Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 42
Filtrar
1.
Chemosphere ; 346: 140557, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38303399

RESUMO

Single-atom nanozymes (SANs) are nanomaterials-based nanozymes with atomically dispersed enzyme-like active sites. SANs offer improved as well as tunable catalytic activity. The creation of extremely effective SANs and their potential uses have piqued researchers' curiosity due to their advantages of cheap cost, variable catalytic activity, high stability, and large-scale production. Furthermore, SANs with uniformly distributed active centers and definite coordination structures offer a distinctive opportunity to investigate the structure-activity correlation and control the geometric and electrical features of metal centers. SANs have been extensively explored in photo-, thermal-, and electro-catalysis. However, SANs suffer from the following disadvantages, such as efficiency, non-mimicking of the 3-D complexity of natural enzymes, limited and narrow range of artificial SANs, and biosafety aspects. Among a quite limited range of artificial SANs, the peroxidase action of SANs has attracted significant research attention in the last five years with the aim of producing reactive oxygen species for use in cancer therapy, and water treatment among many other applications. In this review, we explore the recent progress of different SANs as peroxidase mimics, the role of the metal center in enzymatic activity, possible prospects, and underlying limitations in real-time applications.


Assuntos
Materiais Biomiméticos , Nanoestruturas , Materiais Biomiméticos/química , Nanoestruturas/química , Peroxidase , Catálise , Peroxidases
2.
J Agric Food Chem ; 71(41): 15097-15105, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37781984

RESUMO

The relationship between trimethylamine-N-oxide (TMAO), betaine, and choline with acute myocardial infarction (AMI) end point remains unclear. We analyzed plasma TMAO, betaine, and choline concentrations in AMI cases and non-AMI community-dwelling controls by LC-MS/MS to understand how the balance between these metabolites helps to reduce AMI risk. Results showed that the odds ratio (OR) for the highest versus lowest quartiles of betaine was 0.30 (95% CI, 0.10-0.82) after adjustment for AMI risk factors, and the unadjusted OR for quartile 3 versus quartile 1 of TMAO was 2.47 (95% CI, 1.02-6.17) (p < 0.05). The study populations with "high betaine + low TMAO" had a significant protective effect concerning AMI with a multivariable-adjusted OR of 0.20 (95% CI, 0.07-0.55) (p < 0.01). Multivariate linear regression showed that the chronological age was correlated with TMAO concentrations among AMI patients (95% CI, 0.05-3.24, p < 0.01) but not among the controls. This implies a further potential interplay between age and metabolite combination─AMI risk association.


Assuntos
Betaína , Infarto do Miocárdio , Humanos , Betaína/metabolismo , Colina/metabolismo , Cromatografia Líquida , Espectrometria de Massas em Tandem , Metilaminas/metabolismo , Óxidos
3.
J Hazard Mater ; 455: 131600, 2023 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-37182467

RESUMO

Sewage sludge (SS) is a hazardous by-product of wastewater treatment processes that requires careful management for minimal environmental impacts and effective resource recovery. Through thermochemical processes such as pyrolysis, clean energy is recovered from SS in the form of bio-oil, biogas, and biochar. To improve the yield and quality of products, the co-pyrolysis of more than two materials is increasingly gaining interest. Here, the thermal behaviour, kinetics, and synergistic interactions during the co-pyrolysis of SS with polypropylene (PP) and high-density polyethylene (HDPE) were comparatively evaluated with thermogravimetric analysis at different mixing ratios and heat rates. Activation energies and reaction mechanisms were determined through iso-conversional model-free methods and master plot analysis. Evolved gases were monitored with thermogravimetric-mass spectrometry. Increased volatile conversion and degradation rates, and reduced activation energies during co-pyrolysis were mediated by synergistic interactions between H-radicals of PP/HDPE and oxygenated intermediates of SS. Contrary to the pyrolysis of SS, PP and HDPE, the co-pyrolysis processes are predominantly diffusion-controlled. Insights into the co-pyrolysis processes of SS/PP and SS/HDPE gained from this work provide the theoretical support for subsequent investigation, facilitate design of waste-to-energy reactor, and aid the adoption of the technology to harness the bioenergy potential of the feedstocks.

