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1.
J Affect Disord ; 268: 39-46, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32158005

RESUMO

BACKGROUND: Studies have reported the changes of immune biomakers in post-traumatic stress disorder (PTSD), but the results were conflicting. Our aim was to investigate the changes of immune biomarkers in PTSD. METHODS: Literatures investigating the changes of immune markers in PTSD published in English were systematically searched through PubMed, Embase and Web of Science. We conducted random effects meta-analyses relating PTSD to immune biomarker concentrations and using subgroup analyses to resolve heterogeneity. RESULTS: A total of 2606 articles were screened and 42 samples were included by the systematic review. The levels of interleukin-1ß (IL-1ß, P = 0.01), IL-2 (P = 0.006), IL-6 (P = 0.0002), interferon-γ (IFN-γ, P = 0.004), tumor necrosis factor-α (TNF-α, P = 0.004), C-reactive protein (CRP, P = 0.0003) and white blood cell (WBC, P = 0.01) were higher in PTSD than healthy controls (HC). Subgroup meta-analyses for psychotropic medication showed the levels of IL-1ß and IL-2 were not increased in the PTSD. Subgroup meta-analyses for whether HC exposed to trauma showed the levels of IL-1ß and IL-6 were not increased in the PTSD. Egger´s test revealed there was no publication bias. However, there was significant heterogeneity across studies for immune markers other than for WBC (P = 0.14, I2 = 45%). Subgroup analyses based on sex, HC exposed to trauma, PTSD comorbid major depressive disorder, PTSD on psychotropic medications partially or completely resolved heterogeneity for some immune biomarkers. CONCLUSION: This meta-analysis provides evidence for elevation of IFN-γ, TNF-α, CRP, and WBC in PTSD.

2.
Angew Chem Int Ed Engl ; 59(12): 4800-4805, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-31912940

RESUMO

Immunotherapy has revolutionized cancer treatment, but its efficacy is severely hindered by the lack of effective predictors. Herein, we developed a homogeneous, low-volume, efficient, and sensitive exosomal programmed death-ligand 1 (PD-L1, a type of transmembrane protein) quantitation method for cancer diagnosis and immunotherapy response prediction (HOLMES-ExoPD-L1 ). The method combines a newly evolved aptamer that efficiently binds to PD-L1 with less hindrance by antigen glycosylation than antibody, and homogeneous thermophoresis with a rapid binding kinetic. As a result, HOLMES-ExoPD-L1 is higher in sensitivity, more rapid in reaction time, and easier to operate than existing enzyme-linked immunosorbent assay (ELISA)-based methods. As a consequence of an outstanding improvement of sensitivity, the level of circulating exosomal PD-L1 detected by HOLMES-ExoPD-L1 can effectively distinguish cancer patients from healthy volunteers, and for the first time was found to correlate positively with the metastasis of adenocarcinoma. Overall, HOLMES-ExoPD-L1 brings a fresh approach to exosomal PD-L1 quantitation, offering unprecedented potential for early cancer diagnosis and immunotherapy response prediction.

3.
J Cell Physiol ; 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31943174

RESUMO

Long noncoding RNAs (lncRNAs) have been reported to participate in the development of multiple cancers, including esophageal squamous cell carcinoma (ESCC). A growing number of studies have demonstrated that lncRNA myocardial infarction-associated transcript (MIAT) played an oncogenic role in several human malignancies, but its expression and function in ESCC remain unknown. In this study, we found that MIAT was significantly increased in ESCC tissues, as well as cell lines. Downregulation of MIAT suppressed ESCC cell proliferation, cell cycle, migration, and invasion. Mechanical studies revealed that MIAT promoted ESCC cell proliferation and cell cycle by acting as a competitively endogenous RNA (ceRNA) to upregulate the inner centromere protein (INCENP) expression through sponging miR-1301-3p. Furthermore, we uncovered that MIAT-SOX2 formed a positive feedback loop to facilitate cell proliferation, migration, and invasion of ESCC. Our findings indicated that MIAT promoted ESCC progression via targeting INCENP/miR-1301-3p axis and interacting with SOX2, suggesting novel potential therapeutic targets for ESCC.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31676466

