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1.
Acta Pharmacol Sin ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992119

RESUMO

The escalating obesity epidemic and aging population have propelled metabolic dysfunction-associated steatohepatitis (MASH) to the forefront of public health concerns. The activation of FXR shows promise to combat MASH and its detrimental consequences. However, the specific alterations within the MASH-related transcriptional network remain elusive, hindering the development of more precise and effective therapeutic strategies. Through a comprehensive analysis of liver RNA-seq data from human and mouse MASH samples, we identified central perturbations within the MASH-associated transcriptional network, including disrupted cellular metabolism and mitochondrial function, decreased tissue repair capability, and increased inflammation and fibrosis. By employing integrated transcriptome profiling of diverse FXR agonists-treated mice, FXR liver-specific knockout mice, and open-source human datasets, we determined that hepatic FXR activation effectively ameliorated MASH by reversing the dysregulated metabolic and inflammatory networks implicated in MASH pathogenesis. This mitigation encompassed resolving fibrosis and reducing immune infiltration. By understanding the core regulatory network of FXR, which is directly correlated with disease severity and treatment response, we identified approximately one-third of the patients who could potentially benefit from FXR agonist therapy. A similar analysis involving intestinal RNA-seq data from FXR agonists-treated mice and FXR intestine-specific knockout mice revealed that intestinal FXR activation attenuates intestinal inflammation, and has promise in attenuating hepatic inflammation and fibrosis. Collectively, our study uncovers the intricate pathophysiological features of MASH at a transcriptional level and highlights the complex interplay between FXR activation and both MASH progression and regression. These findings contribute to precise drug development, utilization, and efficacy evaluation, ultimately aiming to improve patient outcomes.

2.
BMC Plant Biol ; 23(1): 7, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36600201

RESUMO

BACKGROUND: Heat stress has adverse effects on the growth and reproduction of plants. Zygophyllum xanthoxylum, a typical xerophyte, is a dominant species in the desert where summer temperatures are around 40 °C. However, the mechanism underlying the thermotolerance of Z. xanthoxylum remained unclear. RESULTS: Here, we characterized the acclimation of Z. xanthoxylum to heat using a combination of physiological measurements and transcriptional profiles under treatments at 40 °C and 45 °C, respectively. Strikingly, moderate high temperature (40 °C) led to an increase in photosynthetic capacity and superior plant performance, whereas severe high temperature (45 °C) was accompanied by reduced photosynthetic capacity and inhibited growth. Transcriptome profiling indicated that the differentially expressed genes (DEGs) were related to transcription factor activity, protein folding and photosynthesis under heat conditions. Furthermore, numerous genes encoding heat transcription shock factors (HSFs) and heat shock proteins (HSPs) were significantly up-regulated under heat treatments, which were correlated with thermotolerance of Z. xanthoxylum. Interestingly, the up-regulation of PSI and PSII genes and the down-regulation of chlorophyll catabolism genes likely contribute to improving plant performance of Z. xanthoxylum under moderate high temperature. CONCLUSIONS: We identified key genes associated with of thermotolerance and growth in Z. xanthoxylum, which provide significant insights into the regulatory mechanisms of thermotolerance and growth regulation in Z. xanthoxylum under high temperature conditions.


Assuntos
Termotolerância , Zanthoxylum , Zygophyllum , Termotolerância/genética , Sódio/metabolismo , Zygophyllum/genética , Zygophyllum/metabolismo , Zanthoxylum/genética , Transcriptoma , Perfilação da Expressão Gênica , Resposta ao Choque Térmico/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Temperatura Alta , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas
3.
Ann Bot ; 131(4): 723-736, 2023 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-36848247

RESUMO

BACKGROUND AND AIMS: Desert plants possess excellent water-conservation capacities to survive in extreme environments. Cuticular wax plays a pivotal role in reducing water loss through plant aerial surfaces. However, the role of cuticular wax in water retention by desert plants is poorly understood. METHODS: We investigated leaf epidermal morphology and wax composition of five desert shrubs from north-west China and characterized the wax morphology and composition for the typical xerophyte Zygophyllum xanthoxylum under salt, drought and heat treatments. Moreover, we examined leaf water loss and chlorophyll leaching of Z. xanthoxylum and analysed their relationships with wax composition under the above treatments. KEY RESULTS: The leaf epidermis of Z. xanthoxylum was densely covered by cuticular wax, whereas the other four desert shrubs had trichomes or cuticular folds in addition to cuticular wax. The total amount of cuticular wax on leaves of Z. xanthoxylum and Ammopiptanthus mongolicus was significantly higher than that of the other three shrubs. Strikingly, C31 alkane, the most abundant component, composed >71 % of total alkanes in Z. xanthoxylum, which was higher than for the other four shrubs studied here. Salt, drought and heat treatments resulted in significant increases in the amount of cuticular wax. Of these treatments, the combined drought plus 45 °C treatment led to the largest increase (107 %) in the total amount of cuticular wax, attributable primarily to an increase of 122 % in C31 alkane. Moreover, the proportion of C31 alkane within total alkanes remained >75 % in all the above treatments. Notably, the water loss and chlorophyll leaching were reduced, which was negatively correlated with C31 alkane content. CONCLUSION: Zygophyllum xanthoxylum could serve as a model desert plant for study of the function of cuticular wax in water retention because of its relatively uncomplicated leaf surface and because it accumulates C31 alkane massively to reduce cuticular permeability and resist abiotic stressors.


