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INTRODUCTION/AIMS: There are no blood biomarkers to monitor treatment effects in myasthenia gravis (MG) or studies visualizing the acetylcholine receptor (AChR) antibody-induced membrane attack complex (MAC) at the human muscle membrane. This study aimed to compare levels of complement activation products and native complement components in MG patients and healthy controls (HCs) and to model the AChR antibody-mediated attacks in human muscle cells. METHODS: We assessed the complement components and activation product levels with enzyme-linked immunosorbent assay and magnetic bead-based sandwich assays in plasma and sera of 23 MG patients and matched HCs. Receiver operator characteristic (ROC) curve analysis evaluated the diagnostic accuracy. Complement levels were correlated with the myasthenia gravis composite (MGC) scores. AChR+ MG modeling in human muscle cells used sera from nine MG patients and three HCs. RESULTS: MG patients had significantly higher plasma levels of C3a (p < .0001), C5 (p = .0003), and soluble C5b-9 (sC5b-9; p < .0001) than HCs. The ROC curve analysis showed a clear separation between MG patients and HCs for plasma C3a (AUC = 0.9720; p < .0001) and sC5b-9 (AUC = 0.8917, p < .0001). MG patients had higher levels of plasma complement Factor I (FI; p = .0002) and lower properdin levels (p < .0001). The MGC had moderate correlations with plasma Factor B (FB), FI, and Factor H. AChR+ MG patient sera triggered the deposition of MAC and reduced AChRs. DISCUSSION: We suggest validating plasma C3a and sC5b-9 as blood biomarkers for complement activation in MG. Further, the in vitro study allowed visualization of MAC deposition after applying AChR+ MG sera on human muscle cells.
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INTRODUCTION/AIMS: The circulating microRNAs (miRNAs) miR-150-5p, miR-30e-5p, and miR-21-5p have been suggested as potential biomarkers for myasthenia gravis (MG); however, the relationships between short-term natural changes of the miRNAs and patient-reported MG outcome scores have not been well-studied. We assessed the short-term fluctuations in miRNA levels and patient-reported outcome measures in MG. METHODS: This prospective cohort study included 39 MG patients with regular follow-ups and unchanged medications at the Neurology outpatient clinic at Uppsala University Hospital. Patients had weekly follow-up visits for 1 month, at which blood samples were drawn, and scores from MG activities of daily living (MG-ADL), MG quality-of-life-15 (MG-QoL15), and Fatigue Severity Scale (FSS) were assessed. Serum levels of miRNA miR-150-5p, miR-30e-5p, and miR-21-5p were analyzed using quantitative real-time PCR. RESULTS: Intra-individual levels of miR-30e-5p and miR-150-5p were stable, whereas a significant reduction in miR-21-5p was observed from week 1 to week 2 (p = .0024) and from week 2 to week 3 (p < .0001). There were intra-individual differences over a short time in MG-ADL, with higher scores in female patients (p = .0281) and a significant reduction from the first to the second weeks (p = .0281), whereas MG-QoL15 and FSS scores were stable. DISCUSSION: The suggested MG biomarkers miR-30e-5p and miR-150-5p were more stable than miR-21-5p over a short time, indicating their short-term stability as biomarkers. Prospective multi-center studies with longer periods of follow-up and matched controls are needed to validate these miRNAs as biomarkers in MG.
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MicroRNAs , Miastenia Gravis , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Humanos , Miastenia Gravis/sangue , Miastenia Gravis/genética , Feminino , MicroRNAs/sangue , Masculino , Pessoa de Meia-Idade , Idoso , Adulto , Estudos Prospectivos , Atividades Cotidianas , Biomarcadores/sangue , Estudos de Coortes , SeguimentosRESUMO
Manipulating the motion of water droplets on surfaces, which is crucial for various applications, such as microfluidics and heat transfer, presents considerable challenges, primarily due to the significant influence of capillary forces. This effect becomes more pronounced when droplets are in close proximity, often resulting in undesired coalescence. Triboelectrification, which involves charging pure water droplets, is a promising approach to enhance the ability to manipulate water droplets. For effective triboelectrification, charges must accumulate within the droplets; this ensures efficient and sustained droplet manipulation while minimizing dissipation. Low-friction, superhydrophobic, insulating surfaces are ideal for this purpose. However, few studies have explored the application of insulating superhydrophobic surfaces to manipulate droplet motion. In this study, we investigated the behavior of water droplets on insulating superhydrophobic quartz surfaces after triboelectrification. The droplets acquired significant charge when dripped onto a superhydrophobic glass surface. Consequently, these charged droplets exhibited behaviors such as repulsion and acceleration from one another, uphill movement, and rapid long-distance transport to specific positions. These advancements in droplet manipulation techniques hold promise for diverse fields such as microfluidics and heat exchangers.