RESUMO

Numerous variants associated with increased risk for SCZ have undergone positive selection and were associated with human brain development, but which brain regions and developmental stages were influenced by the positive selection for SCZ risk alleles are unclear. We analyzed SCZ using summary statistics from a genome-wide association study (GWAS) from the Psychiatric Genomics Consortium (PGC). Machine-learning scores were used to investigate two natural-selection scenarios: complete selection (loci where a selected allele has reached fixation) and incomplete selection (loci where a selected allele has not yet reached fixation). Based on the p value of single nucleotide polymorphisms (SNPs) with selection scores in the top 5%, we formed five subgroups: p < 0.0001, 0.001, 0.01, 0.05, or 0.1. We found that 48 and 29 genes (p < 0.0001) in complete and incomplete selection, respectively, were enrichedfor the transcriptionalco-expressionprofilein theprenatal dorsolateral prefrontal cortex (DFC), inferior parietal cortex (IPC), and ventrolateral prefrontal cortex (VFC). Core genes (GNA13, TBC1D19, and ZMYM4) involved in regulating early brain development were identified in these three brain regions. RNA sequencing for primary cortical neurons that were transfected Gna13 overexpressed lentivirus demonstrated that 135 gene expression levels changed in the Gna13 overexpressed groups compared with the controls. Gene-set analysis identified important associations among common variants of these 13 genes, which were associated with neurodevelopment and putamen volume [p = 0.031; family-wise error correction (FWEC)], SCZ (p = 0.022; FWEC). The study indicate that certain SCZ risk alleles were likely to undergo positive selection during human evolution due to their involvement in the development of prenatal DFC, IPC and VFC, and suggest that SCZ is related to abnormal neurodevelopment.

5.
Eur J Pharmacol ; 861: 172590, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31401160

RESUMO

Increasing evidence displays that microRNAs (miRNAs) participate in the development of various human malignancies, including esophageal squamous cell carcinoma (ESCC). MicroRNA-33a-5p (miR-33a-5p) has recently been reported to function as a tumor suppressor in many human cancers. However, the expression and role of miR-33a-5p in ESCC remains largely unknown. Herein, we discovered that miR-33a-5p was down-regulated in both ESCC tissues and cell lines, compared with their normal counterparts, and decreased expression of miR-33a-5p was found to be closely associated with poor patient prognosis of ESCC. Moreover, functional experiments revealed that up-regulation of miR-33a-5p inhibited cell proliferation and metastasis of ESCC cells. In addition, the expression level of miR-33a-5p was found to be negatively correlated with the long non-coding RNA (lncRNA) differentiation antagonizing non-protein coding RNA (DANCR), in both ESCC tissues and cell lines. Furthermore, zinc-finger-enhancer binding protein 1 (ZEB1) was predicted and confirmed to be a direct target of miR-33a-5p in ESCC. Further mechanistic investigation indicated that DANCR may function as a competing endogenous RNA (ceRNA) to sponge miR-33a-5p, and thereby up-regulate ZEB1 expression in ESCC. This study highlights the functions of miR-33a-5p in the progression of ESCC and suggests that the DANCR/miR-33a-5p/ZEB1 axis may be a potential prognostic and therapeutic target.


