from reactive oxygen species and coloration. This study isolated the cucumber (Cucumis sativus L.) yellow-green leaf mutant (ygl1), which had yellow-green leaves with decreased chlorophyll synthesis, increased relative carotenoid content, and delayed chloroplast development. Genetic analysis demonstrated that the phenotype of ygl1 was caused by a recessive mutation in a nuclear gene. The bulked segregants were resequenced, and the candidate ygl1 locus identified was mapped to the 9.2 kb region of the chromosome 4. Sequence analysis revealed that ygl1 encodes the tandem 13-LOX genes in a cluster. Four missense mutations were found in four tandem 13-LOX genes (Csa4M286960, Csa4M287550, Csa4M288070, and Csa4M288080) in the ygl1 mutant, and the four 13-LOX genes showed high similarity with one another. The transient RNA interference and virus-induced gene silencing of these genes simultaneously resulted in yellow-green leaves with a reduced amount of chloroplasts and increased relative carotenoid content, which were observed in the ygl1 mutant. This evidence supported the non-synonymous SNPs (Single Nucleotide Polymorphism) in the four tandem 13-LOX genes as being the causative mutation for the yellow-green leaves. Furthermore, this study provides a new allele for breeding cucumbers with yellow-green leaves and serves as an additional resource for studying carotenoid biosynthesis.
Assuntos
Cucumis sativus/genética , Lipoxigenase/genética , Família Multigênica , Fenótipo , Pigmentação/genética , Folhas de Planta/genética , Sequências de Repetição em Tandem , Alelos , Sequência de Aminoácidos , Mapeamento Cromossômico , Genótipo , MutaçãoRESUMO
Background: C3 glomerulopathy often presents with a membranoproliferative glomerulonephritis (MPGN) pattern, and is principally caused by unrestricted activation of the complement alternative pathway. Genetic abnormalities of the complement system critically implicate in the pathogenesis of C3 glomerulopathy, but a systemic profile remains open, especially in Asia. Methods: In this study, we completed a comprehensive screen of 11 candidate alternative pathway genes by using targeted genomic enrichment and massively parallel sequencing on 43 patients with sporadic C3 glomerulopathy, which were classified as dense deposit disease (DDD; n = 10) and C3 glomerulonephritis (C3GN; n = 33) cases. An additional 24 patients with immune complex-mediated MPGN were also enrolled. Results: In total, 4 novel and 16 rare variants were identified: one was classified as likely pathogenic, and the remaining 19 were of uncertain significance. Three variants reportedly led to functional deficiency with supporting evidences. Variants in the CFH, CFI, CD46 and C3 genes were most frequently detected. A defective control of the complement alternative pathway due to hereditary abnormalities was found at frequencies of 50%, 27% and 17% in DDD, C3GN and immune complex-mediated MPGN, respectively. Irrespective of histological type, the patients with likely pathogenic and uncertain significant variants were clinically similar to those without. Conclusions: Accurate genetic screening can give rise to progress in understanding the pathogenesis of C3 glomerulopathy, and the correct assignment of pathogenicity classification is of great importance for better patient care and prognostic or therapeutic advice.
Assuntos
Biomarcadores/metabolismo , Complemento C3/metabolismo , Testes Genéticos/métodos , Variação Genética , Glomerulonefrite/genética , Adolescente , Adulto , Biomarcadores/análise , Estudos de Casos e Controles , Criança , Feminino , Estudos de Associação Genética , Glomerulonefrite/metabolismo , Glomerulonefrite/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Adulto JovemRESUMO
Periodontitis is a chronic infectious disease that leads to progressive destruction of periodontal tissue. Human periodontal ligament stem cells (PDLSCs) are the most favorable candidate for the reconstruction of tissues destroyed by periodontal diseases. PDLSCs derived from inflammatory microenvironment show attenuated differentiation potential, however the mechanism is still unclear. MicroRNAs (miRNAs) are a newly discovered class of posttranscriptional regulators, and they play key roles in regulating cell differentiation. Recent studies have demonstrated that inflammatory cytokines could regulate miRNAs and contribute to some inflammatory diseases. Tumor necrosis factor (TNF-α) is a potent negative regulator of cell differentiation. Elevated levels of TNF-α were confirmed to be associated with the severity of periodontal disease. Here, we found TNF-α inhibited the adipogenic and osteogenic differentiation of PDLSCs. Based on this, we hypothesized that TNF-α could participate in PDLSC differentiation by regulating miRNA signal pathway. Moreover, we demonstrated that the expression of miR-21 was suppressed by TNF-α in impaired adipogenic and osteogenic differentiation of PDLSCs. Upregulating miR-21 can partly rescue TNF-α-impaired adipogenesis and osteogenesis by repressing its target gene Spry1, suggested that miR-21/Spry1 functional axis plays critical role in PDLSC differentiation under inflammatory microenvironment. During adipogenesis and osteogenesis, TNF-α significantly increased Spry1 levels and overexpression of miR-21 dramatically decreased Spry1 levels in the presence of TNF-α, indicated important roles of miR-21 in modulating link between TNF-α and Spry1. Our findings introduce a molecular mechanism in which TNF-α suppresses adipogenic and osteogenic differentiation of PDLSCs by inhibiting miR-21/Spry1 functional axis. This study may indicate a molecular basis for novel therapeutic strategies against periodontitis and other inflammatory diseases.