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Benzophenone (BP) and BP derivatives (BPDs) are widely used as ultraviolet (UV) stabilizers in food packaging materials and as photoinitiators in UV-curable inks for printing on food-contact materials. However, our knowledge regarding the sources and risks of dietary exposure to BP and BPDs in cereals remains limited, which prompted us to conduct this study. We measured the levels of BP and nine BPDs-BP-1, BP-2, BP-3, BP-8, 2-hydroxybenzophenone, 4-hydroxybenzophenone, 4-methylbenzophenone (4-MBP), methyl-2-benzoylbenzoate, and 4-benzoylbiphenyl-in three types of cereals (rice flour, oatmeal, and cornflakes; 180 samples in total). A Bayesian Markov-chain Monte Carlo (MC) simulation approach was used for deriving the posterior distributions of BP and BPD residues. This approach helped in addressing the uncertainty in probabilistic distribution for the sampled data under the detection limit. Through an MC simulation, we calculated the daily exposure levels of dietary BP and BPDs and corresponding health risks. The results revealed the ubiquitous presence of BP, BP-3, and 4-MBP in cereals. Older adults (aged >65 years) had the highest (97.5 percentile) lifetime carcinogenic risk for BP exposure through cereals (9.41 × 10-7), whereas children aged 0-3 years had the highest (97.5 percentile) hazard indices for BPD exposure through cereals (2.5 × 10-2). Nevertheless, across age groups, the lifetime carcinogenic risks of BP exposure through cereals were acceptable, and the hazard indices for BPD exposure through cereals were <1. Therefore, BPD exposure through cereals may not be a health concern for individuals in Taiwan.
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Tissue inhibitor of metalloproteinases-3 (TIMP3) is vital in regulating several biological processes. TIMP3 exerts antitumour effects via matrix metalloproteinase (MMP)-dependent and MMP-independent pathways. Due to promoter methylation and miRNA binding, TIMP3 expression has been observed to decrease in various cancers. Consequently, the migration and invasion of cancer cells increases. Conflicting results have reported that expression levels of TIMP3 in primary and advanced cancers are higher than those in healthy tissues. Therefore, the role of TIMP3 in cancer biology and progression needs to be elucidated. This review provides an overview of TIMP3, from its biological function to its effects on various cancers. Moreover, gynaecological cancers are discussed in detail. TIMP3 has been associated with cervical adenocarcinoma as well as cancer development in serous ovarian cancer and breast cancer metastasis. However, the relationship between TIMP3 and endometrial cancers remains unclear. TIMP3 may be a useful biomarker for gynaecological cancers and is a potential target for future cancer therapy.
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Neoplasias da Mama , Neoplasias do Colo do Útero , Feminino , Humanos , Inibidor Tecidual de Metaloproteinase-3/genética , Inibidor Tecidual de Metaloproteinase-3/metabolismoRESUMO
PURPOSE: Investigating the effect of Muller's muscle-conjunctival resection (MMCR) on the eyelid crease position. METHODS: This retrospective study included patients with unilateral acquired blepharoptosis who underwent MMCR during October 2018-December 2021. The following factors were recorded: preoperative, after phenylephrine, postoperative marginal reflex distance1 (MRD1) and tarsal platform show (TPS) of bilateral eyelids. The primary outcome was to measure the change in TPS and evaluate the factors associated with post-operative TPS. The secondary outcomes included exploring the rate of MRD1 and TPS symmetry after the operation. RESULTS: Forty patients were included in the final analysis. The mean MRD1 of the ptotic eye was 1.28 ± 0.78 mm, 2.79 ± 0.66 mm and 3.20 ± 0.67 mm before, after phenylephrine and after the operation, respectively. The mean TPS of the ptotic eye was 5.90 ± 1.86 mm, 3.96 ± 1.49 mm and 2.79 ± 1.63 mm before, after phenylephrine and after the operation, respectively. Changes in mean TPS after the phenylephrine test and post-operation were statistically significant (p < 0.001). The linear regression model revealed that the absolute change in TPS after phenylephrine drop and absolute change in MRD1 post-operation were significantly correlated with the absolute change in TPS post-operation. Besides, the ratio of symmetry in MRD1 and TPS was greatly improved post-operation (82.5% and 70.0% respectively). CONCLUSION: MMCR is an effective surgical method for ptosis correction as it can not only correct the eyelid crease position but also narrow the wide TPS. This method is particularly beneficial to patients with both mild to moderate ptosis and an asymmetric crease height.