4.
J Trace Elem Med Biol ; 77: 127148, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36905853

RESUMO

Acute myocardial infarction (AMI) is a leading cause of mortality and morbidity worldwide. Using a validated and efficient ICP-MS/MS-based workflow, a total of 30 metallomic features were profiled in a study comprising 101 AMI patients and 66 age-matched healthy controls. The metallomic features include 12 essential elements (Ca, Co, Cu, Fe, K, Mg, Mn, Na, P, S, Se, Zn), 8 non-essential/toxic elements (Al, As, Ba, Cd, Cr, Ni, Rb, Sr, U, V), and 10 clinically relevant element-pair product/ratios (Ca/Mg, Ca×P, Cu/Se, Cu/Zn, Fe/Cu, P/Mg, Na/K, Zn/Se). Preliminary linear regression with feature selection confirmed smoking status as a predominant determinant for the non-essential/toxic elements, and revealed potential routes of action. Univariate assessments with adjustments for covariates revealed insights into the ambivalent relationships of Cu, Fe, and P with AMI, while also confirming cardioprotective associations of Se. Also, beyond their roles as risk factors, Cu and Se may be involved in the response mechanism in AMI onset/intervention, as demonstrated via longitudinal data analysis with 2 additional time-points (1-/6-month follow-up). Finally, based on both univariate tests and multivariate classification modelling, potentially more sensitive markers measured as element-pair ratios were identified (e.g., Cu/Se, Fe/Cu). Overall, metallomics-based biomarkers may have utility for AMI prediction.


Assuntos
Espectrometria de Massas em Tandem , Oligoelementos , Humanos , Modelos Lineares , Oligoelementos/análise
5.
Metallomics ; 14(12)2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36271844

RESUMO

In research enabling preclinical development and attaining a deeper understanding of the behavior of metallodrugs in cancer cells with acquired resistance, intracellular Pt accumulation could be considered an important biomarker and analytical focus. In this work, Pt accumulation patterns in terms of the number of cells and Pt mass in single cells were precisely defined by using inductively coupled plasma-mass spectrometry (ICP-MS) operating in a fast time-resolved analysis mode. This technique is otherwise known as single-cell (SC)-ICP-MS. By applying the nascent and validated SC-ICP-MS technique, comparisons across three Pt drugs (cisplatin, carboplatin, and oxaliplatin) in the A2780 and A2780cis ovarian cancer cell models could be made. Additional roles of transporters on top of passive diffusion and the drugs' bioactivity could be postulated. The SC-ICP-MS-based observations also served as a cross-validation point to augment preexisting research findings on Pt-resistance mechanisms. Conjectures regarding S and Fe metabolism were also derived based on an additional and direct ICP-MS analysis of endogenous elements. Overall, our work not only confirms the utility of SC-ICP-MS in chemotherapeutic research, but also provided insights into further ICP-MS-based analytical capacities to be developed.


Assuntos
Antineoplásicos , Neoplasias Ovarianas , Humanos , Feminino , Cisplatino/metabolismo , Compostos Organoplatínicos/farmacologia , Compostos Organoplatínicos/química , Linhagem Celular Tumoral , Neoplasias Ovarianas/tratamento farmacológico , Oxaliplatina , Antineoplásicos/química
7.
Ann Surg Oncol ; 29(12): 7542-7548, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35849291