Assuntos
Progressão da Doença , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , RNA Longo não Codificante/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo/genética , Transição Epitelial-Mesenquimal/genética , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico
6.
J Biol Chem ; 294(19): 7615-7631, 2019 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-30894414

RESUMO

Mycobacteriophages express various peptides/proteins to infect Mycobacterium tuberculosis (M. tb). Particular attention has been paid to mycobacteriophage-derived endolysin proteins. We herein characterized a small mycobacteriophage-derived peptide designated AK15 with potent anti-M. tb activity. AK15 adopted cationic amphiphilic α-helical structure, and on the basis of this structure, we designed six isomers with increased hydrophobic moment by rearranging amino acid residues of the helix. We found that one of these isomers, AK15-6, exhibits enhanced anti-mycobacterial efficiency. Both AK15 and AK15-6 directly inhibited M. tb by trehalose 6,6'-dimycolate (TDM) binding and membrane disruption. They both exhibited bactericidal activity, cell selectivity, and synergistic effects with rifampicin, and neither induced drug resistance to M. tb They efficiently attenuated mycobacterial load in the lungs of M. tb-infected mice. We observed that lysine, arginine, tryptophan, and an α-helix are key structural requirements for their direct anti-mycobacterial action. Of note, they also exhibited immunomodulatory effects, including inhibition of proinflammatory response in TDM-stimulated or M. tb-infected murine bone marrow-derived macrophages (BMDMs) and M.tb-infected mice and induction of only a modest level of cytokine (tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6)) production in murine BMDMs and a T-cell cytokine (interferin-γ (IFN-γ) and TNF-α) response in murine lung and spleen. In summary, characterization of a small mycobacteriophage-derived peptide and its improved isomer revealed that both efficiently restrain M. tb infection via dual mycobactericidal-immunoregulatory activities. Our work provides clues for identifying small mycobacteriophage-derived anti-mycobacterial peptides and improving those that have cationic amphiphilic α-helices.


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Micobacteriófagos/química , Mycobacterium tuberculosis/imunologia , Tuberculose Pulmonar/tratamento farmacológico , Proteínas Virais/farmacologia , Animais , Antibacterianos/química , Peptídeos Catiônicos Antimicrobianos/agonistas , Peptídeos Catiônicos Antimicrobianos/química , Sinergismo Farmacológico , Humanos , Macrófagos/imunologia , Macrófagos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Mycobacterium tuberculosis/virologia , Rifampina/agonistas , Rifampina/farmacologia , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/patologia , Proteínas Virais/química
7.
J Hazard Mater ; 369: 550-560, 2019 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-30818119

RESUMO

Porous carbon is one of the most widely used materials to remove Cr(VI) from polluted water. Here we reported one efficient porous carbon material prepared from corn straw. The results of Fourier transform infrared spectroscopy (FTIR), Energy dispersion spectrum (EDS), and X-ray photoelectron spectroscopy (XPS) indicated that the porous carbon surface had functional groups such as COOH, OH and COC, etc, which could be acted as active sites during the adsorption process. Brunauer-Emmett-Teller (BET) results showed that the surface area and total pore volume of the adsorbent were 2131.181 m2/g and 1.128 cm3/g, respectively. The percentages of micropore surface area and micropore volume achieved 91.93% and 80.43%, respectively. The maximum adsorption capacity of Cr(VI) was 175.44 mg/g at 25 °C with the well-developed microporous structure and abundant oxygen-containing functional groups of porous carbon. The adsorption process was well described by the pseudo-second order model and Langmuir adsorption isotherm model. It was mainly based on chemical adsorption of a single molecular layer, accompanied by ion exchange reaction, Cr(VI) reduction, and complexation, etc. The adsorbent exhibited excellent removal performance of Cr(VI) in the co-existing ions wastewater and electroplating wastewater, and could remain high removal performance for four adsorption-desorption cycles.

