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1.
J Sci Food Agric ; 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31901140

RESUMO

BACKGROUND: Walnut (Juglans regia L.) is one of the most widely cultivated nuts. Walnut milk beverage is very popular in China due to its nutritional value. However, adulterated walnut milk ingredients have been detected in the Chinese market. Peanut and soybean are sold at much lower prices than walnut and are reported to be commonly used for adulteration in the industrial chain of walnut milk production. The purpose of this study is therefore to develop an accurate and efficient method for detecting the authenticity of the raw materials used in walnut milk beverage. RESULTS: DNA barcoding and high-resolution melting (HRM) analyses were used to identify common adulterated raw ingredients such as peanut and soybean in commercial walnut milk beverage samples. The chloroplast psbA-trnH gene was used for sequencing, and HRM analysis was performed. We also prepared experimental mixtures, in the laboratory, with different quantities of walnut, peanut, and soybean. High-resolution melting analysis of the experimental mixtures clearly distinguished all of them. The results revealed that most of the walnut milk beverage samples fell in the same cluster of walnut species. Several samples fell in the peanut cluster, confirming that they were adulterated products. CONCLUSION: The results revealed that HRM analysis based on the psbA-trnH barcode sequence can be used to identify raw ingredients in walnut milk beverages. © 2020 Society of Chemical Industry.

2.
PLoS One ; 14(12): e0226752, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31887119

RESUMO

Presently, concern regarding the effects of selenium (Se) on the environment and organisms worldwide is increasing. Too much Se in the soil is harmful to plants. In this study, Illumina RNA sequencing and the untargeted metabolome of control and Se-treated celery seedlings were analyzed. In total, 297,911,046 clean reads were obtained and assembled into 150,218 transcripts (50,876 unigenes). A total of 36,287 unigenes were annotated using different databases. Additionally, 8,907 differentially expressed genes, including 5,319 up- and 3,588 downregulated genes, were identified between mock and Se-treated plants. "Phenylpropanoid biosynthesis" was the most enriched KEGG pathway. A total of 24 sulfur and selenocompound metabolic unigenes were differentially expressed. Furthermore, 1,774 metabolites and 237 significant differentially accumulated metabolites were identified using the untargeted metabolomic approach. We conducted correlation analyses of enriched KEGG pathways of differentially expressed genes and accumulated metabolites. Our findings suggested that candidate genes and metabolites involved in important biological pathways may regulate Se tolerance in celery. The results increase our understanding of the molecular mechanism responsible for celery's adaptation to Se stress.

3.
IEEE Trans Cybern ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31751264

RESUMO

Most memristor-based Pavlov associative memory neural networks strictly require that only simultaneous food and ring appear to generate associative memory. In this article, the time delay is considered, in order to form associative memory when the food stimulus lags behind the ring stimulus for a certain period of time. In addition, the rate of learning can be changed with the length of time between the ring stimulus and food stimulus. A memristive neural network circuit that can realize Pavlov associative memory with time delay is designed and verified by the simulation results. The designed circuit consists of a synapse module, a voltage control module, and a time-delay module. The functions, such as learning, forgetting, fast learning, slow forgetting, and time-delay learning, are implemented by the circuit. The Pavlov associative memory neural network with time-delay learning provides a reference for further development of the brain-like systems.

4.
Mol Ther Methods Clin Dev ; 15: 133-148, 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31660416

RESUMO

We have demonstrated safe and effective subretinal readministration of recombinant adeno-associated virus serotype (rAAV) to the contralateral eye in large animals and humans even in the setting of preexisting neutralizing antibodies (NAbs). Readministration of AAV to the same retina may be desirable in order to treat additional areas of the retina not targeted initially or to boost transgene expression levels at a later time point. To better understand the immune and structural consequences of subretinal rAAV readministration to the same eye, we administered bilateral subretinal injections of rAAV2-hRPE65v2 to three unaffected non-human primates (NHPs) and repeated the injections in those same eyes 2 months later. Ophthalmic exams and retinal imaging were performed after the first and second injections. Peripheral blood monocytes, serum, and intraocular fluids were collected at baseline and post-injection time points to characterize the cellular and humoral immune responses. Histopathologic and immunohistochemical studies were carried out on the treated retinas. Ipsilateral readministration of AAV2-hRPE65v2 in NHPs did not threaten the ocular or systemic health through the time span of the study. The repeat injections were immunologically and structurally well tolerated, even in the setting of preexisting serum NAbs. Localized structural abnormalities confined to the outer retina and retinal pigmented epithelium (RPE) after readministration of the treatment do not differ from those observed after single or contralateral administration of an AAV carrying a non-therapeutic transgene in NHPs and were not observed in a patient treated with the nearly identical, FDA-approved, AAV2-hRPE65v2 vector (voretigene neparvovec-rzyl), suggesting NHP-specific abnormalities.