RESUMO

PURPOSE: Gastrointestinal stromal tumor (GIST) is associated with increased risk of additional cancers. In this study, synchronous GIST, and peritoneal mesothelioma (PM) were characterized to evaluate the relationship between these two cancers. METHODS: A retrospective chart review was conducted for patients diagnosed with both GIST and PM between July 2010 and June 2021. Patient demographics, past tumor history, intraoperative reports, cross-sectional imaging, peritoneal cancer index (PCI) scoring, somatic next-generation sequencing (NGS) analysis, and histology were reviewed. RESULTS: Of 137 patients who underwent primary GIST resection from July 2010 to June 2021, 8 (5.8%) were found to have synchronous PM, and 4 patients (50%) had additional cancers and/or benign tumors. Five (62.5%) were male, and the median age at GIST diagnosis was 57 years (range: 45-76). Seventy-five percent of GISTs originated from the stomach. Of the eight patients, one patient had synchronous malignant mesothelioma (MM), and the remaining had well-differentiated papillary mesothelioma (WDPM), which were primarily located in the region of the primary GIST (89%). The median PCI score was 2 in the WDPM patients. NGS of GIST revealed oncogenic KIT exon 11 (62.5%), PDGFRA D842V (25%), or SDH (12.5%) mutations, while NGS of the MM revealed BAP1 and PBRM1 alterations. CONCLUSIONS: One in 17 GIST patients undergoing resection in this series have PM, which is significantly higher than expected if these two diseases were considered as independent events. Our results indicate that synchronous co-occurrence of GIST and PM is an underrecognized finding, suggesting a possible relationship that deserves further investigation.


Assuntos
Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Mesotelioma Maligno , Mesotelioma , Neoplasias Peritoneais , Idoso , Feminino , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Masculino , Mesotelioma/genética , Mesotelioma/cirurgia , Pessoa de Meia-Idade , Mutação , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/cirurgia , Proteínas Proto-Oncogênicas c-kit/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Estudos Retrospectivos
8.
Food Chem ; 393: 133452, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-35751219

RESUMO

Glycinebetaine (GB) has long been used as a preservative for refrigerated fruits, but the effect of GB on the global metabolites of cold-stored strawberries is still unclear. In this study, the effects of exogenous application of GB on quality-related metabolites of cold-stored strawberries were investigated by nuclear magnetic resonance (NMR)-based metabolomic analysis. The results showed that the application of GB (especially at the concentration of 10 mM) on cold-stored strawberries effectively stabilized the sugars (d-xylose and d-glucose) and amino acids (tyrosine, leucine, and tryptophan) content, and lowered the acid (acetic acid) content as well. Additionally, the GB content in strawberries also increased. This implies that the appropriate concentration of GB is a natural and safe treatment, which could maintain the quality of cold-stored strawberries by regulating levels of quality-related metabolites, and the ingestion of GB-preserved strawberries may serve as a source of methyl-donor supplementation in our daily diet.


Assuntos
Fragaria , Betaína/análise , Fragaria/química , Frutas/química , Espectroscopia de Ressonância Magnética , Metabolômica , Espectroscopia de Prótons por Ressonância Magnética
9.
Clin Cancer Res ; 28(1): 187-200, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34426440

RESUMO

PURPOSE: Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the gastrointestinal tract, with mutant succinate dehydrogenase (SDH) subunits (A-D) comprising less than 7.5% (i.e., 150-200/year) of new cases annually in the United States. Contrary to GISTs harboring KIT or PDGFRA mutations, SDH-mutant GISTs affect adolescents/young adults, often metastasize, and are frequently resistant to tyrosine kinase inhibitors (TKI). Lack of human models for any SDH-mutant tumors, including GIST, has limited molecular characterization and drug discovery. EXPERIMENTAL DESIGN: We describe methods for establishing novel patient-derived SDH-mutant (mSDH) GIST models and interrogated the efficacy of temozolomide on these tumor models in vitro and in clinical trials of patients with mSDH GIST. RESULTS: Molecular and metabolic characterization of our patient-derived mSDH GIST models revealed that these models recapitulate the transcriptional and metabolic hallmarks of parent tumors and SDH deficiency. We further demonstrate that temozolomide elicits DNA damage and apoptosis in our mSDH GIST models. Translating our in vitro discovery to the clinic, a cohort of patients with SDH-mutant GIST treated with temozolomide (n = 5) demonstrated a 40% objective response rate and 100% disease control rate, suggesting that temozolomide represents a promising therapy for this subset of GIST. CONCLUSIONS: We report the first methods to establish patient-derived mSDH tumor models, which can be readily employed for understanding patient-specific tumor biology and treatment strategies. We also demonstrate that temozolomide is effective in patients with mSDH GIST who are refractory to existing chemotherapeutic drugs (namely, TKIs) in clinic for GISTs, bringing a promising treatment option for these patients to clinic.See related commentary by Blakely et al., p. 3.