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Blefaroplastia , Blefaroptose , Blefaroplastia/métodos , Blefaroptose/cirurgia , Túnica Conjuntiva/cirurgia , Pálpebras/cirurgia , Humanos , Músculos Oculomotores/cirurgia , Fenilefrina , Estudos RetrospectivosRESUMO
A novel wearable multi-sensor data glove system is developed to explore the relation between finger spasticity and voluntary movement in patients with stroke. Many stroke patients suffer from finger spasticity, which is detrimental to their manual dexterity. Diagnosing and assessing the degrees of spasticity require neurological testing performed by trained professionals to estimate finger spasticity scores via the modified Ashworth scale (MAS). The proposed system offers an objective, quantitative solution to assess the finger spasticity of patients with stroke and complements the manual neurological test. In this work, the hardware and software components of this system are described. By requiring patients to perform five designated tasks, biomechanical measurements including linear and angular speed, acceleration, and pressure at every finger joint and upper limb are recorded, making up more than 1000 features for each task. We conducted a preliminary clinical test with 14 subjects using this system. Statistical analysis is performed on the acquired measurements to identify a small subset of features that are most likely to discriminate a healthy patient from patients suffering from finger spasticity. This encouraging result validates the feasibility of this proposed system to quantitatively and objectively assess finger spasticity.
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Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Dedos , Humanos , Espasticidade Muscular/diagnóstico , Acidente Vascular Cerebral/diagnóstico , Extremidade SuperiorRESUMO
OBJECTIVE: To determine the frequencies of fat-water swaps in iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) water-only images of the postinstrumentation spine and discuss the efficiency of in-phase imaging in improving visibility of the thecal sac. MATERIALS AND METHODS: A total of 276 patients (167 women; mean age, 62.3 years; range, 23-89 years) with metallic devices on the lumbar spine who received complete routine 1.5 T MR imaging, including axial and sagittal images of T1-weighted, T2-weighted, and T2-weighted IDEAL sequences, were included. The exclusion criteria were significant motion artifacts and severe metallic artifacts in any one of the sequences. The images were reviewed by two radiologists to identify fat-water swaps that were divided into 3 groups: extraspinal swaps, intraspinal swaps in sagittal images, and intraspinal swaps in axial images. The qualitative evaluations for the spinal canal in axial images were performed by rating on a five-point scale. Side-by-side comparisons of T2-weighted images and IDEAL in-phase images were also performed. RESULTS: In patient-based data of 276 patients, extraspinal fat-water swaps were noted in 10 patients (3.6%) and intraspinal swaps were noted in 160 patients (58.0%). The intraspinal swaps had a higher incidence in the patients with more levels of metallic devices with screws and the trend was not noted in the extraspinal swaps. A total of 928 axial levels were evaluated in the level-based data of axial images. T1-weighted, T2-weighted, and IDEAL in-phase images had significantly better imaging quality than the IDEAL water-only images (3.9 ± 0.4, 3.9 ± 0.3, 3.8 ± 0.4 vs 3.0 ± 1.3, all P < 0.001). Compared with T2-weighted images, most of the IDEAL in-phase images (reader 1, 90.9%; reader 2, 86.7%) present similar quality. CONCLUSION: Iterative decomposition of water and fat with echo asymmetry and least-squares estimation sequence can provide good fat suppression in most spine MRI with metallic devices but the loss of cerebrospinal fluid signal intensities due to fat-water swaps are noted in more than half of postinstrumentation spine. Routine reconstruction of in-phase images is recommended to improve evaluation of the thecal sac by avoiding pitfall caused by fat-water swaps.