5.
Chem Commun (Camb) ; 55(88): 13283-13286, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31626254

RESUMO

Developing efficient and durable catalysts for methanol oxidation is of great significance for direct methanol fuel cells. Herein, we realized the deposition of ultra-trace Pt nanoparticles by atomic layer deposition (ALD) onto a three-dimensional (3D) titanium nitride (TiN) nanowire array grown on carbon cloth (CC), in which the 3D TiN nanowires provide a stable platform for the Pt nanoparticles, besides the inherent properties of high corrosion resistance and conductivity. Owing to the superior characteristics of the 3D TiN nanostructure as the support material and the strong interaction between Pt and TiN, the Pt nanoparticles on the TiN nanowire array show an enhanced electrocatalytic activity toward methanol oxidation compared to a commercial Pt/C catalyst. This work provides an effective strategy to fabricate 3D high-performance electrocatalysts for future energy applications.

6.
Technol Cancer Res Treat ; 18: 1533033819871300, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31564215

RESUMO

Non-coding RNAs, originally considered junk gene products, have taken center stage in view of their significant involvement in a spectrum of biological processes during human development, thereby offering novel therapeutic targets for improvement of treatment options. Accumulating evidence has demonstrated non-coding RNA dysfunction across various human cancers. In particular, microRNAs have emerged as key regulatory molecules in cancer biology. MicroRNAs are noninvasive, readily accessible biomarkers that can be effectively applied for diagnosis and prognosis of different tumor types, including colon cancer. In this study, we reanalyzed the available data with bioinformatics tools to identify differentially expressed microRNAs in colon cancer cells. The top 3 upregulated microRNAs (miR-10, miR-199, and miR-122) in colon cancer cells were further validated in tissues of clinical patients via reverse transcription-quantitative polymerase chain reaction. Our results showed that miR-122 significantly promotes the proliferation and invasion ability of SW480 and SW620 cells through inhibition of Aldolase, Fructose-Bisphosphate A (ALDOA) expression. We further summarized recent advances in our understanding of the functional relevance of microRNAs in cancer development and discussed the possible implications of specific microRNAs in colon cancer. This study extends our knowledge of microRNA involvement in colon cancer biology and presents novel candidates for the development of attractive therapeutic strategies.

7.
Onco Targets Ther ; 12: 5793-5803, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31410024

RESUMO

Background: ASAP3 was first identified as a protein that promotes cell proliferation in hepatocellular carcinoma and later reported to be an Arf6-specific Arf GTPase-activating protein that regulates cell migration associated with cancer cell invasion. Materials and methods: Patients and tissue samples were from Hubei Cancer Hospital, human lung adenocarcinoma cell lines were obtained from the cell bank of the Chinese Academy of Science, nude mice (BALB/c nu/nu) were obtained from Shanghai SLAC Laboratory Animal Co. Ltd. Our methods contained immunohistochemistry, Western blotting, reverse-transcription polymerase chain reaction (RT-PCR), immunofluorescence staining, stable transfection of lung adenocarcinoma cells, chromatin immunoprecipitation (CHIP) and luciferase assay, wound healing and cell migration assay. Results: In this study, we show that ASAP3 overexpression promotes migration and invasiveness in human lung adenocarcinoma cells and accelerates tumor progression in a xenograft mouse model. In patient tumor samples, ASAP3 overexpression was significantly associated with lymph node metastasis and reduced overall survival. We also show that ASAP3 expression is induced under hypoxic conditions through hypoxia-inducible factor 1α (HIF-1α), which binds directly to HER1 or/and HER2 (hypoxia response element) in the ASAP3 promoter. ASAP3 overexpression counteracts the inhibition of lung adenocarcinoma progression caused by HIF-1α knockdown both in vitro and in vivo. Conclusion: Our results identify ASAP3 as a downstream target of HIF-1α that is critical for metastatic progression in lung adenocarcinoma.