Assuntos
Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Adolescente , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/genética , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Humanos , Mutação , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Succinato Desidrogenase/metabolismo , Adulto Jovem
10.
Curr Issues Mol Biol ; 43(3): 1876-1888, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34889896

RESUMO

The present work demonstrated and compared the anti-inflammatory effects of celery leaf (CLE) and stem (CSE) extracts. LC-MS-based metabolomics were an effective approach to achieve the biomarker identification and pathway elucidation associated with the reduction in inflammatory responses. The celery extracts suppressed LPS-induced NO production in RAW 264.7 cells, and CLE was five times more effective than CSE. Distinct differences were revealed between the control and celery-treated samples among the 24 characteristic metabolites that were identified. In celery-treated LPS cells, reversals of intracellular (citrulline, proline, creatine) and extracellular (citrulline, lysine) metabolites revealed that the therapeutic outcomes were closely linked to arginine metabolism. Reversals of metabolites when treated with CLE (aspartate, proline) indicated targeted effects on the TCA and urea cycles, while, in the case of CSE (histidine, glucose), the glycolysis and the pentose phosphate pathways were implicated. Subsequently, apigenin and bergapten in CLE were identified as potential biomarkers mediating the anti-inflammatory response.


Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Apium/química , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Animais , Cromatografia Líquida , Lipopolissacarídeos/imunologia , Ativação de Macrófagos/efeitos dos fármacos , Ativação de Macrófagos/imunologia , Metaboloma , Metabolômica/métodos , Camundongos , Óxido Nítrico/metabolismo , Folhas de Planta/química , Caules de Planta/química , Células RAW 264.7 , Espectrometria de Massas em Tandem
11.
ACS Omega ; 6(23): 15192-15198, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34151098

RESUMO

The capability of pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS) for the direct analysis of endotoxins is demonstrated in this research article using the lipopolysaccharides of Pseudomonas aeruginosa 10. Analytical methods based on evolved gas analysis-MS, single-shot (SS) Py-GC-MS, and multishot heart cut Py-GC-MS were investigated. Among the various methods developed, the SS Py-GC-MS method shows superior potential for identifying bacterial endotoxins effectively through their biomarkers. The results obtained were validated with conventional mass spectral analysis after hydrolysis. The method was also evaluated for its robustness based on quality control criteria indicated by the U.S. EPA Method 8270D. When applied onto endotoxins of different Gram-negative bacteria, this method produced vastly distinct pyrograms. The results show that rapid and sensitive direct detection of endotoxins is possible with the Py-GC-MS method developed.

12.
Gut Microbes ; 11(3): 610-619, 2020 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-32036739

RESUMO

Gaining a complete understanding of transmission risk factors will assist in efforts to reduce new HIV infections, especially within the disproportionally affected population of men who have sex with men (MSM). We recently reported that the fecal microbiota of MSM elevates immune activation in gnotobiotic mice and enhances HIV infection in vitro over that of fecal microbiota from men who have sex with women. We also demonstrated elevation of the gut homing marker CD103 (integrin αE) on CD4+ T cells by MSM-microbiota. Here we provide additional evidence that the gut microbiota is a risk factor for HIV transmission in MSM by showing elevated frequencies of the HIV co-receptor CCR5 on CD4+ T cells in human rectosigmoid colon biopsies. We discuss our interest in specific MSM-associated bacteria and propose the influx of CD103+ and CCR5+ CD4+ T cells into the colon as a potential link between the MSM microbiota and HIV transmission.