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Tecido Adiposo/diagnóstico por imagem , Artefatos , Processamento de Imagem Assistida por Computador/métodos , Fixadores Internos , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Análise dos Mínimos Quadrados , Vértebras Lombares/diagnóstico por imagem , Masculino , Metais , Pessoa de Meia-Idade , Estudos Retrospectivos , Razão Sinal-Ruído , Coluna Vertebral/diagnóstico por imagem , Água , Adulto JovemRESUMO
Denervated-dependent skeletal muscle atrophy is a disease induced by skeletal muscle associated peripheral neuro-disconnection. Its specific molecular mechanisms remain unknown. The treating for denervated-dependent skeletal muscle atrophy is applied with an herbal complex Buyang Huanwu Tang used in traditional Chinese medicine and subjected to the established denervated-dependent skeletal muscle atrophy in rat models, and the therapeutic effects and associated mechanisms were evaluated in the pathogenesis of denervated-dependent skeletal muscle atrophy. Denervated-dependent skeletal muscle atrophy in rats was established and randomly divided into eight groups, including Normal control, Model, Positive control, Model + Buyang Huanwu Tang, Model + astragalus extracts, Model + Buyang Huanwu Tang-astragalus, Buyang Huanwu Tang + LY294002, and astragalus extract + LY294002 group. Hematoxylin-eosin staining and quantitative RT-PCR (qRT-PCR) assay were used to examine the inflammatory response of muscle tissues. Quantitative RT-PCR and Western blotting assay were utilized to analyze mRNA and protein expression. Immunohistochemistry assay was used to detect molecule expression in anterior cervical muscle tissues. Motor endplate activity was examined using the wholemount acetylcholinesterase staining method. The wet mass ratio of anterior cervical muscle was measured. The results indicated that Buyang Huanwu Tang treatment significantly alleviated inflammatory response, enhanced acetylcholinesterase activity, and motor endplate functions, and promoted wet mass of anterior cervical muscle compared to denervated-dependent skeletal muscle atrophy rat models (P < 0.05). Buyang Huanwu Tang regulated molecules of PI3K/PKB/GSK3ß/FOXO1 signaling pathway. Buyang Huanwu Tang significantly reduced muscle atrophy F-box protein, MuFR-1, Bax and caspase 9 expression, significantly enhanced Bcl-2 expression, and remarkably increased element-binding protein and vascular endothelial growth factor levels, compared to Model group (P < 0.05). Buyang Huanwu Tang suppressed caspase 9 and caspase 3 activity and associated apoptosis. Moreover, PI3K specific blocker, LY294002, significantly inhibited the effects of Buyang Huanwu Tang on the above molecule expression (P < 0.05). In conclusion, Buyang Huanwu Tang improved motor endplate functions of denervated-dependent skeletal muscle atrophy rat model through suppressing mitochondria-mediated apoptosis and activating PI3K/PKB/FOXO1 signaling pathway.
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Medicamentos de Ervas Chinesas/administração & dosagem , Placa Motora/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Atrofia Muscular/metabolismo , Animais , Masculino , Placa Motora/metabolismo , Placa Motora/patologia , Músculo Esquelético/inervação , Músculo Esquelético/patologia , Atrofia Muscular/patologia , Ratos Sprague-DawleyRESUMO
BACKGROUND: Previous case reports have demonstrated the occurrence of ischemic optic neuropathy (ION) following intravitreal injections of antivascular endothelial growth factor (anti-VEGF). However, no previous studies have investigated the impact of injection numbers on the risk of ION. The aim of our study was to investigate whether repeated intravitreal injections of anti-VEGF would increase the risk of subsequent ION in patients with neovascular age-related macular degeneration (AMD). METHODS: A population-based, retrospective cohort study using the Taiwan National Health Insurance Research Database was conducted from 2007 to 2013. Neovascular AMD patients receiving intravitreal injections of anti-VEGF during the study period were enrolled in the study cohort. Enrollees were divided into three groups according to the categorized levels of injection number (first level: < 10 times, second level: 10-15 times, and third level: > 15 times). Kaplan-Meier curves were generated to compare the cumulative hazard of subsequent ION among the three groups. Cox regression analyses were used to estimate crude and adjusted hazard ratios (HRs) for ION development with respect to the different levels of injection numbers. The confounders included for adjustment were age, sex, and comorbidities (diabetes, hypertension, hyperlipidemia, ischemic heart disease, and glaucoma). RESULTS: In total, the study cohort included 77,210 patients. Of these, 26,520, 38,010, and 12,680 were in the first-, second-, and third-level groups, respectively. The Kaplan-Meier method revealed that the cumulative hazards of ION were significantly higher in those who had a higher injection number. After adjusting for confounders, the adjusted HRs for ION in the second- and third-level groups were 1.91 (95% confidence interval [CI], 1.32-2.76) and 2.20 (95% CI, 1.42-3.43), respectively, compared with those in the first-level group. CONCLUSIONS: Among patients with neovascular AMD, those who receive a higher number of anti-VEGF injections have a significantly higher risk of developing ION compared with individuals who receive a lower number of injections.
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Inibidores da Angiogênese/efeitos adversos , Neovascularização de Coroide/tratamento farmacológico , Neuropatia Óptica Isquêmica/induzido quimicamente , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Neovascularização de Coroide/diagnóstico , Bases de Dados Factuais , Feminino , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Neuropatia Óptica Isquêmica/diagnóstico , Retratamento , Estudos Retrospectivos , Fatores de Risco , Taiwan , Tomografia de Coerência Óptica , Degeneração Macular Exsudativa/diagnósticoRESUMO
Enabling laser white-lighting at a correlated color temperature (CCT) of 6500K with the use of only red/green/blue (RGB) tri-color laser diodes (LDs) is demonstrated, which can further perform wavelength division multiplexing (WDM) communication with a high-spectral-usage 16 QAM-OFDM data stream at 11.2 Gbps over 0.5 m. The sampling rate of encoded data is optimized to avoid the aliasing effect and to effectively amplify the signal with high on/off extinction and modulation depth. Proper oversampling can decrease the peak-to-average power ratio (PAPR) of the OFDM data and filter out unwanted noise. There are also six different diffusers used to diverge the white-light mixed by the RGB LD beam. By analyzing the color-casting transmittance, surface roughness, CCT uniformity, divergent angle of the diffuser, and the data transmission capacity, the frosted glass (FG2.8) diffuser with high transmittance diverges the white light with the divergent angle of ± 20° and supports the highest data rate of 14 Gbps over 0.5 m. To fit the day-light CCT, the blue LD power at an optimized bias current is further attenuated with a 0.6-optical density filter for reducing CCT from 100000K to 6500K; however, such an adjustment also degrades the SNR ratio to sacrifice the achievable data rate of the blue LD. The polycarbonate (PC1.5) diffuser with proper surface roughness diverged white-light exhibits the best CCT uniformity and a divergent angle of ± 30° but supports a data rate of only 6.4 Gbps over 0.5 m. The poly (methyl methacrylate) PMMA1.5 diffuser scatters the white light with the largest angle of ± 40°; however, the data rate also decreases to 4.8 Gbps over 0.5 m.
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INTRODUCTION: The sonographic changes of the median nerve after steroid injection for carpal tunnel syndrome (CTS) still require investigation. METHODS: Sixty-two patients with CTS were included. The Boston Carpal Tunnel Questionnaire was administered, and ultrasonographic examinations were performed before and at 2, 6, and 12 weeks after steroid injection. At 12 weeks, general improvement was scored on a 6-point Likert scale. RESULTS: After treatment, the cross-sectional area (CSA) of the median nerve was significantly reduced at 2-, 6-, and 12-week follow-ups (for each, P < 0.001, analysis of variance). The "significant improvement" group (n = 39) had a significantly greater reduction in the CSA at the carpal tunnel inlet (P = 0.014) and CSA in the proximal carpal tunnel (P = 0.003) compared with the "little/no improvement" group (n = 23). DISCUSSION: Sonographic measurement of CSA may be considered complementary to the standard clinical evaluation in monitoring of treatment response in patients with CTS. Muscle Nerve 58: 402-406, 2018.
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Síndrome do Túnel Carpal/diagnóstico por imagem , Síndrome do Túnel Carpal/tratamento farmacológico , Nervo Mediano/efeitos dos fármacos , Nervo Mediano/diagnóstico por imagem , Esteroides/administração & dosagem , Ultrassonografia de Intervenção/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Condução Nervosa/efeitos dos fármacos , Condução Nervosa/fisiologiaRESUMO
Nonylphenol (NP) and/or bisphenol A (BPA) may have reproductive effects. Although the mechanisms of action remain unclear, steroid hormones biosynthesis, hypothalamus pituitary adrenal axis activity, oxidative stress, and crosstalk interaction of NP and BPA mixture and its pathways may play a contributory role. This cross-sectional study examined whether the interactive effects of NP/BPA and oxidative stress biomarkers played a role in reproductive indices (penis length and anogenital distance (AGD)) in 244 mother-fetus pairs. Four biomarkers of oxidative stress, (8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO2Gua), 8-iso-prostaglandin F2α (8-isoPF2α), and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)) were simultaneously analyzed using the high-performance liquid chromatography-electrospray ionization tandem mass spectrometry method. No significant associations were found between reproductive indices and NP/BPA or oxidative stress biomarkers. Maternal exposure to a mixture of NP and BPA may enhance 8-OHdG. Interactive effects were found in the high 8-isoPF2α group, and prenatal NP exposure was inversely associated with penis length (ßâ¯=â¯-3.68â¯mm; pâ¯=â¯0.01). Similar results were noted among boys who were born to mothers in the high 8-isoPF2α group, in which BPA was inversely associated with penis length (ßâ¯=â¯-4.43â¯mm; pâ¯=â¯0.005). Our findings suggest important implications for prenatal exposure to oxidative stress, as evidenced by the 8-isoPF2α level. Thus, NP and BPA may interact to shape fetal reproductive tract development, particularly in boys. The interactive effects of NP/BPA, oxidative stress, and reproductive indices should be considered.
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Compostos Benzidrílicos/efeitos adversos , Genitália Masculina/anatomia & histologia , Estresse Oxidativo , Fenóis/efeitos adversos , Estudos Transversais , Feminino , Feto/anatomia & histologia , Humanos , Masculino , GravidezRESUMO
We have shown that collagen type XI alpha 1 (COL11A1) promotes ovarian cancer progression and is associated with chemoresistance to cisplatin and paclitaxel in ovarian cancer cells. Here, we demonstrate how COL11A1 regulates twist family basic helix-loop-helix transcription factor 1-related protein 1 (TWIST1) to induce chemoresistance and inhibit apoptosis in ovarian cancer cells. Small interfering RNA-mediated reduction in COL11A1 protein levels increased the chemosensitivity to cisplatin and paclitaxel via downregulated TWIST1 expression. TWIST1 messenger RNA levels positively associated with COL11A1 messenger RNA expression levels in ovarian tumors. High TWIST1 expression levels were significantly associated with a progression-free interval of ≤ 6 months (p = 0.001) and death (p = 0.040). In addition, patients with high TWIST1 mRNA levels had significantly shorter 5-year overall-survival (p = 0.004) and progression-free survival (p = 0.009) rates, compared to patients with low TWIST1 levels. Increased TWIST1 expression caused by COL11A1-induced transcription of the inhibitor of nuclear factor kappa B kinase subunit beta (IKKß) gene occurred via increased SP1 phosphorylation and binding to the IKKß promoter. COL11A1-mediated nuclear factor-kappa B activation, via transcriptional activation of IKKß, promoted TWIST1, Mcl-1, and GAS6 expression, which were associated with chemoresistance and anti-apoptosis in ovarian cancer cells. We suggest that IKKß and TWIST1 can potentially be targeted in patients with COL11A1-positive ovarian cancer.
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Colágeno Tipo XI/metabolismo , Resistencia a Medicamentos Antineoplásicos/fisiologia , Regulação Neoplásica da Expressão Gênica/fisiologia , Proteínas Nucleares/metabolismo , Neoplasias Ovarianas/patologia , Proteína 1 Relacionada a Twist/metabolismo , Apoptose/fisiologia , Western Blotting , Imunoprecipitação da Cromatina , Intervalo Livre de Doença , Feminino , Técnicas de Silenciamento de Genes , Humanos , Quinase I-kappa B/metabolismo , Estimativa de Kaplan-Meier , Mutagênese Sítio-Dirigida , NF-kappa B/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/mortalidade , Reação em Cadeia da PolimeraseRESUMO
Prenatal exposure to nonylphenol (NP) and/or bisphenol A (BPA) has been reported to be associated with adverse birth outcomes; however, the underlying mechanisms remain unclear. The primary mechanism is endocrine disruption of the binding affinity for the estrogen receptor, but oxidative stress and inflammation might also play a contributory role. We aimed to investigate urinary NP and BPA levels in relation to biomarkers of oxidative/nitrative stress and inflammation and to explore whether changes in oxidative/nitrative stress are a function of prenatal exposure to NP/BPA and inflammation in 241 mother-fetus pairs. Third-trimester urinary biomarkers of oxidative/nitrative stress were simultaneously measured, including products of oxidatively and nitratively damaged DNA (8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-nitroguanine (8-NO2Gua)) as well as products of lipid peroxidation (8-iso-prostaglandin F2α (8-isoPF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)). The antioxidant glutathione peroxidase (GPx) and inflammation biomarkers, including C-reactive protein (CRP) and a panel of cytokines (interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)), were analyzed in maternal and umbilical cord plasma samples. In adjusted models, we observed significant positive associations between NP exposure and 8-OHdG and 8-NO2Gua levels, between BPA and 8-isoPF2α levels, and between maternal CRP levels and HNE-MA levels. Additionally, BPA and TNF-α levels in cord blood were inversely associated with maternal and GPx levels in cord blood as well as maternal TNF-α levels were inversely associated with maternal GPx levels. These results support a role for exposure to NP and BPA and possibly inflammation in increasing oxidative/nitrative stress and decreasing antioxidant activity during pregnancy.
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Compostos Benzidrílicos/toxicidade , Dano ao DNA , Inflamação , Estresse Oxidativo , Fenóis/toxicidade , Adulto , Biomarcadores , Estudos de Coortes , Feminino , Sangue Fetal , Humanos , Exposição Materna , Gravidez , Fator de Necrose Tumoral alfa/sangueRESUMO
BACKGROUND: Advances in cervical cancer management for childbearing women have led to less radical approaches. Use of fertility-sparing treatment to treat small cell neuroendocrine carcinoma (SCNEC) is challenging owing to the aggressive nature of the disease, even in early stage disease. CASE PRESENTATION: A 25-year-old nulligravida woman presented with malodorous vaginal discharge and was diagnosed to have an exophytic cervical SCNEC. A magnetic resonance image scan showed no evidence of parametrial invasion or distant metastasis. Clinical staging allocated her to stage IB1 disease. She underwent radical abdominal trachelectomy for reproductive purpose. Preoperative and postoperative chemotherapy with ifosfamide/etoposide/cisplatin combining gonadotropin-releasing hormone agonist were administered. She had a spontaneous, uneventful pregnancy and successfully delivered a term baby via cesarean section 7 years after treatment. CONCLUSION: To our knowledge, we describe the first success in offering a fertility-preserving multimodality strategy to present favorable oncologic, reproductive, and obstetric outcomes in a fertile woman of stage I SCNEC. Individualized multimodality therapy may be utilized in specific patients with early-stage cervical cancer to preserve their fertility.
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Carcinoma Neuroendócrino/tratamento farmacológico , Nascimento a Termo , Neoplasias do Colo do Útero/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Neuroendócrino/patologia , Cisplatino/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Fertilidade , Humanos , Ifosfamida/administração & dosagem , Estadiamento de Neoplasias , Gravidez , Neoplasias do Colo do Útero/patologiaRESUMO
OBJECTIVE: To compare the effectiveness of local steroid injection plus splinting with that of local steroid injection alone using clinical and electrophysiological parameters in patients with carpal tunnel syndrome (CTS). DESIGN: Randomized controlled study with 12 weeks of follow-up. SETTING: Tertiary care center. PARTICIPANTS: Volunteer sample of patients (N=52) diagnosed with CTS. INTERVENTIONS: Participants were randomly assigned to the steroid injection group (n=26) or the steroid injection-plus-splinting group (n=26). Patients of both groups received ultrasound-guided steroid injection with 1mL of 10mg (10mg/mL) triamcinolone acetonide (Shincort) and 1mL of 2% lidocaine hydrochloride (Xylocaine). Participants in the second group also wore a volar splint in the neutral position while sleeping and also during daytime whenever possible for the 12-week intervention period. MAIN OUTCOME MEASURES: Participants were evaluated before the treatment and at 6 and 12 weeks after the onset of treatment. The primary outcome measure was Boston Carpal Tunnel Questionnaire scores. The secondary outcome measures were as follows: scores on the visual analog scale for pain; electrophysiological parameters, including median nerve distal motor latency, sensory nerve conduction velocity (SNCV), and compound muscle action potential and sensory nerve action potential (SNAP) amplitudes; and patient's subjective impression of improvement. RESULTS: At 12-week follow-up, improvements in symptom severity and functional status scores on the Boston Carpal Tunnel Questionnaire as well as SNCV and SNAP amplitudes were greater in the group that received steroid injection combined with splinting than in the group that received steroid injection alone. The between-group difference was .48 points (95% confidence interval [CI], .09-.88 points; P=.032) in the Symptom Severity Scale score, .37 points (95% CI, .06-.67 points; P=.019) in the Functional Status Scale score, 3.38m/s (95% CI, 0.54-6.22m/s; P=.015) in the SNCV amplitude, and 3.21µV (95% CI, 0.00-6.46µV; P=.025) in the SNAP amplitude. CONCLUSIONS: In people with CTS, steroid injection combined with splinting resulted in modestly greater reduction of symptoms, superior functional recovery, and greater improvement in nerve function at 12-week follow-up as compared with steroid injection alone. However, these small differences are of unclear clinical significance.
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Analgésicos/uso terapêutico , Síndrome do Túnel Carpal/terapia , Lidocaína/uso terapêutico , Contenções , Triancinolona Acetonida/uso terapêutico , Adulto , Idoso , Analgésicos/administração & dosagem , Feminino , Humanos , Lidocaína/administração & dosagem , Masculino , Nervo Mediano/efeitos dos fármacos , Pessoa de Meia-Idade , Condução Nervosa/efeitos dos fármacos , Manejo da Dor , Medição da Dor , Índice de Gravidade de Doença , Método Simples-Cego , Triancinolona Acetonida/administração & dosagem , Ultrassonografia de IntervençãoRESUMO
Chemoresistance is a major hurdle in cancer treatment. Down-regulation of apoptosis pathways is one of the key determinants for chemoresistance. Here, we report higher gelsolin (GSN) levels in chemoresistant gynecological cancer cells compared with their sensitive counterparts. cis-Diammine dichloroplatinium (II) (CDDP)-induced GSN down-regulation is associated with its cleavage and apoptosis. Although the C-terminal GSN fragment (C-GSN) sensitized chemoresistant cells to CDDP, intact GSN and its N-terminal fragment (N-GSN) attenuated this response. GSN silencing also facilitated CDDP-induced apoptosis in chemoresistant cells. In contrast, intact GSN (I-GSN) was prosurvival in the presence of CDDP through a FLICE-like inhibitory protein (FLIP)-Itch interaction. This interaction was colocalized in the perinuclear region that could be dissociated by CDDP in sensitive cells, thereby inducing FLIP ubiquitination and degradation, followed by apoptosis. In resistant cells, GSN was highly expressed and CDDP failed to abolish the I-GSN-FLIP-Itch interaction, resulting in the dysregulation of the downstream responses. In addition, we investigated the association between GSN expression in ovarian serous adenocarcinoma and progression free survival and overall survival, as well as clinical prognosis. GSN overexpression was significantly associated with more aggressive behavior and more cancer deaths and supported our hypothesis that high GSN expression confers chemoresistance in cancer cells by altering the GSN-FLIP-Itch interaction. These findings are in agreement with the notion that GSN plays an important role in the regulation of gynecological cell fate as reflected in dysregulation in chemosensitivity.
Assuntos
Apoptose/efeitos dos fármacos , Cisplatino/farmacologia , Cistadenocarcinoma Seroso/metabolismo , Regulação para Baixo/efeitos dos fármacos , Gelsolina/metabolismo , Neoplasias Ovarianas/metabolismo , Antineoplásicos/farmacologia , Western Blotting , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/metabolismo , Linhagem Celular Tumoral , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Gelsolina/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Microscopia Confocal , Pessoa de Meia-Idade , Modelos Biológicos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Prognóstico , Ligação Proteica/efeitos dos fármacos , Interferência de RNA , Proteínas Repressoras/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sobrevida , Ubiquitina-Proteína Ligases/metabolismoRESUMO
To further explore the underlying antidepressant mechanism of ginseng total saponins (GTS), this study observed the effects on hippocampal astrocyte structural plasticity and hippocampal volume in the corticosterone-induced mouse depression model. Corticosterone (20 mg/kg/day) was administered subcutaneously for 5 weeks, and GTS (12.5, 25, and 50 mg/kg/day; namely GTSL, GTSM, and GTSH) or fluoxetine (10 mg/kg/day) were given intragastrically during the last 3 weeks. On day 33 and day 34, depression-like behavior was observed via a forced swimming test and a tail suspension test, respectively. At 6 h after the last dose of corticosterone (day 35), all mice were sacrificed followed by serum corticosterone assays, stereological analysis of hippocampal glial fibrillary acidic protein-positive (GFAP+ ) astroctyes and hippocampal volume, and hippocampal glycogen tests. Results showed that all doses of GTS ameliorated depression-like behavior and the decrease in hippocampal glycogen without normalizing hypercortisolism. Moreover, GTSH and GTSM reversed the corticosterone-induced reduction in the total number of hippocampal GFAP+ astrocytes and hippocampal volume. Additionally, GTSH alleviated the diminished protrusion length and somal volume of GFAP+ astrocytes induced by corticosterone. These findings imply that the effects of GTS on corticosterone-induced depression-like behavior may be mediated partly through the protection to hippocampal astrocyte structural plasticity. Copyright © 2017 John Wiley & Sons, Ltd.
Assuntos
Antidepressivos/farmacologia , Astrócitos/efeitos dos fármacos , Corticosterona/efeitos adversos , Hipocampo/efeitos dos fármacos , Panax/química , Saponinas/farmacologia , Animais , Atrofia , Corticosterona/sangue , Depressão/induzido quimicamente , Modelos Animais de Doenças , Fluoxetina/farmacologia , Proteína Glial Fibrilar Ácida/metabolismo , Elevação dos Membros Posteriores , Hipocampo/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NataçãoRESUMO
INTRODUCTION AND HYPOTHESIS: The purpose of this study was to explore new preventable risk factors for mesh exposure. METHODS: A retrospective review of 92 consecutive patients treated with transvaginal mesh (TVM) in the urogynecological unit of our university hospital. An analysis of perioperative predictors was conducted in patients after vaginal repairs using a type 1 mesh. Mesh complications were recorded according to International Urogynecological Association (IUGA) definitions. Mesh-exposure-free durations were calculated by using the Kaplan-Meier method and compared between different closure techniques using log-rank test. Hazard ratios (HR) of predictors for mesh exposure were estimated by univariate and multivariate analyses using Cox proportional hazards regression models. RESULTS: The median surveillance interval was 24.1 months. Two late occurrences were found beyond 1 year post operation. No statistically significant correlation was observed between mesh exposure and concomitant hysterectomy. Exposure risks were significantly higher in patients with interrupted whole-layer closure in univariate analysis. In the multivariate analysis, hematoma [HR 5.42, 95 % confidence interval (CI) 1.26-23.35, P = 0.024), Prolift mesh (HR 5.52, 95 % CI 1.15-26.53, P = 0.033), and interrupted whole-layer closure (HR 7.02, 95 % CI 1.62-30.53, P = 0.009) were the strongest predictors of mesh exposure. CONCLUSION: Findings indicate the risks of mesh exposure and reoperation may be prevented by avoiding hematoma, large amount of mesh, or interrupted whole-layer closure in TVM surgeries. If these risk factors are prevented, hysterectomy may not be a relative contraindication for TVM use. We also provide evidence regarding mesh exposure and the necessity for more than 1 year of follow-up and preoperative counselling.