8.
Cells ; 8(6)2019 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-31181634

RESUMO

Intramuscular fat (IMF) is the most important evaluating indicator of chicken meat quality, the content of which is positively correlated with tenderness, flavor, and succulence of the meat. Chicken IMF deposition process is regulated by many factors, including genetic, nutrition, and environment. Although large number of omics' studies focused on the IMF deposition process, the molecular mechanism of chicken IMF deposition is still poorly understood. In order to study the role of miRNAs in chicken intramuscular adipogenesis, the intramuscular adipocyte differentiation model (IMF-preadipocytes and IMF-adipocytes) was established and subject to miRNA-Seq. A total of 117 differentially expressed miRNAs between two groups were obtained. Target genes prediction and functional enrichment analysis revealed that eight pathways involved in lipid metabolism related processes, such as fatty acid metabolism and fatty acid elongation. Meanwhile a putative miRNA, gga-miR-18b-3p, was identified be served a function in the intramuscular adipocyte differentiation. Luciferase assay suggested that the gga-miR-18b-3p targeted to the 3'UTR of ACOT13. Subsequent functional experiments demonstrated that gga-miR-18b-3p acted as an inhibitor of intramuscular adipocyte differentiation by targeting ACOT13. Our findings laid a new theoretical foundation for the study of lipid metabolism, and also provided a potential target to improve the meat quality in the poultry industry.


Assuntos
Diferenciação Celular , MicroRNAs/metabolismo , Tioléster Hidrolases/metabolismo , Regiões 3' não Traduzidas , Adipócitos/citologia , Adipócitos/metabolismo , Adipogenia , Animais , Antagomirs/metabolismo , Sequência de Bases , Galinhas , Biblioteca Gênica , Humanos , Metabolismo dos Lipídeos/genética , Peroxidação de Lipídeos , Redes e Vias Metabólicas/genética , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Alinhamento de Sequência , Tioléster Hidrolases/antagonistas & inibidores , Tioléster Hidrolases/genética
9.
BMC Genomics ; 20(1): 381, 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31096913

RESUMO

BACKGROUND: Salinization seriously threatens land use efficiency and crop yields across the world. Understanding the mechanisms plants use to protect against salt stress will help breeders develop salt-tolerant vegetable crops. Okra (Abelmoschus esculentus L.) is an important vegetable crop of the mallow family, which is now cultivated in warm regions worldwide. To understand the effects of salt stress on the protein level of okra, a comparative proteomic analysis of okra seedlings grown in the presence of 0 or 300 mmol L- 1 NaCl treatment was performed using an integrated approach of Tandem Mass Tag labeling and LC-MS/MS integrated approach. RESULTS: A total of 7179 proteins were identified in this study, for which quantitative information was available for 5774 proteins. In the NaCl/control comparison group, there were 317 differentially expressed proteins (DEPs), of which 165 proteins were upregulated and 152 proteins downregulated in the presence of NaCl. Based on the above data, we carried out a systematic bioinformatics analysis of proteins with information, including protein annotation, domain characteristics, functional classification, and pathway enrichment. Enriched gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the DEPs were most strongly associated with "response to stress" and "protein processing in endoplasmic reticulum". Furthermore, several heat shock proteins were identified as DEPs. CONCLUSIONS: This information provides a reference direction for further research on the okra proteome in the downstream of the salt stress response, with our data revealing that the responses of okra to salt stress involves by various pathways.