Assuntos
Microbioma Gastrointestinal , Infecções por HIV/microbiologia , Infecções por HIV/transmissão , Minorias Sexuais e de Gênero , T-Linfocitopenia Idiopática CD4-Positiva/imunologia , Adolescente , Adulto , Antígenos CD/imunologia , Biópsia , Colo/imunologia , Colo/microbiologia , Feminino , Infecções por HIV/imunologia , Humanos , Cadeias alfa de Integrinas/imunologia , Masculino , Pessoa de Meia-Idade , Receptores CCR5/imunologia , Fatores de Risco , Comportamento Sexual , T-Linfocitopenia Idiopática CD4-Positiva/microbiologia , Adulto Jovem
13.
PLoS Pathog ; 15(4): e1007611, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30947289

RESUMO

Men who have sex with men (MSM) have differences in immune activation and gut microbiome composition compared with men who have sex with women (MSW), even in the absence of HIV infection. Gut microbiome differences associated with HIV itself when controlling for MSM, as assessed by 16S rRNA sequencing, are relatively subtle. Understanding whether gut microbiome composition impacts immune activation in HIV-negative and HIV-positive MSM has important implications since immune activation has been associated with HIV acquisition risk and disease progression. To investigate the effects of MSM and HIV-associated gut microbiota on immune activation, we transplanted feces from HIV-negative MSW, HIV-negative MSM, and HIV-positive untreated MSM to gnotobiotic mice. Following transplant, 16S rRNA gene sequencing determined that the microbiomes of MSM and MSW maintained distinct compositions in mice and that specific microbial differences between MSM and MSW were replicated. Immunologically, HIV-negative MSM donors had higher frequencies of blood CD38+ HLADR+ and CD103+ T cells and their fecal recipients had higher frequencies of gut CD69+ and CD103+ T cells, compared with HIV-negative MSW donors and recipients, respectively. Significant microbiome differences were not detected between HIV-negative and HIV-positive MSM in this small donor cohort, and immune differences between their recipients were trending but not statistically significant. A larger donor cohort may therefore be needed to detect immune-modulating microbes associated with HIV. To investigate whether our findings in mice could have implications for HIV replication, we infected primary human lamina propria cells stimulated with isolated fecal microbiota, and found that microbiota from MSM stimulated higher frequencies of HIV-infected cells than microbiota from MSW. Finally, we identified several microbes that correlated with immune readouts in both fecal recipients and donors, and with in vitro HIV infection, which suggests a role for gut microbiota in immune activation and potentially HIV acquisition in MSM.


Assuntos
Microbioma Gastrointestinal/imunologia , Vida Livre de Germes/imunologia , Infecções por HIV/imunologia , HIV/imunologia , Homossexualidade Masculina , Adolescente , Adulto , Idoso , Animais , Estudos de Coortes , DNA Bacteriano/genética , Fezes/microbiologia , Feminino , HIV/genética , Infecções por HIV/microbiologia , Infecções por HIV/virologia , Humanos , Técnicas In Vitro , Masculino , Camundongos , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Comportamento Sexual , Adulto Jovem
14.
Sci Rep ; 8(1): 16440, 2018 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-30401822

