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1.
Nat Immunol ; 25(3): 525-536, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38356061

RESUMO

Regulatory T (Treg) cells are critical for immune tolerance but also form a barrier to antitumor immunity. As therapeutic strategies involving Treg cell depletion are limited by concurrent autoimmune disorders, identification of intratumoral Treg cell-specific regulatory mechanisms is needed for selective targeting. Epigenetic modulators can be targeted with small compounds, but intratumoral Treg cell-specific epigenetic regulators have been unexplored. Here, we show that JMJD1C, a histone demethylase upregulated by cytokines in the tumor microenvironment, is essential for tumor Treg cell fitness but dispensable for systemic immune homeostasis. JMJD1C deletion enhanced AKT signals in a manner dependent on histone H3 lysine 9 dimethylation (H3K9me2) demethylase and STAT3 signals independently of H3K9me2 demethylase, leading to robust interferon-γ production and tumor Treg cell fragility. We have also developed an oral JMJD1C inhibitor that suppresses tumor growth by targeting intratumoral Treg cells. Overall, this study identifies JMJD1C as an epigenetic hub that can integrate signals to establish tumor Treg cell fitness, and we present a specific JMJD1C inhibitor that can target tumor Treg cells without affecting systemic immune homeostasis.


Assuntos
Doenças Autoimunes , Humanos , Citocinas , Epigenômica , Histona Desmetilases , Homeostase , Oxirredutases N-Desmetilantes , Histona Desmetilases com o Domínio Jumonji/genética
2.
Ann Neurol ; 95(2): 362-364, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37845593

RESUMO

Carotid free-floating thrombus (FFT) is a rare cause of acute ischemic events. The optimal management of carotid FFT remains unclear. The optimal and individualized management of carotid FFT should be determined based on the underlying etiology, clinical manifestation, and imaging characteristics. we reported a case with endovascular thrombectomy for a progressive stroke patient with a high-burden carotid free-floating thrombus. ANN NEUROL 2024;95:362-364.


Assuntos
Trombose das Artérias Carótidas , Procedimentos Endovasculares , Acidente Vascular Cerebral , Trombose , Humanos , Trombose das Artérias Carótidas/complicações , Trombose das Artérias Carótidas/diagnóstico por imagem , Trombose das Artérias Carótidas/cirurgia , Trombectomia/métodos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/cirurgia , Resultado do Tratamento , Procedimentos Endovasculares/métodos
3.
BMC Cancer ; 24(1): 385, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532312

RESUMO

Gliomas are the most common primary intracranial tumor worldwide. The maintenance of telomeres serves as an important biomarker of some subtypes of glioma. In order to investigate the biological role of RTEL1 in glioma. Relative telomere length (RTL) and RTEL1 mRNA was explored and regression analysis was performed to further examine the relationship of the RTL and the expression of RTEL1 with clinicopathological characteristics of glioma patients. We observed that high expression of RTEL1 is positively correlated with telomere length in glioma tissue, and serve as a poor prognostic factor in TERT wild-type patients. Further in vitro studies demonstrate that RTEL1 promoted proliferation, formation, migration and invasion ability of glioma cells. In addition, in vivo studies also revealed the oncogene role of RTEL1 in glioma. Further study using RNA sequence and phospho-specific antibody microarray assays identified JNK/ELK1 signaling was up-regulated by RTEL1 in glioma cells through ROS. In conclusion, our results suggested that RTEL1 promotes glioma tumorigenesis through JNK/ELK1 cascade and indicate that RTEL1 may be a prognostic biomarker in gliomas.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Glioma/patologia , Neoplasias Encefálicas/genética , Transformação Celular Neoplásica/genética , Oncogenes , Biomarcadores , Proliferação de Células , Proteínas Elk-1 do Domínio ets/genética , DNA Helicases/genética
4.
J Magn Reson Imaging ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38376091