Assuntos
Abelmoschus/metabolismo , Biologia Computacional/métodos , Proteínas de Plantas/metabolismo , Proteômica/métodos , Estresse Salino , Plântula/metabolismo , Abelmoschus/crescimento & desenvolvimento , Mapas de Interação de Proteínas , Plântula/crescimento & desenvolvimento
10.
Int J Mol Sci ; 20(6)2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30871161

RESUMO

Soil salinization is a major environmental stresses that seriously threatens land use efficiency and crop yields worldwide. Although the overall response of plants to NaCl has been well studied, the contribution of protein phosphorylation to the detoxification and tolerance of NaCl in okra (Abelmoschus esculentus L.) seedlings is unclear. The molecular bases of okra seedlings' responses to 300 mM NaCl stress are discussed in this study. Using a combination of affinity enrichment, tandem mass tag (TMT) labeling and high-performance liquid chromatography⁻tandem mass spectrometry analysis, a large-scale phosphoproteome analysis was performed in okra. A total of 4341 phosphorylation sites were identified on 2550 proteins, of which 3453 sites of 2268 proteins provided quantitative information. We found that 91 sites were upregulated and 307 sites were downregulated in the NaCl/control comparison group. Subsequently, we performed a systematic bioinformatics analysis including gene ontology annotation, domain annotation, subcellular localization, and Kyoto Encyclopedia of Genes and Genomes pathway annotation. The latter revealed that the differentially expressed proteins were most strongly associated with 'photosynthesis antenna proteins' and 'RNA degradation'. These differentially expressed proteins probably play important roles in salt stress responses in okra. The results should help to increase our understanding of the molecular mechanisms of plant post-translational modifications in response to salt stress.


Assuntos
Abelmoschus/metabolismo , Fosforilação/fisiologia , Proteoma/metabolismo , Estresse Salino/fisiologia , Plântula/metabolismo , Abelmoschus/genética , Biologia Computacional/métodos , Regulação para Baixo/genética , Regulação para Baixo/fisiologia , Ontologia Genética , Genes de Plantas/genética , Genes de Plantas/fisiologia , Genoma de Planta/genética , Genoma de Planta/fisiologia , Fosforilação/genética , Processamento de Proteína Pós-Traducional/genética , Processamento de Proteína Pós-Traducional/fisiologia , Proteoma/genética , Proteômica/métodos , Estresse Salino/genética , Plântula/genética , Regulação para Cima/genética , Regulação para Cima/fisiologia
11.
Front Genet ; 10: 42, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30804984

RESUMO

Poultry meat quality is affected by many factors, among which intramuscular fat (IMF) is predominant. IMF content affects the tenderness, juiciness, and flavor of chicken. An increasing number of studies are focusing on the functions of lncRNAs in adipocyte differentiation. However, little is known about lncRNAs associated with intramuscular adipocyte differentiation. In the present study, we focused on an up-regulated lncRNA during intramuscular adipogenetic differentiation, which we named intramuscular fat-associated long non-coding RNA (IMFNCR). IMFNCR promotes intramuscular adipocyte differentiation. In-depth analyses showed that IMFNCR acts as a molecular sponge for miR-128-3p and miR-27b-3p and that PPARG is a direct target of miR-128-3p and miR-27b-3p in chicken. High-fat and high-protein diet inhibited chicken IMFNCR level in vivo. Moreover, IMFNCR level was positively correlated with PPARG mRNA level in chicken breast muscle tissues, a vital corollary to ceRNA function. Altogether, our research showed that IMFNCR acts as a ceRNA to sequester miR-128-3p and miR-27b-3p, leading to heightened PPARG expression, and thus promotes intramuscular adipocyte differentiation. Taken together, our findings may contribute to a more thorough understanding of chicken IMF deposition and the improvement of poultry meat quality.

12.
Gene ; 685: 106-113, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30389563

RESUMO

Intramuscular fat (IMF) has significant effects on the tenderness, juiciness, and flavor of chicken, which are important determinants of poultry meat quality. Although many studies have focused on microRNAs (miRNAs) involved in adipogenesis, little is known about miRNAs associated with poultry IMF deposition or intramuscular adipocyte differentiation. Bioinformatic analysis identified mitochondrial glycerol­3­phosphate acyltransferase (GPAM) as a putative target of miR-223. To explore the role of miR-223 in the process of chicken IMF deposition, loss and gain of function experiments were performed in primary intramuscular preadipocytes using miR-223 mimics, miR-223 inhibitor, and si-GPAM. Our results showed that miR-223 is significantly down-regulated in the breast muscle tissues of Gushi hens at the later-laying period in comparison with hens at the pre-laying period. Using qRT-PCR, we found that miR-223 expression in chicken tissues and intramuscular adipocytes correlates negatively with GPAM expression. Cell transfection experiments suggest that miR-223 inhibits intramuscular adipocyte differentiation via targeting GPAM. Experiments using a dual luciferase reporter system show that GPAM is a direct target of miR-223. Taken together, our results support the hypothesis that miR-223 regulates intramuscular fat deposition in chickens.