RESUMO

Triphenyl phosphate (TPHP) is one of the most highly utilized organophosphorus flame retardants, and has been frequently detected in various environmental matrices, including soil. So far, limited information is known regarding the potential toxicity of TPHP to the earthworm-soil ecosystem. We investigated the metabolism of TPHP and the perturbation of the endogenous metabolome in the earthworm, Perionyx excavatus, using gas chromatography mass spectrometry (GC-MS) and liquid chromatography quadrupole time-of-flight (LC-QTOF)-based untargeted metabolomics approach after acute exposure to TPHP for one and two days through a filter paper contact test, as well as after chronic exposure for 28 days in a soil microcosm experiment. TPHP showed low bioaccumulation potential in the earthworm-soil ecosystem at concentrations of 10 mg/kg and 50 mg/kg. Identified phase I metabolites include diphenyl phosphate, mono-hydroxylated and di-hydroxylated TPHP. Two groups of phase II metabolites, thiol conjugates (including mercaptolactic acid, cysteine, cysteinylglycine, and mercaptoethanol conjugates) and glucoside conjugates (including glucoside, glucoside-phosphate, and C14H19O10P conjugates), were putatively identified. Only acute TPHP exposure caused significant perturbations of the endogenous metabolome in earthworms, featuring fluctuations in amino acids, glucose, inosine and phospholipids. These results reveal novel phase II metabolism and toxicity of TPHP in P. excavatus.


Assuntos
Biotransformação , Exposição Ambiental/efeitos adversos , Redes e Vias Metabólicas , Metaboloma , Oligoquetos/fisiologia , Organofosfatos/toxicidade , Animais , Cromatografia Gasosa-Espectrometria de Massas , Oligoquetos/efeitos dos fármacos , Oligoquetos/metabolismo
15.
Pain Physician ; 21(5): 497-504, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30282394

RESUMO

BACKGROUND: Abdominal pain from primary cancer or metastatic disease is a significant cause of pain for patients undergoing treatment for the disease. Patient's pain may be resistant to conventional analgesics. The need for timely pain relief in order to facilitate further care in the cancer treatment plan should be a priority. OBJECTIVES: The aim of this retrospective observational review was to assess the relief given with a low volume neurolytic retrocrural celiac plexus nerve block, the duration of the procedure, the duration of relief, the reduction in daily opioid consumption, and the improvement of quality of life in a patient suffering from incapacitating abdominal pain due to primary abdominal malignancy or abdominal metastatic disease. Patients were given a neurolytic celiac plexus block without previous diagnostic block due to multiple comorbidities. STUDY DESIGN: This is a retrospective, observational study. METHODS: Five hundred and seven patients were studied and data at 5 months for 455 patients were retained at the end of the review. They were evaluated in the pain center prior to and after the neurolytic retrocrural celiac plexus nerve block under fluoroscopic guidance. They were assessed on duration of procedure, pain scores (numeric rating scale 0-10), daily opioid consumption, quality of life improvement (simple yes or no question at 3 months) and routine follow-up during treatment for the cancer for 6 months or end of life. All data was gathered by extensive chart review and placed on a spreadsheet for analysis. RESULTS: Follow-up was completed 6 months after the procedure. Pain scores, daily opioid consumption, and quality of life showed improvement for the duration of the study. There was some return in pain during the fourth to sixth month due to disease progression and the anticipated duration of the neurolytic agent. Some short duration known side effects did occur. An initial vascular contrast uptake of 6.7% was noted during the procedure while utilizing digital subtraction angiography with fluoroscopy. LIMITATIONS: A larger sample size would be ideal, as well as, a prospective trial with a control group, but this is unrealistic in our patient population. A proven quality of life questionnaire would be beneficial. Comparing alcohol, phenol and radiofrequency thermocoagulation would be interesting to equate duration, effect, and side effects. CONCLUSION: Low volume neurolytic retrocrural celiac plexus nerve block with phenol is a safe procedure providing up to 6 months of pain relief and is an effective, well-established, minimally time-consuming procedure for abdominal pain due to primary malignancy or metastatic spread. KEY WORDS: Celiac plexus, neurolytic, abdominal cancer pain, pain, retrocrural, cancer pain.


