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1.
J Biol Chem ; 299(10): 105219, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37660913

RESUMO

Rectal prolapse in serious inflammatory bowel disease is caused by abnormal reactions of the intestinal mucosal immune system. The circadian clock has been implicated in immune defense and inflammatory responses, but the mechanisms by which it regulates gut inflammation remain unclear. In this study, we investigate the role of the rhythmic gene Period2 (Per2) in triggering inflammation in the rectum and its contribution to the pathogenesis of rectal prolapse. We report that Per2 deficiency in mice increased susceptibility to intestinal inflammation and resulted in spontaneous rectal prolapse. We further demonstrated that PER2 was essential for the transcription of glycogen synthase 1 by interacting with the NF-κB p65. We show that the inhibition of Per2 reduced the levels of glycogen synthase 1 and glycogen synthesis in macrophages, impairing the capacity of pathogen clearance and disrupting the composition of gut microbes. Taken together, our findings identify a novel role for Per2 in regulating the capacity of pathogen clearance in macrophages and gut inflammation and suggest a potential animal model that more closely resembles human rectal prolapse.

2.
Mol Cancer ; 23(1): 34, 2024 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360682

RESUMO

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer with high aggressive phenotype and poor prognosis. Accumulating evidence suggests that circRNAs have been identified as pivotal mediators in cancers. However, the role of circRNAs in ccRCC progression remains elusive. METHODS: The differentially expressed circRNAs in 4 paired human ccRCC and adjacent noncancerous tissues ccRCC were screened using circRNA microarrays and the candidate target was selected based on circRNA expression level using weighted gene correlation network analysis (WGCNA) and the gene expression omnibus (GEO) database. CircPDHK1 expression in ccRCC and adjacent noncancerous tissues (n = 148) were evaluated along with clinically relevant information. RT-qPCR, RNase R digestion, and actinomycin D (ActD) stability test were conducted to identify the characteristics of circPDHK1. The subcellular distribution of circPDHK1 was analyzed by subcellular fractionation assay and fluorescence in situ hybridization (FISH). Immunoprecipitation-mass spectrometry (IP-MS) and immunofluorescence (IF) were employed to evaluate the protein-coding ability of circPDHK1. ccRCC cells were transfected with siRNAs, plasmids or lentivirus approach, and cell proliferation, migration and invasion, as well as tumorigenesis and metastasis in nude mice were assessed to clarify the functional roles of circPDHK1 and its encoded peptide PDHK1-241aa. RNA-sequencing, western blot analysis, immunoprecipitation (IP) and chromatin immunoprecipitation (ChIP) assays were further employed to identify the underlying mechanisms regulated by PDHK1-241aa. RESULTS: CircPDHK1 was upregulated in ccRCC tissues and closely related to WHO/ISUP stage, T stage, distant metastasis, VHL mutation and Ki-67 levels. CircPDHK1 had a functional internal ribosome entry site (IRES) and encoded a novel peptide PDHK1-241aa. Functionally, we confirmed that PDHK1-241aa and not the circPDHK1 promoted the proliferation, migration and invasion of ccRCC. Mechanistically, circPDHK1 was activated by HIF-2A at the transcriptional level. PDHK1-241aa was upregulated and interacted with PPP1CA, causing the relocation of PPP1CA to the nucleus. This thereby inhibited AKT dephosphorylation and activated the AKT-mTOR signaling pathway. CONCLUSIONS: Our data indicated that circPDHK1-encoded PDHK1-241aa promotes ccRCC progression by interacting with PPP1CA to inhibit AKT dephosphorylation. This study provides novel insights into the multiplicity of circRNAs and highlights the potential use of circPDHK1 or PDHK1-241aa as a therapeutic target for ccRCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Animais , Camundongos , Humanos , Carcinoma de Células Renais/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Circular/genética , Camundongos Nus , Hibridização in Situ Fluorescente , Linhagem Celular Tumoral , Transdução de Sinais/genética , Neoplasias Renais/genética , Serina-Treonina Quinases TOR/metabolismo , Proliferação de Células/genética , Peptídeos/genética , Regulação Neoplásica da Expressão Gênica , Proteína Fosfatase 1/genética , Proteína Fosfatase 1/metabolismo
3.
J Nanobiotechnology ; 22(1): 340, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890722

RESUMO

Recently, the significant benefits of cancer immunotherapy for most cancers have been demonstrated in clinical and preclinical studies. However, the efficacy of these immunotherapies for gliomas is limited, owing to restricted drug delivery and insufficient immune activation. As drug carriers, exosomes offer the advantages of low toxicity, good biocompatibility, and intrinsic cell targeting, which could enhance glioma immunotherapy efficacy. However, a review of exosome-based drug delivery systems for glioma immunotherapy has not been presented. This review introduces the current problems in glioma immunotherapy and the role of exosomes in addressing these issues. Meanwhile, preparation and application strategies of exosome-based drug delivery systems for glioma immunotherapy are discussed, especially for enhancing immunogenicity and reversing the immunosuppressive tumor microenvironment. Finally, we briefly describe the challenges of exosome-based drug delivery systems in clinical translation. We anticipate that this review will guide the use of exosomes as drug carriers for glioma immunotherapy.


Assuntos
Sistemas de Liberação de Medicamentos , Exossomos , Glioma , Imunoterapia , Microambiente Tumoral , Humanos , Glioma/terapia , Glioma/imunologia , Glioma/tratamento farmacológico , Imunoterapia/métodos , Animais , Sistemas de Liberação de Medicamentos/métodos , Microambiente Tumoral/efeitos dos fármacos , Portadores de Fármacos/química , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/tratamento farmacológico
4.
Opt Express ; 31(22): 37197-37211, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-38017854

RESUMO

In this paper, a two-dimensional phased array antenna beamforming system based on mode diversity is demonstrated for the first time. The system uses few-mode long-period fiber gratings to excite different modes, and utilizes few-mode fiber Bragg gratings and 2 × 2 optical switches to control the propagation paths of optical signals, so as to realize the true time delay control of optical signals of different mode channels and complete the two-dimensional scanning of the beam. In order to prove the feasibility of the two-dimensional phased array antenna beamforming system based on mode diversity, we conduct experimental verification and performance testing of the system using optical switches to select the loop structures composed of the optical circulators. The far-field radiation patterns of 2 × 3 phased array antenna system of different frequencies are tested at different beam pointing angles. The experimental results are compared with the simulation results to demonstrate that the beam pointing angles have no squint. The beamforming system based on mode diversity takes modes as independent channels for the transmission of signals, and excites and processes signals of different modes in a single few-mode fiber core, which effectively reduces the volume and complexity of the optically controlled phased array radar system.

5.
Inorg Chem ; 62(20): 7853-7860, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37166382

RESUMO

The purification of natural gas and the removal of carbon dioxide from flue gases are crucial to economize precious resources and effectively relieve a series of environmental problems caused by global warming. Metal-organic framework (MOF) materials have demonstrated remarkable performance and benefits in the area of gas separation; however, obtaining materials with high gas capacity and selectivity simultaneously remains difficult. In addition, harsh synthesis conditions and solvent toxicity have been restricted in large-scale production and industrial application. Therefore, MOF-801(Zr/Ce/Hf) was created based on the green synthesis of the MOF-801 construction unit by altering the kinds of metal salts, and the impact of three metal nodes on the performance of gas adsorption and separation was demonstrated by contrasting the three MOFs. The results showed that MOF-801(Ce) has the best CO2 adsorption capacity (3.3 mmol/g at 298 K), which also was demonstrated with in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) results, CO2/CH4 (ideal adsorbed solution theory (IAST) = 13.28 at 298 K, 1 bar, CO2/CH4 = 1:1, v/v), and the separation performance of CO2/N2 (IAST = 57.46 at 298 K, 1 bar, CO2/N2 = 1:1, v/v) among the group. Green synthesis of MOF-801(Zr/Ce/Hf) is an ideal candidate for flue gas separation and methane purification because of its high regeneration capacity and strong cyclic stability.

6.
BMC Pregnancy Childbirth ; 23(1): 517, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37454102

RESUMO

BACKGROUND: This retrospective study aimed to investigate the most suitable endometrial thickness (EMT) on the day of embryo transfer that could reduce ectopic pregnancy rate (EPR) and improve clinical pregnancy rate (CPR) in fresh embryo transfer patients with early follicular phase long-acting regimen. METHODS: A total of 11,738 IVF/ICSI cycles, comprising 4,489 non-clinical pregnancies, 7,121 intrauterine pregnancies, and 128 ectopic pregnancy cycles after fresh embryo transfer, recorded between September 2017 and December 2020. Clinical pregnancy (CP) and ectopic pregnancy (EP) were the primary outcomes. Multivariate logistic regression was used to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI) for EP and CP. Patients were divided into three groups based on the EMT (6-10 mm, 11-15 mm, and 16-20 mm). CPR and EPR per millimeter of EMT were drawn into a line chart, and three groups were analyzed by Chi-square test. RESULTS: After controlling for potential confounders, EMT had a significant effect on CP (aOR = 1.07; 95% CI, 1.05-1.08; P = 0.00) and EP (aOR = 0.88; 95% CI, 0.82-0.94; P = 0.00). With the increase of EMT, CPR increased and EPR decreased. Pearson correlation coefficients were r = 0.708 (P = 0.00) and r =-0.558 (P = 0.03), respectively. Significant differenceswere detected in the CPRs and EPRs (all P = 0.00). The CPR in the 6-10 mm group (54.88%) was significantly lower than that in the 11-15 mm group (64.23%) and the 16-20 mm group (64.40%) (P = 0.00). The EPR in the 6-10 mm group (2.72%) was significantly higher than that in the other two groups (1.60% and 0.97%, P = 0.00). The difference in CPR and EPR between the 11-15 mm group and the 16-20 mm group was not statistically significant, which indicated that EMT ≥ 11 mm simultaneously reduced the EPR and increased the CPR. CONCLUSIONS: EMT was inversely proportional to EPR and directly proportional to CPR in fresh embryo transfer cycles. The EMT ≥ 11 mm on the day of embryo transfer could simultaneously achieve lower EPR and higher CPR. Accordingly, more attention should be given to the EMT of women who underwent ART treatment.


Assuntos
Endométrio , Gravidez Ectópica , Gravidez , Humanos , Feminino , Estudos Retrospectivos , Taxa de Gravidez , Endométrio/diagnóstico por imagem , Gravidez Ectópica/epidemiologia , Transferência Embrionária , Fertilização in vitro
7.
J Therm Biol ; 114: 103563, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37344025

RESUMO

Thermal burn injury is a severe and life-threatening form of trauma that presents a significant challenge to clinical therapy. Therapeutic hypothermia has been shown to be beneficial in various human pathologies. Adenosine triphosphate (ATP) induces a hypothermic state that resembles hibernation-like suspended animation in mammals. This study investigates the potential protective role of ATP-induced hypothermia in thermal burn injury. Male C57BL/6 mice underwent a sham procedure or third-degree burn, and ATP-induced hypothermia was applied immediately or 1 h after burn injury. Our results show that ATP-induced hypothermia significantly improved burn depth progression and reduced collagen degradation. Moreover, hypothermia induced by ATP alleviated burn-induced hyperinflammatory responses and oxidative stress. Metabolomic profiling revealed that ATP-induced hypothermia reversed the shifts of metabolic profiles of the skin in burn mice. In addition, ATP-induced hypothermia relieved nociceptive and inflammatory pain, as observed in the antinociceptive test. Our findings suggest that ATP-induced hypothermia attenuates burn injury and provides new insights into first-aid therapy after thermal burn injury.


Assuntos
Queimaduras , Hipotermia Induzida , Hipotermia , Animais , Masculino , Camundongos , Trifosfato de Adenosina , Queimaduras/complicações , Queimaduras/terapia , Hipotermia/terapia , Hipotermia Induzida/métodos , Mamíferos , Camundongos Endogâmicos C57BL , Dor
8.
BMC Bioinformatics ; 23(1): 7, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983358

RESUMO

BACKGROUND: Detecting pathogenic proteins is the origin way to understand the mechanism and resist the invasion of diseases, making pathogenic protein prediction develop into an urgent problem to be solved. Prediction for genome-wide proteins may be not necessarily conducive to rapidly cure diseases as developing new drugs specifically for the predicted pathogenic protein always need major expenditures on time and cost. In order to facilitate disease treatment, computational method to predict pathogenic proteins which are targeted by existing drugs should be exploited. RESULTS: In this study, we proposed a novel computational model to predict drug-targeted pathogenic proteins, named as M2PP. Three types of features were presented on our constructed heterogeneous network (including target proteins, diseases and drugs), which were based on the neighborhood similarity information, drug-inferred information and path information. Then, a random forest regression model was trained to score unconfirmed target-disease pairs. Five-fold cross-validation experiment was implemented to evaluate model's prediction performance, where M2PP achieved advantageous results compared with other state-of-the-art methods. In addition, M2PP accurately predicted high ranked pathogenic proteins for common diseases with public biomedical literature as supporting evidence, indicating its excellent ability. CONCLUSIONS: M2PP is an effective and accurate model to predict drug-targeted pathogenic proteins, which could provide convenience for the future biological researches.


Assuntos
Biologia Computacional , Preparações Farmacêuticas , Algoritmos , Proteínas
9.
J Biol Chem ; 297(1): 100846, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34058194

RESUMO

Hepatic gluconeogenesis is the major contributor to the hyperglycemia observed in both patients and animals with type 2 diabetes. The transcription factor FOXO1 plays a dominant role in stimulating hepatic gluconeogenesis. FOXO1 is mainly regulated by insulin under physiological conditions, but liver-specific disruption of Foxo1 transcription restores normal gluconeogenesis in mice in which insulin signaling has been blocked, suggesting that additional regulatory mechanisms exist. Understanding the transcriptional regulation of Foxo1 may be conducive to the development of insulin-independent strategies for the control of hepatic gluconeogenesis. Here, we found that elevated plasma levels of adenine nucleotide in type 2 diabetes are the major regulators of Foxo1 transcription. We treated lean mice with 5'-AMP and examined their transcriptional profiles using RNA-seq. KEGG analysis revealed that the 5'-AMP treatment led to shifted profiles that were similar to db/db mice. Many of the upregulated genes were in pathways associated with the pathology of type 2 diabetes including Foxo1 signaling. As observed in diabetic db/db mice, lean mice treated with 5'-AMP displayed enhanced Foxo1 transcription, involving an increase in cellular adenosine levels and a decrease in the S-adenosylmethionine to S-adenosylhomocysteine ratio. This reduced methylation potential resulted in declining histone H3K9 methylation in the promoters of Foxo1, G6Pc, and Pepck. In mouse livers and cultured cells, 5'-AMP induced expression of more FOXO1 protein, which was found to be localized in the nucleus, where it could promote gluconeogenesis. Our results revealed that adenine nucleotide-driven Foxo1 transcription is crucial for excessive glucose production in type 2 diabetic mice.


Assuntos
Diabetes Mellitus Tipo 2/genética , Proteína Forkhead Box O1/genética , Hiperglicemia/genética , Transcrição Gênica/genética , Nucleotídeos de Adenina/sangue , Animais , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Regulação da Expressão Gênica/genética , Gluconeogênese/genética , Glucose/metabolismo , Humanos , Hiperglicemia/sangue , Hiperglicemia/patologia , Insulina/genética , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos NOD
10.
Appl Microbiol Biotechnol ; 105(2): 769-787, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33404835

RESUMO

Levan, a type of ß (2→6)-linked fructan, is a promising biopolymer with distinct properties and extensive applications in the fields of food, pharmaceutical, cosmetics, etc. However, the commercial availability of levan is still limited due to the relatively high production costs. Here, a new Paenibacillus sp. strain FP01 was isolated and identified as an efficient fructan producer with high yield (around 89.5 g/L fructan was obtained under 180 g/L sucrose) and conversation rate (49.7%). The fructan named Plev was structurally characterized as a linear levan-type fructan with a molecular mass of 3.11 × 106 Da. Aqueous solutions of Plev exhibited a non-Newtonian behavior at concentrations 3-5%. Heating and chilling had no obvious effects on apparent viscosities of Plev solutions. Plev also had good rheological stabilities toward pH (3-11) and metal salts (Na+, K+, Ca2+, Mg2+). Microbiome and metabolome analysis showed that Plev intervention increased the abundance of beneficial bacteria and elevated the levels of short-chain fatty acids (SCFAs) in feces of mice. Taken together, Plev could be considered a potential thickener and prebiotic supplement in food industry.Key points• Paenibacillus sp. strain FP01 was identified as a high-efficient levan producer.• The levan Plev from FP01 exhibited good rheological properties and stabilities.• The in vivo prebiotic activities of linear levan were revealed.


Assuntos
Paenibacillus , Prebióticos , Animais , Suplementos Nutricionais , Fezes , Frutanos , Camundongos
11.
Appl Microbiol Biotechnol ; 105(19): 7439-7450, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34536104

RESUMO

Activating the defense response of plants by elicitors provides a promising method for biocontrol of pathogens. The homogeneous octaose (RiOc) which was depolymerized from the succinoglycan Riclin was investigated as a novel elicitor to activate the immune system of potato (Solanum tuberosum L.). After foliar spray, RiOc quickly induced accumulation of reactive oxygen species in potato leaves in a dose-dependent manner. Transcriptomic analysis revealed that 2712 out of 30,863 genes were differentially expressed at the early stage (24 h), while 367 of them were changed later (72 h). Results from the transcriptome and quantitative RT-PCR suggested that RiOc was probably perceived by the receptor LYK3 and it activated the MKK2/3/9/-MPK6/7 signaling cascade and promoted the salicylic acid-mediated defense response. Meanwhile, RiOc changed the metabolome profile of potato leaves over time as demonstrated by the 1H NMR-based metabolomic analysis. Homeostasis of amino acids was affected at the early stage while the secondary metabolism was strengthened later. More importantly, RiOc significantly reduced the severity of potato leaf lesions caused by the late blight pathogen Phytophthora infestans. In conclusion, RiOc effectively improved the resistance of potato to P. infestans by eliciting the salicylic acid-mediated defense response. RiOc becomes a promising carbohydrate-based elicitor for biocontrol of plant pathogens. KEY POINTS: • Homogeneous Riclin octaose was a novel elicitor for biocontrol of plant pathogens. • Riclin octaose primed the salicylic acid-mediated defense response of potato plants. • Riclin octaose changed the metabolome profile of potato leaves over time.


Assuntos
Solanum tuberosum , Metabolômica , Polissacarídeos Bacterianos , Transcriptoma
12.
Diabetologia ; 62(11): 2106-2117, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31410531

RESUMO

AIMS/HYPOTHESIS: Plasma 5'-AMP (pAMP) is elevated in mouse models of type 2 diabetes. However, the metabolic regulatory role of adenine nucleotides in type 2 diabetes remains unclear. METHODS: Adenine nucleotides and their metabolites in plasma and liver were examined by HPLC. 1H NMR-based metabolomics analysis was performed to explore the changes of metabolites in mouse models of type 2 diabetes. Na+/K+ ATPase and Na+/H+ exchanger activity were measured in response to adenine nucleotide metabolites. Human recombinant protein tyrosine phosphatase 1B (PTP1B) was used for enzyme kinetic assays. Protein binding assays were performed with microscale thermophoresis. The intracellular pH of hepatocyte AML12 cell lines was measured using the BCECF-AM method. We also analysed pAMP levels in participants with type 2 diabetes. RESULTS: Elevation of pAMP was a universal phenomenon in all mouse models of type 2 diabetes including db/db vs lean mice (13.9 ± 2.3 µmol/l vs 3.7 ± 0.9 µmol/l; p < 0.01), ob/ob vs lean mice (9.1 ± 2.0 µmol/l vs 3.9 ± 1.2 µmol/l; p < 0.01) and high-fat diet/streptozotocin-induced vs wild-type mice (6.6 ± 1.5 µmol/l vs 4.1 ± 0.9 µmol/l; p < 0.05); this elevation was required for the occurrence of hyperglycaemia in obese mice. 1H NMR-based metabolomics study following HPLC analysis revealed that the metabolite profile in wild-type mice treated with 5'-AMP was similar to that in db/db diabetic mice, especially the accumulation of a large quantity of ATP and its metabolites. The glucose-lowering drug metformin reduced the severity of hyperglycaemia both in 5'-AMP-induced wild-type mice and db/db mice. Metformin decreased the accumulation of liver ATP but not its metabolites in these hyperglycaemic mice. ATP and metformin reciprocally change cellular pH homeostasis in liver, causing opposite shifts in liver activity of PTP1B, a key negative regulator of insulin signalling. Furthermore, pAMP levels were also elevated in individuals with type 2 diabetes (45.2 ± 22.7 nmol/l vs 3.1 ± 1.9 nmol/l; p < 0.01). CONCLUSIONS/INTERPRETATION: These results reveal an emerging role for adenine nucleotide in the regulation of hyperglycaemia and provide a potential therapeutic target in obesity and type 2 diabetes.


Assuntos
Adenina/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Fígado/metabolismo , Nucleotídeos/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Trifosfato de Adenosina/metabolismo , Adulto , Animais , Estudos de Casos e Controles , Membrana Celular/metabolismo , Diabetes Mellitus Experimental/metabolismo , Modelos Animais de Doenças , Feminino , Hepatócitos/metabolismo , Homeostase , Humanos , Concentração de Íons de Hidrogênio , Hiperglicemia/metabolismo , Resistência à Insulina , Cinética , Espectroscopia de Ressonância Magnética , Masculino , Metformina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade
13.
Inorg Chem ; 57(21): 13586-13593, 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30335373

RESUMO

A bifunctional catalyst, Pd nanoparticles (NPs) encapsulated in MIL-101, has been synthesized by capillary impregnation. The as-prepared Pd@MIL-101 was characterized by powder X-ray diffraction, N2 physisorption, X-ray photoelectron spectroscopy, transmission electron microscopy, and high-angle annular dark field scanning transmission electron microscopy, indicating that Pd NPs were highly dispersed in the pores of MIL-101 without deposition of the nanoparticles on the external surface or aggregation. The bifunctional catalyst of Pd@MIL-101 exhibited highly catalytic activity for alcohol oxidation and aldimine condensation one-pot reactions, where Pd NPs affords good oxidation activity and MIL-101 offers Lewis acidity. In particular, Pd@MIL-101 yielded an effective catalytic performance with toluene as the solvent, K2CO3 as the co-catalyst, and 353 K as the optimum reaction temperature for the one-pot reaction. After five cycles of reuse, Pd@MIL-101 still shows high catalytic performance. Above all, it is found that the enhanced catalytic performance was achieved via the synergistic cooperation of MIL-101 and Pd NPs.

14.
BMC Bioinformatics ; 18(Suppl 16): 550, 2017 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-29297381

RESUMO

BACKGROUND: In recent years, biological interaction networks have become the basis of some essential study and achieved success in many applications. Some typical networks such as protein-protein interaction networks have already been investigated systematically. However, little work has been available for the construction of gene functional similarity networks so far. In this research, we will try to build a high reliable gene functional similarity network to promote its further application. RESULTS: Here, we propose a novel method to construct and refine the gene functional similarity network. It mainly contains three steps. First, we establish an integrated gene functional similarity networks based on different functional similarity calculation methods. Then, we construct a referenced gene-gene association network based on the protein-protein interaction networks. At last, we refine the spurious edges in the integrated gene functional similarity network with the help of the referenced gene-gene association network. Experiment results indicate that the refined gene functional similarity network (RGFSN) exhibits a scale-free, small world and modular architecture, with its degrees fit best to power law distribution. In addition, we conduct protein complex prediction experiment for human based on RGFSN and achieve an outstanding result, which implies it has high reliability and wide application significance. CONCLUSIONS: Our efforts are insightful for constructing and refining gene functional similarity networks, which can be applied to build other high quality biological networks.


Assuntos
Redes Reguladoras de Genes/genética , Mapeamento de Interação de Proteínas/métodos , Mapas de Interação de Proteínas/genética , Algoritmos , Humanos
15.
Int J Cancer ; 141(11): 2336-2347, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-28791697

RESUMO

Genetic variations in genes involved in repairing platinum-induced DNA lesions may contribute to the toxicity of platinum-based chemotherapy. The role of single-nucleotide polymorphisms (SNPs) within DNA repair pathways in the occurrence of severe toxicity is not yet understood. Current studies prefer to do original works rather than analyze previously published data. Our study aimed to replicate associations between previously investigated SNPs and toxicities and to identify new genetic makers. We systematically examined the relevance of 97 SNPs in 54 candidate genes responsible for repairing DNA interstrand and intrastrand cross-links to severe toxicity in a discovery cohort of 437 NSCLC patients receiving platinum-based chemotherapy. Statistically significant SNPs were then assessed for replication in an independent validation cohort of 781 NSCLC patients. We found that 7 SNPs were significant at p < 0.01 (RRM1 rs12806698, XPC rs2228000, XPF rs1799801, hMLH1 rs1800734, PMS2 rs1062372, REV3L rs462779 and FANCC rs4647554) in the discovery cohort. Among them, two SNPs (RRM1 rs12806698 and hMLH1 rs1800734) remained significant after Bonferroni correction. XPC rs2228000 showed a significant relationship with severe gastrointestinal toxicity in the validation cohort. When the two cohorts were combined, XPC rs2228000 presented better tolerance of severe hematologic toxicity, gastrointestinal toxicity and leukopenia (OR = 0.677, 95% CI: 0.510-0.899, p = 0.007; OR = 0.565, 95% CI: 0.368-0.869, p = 0.009; OR = 0.628, 95% CI: 0.439-0.899, p = 0.011, respectively). Our findings can offer comprehensive pharmacogenetic information for platinum-induced toxicities.


Assuntos
Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/genética , Reparo do DNA/genética , Neoplasias Pulmonares/genética , Idoso , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Estudos de Coortes , Feminino , Genótipo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Polimorfismo de Nucleotídeo Único
16.
Appl Microbiol Biotechnol ; 101(2): 585-598, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27678113

RESUMO

Salecan, a soluble ß-1,3-D-glucan produced by a salt-tolerant strain Agrobacterium sp. ZX09, has been the subject of considerable interest in recent years because of its multiple bioactivities and unusual rheological properties in solution. In this study, both succinyl and pyruvyl substituent groups on salecan were identified by an enzymatic hydrolysis following nuclear magnetic resonance (NMR), HPLC, and MS analysis. The putative succinyltransferase gene (sleA) and pyruvyltransferase gene (sleV) were determined and cloned. Disruption of the sleA gene resulted in the absence of succinyl substituent groups on salecan. This defect could be complemented by expressing the sleA cloned in a plasmid. Thus, the sleA and sleV genes located in a 19.6-kb gene cluster may be involved in salecan biosynthesis. Despite the lack of succinyl substituents, the molecular mass of salecan generated by the sleA mutant did not substantially differ from that generated by the wild-type strain. Loss of succinyl substituents on salecan changed its rheological characteristics, especially a decrease in intrinsic viscosity.


Assuntos
Agrobacterium/genética , Agrobacterium/metabolismo , Vias Biossintéticas/genética , beta-Glucanas/metabolismo , Cromatografia Líquida de Alta Pressão , Clonagem Molecular , Deleção de Genes , Teste de Complementação Genética , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Família Multigênica , Piruvatos/química , Piruvatos/metabolismo , Succinatos/química , Succinatos/metabolismo , Transferases/genética , beta-Glucanas/química
17.
BMC Ophthalmol ; 17(1): 100, 2017 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-28646864

RESUMO

BACKGROUND: Cataract surgery after penetratingkeratoplasty (PKP) is often challenging due to changes in the integrity of the cornea caused by PKP. For example, corneal endothelial cell (CEC) loss and corneal edema commonly occur after traditional phacoemulsification cataract surgery in patients that previously had successful PKP. Recent studies have reported that femtosecond laser-assisted cataract surgery (FLACS) significantly reduces the need for ultrasound energy minimizing mechanical damage to the cornea and results in a reduction of CEC loss and corneal edema. CASE PRESENTATION: We report a case in which FLACS was used in a patient with previous PKP. CONCLUSION: This case supports the suggestion that the use of the femtosecond laser improves the surgical outcome of cataract surgery after PKP. This improvement may be result of the precise incision, controlled capsulorhexis, and reduced lens fragmentation experienced with the femtosecond laser which helps to reduce potential complications of cataract surgery after PKP.


Assuntos
Extração de Catarata/métodos , Catarata/complicações , Doenças da Córnea/cirurgia , Ceratoplastia Penetrante/métodos , Terapia a Laser/métodos , Acuidade Visual , Catarata/diagnóstico , Doenças da Córnea/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia de Coerência Óptica
18.
World J Microbiol Biotechnol ; 33(9): 165, 2017 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-28819739

RESUMO

Oligosaccharides from the water-soluble ß-glucan, Salecan, were investigated to evaluate the activation effect on the defense responses of Arabidopsis thaliana Col0. Salecan oligosaccharides (ScOs, DP 5-10) were prepared at first by acid hydrolysis and gel filtration chromatography and then employed for foliar spray on Arabidopsis seedlings and plants. After ScOs treatment, increase of hydrogen peroxide was histologically and analytically detected in leaves. Transcription levels of several indicator genes which correspond to the signaling pathways and pathogenesis-related proteins were up-regulated at different time by means of quantitative RT-PCR analysis. Importantly, the sequential activation of salicylic acid-mediated and jasmonate-mediated signaling pathway was observed in leaves. Furthermore, pot test and antimicrobial test gave the fact that pretreatment with ScOs restrained the leaf lesions caused by infection of Botrytis cinerea Bc0510 via the enhancement of defense responses of A. thaliana. In conclusion, Salecan oligosaccharides serve as an elicitor which can be used for biological control of plant pathogen.


Assuntos
Arabidopsis/crescimento & desenvolvimento , Resistência à Doença , Oligossacarídeos/farmacologia , beta-Glucanas/química , Arabidopsis/efeitos dos fármacos , Arabidopsis/microbiologia , Proteínas de Arabidopsis , Botrytis/patogenicidade , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Oligossacarídeos/química , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Folhas de Planta/efeitos dos fármacos , Plântula/efeitos dos fármacos
19.
Yi Chuan ; 39(3): 250-262, 2017 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-28420621

RESUMO

Platinum-based chemotherapy is an important treatment for non-small cell lung cancer. However, the effectiveness of the treatment varies among the patients. We investigated the association between DNA polymorphisms of the autophagy pathway and responses of such treatment among 1004 Chinese patients. Ninety-nine SNPs located on 13 genes of the autophagy pathway were genotyped and assessed for their association with clinical benefit, progression-free survival (PFS) and overall survival (OS). The results showed that rs7953348 (G>A) (P=0.017, OR: 0.67, 95%CI: 0.49-0.93) and rs12303764 (A>C) (P=0.009, OR: 0.63, 95%CI: 0.45-0.89) at the ULK1 gene, and rs17742719 (C>A) (P=0.002, OR: 1.83, 95%CI: 1.26-2.66), rs8003279 (A>G) (P=0.006, OR: 1.65, 95%CI: 1.16~2.35) and rs1009647 (G>A) (P=0.002, OR: 1.70, 95%CI: 1.22-2.37) at the ATG14 gene were associated with clinical benefit. Polymorphisms at rs7955890 (G>A) (P=0.004, HR: 0.63; 95%CI: 0.46-0.86) and rs17032060 (G>A) (P=0.006, HR: 0.65, 95%CI: 0.48-0.88) at the DRAM gene, and rs13082005 (G>A) (P=0.012, HR: 1.27, 95%CI: 1.05-1.53) at the ATG3 gene were significantly associated with PFS. We also found that rs7953348 (G>A) (P=0.011, HR: 0.74, 95%CI: 0.58-0.93) at the ULK1 gene and rs1864183 (G>A) (P=0.016, HR: 0.42, 95%CI: 0.21-0.85) at the ATG10 gene were associated with OS. Thus, the study demonstrated that the autophagy pathway might play important role(s) in platinum-based chemotherapy. DNA polymorphisms in its component genes can potentially be predictors for clinical responses of platinum-based chemotherapy among the patients with non-small lung cancer.


Assuntos
Autofagia/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Platina/uso terapêutico , Polimorfismo Genético/genética , Adulto , Idoso , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Proteínas Relacionadas à Autofagia/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Feminino , Genótipo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Enzimas de Conjugação de Ubiquitina/genética , Proteínas de Transporte Vesicular/genética
20.
Inorg Chem ; 55(7): 3558-65, 2016 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-26974010

RESUMO

An In-based metal-organic framework, with 1D nanotubular open channels, In2(OH)(btc)(Hbtc)0.4(L)0.6·3H2O (1), has been synthesized via an in situ ligand reaction, in which 1,2,4-H3btc is partially transformed into the L ligand. Compound 1 exhibits exceptional thermal and chemical stability, especially in water or acidic media. The activated 1 presents highly selective sorption of carbon dioxide (CO2) over dinitrogen. Interestingly, diffuse-reflectance infrared Fourier transform spectroscopy with a carbon monoxide probe molecule demonstrates that both Lewis and Brønsted acid sites are involved in compound 1. As a result, as a heterogeneous Lewis and Brønsted acid bifunctional catalyst, 1 possesses excellent activity and recyclability for chemical fixation of CO2 coupling with epoxides into cyclic carbonates under mild conditions. In addition, the mechanism for the CO2 cycloaddition reaction has also been discussed.

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