Assuntos
Adipócitos/citologia , Adipócitos/metabolismo , Diferenciação Celular/genética , Regulação da Expressão Gênica no Desenvolvimento , Glicerol-3-Fosfato O-Aciltransferase/genética , MicroRNAs/genética , Animais , Interferência de RNA
13.
Plant Physiol ; 177(4): 1691-1703, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29925586

RESUMO

MicroRNAs (miRNAs) are 20- to 24-nucleotide small noncoding RNAs that regulate gene expression in eukaryotic organisms. Several plant miRNAs, such as miR166, have vital roles in plant growth, development and responses to environmental stresses. One such environmental stress encountered by crop plants is exposure to cadmium (Cd), an element highly toxic to most organisms, including humans and plants. In this study, we analyzed the role of miR166 in Cd accumulation and tolerance in rice (Oryza sativa). The expression levels of miR166 in both root and leaf tissues were significantly higher in the reproductive stage than in the seedling stage in rice. The expression of miR166 in the roots of rice seedlings was reduced after Cd treatment. Overexpression of miR166 in rice improved Cd tolerance, a result associated with the reduction of Cd-induced oxidative stress in transgenic rice plants. Furthermore, overexpression of miR166 reduced both Cd translocation from roots to shoots and Cd accumulation in the grains. miR166 targets genes encoding the class-III homeodomain-Leu zipper (HD-Zip) family proteins in plants. In rice, HOMEODOMAIN CONTAINING PROTEIN4 (OsHB4) gene (Os03g43930), which encodes an HD-Zip protein, was up-regulated by Cd treatment but down-regulated by overexpression of miR166 in transgenic rice plants. Overexpression of OsHB4 increased Cd sensitivity and Cd accumulation in the leaves and grains of transgenic rice plants. By contrast, silencing OsHB4 by RNA interference enhanced Cd tolerance in transgenic rice plants. These results indicate a critical role for miR166 in Cd accumulation and tolerance through regulation of its target gene, OsHB4, in rice.


Assuntos
Cádmio/farmacocinética , MicroRNAs/genética , Oryza/efeitos dos fármacos , Oryza/genética , Cádmio/toxicidade , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Oryza/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Interferência de RNA
14.
Cell Physiol Biochem ; 46(6): 2421-2433, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29742492

RESUMO

BACKGROUND/AIMS: Poultry meat quality is affected by many factors, among which intramuscular fat (IMF) is predominant. IMF content affects the tenderness, juiciness, and favor of chicken. An increasing number of studies are focusing on the functions of microRNAs (miRNAs) during the adipogenic process. However, little is known about miRNAs associated with poultry IMF deposition, especially intramuscular adipocyte differentiation. METHODS: The IMF content of two physiological stages was measured, and miRNA-Seq and RNA-Seq data were integrated and analyzed. A chicken intramuscular adipocyte cell differentiation model was constructed. A luciferase reporter assay, miRNA overexpression, and Oil Red O staining were used to confirm the targets of gga-miR-140-5p. RESULTS: Our results showed that late-laying-period hens, which had a higher IMF content, exhibited lower global expression levels of miRNAs than juvenile hens. A total of 104 differentially expressed (DE) miRNAs were identified between the two groups. Integrated analysis of differentially expressed genes and DE miRNAs identified a total of 378 miRNA-mRNA pairs. Functional enrichment analysis revealed that these intersecting genes are involved in ubiquitin-mediated proteolysis, the peroxisome proliferator-activated receptor signaling pathway, glycerophospholipid metabolism, and fatty acid elongation and degradation pathways. Furthermore, we demonstrated that gga-miR-140-5p promoted intramuscular adipocyte differentiation via targeting retinoid X receptor gamma. CONCLUSION: Our findings may contribute to a more thorough understanding of chicken IMF deposition and the improvement of poultry meat quality.