Assuntos
Bloqueio Nervoso Autônomo/métodos , Dor do Câncer/tratamento farmacológico , Manejo da Dor/métodos , Dor Visceral/tratamento farmacológico , Neoplasias Abdominais/complicações , Plexo Celíaco/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Dor Visceral/etiologia
16.
Chem Sci ; 9(17): 4044-4051, 2018 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-29780533

RESUMO

Chloride-selective transmembrane carriers or channels might have possible uses in treating channelopathies or cancers. While chloride carriers have been extensively investigated, the corresponding chloride channels have remained limitedly studied. Moreover, all hitherto reported channel systems lack clearly definable and readily modifiable positions in their structures for the reliable construction and combinatorial optimization of their ion transport properties. As a result, the existing channels are limited by their large molecular weight, weak activity or low anion selectivity. In this report, we describe a readily accessible and robust monopeptide-based scaffold for the reliable construction of halogen bond-mediated artificial anion channels via directional assembly of electron-deficient iodine atoms, which create a transmembrane pathway for facilitating anion transport. The high intrinsic modularity of the backbone of the scaffold, which enables the rapid and combinatorial optimization of the transport activity and selectivity of channels, effectively delivers a highly active chloride channel A10. Such high activity in chloride transport subsequently leads to an excellent IC50 value of 20 µM toward inhibiting the growth of human breast cancer cells (BT-474), an anticancer activity that is even higher than that of the well-known anticancer agent cisplatin.

17.
EBioMedicine ; 30: 192-202, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29650491

RESUMO

The inflammatory properties of the enteric microbiota of Human Immunodeficiency Virus (HIV)-infected individuals are of considerable interest because of strong evidence that bacterial translocation contributes to chronic immune activation and disease progression. Altered enteric microbiota composition occurs with HIV infection but whether altered microbiota composition or increased intestinal permeability alone drives peripheral immune activation is controversial. To comprehensively assess the inflammatory properties of HIV-associated enteric microbiota and relate these to systemic immune activation, we developed methods to purify whole fecal bacterial communities (FBCs) from stool for use in in vitro immune stimulation assays with human cells. We show that the enteric microbiota of untreated HIV-infected subjects induce significantly higher levels of activated monocytes and T cells compared to seronegative subjects. FBCs from anti-retroviral therapy (ART)-treated HIV-infected individuals induced intermediate T cell activation, indicating an only partial correction of adaptive immune cell activation capacity of the microbiome with ART. In vitro activation levels correlated with activation levels and viral load in blood and were particularly high in individuals harboring specific gram-positive opportunistic pathogens. Blockade experiments implicated Tumor Necrosis Factor (TNF)-α and Toll-Like Receptor-2 (TLR2), which recognizes peptidoglycan, as strong mediators of T cell activation; This may contradict a previous focus on lipopolysaccharide as a primary mediator of chronic immune activation. These data support that increased inflammatory properties of the enteric microbiota and not increased permeability alone drives chronic inflammation in HIV.


Assuntos
Fezes/microbiologia , Infecções por HIV/imunologia , Infecções por HIV/microbiologia , Microbiota , Bactérias/crescimento & desenvolvimento , Contagem de Colônia Microbiana , Citocinas/metabolismo , Feminino , HIV-1/fisiologia , Homossexualidade Masculina , Humanos , Mediadores da Inflamação/metabolismo , Ativação Linfocitária/imunologia , Masculino , Análise de Componente Principal , RNA Ribossômico 16S/genética , Linfócitos T/imunologia , Receptores Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Carga Viral
18.
Molecules ; 22(2)2017 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-28212342

RESUMO

Amentoflavone (C30H18O10) is a well-known biflavonoid occurring in many natural plants. This polyphenolic compound has been discovered to have some important bioactivities, including anti-inflammation, anti-oxidation, anti-diabetes, and anti-senescence effects on many important reactions in the cardiovascular and central nervous system, etc. Over 120 plants have been found to contain this bioactive component, such as Selaginellaceae, Cupressaceae, Euphorbiaceae, Podocarpaceae, and Calophyllaceae plant families. This review paper aims to profile amentoflavone on its plant sources, natural derivatives, pharmacology, and pharmacokinetics, and to highlight some existing issues and perspectives in the future.