RESUMO

BACKGROUND: Imaging techniques that quantitatively and automatically measure changes in the myocardial microcirculation in patients with diabetes are lacking. PURPOSE: To detect diabetic myocardial microvascular complications using a novel automatic quantitative perfusion MRI technique, and to explore the relationship between myocardial microcirculation dysfunction and fibrosis. STUDY TYPE: Prospective. SUBJECTS: 101 patients with type 2 diabetes mellitus (T2DM) (53 without and 48 with complications), 20 healthy volunteers. FIELD STRENGTH/SEQUENCE: 3.0T; modified Look-Locker inversion-recovery sequence; saturation recovery sequence and dual-bolus technique; segmented fast low-angle shot sequence. ASSESSMENT: All participants underwent MRI to determine the rest myocardial blood flow (MBF), stress MBF, myocardial perfusion reserve (MPR), and extracellular volume (ECV), which represents the extent of myocardial fibrosis. STATISTICAL TESTS: Kolmogorov-Smirnov test, Shapiro-Wilk test, Kruskal-Wallis H test, Mann-Whitney U test, chi-square test, Spearman correlation coefficient, multivariable linear regression analysis. P < 0.05 was considered statistically significant. RESULTS: The rest MBF was not significantly different between the T2DM without complications group (1.1, IQR: 0.9-1.3) and the control group (1.1, 1.0-1.3) (P = 1.000), but it was significantly lower in the T2DM with complications group (0.8, 0.6-1.0) than in both other groups. The stress MBF and MPR were significantly lower in the T2DM without complications group (1.9, 1.5-2.3, and 1.7, 1.4-2.1, respectively) than in the control group (3.0, 2.6-3.5, and 2.7, 2.4-3.1, respectively), and were also significantly lower in the T2DM with complications group (1.1, 0.9-1.4, and 1.4, 1.2-1.8, respectively) than in the T2DM without complications group. A decrease in MBF and MPR were significantly associated with an increase in the ECV. DATA CONCLUSION: Quantitative perfusion MRI can evaluate myocardial microcirculation dysfunction. In T2DM, there was a significant decrease in both MBF and MPR compared to healthy controls, with the decrease being significantly different between T2DM with and without complications groups. The decrease of MBF was significantly associated with the development of myocardial fibrosis, as determined by ECV. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

5.
Crit Rev Food Sci Nutr ; : 1-12, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37395610

RESUMO

Soy sauce is a popular fermented seasoning due to its distinct flavor and rich umami taste. Its traditional production involves two stages: solid-state fermentation and moromi (brine fermentation). During moromi, the dominant microbial population in the soy sauce mash changes, which is called microbial succession and is essential for the formation of soy sauce flavor compounds. Research has identified the sequence of succession, starting with Tetragenococcus halophilus, then Zygosaccharomyces rouxii, and lastly, Starmerella etchellsii. Factors such as the environment, microbial diversity, and interspecies relationships drive this process. Salt and ethanol tolerance influence microbial survival, while nutrients in the soy sauce mash support the cells in resisting external stress. Different microbial strains have varying abilities to survive and respond to external factors during fermentation, which impacts soy sauce quality. In this review, we would examine the factors behind the succession of common microbial populations in the soy sauce mash and explore how microbial succession affects soy sauce quality. The insights gained can help better manage the dynamic changes in microbes during fermentation, leading to improved production efficiency.

6.
Women Health ; 63(2): 105-114, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36576239

RESUMO

To evaluate the clinical features, molecular subtypes, therapeutic strategies, and prognostic factors of occult breast cancer (OBC). Patients with T0-3/N1-3/M0 breast cancer diagnosed in 2010-2018 (n = 114,303, including 691 with OBC) were retrieved from the Surveillance, Epidemiology, and End-Results (SEER) database. The endpoints were overall survival (OS) and breast cancer-specific survival (BCSS). Compared with non-OBC, OBC presented significantly more adverse clinicopathological prognostic features. More patients with OBC underwent breast-conserving treatment (BCT) and less had axillary lymphadenectomy (ALD). Outcomes were more favorable in OBC cases compared with non-OBC cases (p = .002 for OS, p = .002 for BCSS). Triple-negative (TNBC) and HER2-enriched were the subtypes with the worst prognosis in OBC (p < .05). Prognosis was better for triple-negative OBC compared with the same subtype of non-OBC. N-stage was not a strong prognostic indicator of OBC (p > .05 for OS). Cases who underwent systemic chemotherapy alone without surgery had the worst prognosis among OBC patients. For locoregional therapy, mastectomy and radiotherapy could confer survival advantage; standard axillary lymph node dissection (ALND) and positive lymph node dissection (PLND) contributed notably to OS in OBC patients. Both OS and BCSS were better in OBC cases compared with non-OBC. Systemic chemotherapy alone without surgery is not appropriate for OBC treatment, and mastectomy plus standard axillary surgery is recommended. Patients with hormone receptor-positive and low burden of axillary lymph node metastasis may be spared from radiotherapy after undergoing standard axillary lymphadenectomy.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/terapia , Neoplasias da Mama/diagnóstico , Mastectomia , Prognóstico , Mama , Excisão de Linfonodo
7.
Nano Lett ; 22(7): 2995-3002, 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35318847

RESUMO

Two-dimensional (2D) halide perovskites represent the natural semiconductor quantum wells (QWs), which hold great promise for optoelectronics. However, due to the hybrid structure of Ruddlesden-Popper 2D perovskites, the intrinsic nature of hot-carrier kinetics remains shielded within. Herein, we adopt CsPbBr3 nanoplates as a model system to reveal the intrinsic carrier dynamics in inorganic perovskite QWs. Interestingly, we revealed an ultrafast and hot-phonon-bottleneck (HPB)-free carrier cooling in monodisperse CsPbBr3 QWs, which is in sharp contrast to the bulk and nanocrystalline perovskites. The absence of HPB was attributed to the efficient out-of-plane triplet-exciton-LO-phonon coupling in 2D perovskites because of the structural anisotropy. Accordingly, the HPB can be activated by shutting down the out-of-plane energy loss route through forming the layer-stacked perovskite superlattice. The controllable on and off of HPB may provide new possibilities in optoelectronic devices and these findings deepen the understanding of a hot-carrier cooling mechanism in 2D perovskites.

8.
Cytogenet Genome Res ; 162(3): 109-118, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35654004

RESUMO

RAD21 plays multiple roles in numerous cancers. In breast cancer (BC), a high level of RAD21 correlates with poor disease outcomes and resistance to chemotherapy. However, data regarding RAD21 promoter methylation in BC tissue and its correlation with clinical outcomes in patients with BC remain limited. Here, we investigated the clinicopathological features associated with the methylation status of RAD21 in BC to figure out its possible role in pathogenesis and the formation of breast carcinogenesis. The methylation status of the RAD21 gene was significantly associated with better clinical outcomes in patients with BC.


Assuntos
Neoplasias da Mama , Proteínas de Ciclo Celular , Proteínas de Ligação a DNA , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Proteínas de Ciclo Celular/genética , Proteínas Cromossômicas não Histona , Metilação de DNA , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Prognóstico , Regiões Promotoras Genéticas , Coesinas
9.
BMC Cancer ; 22(1): 951, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064388

RESUMO

Breast cancer is the most common female tumors arising worldwide, and genetic and epigenetic events are constantly accumulated in breast tumorigenesis. The melastatin-related transient receptor potential 7 channel (TRPM7) is a nonselective cation channel, mainly maintaining Zn2+, Ca2+ and Mg2+ homeostasis. It is also involved in regulating proliferation and migration in various cancers including breast cancer. However, epigenetic alterations (such as promoter methylation) of TRPM7 and their correlation with clinical outcomes in breast cancer patients remain largely unclear. In this study, we found that TRPM7 was highly expressed in the luminal A subtype of breast cancers but no other subtypes compared with GTEx (Genotype-Tissue Expression Rad) or normal samples by analyzing the TCGA database. Correspondingly, TRPM7 was methylated in 42.7% (93 of 219) of breast cancers. Further studies found that promoter methylation of TRPM7 were significantly associated with better clinical outcomes in breast cancer patients, especially in the Luminal A subtype. Besides, methylated TRPM7 was correlated with less number of metastatic lymph nodes and longer local failure free survival time in this subtype. In summary, our data indicate that promoter methylation of TRPM7 may predict poor prognosis in patients with luminal A breast cancer.


Assuntos
Neoplasias da Mama , Canais de Cátion TRPM , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Metilação de DNA , Feminino , Humanos , Prognóstico , Regiões Promotoras Genéticas , Proteínas Serina-Treonina Quinases/genética , Canais de Cátion TRPM/genética , Canais de Cátion TRPM/metabolismo
10.
Plant Cell Physiol ; 61(12): 2031-2042, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32946565

RESUMO

Mitochondrial processes are implicated in plant response to biotic stress caused by viruses, actinomyces, bacteria and pests, but their function in defense against fungal invasion remains unclear. Here, we investigated the role and regulation of mitochondrial alternative oxidase (AOX) in response to black spot disease caused by the hemibiotrophic fungus Marssonina brunnea in poplar. M. brunnea inoculation induced the transcription of the AOX1a gene in the mitochondrial electron transport chain and of jasmonic acid (JA) and ethylene (ET) biosynthetic genes, with the accumulation of these phytohormones in poplar leaf, while inhibiting the transcript amount of the mitochondrial cytochrome c oxidase gene (COX6b) and genes related to salicylic acid (SA). Enhanced AOX reduced poplar susceptibility to M. brunnea with a higher ATP/ADP ratio while the repressed AOX caused the reverse effect. Exogenous JA and 1-aminocyclopropane-1-carboxylic acid (ACC, a biosynthetic precursor of ET) inhibited the transcript amount of COX6b and consequently increased the ratio of AOX pathway to total respiration. Furthermore, the transcription of CYS C1 and CYS D1 genes catalyzing cyanide metabolism was induced, while the cysteine (CYS) substrate levels reduced upon M. brunnea inoculation; exogenous JA and ACC mimicked the effect of M. brunnea infection on cysteine. Exogenous SA enhanced, while JA and ACC reduced, poplar susceptibility to M. brunnea. Moreover, inhibiting AOX completely prohibited JA- and ET-increased tolerance to M. brunnea in poplar. These observations indicate that the JA- and ET-induced mitochondrial AOX pathway triggers defense against M. brunnea in poplar. This effect probably involves cyanide. These findings deepen our understanding of plant-pathogenic fungi interactions.


Assuntos
Ascomicetos , Ciclopentanos/metabolismo , Resistência à Doença/efeitos dos fármacos , Etilenos/metabolismo , Proteínas Mitocondriais/fisiologia , Oxirredutases/fisiologia , Oxilipinas/metabolismo , Doenças das Plantas/imunologia , Reguladores de Crescimento de Plantas/fisiologia , Proteínas de Plantas/fisiologia , Populus/imunologia , Proteínas Mitocondriais/metabolismo , Oxirredutases/metabolismo , Doenças das Plantas/microbiologia , Reguladores de Crescimento de Plantas/metabolismo , Folhas de Planta/metabolismo , Folhas de Planta/microbiologia , Proteínas de Plantas/metabolismo , Populus/enzimologia , Populus/microbiologia
11.
Endocr Res ; 46(1): 14-19, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33043720

RESUMO

OBJECTIVES: The diagnosis and management of osteoporosis and osteoporotic fractures are challenging in rural and underdeveloped areas of China because medical resources are inaccessible; thus, a simple and accurate method is essential for the detection of vertebral fractures. We aimed to examine the relationship between historical height loss (HHL) and vertebral fractures in postmenopausal Chinese women. MATERIAL AND METHODS: A cross-sectional study of 255 postmenopausal women aged 50 years or older was conducted in September 2017. Demographic data, including self-reported tallest historical height and current height were analyzed. Vertebral fractures were assessed using X-ray radiography and HHL thresholds were examined using specificity and sensitivity testing. RESULTS: The average age of the 255 participants was 66.3 ± 9.0 years and their mean HHL was 3.5 ± 2.8 cm. The 24 women who were found to have vertebral fractures were older, had more years since menopause (YSM), and a larger HHL compared to those without vertebral fractures. Logistic regression analysis showed that age was a better predictor of vertebral fractures than HHL was, and the cutoff age for detecting vertebral fractures was 71 years, with an area under the receiver operating characteristic curve of 0.750. CONCLUSIONS: Although the women in this study with vertebral fractures had a greater height loss than those without fractures, it was apparent that age, rather than HHL, is the best way to determine who is most likely to develop vertebral fractures.


Assuntos
Estatura , Osteoporose Pós-Menopausa/diagnóstico , Fraturas por Osteoporose/diagnóstico , Fraturas da Coluna Vertebral/diagnóstico , Fatores Etários , Idoso , China , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Prognóstico , Tomografia por Raios X
12.
J Pineal Res ; 68(3): e12631, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31943334

RESUMO

In the elderly with atherosclerosis, hypertension and diabetes, vascular calcification and ageing are ubiquitous. Melatonin (MT) has been demonstrated to impact the cardiovascular system. In this study, we have shown that MT alleviates vascular calcification and ageing, and the underlying mechanism involved. We found that both osteogenic differentiation and senescence of vascular smooth muscle cells (VSMCs) were attenuated by MT in a MT membrane receptor-dependent manner. Moreover, exosomes isolated from VSMCs or calcifying vascular smooth muscle cells (CVSMCs) treated with MT could be uptaken by VSMCs and attenuated the osteogenic differentiation and senescence of VSMCs or CVSMCs, respectively. Moreover, we used conditional medium from MT-treated VSMCs and Transwell assay to confirm exosomes secreted by MT-treated VSMCs attenuated the osteogenic differentiation and senescence of VSMCs through paracrine mechanism. We also found exosomal miR-204/miR-211 mediated the paracrine effect of exosomes secreted by VSMCs. A potential target of these two miRs was revealed to be BMP2. Furthermore, treatment of MT alleviated vascular calcification and ageing in 5/6-nephrectomy plus high-phosphate diet-treated (5/6 NTP) mice, while these effects were partially reversed by GW4869. Exosomes derived from MT-treated VSMCs were internalised into mouse artery detected by in vivo fluorescence image, and these exosomes reduced vascular calcification and ageing of 5/6 NTP mice, but both effects were largely abolished by inhibition of exosomal miR-204 or miR-211. In summary, our present study revealed that exosomes from MT-treated VSMCs could attenuate vascular calcification and ageing in a paracrine manner through an exosomal miR-204/miR-211.


Assuntos
Melatonina/farmacologia , MicroRNAs/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Calcificação Vascular/metabolismo , Envelhecimento , Animais , Diferenciação Celular/efeitos dos fármacos , Exossomos/química , Exossomos/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Músculo Liso Vascular/fisiopatologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Calcificação Vascular/fisiopatologia
13.
Future Oncol ; 16(2): 4381-4393, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31814446

RESUMO

Aim: A gene set based systematic analysis strategy is used to investigate prostate tumors and its subclusters with focuses on similarities and differences of biological functions. Results: Dysregulation of methylation status, as well as RAS/RAF/ERK and PI3K-ATK signaling pathways, were found to be the most dramatic changes during prostate cancer tumorigenesis. Besides, neural and inflammation microenvironment is also significantly divergent between tumor and adjacent tissues. Insights of subclasses within prostate tumor cohorts revealed four different clusters with distinct gene expression patterns. We found that samples are mainly clustered by immune environments and proliferation traits. Conclusion: The findings of this article may help to advance the progress of identifying better diagnosis biomarkers and therapeutic targets.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Próstata/classificação , Neoplasias da Próstata/genética , Tirosina Quinase da Agamaglobulinemia/genética , Biologia Computacional/métodos , MAP Quinases Reguladas por Sinal Extracelular/genética , Perfilação da Expressão Gênica , Humanos , Masculino , Gradação de Tumores , PTEN Fosfo-Hidrolase/genética , Fosfatidilinositol 3-Quinases/genética , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Análise de Sequência de RNA/métodos , Transdução de Sinais , Taxa de Sobrevida
14.
Scand J Clin Lab Invest ; 80(4): 336-342, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32189531

RESUMO

Renin-Angiotensin-Aldosterone System (RAAS) measurements are influenced by several factors. We investigated the effect of sample delivery conditions on RAAS measurements including sample storage temperature and time. Blood samples were collected from thirty participants using enzyme inhibitor tubes and serum separation gel evacuated tubes. Plasma and serum from fresh blood samples without further storage (as baseline), and from blood samples that were stored at either 0 °C, 4 °C, or 25 °C for 3 h, 6 h and 24 h, respectively, were extracted and stored at -30 °C for batch measurements using radioimmunoassay. Concentrations of Aldosterone (Ald) decreased following delivery temperature and time, and were significantly different when samples were set aside at 0 °C for 24 h (p < .01), 4 °C for 6 h (p < .01), and 25 °C for 3 h (p < .05). However, levels of Angiotensin (Ang I) increased following delivery temperature and time, and were significantly different when samples were set aside at 0 °C and 4 °C for 6 h (p < .05) and at 25 °C for 3 h (p < .001). However, no changes were observed for the concentrations of plasma renin activity (PRA) and Ang II, except for Ang II which increased significantly when samples were set aside at 25 °C for 24 h (p < .001). Our results indicate that samples used for RAAS measurement should be placed at a low temperature and analyzed as soon as possible after collection.


Assuntos
Aldosterona/sangue , Angiotensina II/sangue , Angiotensina I/sangue , Radioimunoensaio/normas , Renina/sangue , Manejo de Espécimes/normas , Adulto , Idoso , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Refrigeração/normas , Sistema Renina-Angiotensina/genética
15.
Neurol Sci ; 39(5): 811-820, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29349657

RESUMO

Recently, mutations in TBK1 (TANK-binding kinase 1) have been reported to be a cause of amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) spectrum, but the relationship between them remains unclear owing to the small sample size and low mutation rate. Therefore, we performed a two-stage meta-analysis to investigate the frequency of TBK1 mutations in ALS/FTD patients and the association between the mutations and risk of ALS/FTD spectrum. In the first stage, 12 studies involving 4173 ALS/FTD patients were included. The frequencies of loss of function (LoF) and missense mutations were 1.0% (95% CI 0.6-1.7%) and 1.8% (95% CI 0.9-3.4%) in ALS/FTD patients respectively. Subgroup analysis suggested a higher prevalence of TBK1 mutations in European patients than that in Asian patients. In the second stage, 7 studies involving 3146 cases and 4856 controls were enrolled. Results showed that TBK1 LoF mutations were associated with a significant increased risk for ALS/FTD spectrum (OR 11.78; 95% CI 4.21-33.00; p < 0.0001), while TBK1 missense mutations were associated with a moderately increased susceptibility for ALS/FTD spectrum (OR 1.62; 95% CI 1.19-2.19; p = 0.002). In conclusion, TBK1 LoF and missense mutations are not frequently found in ALS/FTD patients, and both of them are associated with an increased risk for ALS/FTD spectrum.


Assuntos
Esclerose Lateral Amiotrófica/genética , Demência Frontotemporal/genética , Proteínas Serina-Treonina Quinases/genética , Esclerose Lateral Amiotrófica/enzimologia , Demência Frontotemporal/enzimologia , Predisposição Genética para Doença , Humanos , Mutação
16.
J Comput Assist Tomogr ; 41(2): 231-235, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27824667

RESUMO

OBJECTIVE: The aim of this study was to longitudinally evaluate the changes in marrow fat content of ovariectomized (OVX) rabbits treated with epigallocatechin-3-gallate (EGCG) using proton magnetic resonance spectroscopy (H-MRS). METHODS: Thirty-six female New Zealand rabbits were equally divided into sham operation, OVX controls, and OVX treated with EGCG (intraperitoneally, 1.8 mg/kg) for 5 months. Marrow fat fraction by H-MRS and bone density by peripheral quantitative computed tomography were determined at 0, 3, and 5 months. Serum biomarkers and marrow adipocytes were determined at the end of experiment. RESULTS: Estrogen deficiency increased marrow fat content in a time-dependent manner, with a variation of marrow fat fraction (FF) (+25.3%) at month 3 from baseline, and it was maintained until month 5 (+66.6%, all P < 0.001). In comparison with the sham-operated controls, adipocytes density, size, and percentage of adipocytes area in the OVX controls increased by 62.9%, 44.4%, and 178%, respectively (all P < 0.05). These OVX-induced pathological changes were partly reversed by EGCG treatment. In addition, EGCG treatment reduced bone turnover and increased bone density of OVX rabbits. CONCLUSIONS: Epigallocatechin-3-gallate exhibits an anabolic effect on osteoporotic bone by concomitantly rescuing bone mass and mitigating marrow adiposity. H-MRS appears to be a useful tool for monitoring osteoporosis-related treatments.


Assuntos
Tecido Adiposo/diagnóstico por imagem , Medula Óssea/diagnóstico por imagem , Catequina/análogos & derivados , Osteoporose/diagnóstico por imagem , Osteoporose/tratamento farmacológico , Espectroscopia de Prótons por Ressonância Magnética/métodos , Animais , Antioxidantes/uso terapêutico , Catequina/uso terapêutico , Modelos Animais de Doenças , Feminino , Coelhos
17.
Biochim Biophys Acta ; 1847(2): 286-293, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25482259

RESUMO

Plant photosystem II (PSII) is a multicomponent pigment-protein complex that harvests sunlight via pigments photoexcitation, and converts light energy into chemical energy. Against high light induced photodamage, excess light absorption of antenna pigments triggers the operation of photoprotection mechanism in plant PSII. Non-photochemical energy relaxation as a major photoprotection way is essentially correlated to the excess light absorption. Here we investigate the energy relaxation of plant PSII complexes with varying incident light density, by performing steady-state and transient chlorophyll fluorescence measurements of the grana membranes (called as BBY), functional moiety PSII reaction center and isolated light-harvesting complex LHCII under excess light irradiation. Based on the chlorophyll fluorescence decays of these samples, it is found that an irradiation density dependent energy relaxation occurs in the LHCII assemblies, especially in the antenna assembly of PSII supercomplexes in grana membrane, when irradiation increases to somewhat higher density levels. Correspondingly, the average chlorophyll fluorescence lifetime of the highly isolated BBY fragments gradually decreases from ~1680 to ~1360 ps with increasing the irradiation density from 6.1×10(9) to 5.5×10(10) photon cm(-2) pulse(-1). Analysis of the relation of fluorescence decay change to the aggregation extent of LHCIIs suggests that a dense arrangement of trimeric LHCIIs is likely the structural base for the occurrence of this irradiation density dependent energy relaxation. Once altering the irradiation density, this energy relaxation is quickly reversible, implying that it may play an important role in photoprotection of plant PSII.


Assuntos
Complexos de Proteínas Captadores de Luz/química , Complexo de Proteína do Fotossistema II/química , Plantas/metabolismo , Clorofila/metabolismo , Luz , Espectrometria de Fluorescência
18.
Small ; 12(23): 3143-54, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27121203

RESUMO

The wide-ranging applications of fluorescent semiconductor quantum dots (QDs) have triggered increasing concerns about their biosafety. Most QD-related toxicity studies focus on the subcellular processes in cultured cells or global physiological effects on whole animals. However, it is unclear how QDs affect subcellular processes in living organisms, or how the subcellular disturbance contributes to the overall toxicity. Here the behavior and toxicity of QDs of three different sizes in Caenorhabditis elegans (C. elegans) are systematically investigated at both the systemic and the subcellular level. Specifically, clear size-dependent distribution and toxicity of the QDs in the digestive tract are observed. Short-term exposure of QDs leads to acute toxicity on C. elegans, yet incurring no lasting, irreversible damage. In contrast, chronic exposure of QDs severely inhibits development and shortens lifespan. Subcellular analysis reveals that endocytosis and nutrition storage are disrupted by QDs, which likely accounts for the severe deterioration in growth and longevity. This work reveals that QDs invasion disrupts key subcellular processes in living organisms, and may cause permanent damage to the tissues and organs over long-term retention. The findings provide invaluable information for safety evaluations of QD-based applications and offer new opportunities for design of novel nontoxic nanoprobes.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Pontos Quânticos/efeitos adversos , Animais , Compostos de Cádmio/efeitos adversos , Compostos de Cádmio/química , Semicondutores/efeitos adversos , Telúrio/efeitos adversos , Telúrio/química
19.
Angew Chem Int Ed Engl ; 55(42): 13067-13071, 2016 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-27633183

RESUMO

Although the power conversion efficiency of perovskite solar cells has improved rapidly, a rational path for further improvement remains unclear. The effect of large morphological heterogeneity of polycrystalline perovskite films on their device performance by photoluminescence (PL) microscopy has now been studied. Contrary to the common belief on the deleterious effect of morphological heterogeneity on carrier lifetimes and diffusivities, in neat CH3 NH3 PbI3 (Cl) polycrystalline perovskite films, the local (intra-grain) carrier diffusivities in different grains are all surprisingly high (1.5 to 3.3 cm2 s-1 ; comparable to bulk single-crystals), and the local carrier lifetimes are long (ca. 200 ns) and surprisingly homogenous among grains, and uniform across grain boundary and interior. However, there is a large heterogeneity of carrier extraction efficiency at the perovskite grain-electrode interface. Improving homogeneity at perovskite grain-electrode contacts is thus a promising direction for improving the performance of perovskite thin-film solar cells.

20.
J Am Chem Soc ; 137(39): 12458-61, 2015 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-26390276

RESUMO

Single-crystal CH3NH3PbX3 (X = I(-), Cl(-), Br(-)) perovskite nanowires (NWs) and nanoplates (NPs), which demonstrate ultracompact sizes and exceptional photophysical properties, offer promises for applications in nanoscale photonics and optoelectronics. However, traditional electronic and transient techniques are limited by the dimensions of the samples, and characterizations of the carrier behavior (diffusion coefficient, charge mobility and diffusion length) in these NWs and NPs are extremely difficult. Herein, we report the direct visualization of the carrier diffusion process in individual single-crystal CH3NH3PbI3 and CH3NH3PbBr3 NWs and NPs using time-resolved and photoluminescence-scanned imaging microscopy. We report the diffusion coefficient (charge motility), which varies significantly between different NWs and NPs, ranging from 1.59 to 2.41 cm(2) s(-1) (56.4 to 93.9 cm(2) V(-1) s(-1)) for CH3NH3PbI3 and 0.50 to 1.44 cm(2) s(-1) (19.4 to 56.1 cm(2) V(-1) s(-1)) for CH3NH3PbBr3 and find this variation is independent of the shape and size of the sample. The average diffusion length is 14.0 ± 5.1 µm for CH3NH3PbI3 and 6.0 ± 1.6 µm for CH3NH3PbBr3. These results provide information that is essential for the practical applications of the single-crystal perovskite NWs and NPs, and the imaging microscopy may also be applicable to other optoelectronic materials.

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