Assuntos
Zanthoxylum , Zygophyllum , Zygophyllum/metabolismo , Zanthoxylum/metabolismo , Alcanos , Folhas de Planta/metabolismo , Cloreto de Sódio , Clorofila , Estresse Fisiológico , Água/metabolismo , Ceras , Regulação da Expressão Gênica de Plantas
4.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(6): 633-638, 2023 Jun 15.
Artigo em Chinês | MEDLINE | ID: mdl-37382134

RESUMO

OBJECTIVES: To investigate the distribution characteristics of non-bacterial pathogens in community-acquired pneumonia (CAP) in children. METHODS: A total of 1 788 CAP children admitted to Shenyang Children's Hospital from December 2021 to November 2022 were selected. Multiple RT-PCR and capillary electrophoresis were used to detect 10 viral pathogens and 2 atypical pathogens, and serum antibodies of Chlamydial pneumoniae (Ch) and Mycoplasma pneumoniae (MP) were detected. The distribution characteristics of different pathogens were analyzed. RESULTS: Among the 1 788 CAP children, 1 295 children were pathogen-positive, with a positive rate of 72.43% (1 295/1 788), including a viral pathogen positive rate of 59.68% (1 067/1 788) and an atypical pathogen positive rate of 22.04% (394/1 788). The positive rates from high to low were MP, respiratory syncytial virus (RSV), influenza B virus (IVB), human metapneumovirus (HMPV), human rhinovirus (HRV), human parainfluenza virus (HPIV), influenza A virus (IVA), bocavirus (BoV), human adenovirus (HADV), Ch, and human coronavirus (HCOV). RSV and MP were the main pathogens in spring; MP had the highest positive rate in summer, followed by IVA; HMPV had the highest positive rate in autumn; IVB and RSV were the main pathogens in winter. The positive rate of MP in girls was higher than that in boys (P<0.05), and there were no significant differences in other pathogens between genders (P>0.05). The positivity rates of certain pathogens differed among age groups (P<0.05): the positivity rate of MP was highest in the >6 year-old group; the positivity rates of RSV and Ch were highest in the <1 year-old group; the positivity rates of HPIV and IVB were highest in the 1 to <3 year-old group. RSV, MP, HRV, and HMPV were the main pathogens in children with severe pneumonia, while MP was the primary pathogen in children with lobar pneumonia, and MP, IVB, HMPV, RSV, and HRV were the top 5 pathogens in acute bronchopneumonia. CONCLUSIONS: MP, RSV, IVB, HMPV, and HRV are the main pathogens of CAP in children, and there are certain differences in the positive rates of respiratory pathogens among children of different ages, genders, and seasons.


Assuntos
Infecções Comunitárias Adquiridas , Pneumonia , Vírus Sincicial Respiratório Humano , Humanos , Criança , Feminino , Masculino , Lactente , Pré-Escolar , Anticorpos , Hospitalização , Vírus da Influenza B , Mycoplasma pneumoniae
5.
Acta Pharmacol Sin ; 42(2): 264-271, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32737468