Assuntos
Biflavonoides/química , Biflavonoides/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Biflavonoides/isolamento & purificação , Humanos , Estrutura Molecular , Extratos Vegetais/isolamento & purificação
19.
PLoS One ; 11(11): e0166322, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27880772

RESUMO

Knowledge of the processes that underlie IgG subclass switching could inform strategies designed to counteract infections and autoimmunity. Here we show that TLR7 ligands induce subsets of memory CD4 and CD8 T cells to secrete interferon γ (IFNγ) in the absence of antigen receptor stimulation. In turn, TLR ligation and IFNγ cause B cells to express the transcription factor, T-bet, and to switch immunoglobulin production to IgG2a/c. Absence of TLR7 in T cells leads to the impaired T-bet expression in B cells and subsequent inefficient IgG2a isotype switching both in vitro and during the infection with Friend virus in vivo. Our results reveal a surprising mechanism of antiviral IgG subclass switching through T-cell intrinsic TLR7/IL-12 signaling.


Assuntos
Vírus da Leucemia Murina de Friend/fisiologia , Interferon gama/metabolismo , Interleucina-12/farmacologia , Transdução de Sinais/efeitos dos fármacos , Receptor 7 Toll-Like/metabolismo , Animais , Linfócitos B/citologia , Linfócitos B/imunologia , Linfócitos B/virologia , Células da Medula Óssea/citologia , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Imidazóis/farmacologia , Imunoglobulina G/metabolismo , Interferon gama/análise , Camundongos , Camundongos Endogâmicos C57BL , Fator 88 de Diferenciação Mieloide/metabolismo , Baço/citologia , Baço/efeitos dos fármacos , Baço/metabolismo , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Receptor 7 Toll-Like/agonistas , Receptor 7 Toll-Like/genética
20.
J Chromatogr A ; 1458: 25-34, 2016 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-27373376

RESUMO

A method of analyzing environmental contaminants in water based on micro-solid phase extraction (µ-SPE) followed by thermal extraction (TE) and a cold-trapping step, coupled with gas chromatography-mass selective detection (GC-MSD) was developed and validated. µ-SPE-TE- GC-MSD was employed in the determination of five polybrominated diphenyl ethers. The µ-SPE sorbent was chitosan-graphene oxide (CS-GO) composite, which was prepared by mixing CS and GO by means of ultrasonication. The CS in the composite was cross-linked with glutaraldehyde. After µ-SPE, the analytes in the extract were extracted thermally in a thermal desorption unit tube combined with a cooled injection system, coupled to GC-MSD. The extraction conditions were optimized for the detection of the target compounds in water. This method provided linearity ranges of between 0.1 and 20µgL(-1) (depending on the analytes), with coefficients of determination, r(2), ≥0.9982. The calculated relative recoveries were between 71.52 and 96.15% whereas precision (based on % relative standard deviations) was between 3.54 and 11.36%. The method showed limit of detection and limit of quantification ranges of between 0.007 and 0.016µgL(-1), and between 0.023 and 0.054µgL(-1), for the two groups of analytes, respectively. The method was applied to the determination of the target analytes in water.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas , Éteres Difenil Halogenados/análise , Éteres Difenil Halogenados/isolamento & purificação , Microextração em Fase Sólida/métodos , Temperatura , Água/química , Quitosana/química , Reagentes de Ligações Cruzadas/química , Glutaral/química , Grafite/química , Limite de Detecção , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/isolamento & purificação
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA