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INTRODUCTION: Immunosuppressive therapy for uveitis may cause liver damage. METHODS: To investigate incidence of liver damage during uveitis treatment, we compared serological Hepatitis B core antibody (HBcAb) status with risk of liver dysfunction in all participants (n = 992), in anterior uveitis (AU) (n = 489), and combined of intermediate, posterior, or panuveitis (IPPU) patients (n = 503). The primary endpoint was incidence of elevated serum alanine aminotransferase level above 2-fold upper limits of normal within 6 months. RESULTS: The incidence rate of primary endpoint for HBcAb-negative and HBcAb-positive patients was 65 and 212 per 1,000 person years, respectively. The absolute rate difference was 147 (95% confidence interval [CI], 80-213) per 1,000 person years. HBcAb positivity was associated with a higher risk for primary endpoint in all participants (adjusted hazard ratio [aHR], 3.53; 95% CI, 1.79-6.99; p value = 2.8 × 10-4) and in IPPU (aHR, 3.80; 95% CI, 1.61-9.01; p value = 0.002). No significant association with primary endpoint was observed for HBcAb positivity in AU (aHR, 3.21; 95% CI, 0.94-10.95; p value = 0.063). AU was mainly treated with topical eye drops (74.0%), whereas IPPU cases received systemic therapy including prednisone (94.0%), cyclosporine (80.9%), or other additionally combined immunomodulatory agents (14.9%). CONCLUSION: Noninfectious uveitis cases with HBcAb positivity have an increased risk of liver damage. This association was predominantly driven by IPPU but was not significant in AU, suggesting that the association is mediated by systemic therapy.
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Hepatitis B , Uveítis , Hepatitis B/complicaciones , Hepatitis B/epidemiología , Anticuerpos contra la Hepatitis B , Virus de la Hepatitis B , Humanos , Estudios Retrospectivos , Uveítis/complicaciones , Uveítis/diagnóstico , Uveítis/tratamiento farmacológicoRESUMEN
Background: Aflibercept has been widely used in treating diabetic macular edema (DME). However, the effect of aflibercept in treating DME refractory to bevacizumab or ranibizumab has not been well established. Objective: To assess the therapeutic effect of switching from bevacizumab or ranibizumab to aflibercept in the treatment of refractory DME. Methods: Relevant studies were searched from 3 databases: the Cochrane Library, PubMed, and Web of Science. Data on changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), and adverse events within the follow-up period were collected and pooled using weighted mean differences (WMDs) with corresponding 95% CIs in a random effects model. The between-study heterogeneity was tested using the χ2 test and the I2 statistic, and funnel plots were used to evaluate the publication bias. Results: A total of 11 nonrandomized trials met the inclusion criteria and were included in the meta-analysis. Our studies showed significant improvements in the BCVA (WMD = 100.55; 95% CI = 68.46 to 132.63; P < 0.01) and reduction in CMT (WMD = 0.09; 95% CI = 0.03 to 0.14; P < 0.01) after switching to aflibercept. Although a large amount of heterogeneity was detected in the CMT results among these studies, the sensitivity analyses showed the reliability and stability of our results. Conclusion and Relevance: There were significant improvements in both visual and anatomical outcomes after switching from bevacizumab or ranibizumab to aflibercept, without risk of adverse events. Thus, switching therapy may be a safe and effective treatment for patients with refractory DME.
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Inhibidores de la Angiogénesis/uso terapéutico , Diabetes Mellitus/tratamiento farmacológico , Retinopatía Diabética/tratamiento farmacológico , Sustitución de Medicamentos , Edema Macular/tratamiento farmacológico , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/efectos adversos , Bevacizumab/administración & dosificación , Bevacizumab/efectos adversos , Bevacizumab/uso terapéutico , Humanos , Inyecciones Intravítreas , Investigación Cualitativa , Ranibizumab/administración & dosificación , Ranibizumab/efectos adversos , Ranibizumab/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/efectos adversos , Reproducibilidad de los Resultados , Resultado del Tratamiento , Agudeza VisualRESUMEN
Chenopodium album is an annual herb from Amaranthaceae with worldwide distribution. It is a leafy vegetable as well as an important subsidiary grain crop with high nutritional value and medicinal value. In this study, we reported the complete chloroplast genome of C. album. The total chloroplast genome was 152,167 bp in length, containing a large single-copy region (LSC, 83,676 bp), a small single-copy region (SSC, 18,105 bp), and a pair of inverted repeat regions (IRs, 25,193 bp). The complete chloroplast genome contains 110 genes, including 78 protein-coding genes, 28 transfer RNA (tRNA) genes, and 4 ribosomal RNA (rRNA) genes with an overall GC content of 37.3%. Phylogenetic analysis showed that C. album was sister to C. acuminatum within Chenopodioideae. The complete chloroplast genome of C. album will provide useful resources for the development and utilization of this species and the phylogenetic study of Amaranthaceae.
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Arachis pintoi Krapov. & W.C.Greg. is an important leguminous forage grass species that have extremely wide ranges of distribution in the tropical and sub-tropical regions. It has high feeding value and horticultural value. In this study, we sequenced and assembled the complete chloroplast genome of A. pintoi. The chloroplast genome is 156,185 bp in length, containing a pair of inverted repeated (IR) regions of 25,820 bp that are separated by a large single copy (LSC) region of 85,637 bp, and a small single copy (SSC) region of 18,908 bp. The complete chloroplast genome contains 112 unique genes, including 80 protein-coding genes, 28 transfer RNA genes (tRNAs), and four ribosomal RNA genes (rRNAs). The overall GC content was 36.4%. The phylogenetic analysis demonstrated that A. pintoi formed a single branch among genus Arachis. The whole chloroplast genome of A. pintoi will be a useful resource for future studies on phylogeny and conservation in Arachis.
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AIM: To study the potential role of fasudil as a treatment for posterior capsular opacification (PCO) of the human crystalline lens. METHODS: Human lens epithelial cells (HLECs; line SRA01/04) was exposed to transforming growth factor-ß2 (TGF-ß2) to induce the process of epithelial-mesenchymal transition (EMT). Fasudil was applied to the cell samples. Its effect on overall HLECs proliferation and migration was studied, as was its influence on EMT induction by TGF-ß2 using cell migration assay, MTT colorimetric assay and Western blot assay. RESULTS: Fasudil inhibited the proliferation of SRA01/04. Its effect was time- and concentration-dependent. The migration of SRA01/04 cells was significantly reduced 24-72h after fasudil treatment, and the half maximal inhibitory concentration (IC50) was 22.37 µmol/mL at 72h. Reversal of the elongated, fibroblast-like shape changes induced by TGF-ß2 in SRA01/04 cells was observed. Fasudil up-regulated the expression of Connexin43 protein and down-regulated the expression of α-SMA protein compared with the cells treated with TGF-ß2. Furthermore, when exposed to fasudil, the phosphorylation of Rho-associated protein kinase (Rock) and myosin light chain (MLC) could not be activated in the cell preparations. CONCLUSION: Fasudil suppresses the proliferation and migration of SRA01/04 cells, and inhibits the process of EMT induced by TGF-ß2. These results suggest that fasudil may serve as a therapeutic agent for PCO.
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A rice pse(t) (premature senescence, tentatively) mutant line, was isolated from 4,500 independent T-DNA inserted transgenic lines. The symptoms of premature senescence appeared more severely than those of the control plants (Zhonghua 11, japonica) at the last development stage. To characterize the mutant and provide basic information on the candidate genes by mapping to a physical region of 220-kb, experiments were carried out in two phytotrons under controlled temperature of 24 degrees C and 28 degrees C, respectively. The content of chlorophyll, soluble protein and MDA (malondialdehyde), net photosynthesis, the antioxidant enzyme activities of SOD (superoxide dismuase) (EC 1.15.1.1) and POD (peroxidase) (EC 1.11.1.7) and the peptidase activities of leaves were measured from top to bottom according to the leaf positions at the flowering stage. Compared with the control plant, the mutant showed the following characteristics: (1) Higher net photosynthesis rate (P(n)) appeared in the 1st and 2nd leaves, contents of chlorophyll and soluble protein were also higher in the 1st leaf; (2) The activities of SOD, POD and peptidase were higher according to the leaf position from top to bottom; (3) The symptom of premature senescence was accelerated in the mutant at 28 degrees C treatment. The MDA content and the SOD and POD activities between the 24 degrees C and 28 degrees C treatment mutants were not significantly different. Content of chlorophyll and soluble protein of leaves mutant decreased rapidly at 28 degrees C treatment. The results show that pse(t) is sensitive to high temperature. The probable function of PSE(T) is discussed.