RESUMO

Previous studies demonstrated that prolonged exposure to elevated levels of free fatty acids (FFA), especially saturated fatty acids, could lead to pancreatic ß-cell apoptosis, which plays an important role in the progression of type 2 diabetes (T2D). Diacylglycerol acyltransferase 1 (DGAT1), an enzyme that catalyzes the final step of triglyceride (TG) synthesis, has been reported as a novel target for the treatment of multiple metabolic diseases. In this study we evaluated the potential beneficial effects of DGAT1 inhibitors on pancreatic ß-cells, and further verified their antidiabetic effects in db/db mice. We showed that DGAT1 inhibitors (4a and LCQ908) at the concentration of 1 µM significantly ameliorated palmitic acid (PA)-induced apoptosis in MIN6 pancreatic ß-cells and primary cultured mouse islets; oral administration of a DGAT1 inhibitor (4a) (100 mg/kg) for 4 weeks significantly reduced the apoptosis of pancreatic islets in db/db mice. Meanwhile, 4a administration significantly decreased fasting blood glucose and TG levels, and improved glucose tolerance and insulin tolerance in db/db mice. Furthermore, we revealed that pretreatment with 4a (1 µM) significantly alleviated PA-induced intracellular lipid accumulation, endoplasmic reticulum (ER) stress, and proinflammatory responses in MIN6 cells, which might contribute to the protective effects of DGAT1 inhibitors on pancreatic ß-cells. These findings provided a better understanding of the antidiabetic effects of DGAT1 inhibitors.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diacilglicerol O-Aciltransferase/antagonistas & inibidores , Hipoglicemiantes/farmacologia , Animais , Apoptose/efeitos dos fármacos , Glicemia/efeitos dos fármacos , Linhagem Celular , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Insulina/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/patologia , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ácido Palmítico/toxicidade
6.
Small ; 15(36): e1902135, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31322829

RESUMO

Self-powered photodetectors (PDs) based on inorganic metal halide perovskites are regarded as promising alternatives for the next generation of photodetectors. However, uncontrollable film growth and sluggish charge extraction at interfaces directly limit the sensitivity and response speed of perovskite-based photodetectors. Herein, by assistance of an atomic layer deposition (ALD) technique, CsPbBr3 perovskite thin films with preferred orientation and enlarged grain size are obtained on predeposited interfacial modification layers. Thanks to improved film quality and double side interfacial engineering, the optimized CsPbBr3 (Al2 O3 /CsPbBr3 /TiO2 , ACT) perovskite PDs exhibit outstanding performance with ultralow dark current of 10-11 A, high detectivity of 1.88 × 1013 Jones and broad linear dynamic range (LDR) of 172.7 dB. Significantly, excellent long-term environmental stability (ambient conditions >100 d) and flexibility stability (>3000 cycles) are also achieved. The remarkable performance is credited to the synergistic effects of high carrier conductivity and collection efficiency, which is assisted by ALD modification layers. Finally, the ACT PDs are successfully integrated into a visible light communication system as a light receiver on transmitting texts, showing a bit rate as high as 100 kbps. These results open the window of high performance all-inorganic halide perovskite photodetectors and extends to rational applications for optical communication.

7.
Acta Pharmacol Sin ; 40(9): 1193-1204, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30833709

RESUMO

Gluconeogenesis is a major source of hyperglycemia in patients with type 2 diabetes mellitus (T2DM), thus targeting gluconeogenesis to suppress glucose production is a promising strategy for anti-T2DM drug discovery. In our preliminary in vitro studies, we found that a small-molecule (E)-3-(2-(quinoline-4-yl)vinyl)-1H-indol-6-ol (QVO) inhibited the hepatic glucose production (HGP) in primary hepatocytes. We further revealed that QVO suppressed hepatic gluconeogenesis involving calmodulin-dependent protein kinase kinase ß- and liver kinase B1-adenosine monophosphate-activated protein kinase (AMPK) pathways as well as AMPK-independent mitochondrial function-related signaling pathway. To evaluate QVO's anti-T2DM activity in vivo, which was impeded by the complicated synthesis route of QVO with a low yield, we designed and synthesized 4-[2-(1H-indol-3-yl)vinyl]quinoline (IVQ) as a prodrug with easier synthesis route and higher yield. IVQ did not inhibit the HGP in primary hepatocytes in vitro. Pharmacokinetic studies demonstrated that IVQ was quickly converted to QVO in mice and rats following administration. In both db/db and ob/ob mice, oral administration of IVQ hydrochloride (IVQ-HCl) (23 and 46 mg/kg every day, for 5 weeks) ameliorated hyperglycemia, and suppressed hepatic gluconeogenesis and activated AMPK signaling pathway in the liver tissues. Furthermore, IVQ caused neither cardiovascular system dysfunction nor genotoxicity. The good druggability of IVQ has highlighted its potential in the treatment of T2DM and the prodrug design for anti-T2DM drug development.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Gluconeogênese/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Indóis/uso terapêutico , Pró-Fármacos/uso terapêutico , Quinolinas/uso terapêutico , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Complexo I de Transporte de Elétrons/antagonistas & inibidores , Complexo III da Cadeia de Transporte de Elétrons/antagonistas & inibidores , Ativadores de Enzimas/uso terapêutico , Ativadores de Enzimas/toxicidade , Inibidores Enzimáticos/uso terapêutico , Inibidores Enzimáticos/toxicidade , Glucose-6-Fosfatase/antagonistas & inibidores , Hepatócitos/efeitos dos fármacos , Hipoglicemiantes/toxicidade , Indóis/toxicidade , Fígado/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Fosfoenolpiruvato Carboxiquinase (GTP)/antagonistas & inibidores , Pró-Fármacos/toxicidade , Quinolinas/toxicidade , Transdução de Sinais/efeitos dos fármacos
8.
Fish Shellfish Immunol ; 73: 11-21, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29162543

RESUMO

Natural killer lysin (NK-lysin), produced by cytotoxic T lymphocytes and natural killer cells, is a cationic antimicrobial peptide that has a broad antimicrobial spectrum, including bacteria, viruses, and parasites. Nevertheless, the implication of NK-lysin in the protection against bacterial infection is not aware in common carp. In this study, six different NK-lysin genes (nkl1, nkl2, nkl3, nkl4, nkl5 and nkl6) were identified in the common carp genome. Each of the mature peptides of common carp NK-lysin has six well-conserved cysteine residues, and shares a Saposin B domain, characteristic of saposin-like protein (SALIP) family. The gene nkl1 contains 5 extrons and 4 introns, and nkl2, nkl3, nkl4 or nkl5 contains 4 extrons and 3 introns, however, the nkl6 has 3 extrons and 2 introns. By quantitative real-time PCR, nkl2 transcripts were predominantly expressed in spleen of healthy common carp, while elevated mainly in gill and spleen upon Aeromonas hydrophila infection. The recombinant NK-lysin-2 purified from Pichia pastoris shows antibacterial activity against Staphylococcus aureus (Gram-positive), and Escherichia coli M15, Aeromonas hydrophila, as well as Edwardsiella tarda (Gram-negative), the latter two are important pathogens of aquaculture. Our results indicate that NK-lysin in common carp might play an important role in fish immune response by enhancing antibacterial defense against bacterial pathogens.


Assuntos
Carpas/genética , Carpas/imunologia , Doenças dos Peixes/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Proteolipídeos/genética , Proteolipídeos/imunologia , Aeromonas hydrophila/fisiologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Proteínas de Peixes/química , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Perfilação da Expressão Gênica , Infecções por Bactérias Gram-Negativas/imunologia , Filogenia , Proteolipídeos/química , Alinhamento de Sequência/veterinária
9.
Zhonghua Nan Ke Xue ; 24(2): 147-151, 2018 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-30156075

RESUMO

OBJECTIVE: To investigate the prevalence of Ureaplasma urealyticum (UU) infection in infertile men, its influence on routine semen parameters and the distribution of antisperm antibody (AsAb) and its types in infertile patients with UU infection. METHODS: We detected the positive rate of UU infection, semen parameters, and the distribution of AsAb and its types in 662 infertile men and 25 normal fertile male controls followed by comparison of the obtained data between the two groups of subjects. RESULTS: The positive rate of UU infection was significantly higher in the infertile men than in the normal controls (52.87% ï¼»350/662ï¼½ vs 16.00% ï¼»4/25ï¼½, χ2 = 11.68, P <0.05). The semen volume, sperm count, sperm concentration and percentage of progressively motile sperm were remarkably lower in the UU-positive infertile males than in the control group (P <0.05). No statistically significant difference was observed between the UU-positive and UU-negative groups in the positive rates of total AsAb (43.4% vs 36.5%, χ2 = 3.25, P >0.05) and AsAb IgA, IgM and IgG in the seminal plasma, or in the percentages of serum AsAb IgM (16.9% vs 20.5%, χ2 = 1.22, P >0.05) and IgG (32.7% vs 28.9%, χ2 = 0.99, P >0.05) except in that of serum AsAb IgA (23.6% vs 17.0%, χ2 = 4.03, P <0.05). CONCLUSIONS: The UU infection rate is high in infertile males, which decreases the semen volume, total sperm count, motile sperm concentration and percentage of progressively motile sperm and increases the positive rate of serum AsAb IgA.


Assuntos
Anticorpos Antibacterianos/análise , Infertilidade Masculina/microbiologia , Espermatozoides/imunologia , Infecções por Ureaplasma/diagnóstico , Ureaplasma urealyticum/imunologia , Humanos , Infertilidade Masculina/imunologia , Masculino , Sêmen , Contagem de Espermatozoides , Infecções por Ureaplasma/imunologia
10.
Fish Shellfish Immunol ; 66: 112-119, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28478260

RESUMO

Interleukin-8 (IL-8), a CXC-type chemokine, plays a key role in acute inflammation by recruiting neutrophils in mammals. In the present study, the open reading frame (ORF) of IL-8, encoding 99 amino acids was cloned in mandarin fish, and its function in inflammation was investigated. The IL-8 contains four conserved cysteine residues, with the first two forming the CXC signature motif. The genomic sequence of mandarin fish IL-8 has four exons and three introns, a typical gene organization of the CXC chemokine. Bioactive recombinant IL-8 (rIL-8) exhibited a chemotactic effect on head kidney leukocytes in vitro, and activates the transcription of the inflammatory genes, IL-8 and IL-1ß. When mandarin fish was challenged intraperitoneally with the pathogenic bacterium Flavobacterium columnare G4, the steady-state protein level of IL-8 was up-regulated in trunk kidney and head kidney. These results suggest that IL-8 is a functional CXC chemokine in mandarin fish, and plays a key role in the inflammatory responses towards bacterial infection.


Assuntos
Doenças dos Peixes/imunologia , Proteínas de Peixes/imunologia , Infecções por Flavobacteriaceae/veterinária , Flavobacterium/fisiologia , Interleucina-8/genética , Interleucina-8/imunologia , Perciformes , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , DNA Complementar/genética , DNA Complementar/metabolismo , Proteínas de Peixes/química , Proteínas de Peixes/genética , Infecções por Flavobacteriaceae/imunologia , Rim Cefálico/imunologia , Imunomodulação , Interleucina-1beta/genética , Interleucina-8/química , Leucócitos/imunologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Alinhamento de Sequência/veterinária , Transcrição Gênica
11.
Neurol Sci ; 38(5): 873-877, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28229304

RESUMO

Early brain injury (EBI) contributes to poor prognosis of subarachnoid hemorrhage (SAH). This study aimed to clarify whether triggering receptor expressed on myeloid cells-1 (TREM-1) was implicated in the inflammatory mechanisms of EBI. The cerebrospinal fluid (CSF) levels of soluble TREM-1 (sTREM-1), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) as well as plasma levels of white blood cells (WBC) count and C-reactive protein in 17 SAH patients at early stage (within the EBI period) and 9 volunteers were observed. Also World Federation of Neurosurgical Societies (WFNS) scale of SAH patients was calculated on admission. Compared to controls, increased CSF levels of sTREM-1 (t = 5.66, P < 0.001), TNF-α (t = 5.41, P < 0.001) and IL-6 (t = 2.98, P = 0.007) as well as elevated plasma WBC counts (t = 7.61, P < 0.001) and C-reactive protein levels (t = 3.91, P = 0.001) were found in SAH patients. Considering the increased WBC counts in SAH group, covariate analysis was also performed when comparing patients' sTREM-1 levels with respect to controls and no obvious difference was found (F = 0.982, P = 0.332). For SAH group, early CSF concentrations of sTREM-1 were correlated with those of both TNF-α (r = 0.582, P = 0.014) and IL-6 (r = 0.593, P = 0.012). Also the CSF sTREM-1 levels were positively correlated with WBC counts (r = 0.629, P = 0.007) and C-reactive protein levels (r = 0.804, P < 0.001) as well as WFNS scale (r = 0.835, P < 0.001). This study showed an early increased sTREM-1 CSF level in SAH patients, which correlated with inflammation intensity post-SAH and clinical severity, indicating that TREM-1 may participate in the inflammatory mechanisms of EBI.


Assuntos
Interleucina-6/líquido cefalorraquidiano , Células Mieloides/metabolismo , Hemorragia Subaracnóidea/líquido cefalorraquidiano , Hemorragia Subaracnóidea/patologia , Receptor Gatilho 1 Expresso em Células Mieloides/metabolismo , Fator de Necrose Tumoral alfa/líquido cefalorraquidiano , Idoso , Encefalite/etiologia , Encefalite/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hemorragia Subaracnóidea/complicações
12.
Molecules ; 22(9)2017 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-28872627

RESUMO

Protein pupylation is a type of post-translation modification, which plays a crucial role in cellular function of bacterial organisms in prokaryotes. To have a better insight of the mechanisms underlying pupylation an initial, but important, step is to identify pupylation sites. To date, several computational methods have been established for the prediction of pupylation sites which usually artificially design the negative samples using the verified pupylation proteins to train the classifiers. However, if this process is not properly done it can affect the performance of the final predictor dramatically. In this work, different from previous computational methods, we proposed an enhanced positive-unlabeled learning algorithm (EPuL) to the pupylation site prediction problem, which uses only positive and unlabeled samples. Firstly, we separate the training dataset into the positive dataset and the unlabeled dataset which contains the remaining non-annotated lysine residues. Then, the EPuL algorithm is utilized to select the reliably negative initial dataset and then iteratively pick out the non-pupylation sites. The performance of the proposed method was measured with an accuracy of 90.24%, an Area Under Curve (AUC) of 0.93 and an MCC of 0.81 by 10-fold cross-validation. A user-friendly web server for predicting pupylation sites was developed and was freely available at http://59.73.198.144:8080/EPuL.


Assuntos
Algoritmos , Biologia Computacional/métodos , Aprendizado de Máquina , Processamento de Proteína Pós-Traducional , Proteínas/química , Bases de Dados de Proteínas , Ligação Proteica , Software
13.
Zhonghua Nan Ke Xue ; 23(4): 329-336, 2017 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-29714418

RESUMO

OBJECTIVE: Sperm DNA fragmentation (SDF) is widely used to predict male infertility and the methods of detecting SDF are varied. This study aimed to compare two methods of SDF detection and investigate the correlation between SDF and sperm quality. METHODS: Using sperm chromatin structure assay (SCSA) and sperm chromatin dispersion test (SCD), we detected SDF in 108 semen samples collected in the Center of Reproduction and Genetics of Suzhou Municipal Hospital. We compared the results of the two methods and analyzed the correlations of SDF routine semen parameters, sperm morphology and the age of the patients. RESULTS: A significant consistency was found in the SDF index (DFI) between the two methods (P<0.01). The DFI was correlated negatively with sperm motility, the percentage of progressively motile sperm, and that of morphologically normal sperm (P <0.01), but positively with the teratozoospermia index (P <0.01 in SCSA and P <0.05 in SCD). The DFI measured by SCSA showed a significantly positive correlation with the patients' age (P <0.01), but not that obtained by SCD. CONCLUSIONS: The results of both SCSA and SCD play an important role in predicting sperm quality. As a clinical index, the DFI has a predictive value for male infertility. However, the results of different detecting methods vary widely, which calls for further studies on their standardization.


Assuntos
Cromatina/fisiologia , Fragmentação do DNA , Infertilidade Masculina/diagnóstico , Sêmen/fisiologia , Espermatozoides/fisiologia , Cromatina/genética , Humanos , Masculino , Análise do Sêmen , Motilidade dos Espermatozoides , Espermatozoides/ultraestrutura
14.
Infect Immun ; 84(1): 2-10, 2016 01.
Artigo em Inglês | MEDLINE | ID: mdl-26459509

RESUMO

The type III secretion system (T3SS) of Edwardsiella tarda is crucial for its intracellular survival and pathogenesis in fish. The orf13 gene (escE) of E. tarda is located 84 nucleotides (nt) upstream of esrC in the T3SS gene cluster. We found that EscE is secreted and translocated in a T3SS-dependent manner and that amino acids 2 to 15 in the N terminus were required for a completely functional T3SS in E. tarda. Deletion of escE abolished the secretion of T3SS translocators, as well as the secretion and translocation of T3SS effectors, but did not influence their intracellular protein levels in E. tarda. Complementation of the escE mutant with a secretion-incompetent EscE derivative restored the secretion of translocators and effectors. Interestingly, the effectors that were secreted and translocated were positively correlated with the EscE protein level in E. tarda. The escE mutant was attenuated in the blue gourami fish infection model, as its 50% lethal dose (LD50) increased to 4 times that of the wild type. The survival rate of the escE mutant-strain-infected fish was 69%, which was much higher than that of the fish infected with the wild-type bacteria (6%). Overall, EscE represents a secreted T3SS regulator that controls effector injection and translocator secretion, thus contributing to E. tarda pathogenesis in fish. The homology of EscE within the T3SSs of other bacterial species suggests that the mechanism of secretion and translocation control used by E. tarda may be commonly used by other bacterial pathogens.


Assuntos
Proteínas de Bactérias/genética , Edwardsiella tarda/patogenicidade , Doenças dos Peixes/microbiologia , Proteínas de Peixes/genética , Sistemas de Secreção Tipo III/genética , Sequência de Aminoácidos , Animais , Proteínas de Bactérias/metabolismo , Sequência de Bases , Linhagem Celular , Edwardsiella tarda/genética , Doenças dos Peixes/patologia , Proteínas de Peixes/metabolismo , Peixes , Regulação Bacteriana da Expressão Gênica , Células HeLa , Humanos , Camundongos , Transporte Proteico , Análise de Sequência de DNA , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
15.
Dig Dis Sci ; 61(9): 2522-34, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27146412

RESUMO

BACKGROUND/AIM: Obstructive jaundice (OJ) is frequently complicated by infections and has been associated with increased bacterial translocation, intestinal epithelial hyperpermeability, and oxidative stress, but the mechanism remains unclear. The potential effect of resveratrol (Res) on modifying intestinal epithelial dysfunction was evaluated both in vitro and in vivo. METHODS: Caco-2 cells (in vitro) and male Wistar rats (n = 60; in vivo) were used to evaluate the role of Res on intestinal epithelial dysfunction. Hydrogen peroxide was used to induce oxidative stress in the Caco-2 cells. In bile duct-ligated group, OJ was successfully established on Day 7 after bile duct ligation, whereas sham-operated and vehicle-treated rats served as controls. Western blot and RT-qPCR were performed to analyze TJ proteins expression in epithelium isolated from rat intestine. RESULTS: Intestinal hyperpermeability was associated with decreased expression and phosphorylation of occludin and zonula occluden (ZO-1), but increased oxidation in Caco-2 cells and the intestinal epithelium. Res treatment increased the epithelial expression and phosphorylation of occludin and ZO-1 in a concentration-dependent manner. Moreover, Res which protected Caco-2 cells from H2O2-induced oxidative damage clearly reduced malondialdehyde level and intracellular reactive oxygen species accumulation, but increased the expression levels of superoxide dismutase and heme oxygenase-1 (HO-1). Further studies showed that Res also inhibited H2O2-induced protein kinase C activity and p38 phosphorylation. Interestingly, these effects of Res were abolished by the HO-1 inhibitor zinc protoporphyrin or knockdown of HO-1 by siRNA. CONCLUSIONS: Res protected gut barrier function possibly by initiating HO-1-dependent signaling which is essential for common expression of key tight junction proteins. It also provides a rationale to develop Res clinical applications of intestinal disorders.


Assuntos
Antioxidantes/farmacologia , Heme Oxigenase-1/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Icterícia Obstrutiva/genética , Estresse Oxidativo/efeitos dos fármacos , Estilbenos/farmacologia , Junções Íntimas/efeitos dos fármacos , Animais , Ductos Biliares/cirurgia , Western Blotting , Células CACO-2 , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Técnicas In Vitro , Mucosa Intestinal/metabolismo , Icterícia Obstrutiva/metabolismo , Ligadura , Masculino , Malondialdeído/metabolismo , Ocludina/efeitos dos fármacos , Ocludina/metabolismo , Permeabilidade/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proteína Quinase C/efeitos dos fármacos , Proteína Quinase C/metabolismo , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Resveratrol , Junções Íntimas/metabolismo , Regulação para Cima , Proteína da Zônula de Oclusão-1/efeitos dos fármacos , Proteína da Zônula de Oclusão-1/metabolismo
16.
J Nanosci Nanotechnol ; 15(4): 2845-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26353503

RESUMO

Novel, carbonized bacterial cellulose (CBC)/Fe3O4 nanocomposites were synthesized using vacuum filtration and annealing (VFA) methods. The as-synthesized products were characterized by scanning electron microscopy, vibrating sample magnetometry, and transmission electron microscopy. The complex permittivity and permeability of Fe3O4-CBC (5 wt.% CBC)/paraffin wax composites were measured by vector network analysis. To study the microwave absorption (MA) performances, we compared the VFA products with the vacuum filtration (VF) products. The VFA products exhibited better absorption performances because of their larger dielectric loss. When the matching thickness was 2.4 mm, the calculated reflection loss reached a minimum value of -27 dB when VFA was used and a value of -11 dB when VF was used. The wide-range MA properties of these materials lead to potential applications in MA fields.


Assuntos
Carbono/química , Nanopartículas de Magnetita/química , Micro-Ondas , Nanocompostos/química , Nanofibras/química , Nanotecnologia/métodos , Absorção de Radiação
17.
Phytother Res ; 29(7): 1040-5, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25826437

RESUMO

(2'R)-2',3'-Dihydro-2'-(1-hydroxy-1-methylethyl)-2,6'-bibenzofuran-6,4'-diol (DHMB) is a natural compound extracted from Morus notabilis. It was found that DHMB acts as a competitive inhibitor against mushroom tyrosinase with a Ki value of 14.77 µM. Docking results further indicated that it could form strong interactions with one copper ion with a distance of 2.7 Å, suggesting the mechanism of inhibition might be due to chelating copper ions in the active site. Furthermore, melanin production in B16-F10 murine melanoma cells was significantly inhibited by DHMB in a concentration-dependent manner without cytotoxicity. The results of western blotting also showed that DHMB decreased 3-isobuty-1-methxlzanthine-induced mature tyrosinase expression. Taken together, these findings indicated that DHMB may be a new promising pigmentation-altering agent for agriculture, cosmetic, and therapeutic applications.


Assuntos
Agaricales/enzimologia , Benzofuranos/química , Melaninas/biossíntese , Melanoma Experimental/metabolismo , Monofenol Mono-Oxigenase/antagonistas & inibidores , Animais , Linhagem Celular Tumoral , AMP Cíclico/metabolismo , Inibidores Enzimáticos/química , Camundongos , Simulação de Acoplamento Molecular , Morus/química
18.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(8): 2292-6, 2015 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-26672311

RESUMO

In this dissertation, we study the synthesis and character of new substituted Phthalocyanine. Due to the widely application of Pcs in the fields, such as the communication, medical treatment, chemical industry and so on, therefore, they have been a hot topic over several decades by scientists. Nowadays, scientists have prepared thousands of Pcs and their derivatives. However, along with the human society development and the progress in science and technology, the new phthalocyanine with novle characteristics are still the goal of the scientists. In this dissertion, the synthetic methods of the phthlocyanine is improved. The synthesis and characterization of 1,11,15,25-tetrahydroxy-4,8,18,22-di(bridged dipropionate carboxyl) phthalocyanines are reported in this paper. The mixtures of malonic acid and 3,6-dihydroxy-phthalonitrile was added to water under stiriing. Then, a catalyst amount of sulfuric acid was added. The first synthetic precursor, i. e., malonic acid 3,3'-bis(6-hydroxy phthalonitrile) butter, its molecular formula is C19H8N4O6. phthalocyanines was prepared by malonic acid 3,3'-bis(6-hydroxy phthalonitrile) butter and dihydrate zinc acetate, copper acetate monohydrate in n-amyl alcohol, using DBU as a catalyst under the 135 °C, molecular formula of phthalocyanine complexes is C38H16N8O12M. The product was characterized by Ultraviolet-visible (UV/Vis) Spectrum absorption and fluorescence, The results are agreement with the proposed structures. And electrochemical properties were studied.

19.
J Org Chem ; 79(2): 599-607, 2014 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-24344740

RESUMO

Aphadilactones A-D (1-4), four diastereoisomers possessing an unprecedented carbon skeleton, were isolated from the Meliaceae plant Aphanamixis grandifolia. Their challenging structures and absolute configurations were determined by a combination of spectroscopic data, chemical degradation, fragment synthesis, experimental CD spectra, and ECD calculations. Aphadilactone C (3) with the 5S,11S,5'S,11'S configuration showed potent and selective inhibition against the diacylglycerol O-acyltransferase-1 (DGAT-1) enzyme (IC50 = 0.46 ± 0.09 µM, selectivity index > 217) and is the strongest natural DGAT-1 inhibitor discovered to date. In addition, compounds 1-4 showed significant antimalarial activities with IC50 values of 190 ± 60, 1350 ± 150, 170 ± 10, and 120 ± 50 nM, respectively.


Assuntos
Antimaláricos/farmacologia , Diacilglicerol O-Aciltransferase/antagonistas & inibidores , Diterpenos/farmacologia , Inibidores Enzimáticos/farmacologia , Meliaceae/química , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/química , Antimaláricos/isolamento & purificação , Diacilglicerol O-Aciltransferase/metabolismo , Dimerização , Diterpenos/química , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Humanos , Conformação Molecular , Testes de Sensibilidade Parasitária , Proteínas Recombinantes/metabolismo , Relação Estrutura-Atividade
20.
ScientificWorldJournal ; 2014: 183809, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25013845

RESUMO

Nowadays, swarm intelligence optimization has become an important optimization tool and wildly used in many fields of application. In contrast to many successful applications, the theoretical foundation is rather weak. Therefore, there are still many problems to be solved. One problem is how to quantify the performance of algorithm in finite time, that is, how to evaluate the solution quality got by algorithm for practical problems. It greatly limits the application in practical problems. A solution quality assessment method for intelligent optimization is proposed in this paper. It is an experimental analysis method based on the analysis of search space and characteristic of algorithm itself. Instead of "value performance," the "ordinal performance" is used as evaluation criteria in this method. The feasible solutions were clustered according to distance to divide solution samples into several parts. Then, solution space and "good enough" set can be decomposed based on the clustering results. Last, using relative knowledge of statistics, the evaluation result can be got. To validate the proposed method, some intelligent algorithms such as ant colony optimization (ACO), particle swarm optimization (PSO), and artificial fish swarm algorithm (AFS) were taken to solve traveling salesman problem. Computational results indicate the feasibility of proposed method.


Assuntos
Algoritmos , Inteligência Artificial/normas , Controle de Qualidade
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