8.
Acta Biochim Biophys Sin (Shanghai) ; 51(2): 139-149, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30615070

RESUMO

Mycobacterium tuberculosis (Mtb) is the key devastating bacterial pathogen responsible for tuberculosis. Increasing emergence of multi-drug-resistant, extensively drug-resistant, and rifampicin/isoniazid-resistant strains of Mtb makes the discovery of validated drug targets an urgent priority. As a vital translational component of the protein biosynthesis system, elongation factor Tu (EF-Tu) is an important molecular switch responsible for selection and binding of the cognate aminoacyl-tRNA to the acceptor site on the ribosome. In addition, EF-Tu from Mtb (MtbEF-Tu) is involved in the initial step of trans-translation which is an effective system for rescuing the stalled ribosomes from non-stop translation complexes under stress conditions. Given its crucial role in protein biosynthesis, EF-Tu is identified as an excellent molecular target for drug design. Here, we reported the recombinant expression, purification, biophysical characterization, and structural modeling of the MtbEF-Tu protein. Our results demonstrated that prokaryotic expression plasmids of pET28a-MtbEF-Tu could be expressed efficiently in Escherichia coli. We successfully purified the 6× His-tagged proteins with a yield of 16.8 mg from 1 l of Luria Bertani medium. Dynamic light scattering experiments showed that MtbEF-Tu existed in a monomeric form, and circular dichroism experiments indicated that MtbEF-Tu was well structured. Moreover, isothermal titration calorimetry experiments displayed that the purified MtbEF-Tu protein possessed intermediate binding affinities for guanosine-5'-triphosphate (GTP) and GDP. The GTP/GDP-binding sites were predicted by flexible molecular docking approach which reveals that GTP/GDP binds to MtbEF-Tu mainly through hydrogen bonds. Our work lays the essential basis for further structural and functional studies of MtbEF-Tu as well as MtbEF-Tu-related novel drug developments.


Assuntos
Proteínas de Bactérias/metabolismo , Mycobacterium tuberculosis/metabolismo , Fator Tu de Elongação de Peptídeos/metabolismo , Biossíntese de Proteínas , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Sítios de Ligação , Guanosina Difosfato/química , Guanosina Difosfato/metabolismo , Guanosina Trifosfato/química , Guanosina Trifosfato/metabolismo , Ligantes , Modelos Moleculares , Mutação , Mycobacterium tuberculosis/genética , Fator Tu de Elongação de Peptídeos/química , Fator Tu de Elongação de Peptídeos/genética , Ligação Proteica , Domínios Proteicos , Aminoacil-RNA de Transferência/metabolismo , Ribossomos/metabolismo
9.
Bioorg Chem ; 82: 58-67, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30268974

RESUMO

Ribosomal protein S1 (RpsA) has been identified as a novel target of pyrazinoic acid (POA), which is the active form of pyrazinamide (PZA), in vivo. RpsA plays a crucial role in trans-translation, which is widespread in microbes. In our investigation, we first described the discovery of promising RpsA antagonists for drug-resistant mycobacterium (MtRpsAd438A) and M. smegmatis, as well as wild-type M. tuberculosis. These antagonists were discovered via structure/ligand-based virtual screening approaches. A total of 21 targeted compounds were selected by virtual screening, combined scores, affinity, similarities and rules for potential as drugs. Next, the affinities of these compounds for three targeted proteins were tested in vitro by applying various technologies, including fluorescence quenching titration (FQT), saturation transfer difference (STD), and chemical shift perturbation (CSP) assays. The results showed that seven compounds had a high affinity for the targeted proteins. Our discovery set the stage for discovering new chemical entities (NCEs) for PZA-resistant tuberculosis and providing key residues for rational drug design to target RpsA.


Assuntos
Antituberculosos/farmacologia , Azóis/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Compostos Heterocíclicos com 2 Anéis/farmacologia , Proteínas Ribossômicas/antagonistas & inibidores , Antituberculosos/química , Azóis/química , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Sítios de Ligação , Avaliação Pré-Clínica de Medicamentos , Compostos Heterocíclicos com 2 Anéis/química , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Mutação , Mycobacterium smegmatis/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Proteínas Ribossômicas/química , Proteínas Ribossômicas/genética , Software
10.
Onco Targets Ther ; 11: 7459-7469, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30498360

RESUMO

Background: Lung cancer is one of the most common malignancies in the world and is at the forefront of causes of all cancer deaths. Identification of new prognostic predictors or therapeutic targets might improve a patient's survival rate. Purpose: The Homeodomain interacting protein kinases (HIPKs) function as modulators of cellular stress responses and regulate cell differentiation, proliferation and apoptosis, but the function of HIPK3 is remain unknown. Patients and methods: We used quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting methods to detective the expression of HIPK3. A total of 206 samples were obtained from patients and Immunochemical evaluation to determine HIPK3 protein expression. HIPK3 protein levels in in non-small cell lung cancer (NSCLC) were correlated with the clinical characteristics of patients and their 5-year survival rate. In addition, HIPK3 knockdown by specific RNAi promoted cell proliferation, migration, and invasion in A549 and HCC827 cancer cell lines. Results: The quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting methods to demonstrate that HIPK3 expression was significantly down-regulated in non-small cell lung cancer (NSCLC) tissues compared with that in normal lung tissues. At the same time, the results of immunohistochemistry assays showed that low expression of HIPK3 was significantly associated with pathology grade; tumor, node, and metastases (TNM) stage; lymph node metastasis; Ki-67 expression; and the 5-year survival rate in NSCLC patients. Univariate analysis revealed that HIPK3 expression, Ki-67 expression, tumor diameter, TNM stage, and age were significantly associated with a poor prognosis. The multivariable analysis illustrated that HIPK3, tumor diameter, TNM, Ki-67 expression, and age had effects on the overall survival of NSCLC patients independently. Kaplan-Meier survival curves revealed that NSCLC patients with a lower HIPK3 expression had a poorer prognosis. In addition, in vivo results also confirmed that HIPK3 over-expression could inhibit tumor growth. Conclusion: Our findings confirmed that low expression of HIPK3 in NSCLC tissues was significantly correlated with poor survival rates after curative resection. HIPK3 could potentially be used as a valuable biomarker in the prognosis of the survival of NSCLC patients.

11.
Zhen Ci Yan Jiu ; 43(8): 492-4, 2018 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-30232851

RESUMO

OBJECTIVE: To observe the influence of repeated shallow fire-needle acupuncture stimulation plus cupping on local neuralgia and serum substance P(SP)content in patients with acute herpes zoster (AHZ). METHODS: A total of 60 cases of AHZ patients were randomly divided into control (medication) group and treatment (medication plus fire-needle) group (n=30 in each). Patients of both groups were ordered to take Famciclovir (0.25 g/time, three times a day) and Mecobalamin (0.5 g/time, three times a day) orally for 7 days. In addition, patients of the treatment group were also treated by repeated shallow fire-needle stimulation and cupping, once a day for 7 days. Before and after the treatment, the patient's pain severity was assessed using visual analogue scale (VAS) and serum SP concentration was measured using ELISA. RESULTS: After the treatment, the VAS scores and serum SP concentrations in both groups were significantly decreased in comparison with those of their own pre-treatment (P<0.01), and were significantly lower in the treatment group than in the control group(P<0.01). There was a highly positive correlation between the decreased VAS score and serum SP content in the treatment group(P<0.01). CONCLUSION: Repeated shallow fire-needle stimulation plus cupping can accelerate the relief of local neuralgia in AHZ patients, which may be associated with its effect in down-regulating serum SP level.


Assuntos
Terapia por Acupuntura , Herpes Zoster , Moxibustão , Neuralgia , Humanos , Substância P , Resultado do Tratamento
12.
Colloids Surf B Biointerfaces ; 172: 480-486, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30199765

RESUMO

In this work, the effect of silica nanoparticles (NPs) adding to DPPC monolayer and the interaction between DPPC and silica nanoparticles are studied. Silica nanoparticles are prepared by microemulsion, meanwhile, DMDCS and APTES are used to modify silica NPs to get three types of modified silica NPs. These samples are mixed with DPPC to form mixed monolayer. By using the atomic force microscope (AFM), surface pressure-area and pressure-time isotherms, the effects of different hydrophilic-hydrophobic silica nanoparticles on the interface of lipid monolayer is analyzed. The data shows that the addition of silica nanoparticles changes the phase behavior, the collapse time and the structure of monolayer. Hydrophilic silica NPs decreases the collapse pressure and rigidity of DPPC monolayer, and makes monolayer collapse earlier since the steric hindrance leads to the resistance to compression, while hydrophobic silica NPs have less effect on monolayer in collapse pressure or rigidity but the texture of monolayer, and the addition of hydrophobic NPs causes the appearance of holes in the monolayer. We suppose that there are several possible locations of hydrophobic and hydrophilic silica nanoparticles in the air-water interface, which leads to different effects on the structure and rheological behavior of monolayer. This study can deepen the understanding on how nanoparticles affect human body since industries of nanoparticles on drug delivery, oil recovery and floatation are developing rapidly and getting more and more outside interest on a daily basis.


Assuntos
1,2-Dipalmitoilfosfatidilcolina/química , Nanopartículas/química , Dióxido de Silício/química , Ar , Microscopia de Força Atômica , Pressão , Temperatura Ambiente , Água/química , Difração de Raios X
13.
ACS Appl Mater Interfaces ; 10(28): 23693-23699, 2018 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-29963858

RESUMO

DNA nanostructures are promising biomaterials capable of arranging multiple functional components with nanometer precision. Here, a double-bundle DNA tetrahedron is rationally designed to integrate with antisense oligonucleotides silencing proto-oncogene c-raf and nuclear targeting peptides. The functionalized DNA tetrahedron can be internalized by A549 cells and assists the delivery of antisense oligonucleotides toward the nucleus to increase the chance to downregulate target mRNA in nucleus and cytoplasm. Antisense strands released from the tetrahedron in response to the intracellular reducing environment can inhibit cell proliferation at a low concentration without transfection reagent. Finally, efficient knockdown of c-raf gene is observed, which verified our design. This designer DNA-based nanocarrier system will open a new avenue for efficient delivery of nucleic acid drugs.


Assuntos
DNA/química , Oligonucleotídeos Antissenso , Preparações Farmacêuticas , RNA Mensageiro , Transfecção
14.
PLoS One ; 13(7): e0200021, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29985955

RESUMO

Proteins were extracted from perilla (Perilla frutescens L. Britton) seed by-products and hydrolyzed with an alkaline protease. Antioxidant peptides were purified from the hydrolysate by size-exclusion chromatography and RP-HPLC. Two peptides with strong antioxidant activity were identified as Tyr-Leu (YL) and Phe-Tyr (FY) with the molecular mass of 294.33 Da and 328.33 Da, respectively. Synthesized YL and FY efficiently quenched free radicals (DPPH, ABTS and hydroxyl radicals) and showed high oxygen radical absorbance capacity. The two peptides also inhibited lipid peroxidation in the rat liver. Furthermore, YL and FY could protect HepG-2 cells against hydrogen peroxide-induced oxidative damage without cytotoxicity. Based on the structure-activity analysis, the Tyr residue was crucial for the antioxidant activity of YL and FY. The results indicate that the protein hydrolysate from perilla seed by-products possessed potent biological activity and can be utilized to develop health-related nutraceutical ingredients.


Assuntos
Antioxidantes/análise , Antioxidantes/farmacologia , Peptídeos/análise , Peptídeos/farmacologia , Perilla frutescens/química , Proteínas de Plantas/química , Sementes/química , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Células CHO , Cricetulus , Citoproteção/efeitos dos fármacos , Células Hep G2 , Humanos , Peróxido de Hidrogênio/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peptídeos/química , Peptídeos/isolamento & purificação , Ratos , Relação Estrutura-Atividade
15.
Protein Expr Purif ; 151: 9-17, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29857035

RESUMO

The trans-translation system is recognized as an excellent target for developing new drugs to rapidly sterilize Mycobacterium tuberculosis (TB) infection and significantly shorten TB treatment duration. As a vital component of the trans-translation system for rescuing stalled ribosomes, the SmpB protein from Mycobacterium tuberculosis (MtbSmpB, 1-160 a. a.) mediates tmRNA binding to stalled ribosomes through forming a complex with tmRNA. So far, few works have been conducted to prepare, characterize biophysical properties and determine three-dimensional structure for the full-length MtbSmpB protein. In the present work, we successfully expressed and purified the His-tagged full-length MtbSmpB protein in Escherichia coli with a yield of 26.9 mg from 1 L of Luria Bertani medium. We also obtained MtbSmpB with a yield of 18.5 mg from 1 L of M9 minimal medium. The MtbSmpB protein showed a single band in SDS-PAGE with a molecular weight of ∼20 kDa consistent with the measurement from MALDI-TOF-mass spectrometry. The dynamic light scattering experiment indicated that MtbSmpB existed in a monomeric form. Moreover, both circular dichroism and nuclear magnetic resonance (NMR) experiments exhibited that MtbSmpB was well structured, suggesting that it could be feasible to determine its solution structure by NMR spectroscopy. NMR titration experiments showed that MtbSmpB specifically bound to tmRNA. This work lays the essential basis for further determining the solution structure and dynamics of the full-length MtbSmpB protein.


Assuntos
Proteínas de Bactérias/biossíntese , Mycobacterium tuberculosis/metabolismo , Proteínas de Ligação a RNA/biossíntese , Proteínas de Bactérias/isolamento & purificação , Escherichia coli/genética , Modelos Moleculares , Conformação Proteica , Proteínas de Ligação a RNA/isolamento & purificação
16.
Int J Ophthalmol ; 11(3): 484-492, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29600184

RESUMO

AIM: To compare a trifocal intraocular lens (IOL) and a bifocal IOL implantation in improving visual function after cataract surgery. METHODS: Eligible literatures were systematically searched through EMBASE and PubMed databases. The inclusion criteria were prospective comparative clinical trials on cataract surgery comparing trifocal IOL with bifocal IOL implantation that assessed visual acuity, contrast sensitivity and subjective vision quality. The effects were computed as standardized mean differences and pooled using fixed-effect or random-effect models. RESULTS: Four prospective randomized controlled trials (RCTs) and five cohorts provided data were included by a systematic review, comprising 265 eyes implanted with trifocal IOLs and 264 eyes implanted with bifocal IOLs. Monocular distance visual acuity (VA) showed a statistically significant but small difference that favored trifocal IOLs (MD=-0.06; 95%CI, -0.10 to -0.02; Z=2.90, P=0.004 for uncorrected distance VA, and MD= -0.02; 95%CI, -0.03 to -0.00; Z=2.02, P=0.04 for corrected distance VA), but the data did not suggest that the effect of trifocal IOL implantation would clinically outperform bifocal IOL implantation. There was no significant difference in monocular near VA (MD=-0.01; 95%CI, -0.07 to 0.04; Z=0.42, P=0.68 for distance-corrected near VA, and MD=-0.01; 95%CI, -0.06 to 0.03; Z=0.55, P=0.58 for corrected near VA) or refraction between two groups. Contrast sensitivity and subjective visual quality had no conclusive results. CONCLUSION: All results indicate that trifocal IOL and bifocal IOL had similar levels of monocular distance and near VA.

17.
J Inequal Appl ; 2018(1): 354, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30839907

RESUMO

An efficient inner approximation algorithm is presented for solving the generalized linear multiplicative programming problem with generalized linear multiplicative constraints. The problem is firstly converted into an equivalent generalized geometric programming problem, then some magnifying-shrinking skills and approximation strategies are used to convert the equivalent generalized geometric programming problem into a series of posynomial geometric programming problems that can be solved globally. Finally, we prove the convergence property and some practical application examples in optimal design domain, and arithmetic examples taken from recent literatures and GLOBALLib are carried out to validate the performance of the proposed algorithm.

18.
Colloids Surf B Biointerfaces ; 161: 614-619, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29156338

RESUMO

In this paper, we examined the effect of Laminaria japonica polysaccharides (LJP) on cationic 1,2-Dioleoyl-3-Trimethylammonium-Propane (DOTAP) and anionic 1,2-dipalmitoyl-sn-glycero-3-[phospho-rac-1-glycerol] (DPPG) monolayers at the air-water interface by the pressure-area isotherms (π-A), adsorption curves (π-t) and morphology measurements with atomic force microscopy (AFM) technique. The π-A curves revealed that the isotherms shifted to larger mean molecular area with progressive addition of LJP into subphase for both DOTAP and DPPG monolayers. And the compression modulus Cs-1 obtained from π-A curves showed that the elasticity of the films decreased with the addition of LJP. Adsorption curves were measured at the surface pressure of 10 and 20mN/m, which were fitted by the adsorption kinetics equation. It revealed that DOTAP monolayer changed into a mixed film with the insertion of polysaccharides molecules. However, there was no significant effect on the surface pressure for DPPG monolayer. Besides, surface morphology was observed by AFM, which was consistent with the results of fitted adsorption curves.


Assuntos
Laminaria/química , Lipídeos/química , Membranas Artificiais , Polissacarídeos/química , Adsorção , Ar , Cátions/química , Ácidos Graxos Monoinsaturados/química , Microscopia de Força Atômica , Fosfatidilgliceróis/química , Pressão , Compostos de Amônio Quaternário/química , Propriedades de Superfície , Termodinâmica , Água/química
19.
J Food Drug Anal ; 25(4): 766-775, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28987352

RESUMO

In this study, polysaccharides from Angelica sinensis were extracted using the ultrasound-assisted extraction method. Based on the results of single factor experiments and orthogonal tests, three independent variables-water/raw material ratio, ultrasound time, and ultrasound power-were selected for investigation. Then, we used response surface methodology to optimize the extraction conditions. The experimental data were fitted to a quadratic equation using multiple regression analysis, and the optimal conditions were as follows: water/raw material ratio, 43.31 mL/g; ultrasonic time, 28.06 minutes; power, 396.83 W. Under such conditions, the polysaccharide yield was 21.89±0.21%, which was well matched with the predicted yield. In vitro assays, scavenging activity of superoxide anion radicals, hydroxyl radicals, and 2,2-diphenyl-1-picry-hydrazyl radical showed that polysaccharides had certain antioxidant activities and that hydroxyl radicals have a remarkable scavenging capability. Therefore, these studies provide reference for further research and rational development of A. sinensis polysaccharide.


Assuntos
Angelica sinensis/química , Antioxidantes/isolamento & purificação , Fracionamento Químico/métodos , Extratos Vegetais/isolamento & purificação , Polissacarídeos/isolamento & purificação , Antioxidantes/análise , Extratos Vegetais/análise , Polissacarídeos/análise
20.
ACS Appl Mater Interfaces ; 9(24): 20324-20329, 2017 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-28570804

RESUMO

Dendrimer-like DNA nanostructures have attractive properties such as mechanical stability, highly branched nanostructure, customized sizes, and biocompatibility. In this study, we construct programmable DNA dendrimeric nanoparticles as efficient vehicles to deliver immunostimulatory cytosine-phosphate-guanosine (CpG) sequences for activation of the immune response. DNA dendrimers decorated with CpG-containing hairpin-loops triggered stronger immune response characterized by pro-inflammatory cytokines production, in contrast to DNA dendrimers loading linear CpG. After further modification with TAT peptide, a typical cell-penetrating peptide, on the surface of the nanocarriers, CpG loops-loaded DNA dendrimers showed the enhanced cell internalization and cytokines production. The TAT-DNA dendrimer-CpG loops constructs did not affect the viability of immune cells and no detectable cytotoxicity was observed. Our results demonstrate that the DNA dendrimers can serve as designable and safe vehicles for delivery of immune modulators and anticancer drugs.


Assuntos
Nanopartículas , Ilhas de CpG , Citosina , DNA , Dendrímeros , Guanosina
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