Assuntos
Diferenciação Celular/genética , Proteínas de Membrana/genética , MicroRNAs/genética , Fosfoproteínas/genética , Fator de Necrose Tumoral alfa/genética , Adipogenia/genética , Adulto , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Osteogênese/genética , Ligamento Periodontal/citologia , Ligamento Periodontal/crescimento & desenvolvimento , Transdução de Sinais/efeitos dos fármacos , Células-Tronco/citologia , Fator de Necrose Tumoral alfa/administração & dosagemRESUMO
OBJECTIVE: To evaluate the effect of the maxillary dentition distalization with miniscrews implanted in the infrazygomatic (IZ) crest with 3D reconstruction module from cone-beam computed tomography (CBCT). METHODS: Twenty patients who previously underwent dentition distalization treatment with miniscrews were recruited. A total of 40 images were obtained using CBCT, taken immediately before placement of the miniscrew anchorage and at the end of distalization. The 3D-line measurements were recorded to monitor dental changes. RESULTS: There was significant movement of maxillary dentition before and after treatment with miniscrews. The miniscrews induced maxillary dentition distalization and corrected Class II relationship in 8 months on average. The incisors were retracted 4.3 mm and extruded 3.8 mm at the crown on average. The crown of canines showed 3.7 mm of distalization and the width increased by 3.1 mm averagely. The mesial buccal cusp of first molars' crowns showed 3.5-mm distalization and 2.1-mm intrusion, and the width increased by 5.0 mm averagely. The distal buccal cusp of first molars' crowns showed 2.8-mm distalization and 3.7-mm intrusion, and the width increased by 6.2 mm averagely. CONCLUSIONS: The anchorage of miniscrews implanted in the IZ crest is an efficient device for maxillary dentition distalization.
Assuntos
Parafusos Ósseos , Tomografia Computadorizada de Feixe Cônico , Técnicas de Movimentação Dentária/métodos , Zigoma/cirurgia , Parafusos Ósseos/efeitos adversos , Feminino , Humanos , Imageamento Tridimensional , Masculino , Procedimentos de Ancoragem Ortodôntica/instrumentação , Técnicas de Movimentação Dentária/instrumentação , Resultado do Tratamento , Adulto Jovem , Zigoma/diagnóstico por imagemRESUMO
PURPOSE: MicroRNAs (miRs) are endogenous, noncoding small RNAs that play a key role in regulating biological and pathological processes. The oncogenic properties of miR-199b-5p have been demonstrated in previous studies but the effect of miR-199b-5p on osteosarcoma (OS) has not yet been clarified. This study aimed to investigate the effect of miR-199b-5p on OS and the relationship between this miR and the pathological parameters and prognosis of OS. METHODS: MiR-199b-5p expression in 57 pairs of OS tissues, corresponding adjacent normal tissues and OS cells was measured by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR).The relationship between miR-199b-5p and the pathological features and prognosis of OS patients was examined. We constructed small interfering (si) RNA to knock down miR-199b-5p expression in OS cell lines MG63 and U2OS. Cell Counting Kit-8 (CCK-8), cell cloning assay and Transwell cell migration and invasion assay were applied for investigating the biological function of miR-199b-5p, respectively. Finally, western blot was used for exploring its underlying mechanism. RESULTS: MiR-199b-5p expression in OS was significantly higher than that of normal tissues. Compared to patients w\sith low expression of miR-199b-5p, patients with high expression level tended to be with younger age, higher incidence of distant metastases and lower overall survival. Compared with interference sequence negative control (si-NC) group, the abilities of proliferation, invasion and metastasis of cells transfected with si-miR-199b-5p were significantly decreased. Western blot analysis indicated that expressions of key proteins related to epithelial to mesenchymal transition (EMT) signaling pathway, including N-cadherin, Vimentin, ß-catenin and matrix metalloproteinase-9 (MMP9), were significantly decreased after transfection with si-miR-199b-5p. Furthermore, we found that miR-199b-5p promoted the progression of OS mainly through regulating HER2. CONCLUSIONS: Upregulated miR-199b-5p is significantly related with stage, distant metastasis and poor prognosis of OS. This MiR may promote progression of OS through regulating HER2.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/patologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Osteossarcoma/secundário , Receptor ErbB-2/metabolismo , Adulto , Biomarcadores Tumorais/genética , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Estudos de Casos e Controles , Movimento Celular , Proliferação de Células , Progressão da Doença , Transição Epitelial-Mesenquimal , Feminino , Seguimentos , Humanos , Masculino , Invasividade Neoplásica , Metástase Neoplásica , Osteossarcoma/genética , Osteossarcoma/metabolismo , Prognóstico , Receptor ErbB-2/genética , Transdução de Sinais , Taxa de Sobrevida , Adulto JovemRESUMO
Oxidized tyrosine products are commonly found in food with high protein content and have been demonstrated to cause damage of liver and kidney in our previous studies. Dityrosine (Dityr) is a typical oxidized tyrosine product. Due to its structural homology with thyroid hormones T3, we assumed that one of the endocrine systems most likely considered in connection with its disruption by Dityr may be the T3 action. T3 plays important roles in insulin synthesis, and thyroid hormone resistance (RTH) is associated with the impairment of glucose metabolism. Therefore, this study determined whether Dityr exposure impaired T3 function in pancreas leading to glucose metabolism disruption. After 10-week gavage with Dityr, mice exhibited impaired glucose tolerance and disturbed energy metabolism. The elevated free THs content in plasma, the up-regulation of THs synthesis-specific genes expressions in thyroid glands, and the increased thyroid follicles histology shapes and areas indicated that Dityr enhanced the THs synthesis in thyroid glands. In addition, Dityr-induced RTH, which reflected as elevated plasma free THs in the presence of unsuppressed thyroid stimulating hormone. The mRNA downregulation of membrane transporter of T3 (MCT8) and co-activator factors (RXRα, Src-1), together with the decreased protein level of thyroid hormone receptor ß1 (TRß1) in pancreas illustrated that the activation ability of T3 to downstream gene involved in insulin synthesis was suppressed by Dityr. In MIN-6 cell experiment, T3 improved glucose-stimulated insulin secretion by upregulating mRNA levels of insulin synthesis-related genes (Ins2, MafA, Pdx1) and T3 action-related genes, as well as increasing protein level of TRß1. These data suggest that Dityr suppress T3-regulated insulin synthesis stimulated by glucose via an indirect way of decreasing sensibility to T3 in pancreas. All these findings indicate that Dityr can disrupt THs function in pancreas leading to glucose metabolism disorder.
Assuntos
Células Secretoras de Insulina/efeitos dos fármacos , Insulina/metabolismo , Tri-Iodotironina/metabolismo , Tirosina/análogos & derivados , Animais , Células Cultivadas , Metabolismo Energético/efeitos dos fármacos , Secreção de Insulina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tirosina/administração & dosagemRESUMO
INTRODUCTION: The purpose of this study was to assess the anatomic structure of the buccal alveolar bone in the infrazygomatic crest region with cone-beam computed tomography to locate safe zones for miniscrews in maxillary dentition distalization. METHODS: The buccal alveolar bone was analyzed in 3 regions of 60 patients: between the maxillary second premolar and first molar (U5-U6), between the mesiodistal roots of the first molar (U6), and between the maxillary first and second molars (U6-U7). Alveolar bone thickness at the buccal side of the roots and the interradicular space at the buccal side of the roots were measured at the planes of 5, 7, 9, and 11 mm apically from the alveolar crest to the maxillary sinus floor. The buccal bone height was measured from the alveolar crest edge to the sinus floor. RESULTS: The buccal alveolar bone was thicker in the U6-U7 region than in the U6 and U5-U6 regions. The buccal alveolar bone thickness tended to get thicker from the alveolar crest to the sinus floor. The thickest buccal alveolar bone of 4.07 mm was observed at the plane of 11 mm of the U6-U7 region. The percentages for the height of bone from the crest edge to the sinus floor were smaller than 10 mm at the regions of U5-U6, U6, and U6-U7: 38%, 52%, and 43%, respectively. The interradicular space was smallest in the U6 region and largest in the U5-U6 region. CONCLUSIONS: The results of this study suggest that the U6-U7 region is the most ideal safe zone for placing miniscrews in the buccal alveolar bone in the infrazygomatic crest region for maxillary dentition distalization.
Assuntos
Processo Alveolar/diagnóstico por imagem , Parafusos Ósseos , Tomografia Computadorizada de Feixe Cônico , Má Oclusão Classe II de Angle/terapia , Procedimentos de Ancoragem Ortodôntica/instrumentação , Adulto , China , Feminino , Humanos , Masculino , Interpretação de Imagem Radiográfica Assistida por ComputadorRESUMO
Accumulating data suggest that sodium-hydrogen exchangers (NHEs) play a key role in modulating seizure activity by regulating neuronal pH in the brain. Amiloride, an inhibitor of NHEs, has been demonstrated to be effective in many seizure models, although its efficacy for prolonged febrile seizures (FS) remains unclear. In this study, we investigated whether amiloride could produce neuroprotective effects in a prolonged FS model in which FS were induced in rat pups at postnatal day 10 using a heated air approach. Amiloride was administered by intraperitoneal injection at three different doses (0.65, 1.3 and 2.6 mg/kg). Pretreatment with amiloride significantly delayed the onset of the first episode of limbic seizures, whereas posttreatment with amiloride decreased escape latency in the Morris water maze test compared to post-FS treatment with saline. Amiloride also inhibited seizure-induced aberrant neurogenesis. In conclusion, this study demonstrated the antiseizure activity of amiloride. In particular, posttreatment with amiloride resulted in cognitive improvement; this finding provides crucial evidence of the neuroprotective function of amiloride and of the therapeutic potential of amiloride in FS.
Assuntos
Amilorida/uso terapêutico , Proteínas de Transporte de Cátions/antagonistas & inibidores , Transtornos Cognitivos/tratamento farmacológico , Convulsões Febris/tratamento farmacológico , Trocadores de Sódio-Hidrogênio/antagonistas & inibidores , Animais , Pressão Sanguínea/efeitos dos fármacos , Proteínas de Transporte de Cátions/metabolismo , Transtornos Cognitivos/psicologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Aprendizagem em Labirinto/efeitos dos fármacos , Neurogênese , Neurônios/patologia , Ratos Sprague-Dawley , Convulsões Febris/patologia , Convulsões Febris/fisiopatologia , Convulsões Febris/psicologia , Trocador 1 de Sódio-Hidrogênio , Trocadores de Sódio-Hidrogênio/metabolismo , Fatores de TempoRESUMO
OBJECTIVE: Follicle-stimulating hormone plays a crucial role in spermatogenesis. The aim of this study was to evaluate the efficacy of treatment with FSH in Chinese infertility population. DESIGN: Prospective, randomized, double-blind, placebo-controlled clinical study. PATIENTS: A total of 354 men affected by idiopathic oligozoospermia from three medical centres. MEASUREMENTS: This study contained three parts: (i) treatment with different doses of rhFSH (50 IU, 100 IU, 200 IU and 300 IU); (ii) the efficacy of rhFSH at different periods (2, 3, 4, 5 months); (iii) FSH treatment in patients with different levels of inhibin B (normal-level group, low-level group and high-level group). Semen parameters were evaluated in all subjects. The patients who had not reached spontaneous pregnancy underwent assisted reproductive techniques. RESULTS: Sperm number was significantly increased after treatment with FSH at doses of at least 200 IU, and the improvement was observed beginning at the third month. The significant improvement in both morphology and forward motility was observed beginning at the fifth month. Moreover, 300 IU rhFSH administration for 5 months could significantly improve the spontaneous pregnancy rate (12/40) and ART pregnancy rate (14/28), while the rates for placebo group were two of twenty-nine and five of twenty-seven, respectively. The seminal parameters (total sperm count, sperm concentration, forward motility and morphology) were significantly improved in the normal- and low-level inhibin B groups, but no significant variation was observed in the high-level group at the end of the study. CONCLUSIONS: The efficacy of FSH treatment was associated with the dose of FSH and duration of treatment, and FSH therapy was more effective in patients with normal level and low level of inhibin B.
Assuntos
Hormônio Foliculoestimulante/uso terapêutico , Oligospermia/tratamento farmacológico , Adulto , Método Duplo-Cego , Feminino , Humanos , Infertilidade Masculina/tratamento farmacológico , Masculino , Gravidez , Taxa de Gravidez , Contagem de Espermatozoides , Resultado do TratamentoRESUMO
We investigated the possible role of miR-143 in the development of cisplatin resistance in human gastric cancer cell line. miR-143 was detected by quantitative real-time PCR. Cisplatin resistance changes of cells was tested via MTT assay. Target genes of miR-143 were verified by dual-luciferase activity assay. Immunohistochemistry, immunofluorescence staining, Western blot, cell proliferation, and clonogenic and apoptosis assay were used to elucidate the mechanism of miR-143 in cisplatin resistance formation. miR-143 was downregulated in gastric cancer tissues and cell lines. It was also downregulated in cisplatin-resistant gastric cancer cell line SGC7901/cisplatin (DDP), which was concurrent with the upregulation of IGF1R and BCL2, compared with the parental SGC7901 cell line, respectively. Overexpressed miR-143 sensitized SGC7901/DDP cells to cisplatin. The luciferase activity suggested that IGF1R and BCL2 were both target genes of miR-143. Enforced miR-143 reduced its target proteins, inhibited SGC7901/DDP cells proliferation, and sensitized SGC7901/DDP cells to DDP-induced apoptosis. Our findings suggested that hsa-miR-143 could modulate cisplatin resistance of human gastric cancer cell line at least in part by targeting IGF1R and BCL2.
Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Genes bcl-2/genética , MicroRNAs/genética , Receptores de Somatomedina/biossíntese , Neoplasias Gástricas/genética , Apoptose , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/administração & dosagem , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , MicroRNAs/biossíntese , Receptor IGF Tipo 1 , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: Optical coherence tomography offers a potential biomarker tool in Parkinson's disease (PD). A mathematical model quantifying symmetry, breadth, and depth of the fovea was applied. METHODS: Nintey-six subjects (72 PD and 24 healthy controls) were included in the study. Macular scans of each eye were obtained on two different optical coherence tomography devices: Cirrus and RTVue. RESULTS: The variables corresponding to the cardinal gradients of the fovea were the most sensitive indicators of PD for both devices. Principal component analysis distinguished 65% of PD patients from controls on Cirrus, 57% on RTVue. CONCLUSION: Parkinson's disease shallows the superior/inferior and to a lesser degree nasal-temporal foveal slope. The symmetry, breadth, and depth model fits optical coherence tomography data derived from two different devices, and it is proposed as a diagnostic tool in PD.
Assuntos
Fóvea Central/patologia , Doença de Parkinson/patologia , Retina/patologia , Idoso , Biomarcadores , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Componente Principal , Índice de Gravidade de Doença , Tomografia de Coerência ÓpticaRESUMO
A circular hydrophobic-hydrophilic-Ti(4+) immobilized phosphate polymer is patterned on a silicon wafer. Such a wafer is used as a novel sample support to allow fast selective enrichment, wash-free self-desalting and mass spectroscopy (MS) analysis of phosphopeptides, thanks to the high Ti(4+) loading amount, pure phosphate polymer-Ti(4+) interface, and strong hydrophobic-hydrophilic attraction pattern. The detection sensitivity was enhanced 300 folds compared with what was obtained using the common MALDI plate. Remarkable selectivity for phosphopeptides can be achieved at a molar ratio as low as 1 : 500 of phosphopeptides (casein digest)/nonphosphopeptides (BSA). High-quality mass spectra can be obtained even in the presence of NaCl (1 M), NH4HCO3 (100 mM), or urea (1 M). These microspots were also used to selectively capture phosphopeptides from milk and human serum, which further demonstrated that they were capable of identifying low-abundance phosphopeptides from real complex samples. They provide a low detection limit (3 fmol µL(-1)), small sample size, and excellent enrichment and desalting efficiency. Such a method significantly simplifies the analytical procedures, reduces possible sample loss, and is relatively low cost. Therefore, this on-plate patterned technique is very promising in the high-throughput phosphoproteomic research, especially for the detection of tiny amounts of samples.