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Envejecimiento/fisiología , Apoptosis/fisiología , Oryza/crecimiento & desarrollo , Oryza/genética , Fotosíntesis/fisiología , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/genética , Proteínas de Plantas/metabolismo , Antioxidantes/metabolismo , Mutación , Oryza/clasificación , Hojas de la Planta/clasificación , Proteínas de Plantas/genéticaRESUMEN
Glial cell line-derived neurotrophic factor (GDNF) has an essential role in the survival and maturation of the dopaminergic (DA) neurons in the substantia nigra (SN) of mammalian embryonic brain. In addition to Ret, cell adhesion molecules (CAMs) were also proposed to function as transmembrane signaling receptors of GDNF. The present study was to investigate whether these transmembrane receptors of GDNF were correlated with the tyrosine hydroxylase (TH) expression of SN DA neurons during early developmental stage. RT-PCR and Western blot were performed to detect TH expression in SN of perinatal rats at mRNA and protein level respectively; meanwhile, Western blot was performed to detect the expressions of the transmembrane proteins including Ret, neural cell adhesion molecule-140 (NCAM-140), integrin ß1 and N-cadherin. The results showed that TH mRNA expression was positively correlated with both Ret and N-cadherin protein, while there was no correlation with NCAM-140 and integrin ß1; TH protein expression was correlated with all of these transmembrane molecules. These data suggested that the expression of either TH mRNA or TH protein was subject to the mediation of different transmembrane receptor combinations of GDNF.
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Regulación del Desarrollo de la Expresión Génica/fisiología , Receptores del Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Neuronas/metabolismo , Sustancia Negra , Tirosina 3-Monooxigenasa/metabolismo , Factores de Edad , Análisis de Varianza , Animales , Animales Recién Nacidos , Cadherinas/metabolismo , Moléculas de Adhesión Celular Neuronal/metabolismo , Recuento de Células/métodos , Embrión de Mamíferos , Receptores del Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Integrina beta1/metabolismo , Proteínas Proto-Oncogénicas c-ret/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Estadística como Asunto , Sustancia Negra/citología , Sustancia Negra/embriología , Sustancia Negra/crecimiento & desarrollo , Tirosina 3-Monooxigenasa/genéticaRESUMEN
Insulin-like growth factor I (IGF-I) plays an important role in regulating gonad function, which is essential for normal reproduction in animals, especially in sexual receptivity and reproductive behavior. In this study, a cDNA encoding Amur tiger (Panthera tigris altaica) IGF-I was isolated from liver total RNA using RT-PCR. The IGF-I cDNA of Amur tiger (ATIGF-I) was highly homologous to that of other animals, 84.8% to rat, 93.7% to human and horse. Alignment analysis showed that the cysteine residues and many amino acid residues of putative mature ATIGF-I are highly conserved in mammalian species, confirming the high sequence homology observed in other species. DNA encoding the mature ATIGF-I peptide was ligated with pET-DsbA expression vector and highly expressed in Escherichia coli BL21 with IPTG induction. The recombinant proteins expressed existed mostly in the soluble protein fraction, and were purified with metal affinity resins. Western blotting confirmed that the recombinant proteins reacted with antibodies against IGF-I. The results obtained here should be useful for large-scale production of biological active ATIGF-I protein, as well as for further research on growth, development, and reproduction in the Amur tiger. Tissue specific expression of ATIGF-I mRNA in the Amur tiger was examined by reverse transcription-polymerase chain reaction (RT-PCR), The major ATIGF-I mRNA expression tissue was the liver, while medium signals were found in the uterus, ovary, and pituitary, and minor signals were detected in various tissues including the heart, spleen, pancreas, and kidney. The results indicate that IGF-I might play an important role in the reproductive system and in cub development in the Amur tiger.