Assuntos
Adipogenia , Galinhas/genética , Carne , MicroRNAs/genética , Transcriptoma , Animais , Galinhas/metabolismo , Feminino , Qualidade dos Alimentos , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Carne/análise , Redes e Vias Metabólicas , Músculos/metabolismo , RNA Mensageiro/genética
15.
Sensors (Basel) ; 18(5)2018 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-29748508

RESUMO

Navigational assistance aims to help visually-impaired people to ambulate the environment safely and independently. This topic becomes challenging as it requires detecting a wide variety of scenes to provide higher level assistive awareness. Vision-based technologies with monocular detectors or depth sensors have sprung up within several years of research. These separate approaches have achieved remarkable results with relatively low processing time and have improved the mobility of impaired people to a large extent. However, running all detectors jointly increases the latency and burdens the computational resources. In this paper, we put forward seizing pixel-wise semantic segmentation to cover navigation-related perception needs in a unified way. This is critical not only for the terrain awareness regarding traversable areas, sidewalks, stairs and water hazards, but also for the avoidance of short-range obstacles, fast-approaching pedestrians and vehicles. The core of our unification proposal is a deep architecture, aimed at attaining efficient semantic understanding. We have integrated the approach in a wearable navigation system by incorporating robust depth segmentation. A comprehensive set of experiments prove the qualified accuracy over state-of-the-art methods while maintaining real-time speed. We also present a closed-loop field test involving real visually-impaired users, demonstrating the effectivity and versatility of the assistive framework.


Assuntos
Auxiliares Sensoriais , Pessoas com Deficiência Visual/reabilitação , Dispositivos Eletrônicos Vestíveis , Percepção de Profundidade , Humanos , Interpretação de Imagem Assistida por Computador , Reconhecimento Automatizado de Padrão , Caminhada
16.
Medicine (Baltimore) ; 97(21): e10681, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29794744

RESUMO

RATIONALE: This combination of fluticasone propionate (FP) and the long-acting ß2-agonist salmeterol (Salm) can control the symptoms of asthma and COPD better than FP or Salm on their own and better than the combination of inhaled corticosteroids plus montelukast. FP/Salm has been shown to control symptoms of asthma and COPD better than a double dose of inhaled steroids. The patient in our report had a history of COPD, and suffered relapse of RP when given only steroids. It is possible that COPD history helps explain this patient's more difficult treatment course. Therefore, this combination may be more effective than inhaled steroids for patients with a history of COPD. PATIENT CONCERS: This patient suffered adverse reactions triggered by methylprednisolone: weight gain, hyperglycaemia and sleep disturbance after more than two months of intravenous and oral prednisolone. These reactions disappeared when we switched the patients to FP/Salm maintenance therapy. DIAGNOSES: The patient underwent upper right lobectomy in September 2011. Immunohistochemistry indicated low squamous cell differentiation, and he was diagnosed with stage IIB disease (T2N1M0) according to the Union for International Cancer Control (UICC) (7th edition).One month after repeat radiotherapy, the patient experienced fever (37.6°C), cough, chest distress and shortness of breath. We performed serologic tests, laboratory tests for procalcitonin and C-reactive protein, as well as sputum and blood cultures to rule out bacterial infection. Chest CT showed consolidation with air bronchogram in the hilum of the right lung and ground-glass densities in the right lower lobe and left upper lobe. These radiographic signs are typical of RP. Since the patient required oxygen, he was diagnosed with grade III RP. INTERVENTIONS: After the patinet was diagnosed with grade III RP. The patient was immediately prescribed oxygen, anti-infectives for prophylaxis, treatments to facilitate expectoration and prevent asthma, and most importantly, intravenous methylprednisone at an initial dose of 60  per day. And we cut the steroid dose in half every one week when the patient's symptoms improved obviously, and the patchy shadow on the chest radiograph sharply reduced. Then we give him FP (500 mg)/Salm (50 mg) twice daily for two months. Then the dose was halved for an additional two months. OUTCOMES: The patient showed no signs of tumor or RP relapse by the last follow-up in March 2018. LESSONS: This maintenance therapy of FP/Salm for patient with grade III RP may help avoid relapse when steroid therapy is tapered, particularly for patients with a history of COPD. It may also reduce risk of steroid-associated adverse effects. Based on the results observed with our patient, we intend to design a prospective trial to assess the efficacy of FP/Salm when used as preventive treatment for patients at high risk of RP, and when used as maintenance treatment for patients with grade III RP.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Combinação Fluticasona-Salmeterol/uso terapêutico , Neoplasias Pulmonares/terapia , Pneumonite por Radiação/tratamento farmacológico , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Humanos , Pulmão/patologia , Pulmão/efeitos da radiação , Masculino , Metilprednisolona/efeitos adversos , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Pneumonectomia , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Pneumonite por Radiação/diagnóstico , Tomografia Computadorizada por Raios X , Resultado do Tratamento
17.
Mol Ther ; 26(6): 1581-1593, 2018 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-29673930

RESUMO

Most genetically distinct inherited retinal degenerations are primary photoreceptor degenerations. We selected a severe early onset form of Leber congenital amaurosis (LCA), caused by mutations in the gene LCA5, in order to test the efficacy of gene augmentation therapy for a ciliopathy. The LCA5-encoded protein, Lebercilin, is essential for the trafficking of proteins and vesicles to the photoreceptor outer segment. Using the AAV serotype AAV7m8 to deliver a human LCA5 cDNA into an Lca5 null mouse model of LCA5, we show partial rescue of retinal structure and visual function. Specifically, we observed restoration of rod-and-cone-driven electroretinograms in about 25% of injected eyes, restoration of pupillary light responses in the majority of treated eyes, an ∼20-fold decrease in target luminance necessary for visually guided behavior, and improved retinal architecture following gene transfer. Using LCA5 patient-derived iPSC-RPEs, we show that delivery of the LCA5 cDNA restores lebercilin protein and rescues cilia quantity. The results presented in this study support a path forward aiming to develop safety and efficacy trials for gene augmentation therapy in human subjects with LCA5 mutations. They also provide the framework for measuring the effects of intervention in ciliopathies and other severe, early-onset blinding conditions.


Assuntos
Cegueira/metabolismo , Cegueira/terapia , Dependovirus/genética , Terapia Genética/métodos , Animais , Eletrorretinografia , Proteínas do Olho/genética , Proteínas do Olho/metabolismo , Feminino , Humanos , Amaurose Congênita de Leber/metabolismo , Amaurose Congênita de Leber/terapia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo
18.
J Agric Food Chem ; 65(29): 5860-5867, 2017 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-28657742

RESUMO

MicroRNAs (miRNAs) are 21-24-nucleotide-long RNAs that function as ubiquitous post-transcriptional regulators of gene expression in plants and animals. Increasing evidence points to the important role of miRNAs in plant responses to abiotic and biotic stresses. Cadmium (Cd) is a nonessential heavy metal highly toxic to plants. Although many genes encoding metal transporters have been characterized, the mechanisms for the regulation of the expression of the heavy-metal transporter genes are largely unknown. In this study, we found that the expression of miR268 in rice was significantly induced under Cd stress. By contrast, expression of natural resistance-associated macrophage protein 3 (NRAMP3), a target gene of miR268, was dramatically decreased by Cd treatment. Overexpression of miR268 inhibited rice seedling growth under Cd stress. The transgenic miR268-overexpressing plant leaves contained increased levels of hydrogen peroxide and malondialdehyde, and their seedlings accumulated increased levels of Cd when compared to those in wild-type plants. These results indicate that miR268 acts as a negative regulator of rice's tolerance to Cd stress. Thus, miRNA-guided regulation of gene expression plays an important role in plant responses to heavy-metal stress.


Assuntos
Cádmio/metabolismo , MicroRNAs/metabolismo , Oryza/metabolismo , Plantas Geneticamente Modificadas/metabolismo , RNA de Plantas/metabolismo , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Regulação da Expressão Gênica de Plantas , MicroRNAs/genética , Oryza/genética , Oryza/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , RNA de Plantas/genética , Plântula/genética , Plântula/crescimento & desenvolvimento , Plântula/metabolismo
19.
Plant Cell Rep ; 36(2): 235-242, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27933379

RESUMO

KEY MESSAGE: We review and introduce recent studies on RLK s involved in the abiotic stress response and provide insights into potential regulatory mechanisms for alleviating abiotic stress. Abiotic stresses are important factors affecting plant growth and development, resulting in crop production reduction and even plant death. To survive, plants utilize different mechanisms to respond and adapt to continuously changing environmental factors. Understanding of the molecular mechanisms of plant response to various stresses will aid in improving tolerance of plants to abiotic stress through genetic engineering, which would greatly promote the development of modern agriculture. RLKs, the largest gene family in plants, play critical roles in the regulation of plant developmental processes, signaling networks and disease resistance. Many RLKs have been shown to be involved in abiotic stress responses, including the abscisic acid response, calcium signaling and antioxidant defense. This review summarizes recent studies on RLKs involved in plant responses to abiotic stress, including drought, salt, cold, toxic metals/metalloids and other stresses, and emphasizes the upstream and downstream factors in RLK signal transduction pathways under abiotic stress.


Assuntos
Plantas/enzimologia , Proteínas Quinases/metabolismo , Receptores de Superfície Celular/metabolismo , Secas , Cloreto de Sódio/farmacologia , Estresse Fisiológico/genética
20.
Lancet ; 388(10045): 661-72, 2016 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-27375040

RESUMO

BACKGROUND: Safety and efficacy have been shown in a phase 1 dose-escalation study involving a unilateral subretinal injection of a recombinant adeno-associated virus (AAV) vector containing the RPE65 gene (AAV2-hRPE65v2) in individuals with inherited retinal dystrophy caused by RPE65 mutations. This finding, along with the bilateral nature of the disease and intended use in treatment, prompted us to determine the safety of administration of AAV2-hRPE65v2 to the contralateral eye in patients enrolled in the phase 1 study. METHODS: In this follow-on phase 1 trial, one dose of AAV2-hRPE65v2 (1.5 × 10(11) vector genomes) in a total volume of 300 µL was subretinally injected into the contralateral, previously uninjected, eyes of 11 children and adults (aged 11-46 years at second administration) with inherited retinal dystrophy caused by RPE65 mutations, 1.71-4.58 years after the initial subretinal injection. We assessed safety, immune response, retinal and visual function, functional vision, and activation of the visual cortex from baseline until 3 year follow-up, with observations ongoing. This study is registered with ClinicalTrials.gov, number NCT01208389. FINDINGS: No adverse events related to the AAV were reported, and those related to the procedure were mostly mild (dellen formation in three patients and cataracts in two). One patient developed bacterial endophthalmitis and was excluded from analyses. We noted improvements in efficacy outcomes in most patients without significant immunogenicity. Compared with baseline, pooled analysis of ten participants showed improvements in mean mobility and full-field light sensitivity in the injected eye by day 30 that persisted to year 3 (mobility p=0.0003, white light full-field sensitivity p<0.0001), but no significant change was seen in the previously injected eyes over the same time period (mobility p=0.7398, white light full-field sensitivity p=0.6709). Changes in visual acuity from baseline to year 3 were not significant in pooled analysis in the second eyes or the previously injected eyes (p>0.49 for all time-points compared with baseline). INTERPRETATION: To our knowledge, AAV2-hRPE65v2 is the first successful gene therapy administered to the contralateral eye. The results highlight the use of several outcome measures and help to delineate the variables that contribute to maximal benefit from gene augmentation therapy in this disease. FUNDING: Center for Cellular and Molecular Therapeutics at The Children's Hospital of Philadelphia, Spark Therapeutics, US National Institutes of Health, Foundation Fighting Blindness, Institute for Translational Medicine and Therapeutics, Research to Prevent Blindness, Center for Advanced Retinal and Ocular Therapeutics, Mackall Foundation Trust, F M Kirby Foundation, and The Research Foundation-Flanders.


Assuntos
Cegueira/genética , Cegueira/terapia , Dependovirus , Terapia Genética/métodos , Mutação , Lobo Occipital/fisiopatologia , Visão Ocular , cis-trans-Isomerases/genética , Administração Oftálmica , Adolescente , Adulto , Idade de Início , Cegueira/patologia , Cegueira/fisiopatologia , Criança , Medicina Baseada em Evidências , Feminino , Seguimentos , Terapia Genética/efeitos adversos , Vetores Genéticos , Humanos , Injeções Intraoculares , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Células Fotorreceptoras Retinianas Cones/patologia , Células Fotorreceptoras Retinianas Bastonetes/patologia , Retratamento
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