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1.
J Chromatogr A ; 1634: 461659, 2020 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-33166890

RESUMO

Excess bilirubin can accumulate in body organs and has serious effects on human health. In this work, a simple engineering strategy, based on cellulose-assisted high-quality dispersion of carbon nanotubes (CNTs), is proposed to produce high-performance bilirubin adsorbents. By dispersing cellulose and CNTs in NaOH/thiourea aqueous solution, a homogeneous and stable cellulose/CNTs solution is achieved. The obtained cellulose/CNTs solution is applied for the fabrication of cellulose/CNTs microspheres (CCMs), in which cellulose serves as a base material and guarantees the blood compatibility of the composite material, and CNTs contribute to the improved mechanical strength and high adsorption capacity. To further improve blood compatibility and adsorption capacity, lysine is immobilized on the CCMs. The obtained lysine-modified CCMs (LCCMs) exhibit a large surface area (171.31 m2/g) and hierarchically porous structure. Experimental results demonstrate LCCMs have high bilirubin adsorption capacity (204.12 mg/g) that is significantly higher than most of the reported adsorbents. The combination of high strength, blood compatibility, and high adsorption capacity positions the LCCMs as a promising candidate for bilirubin removal.


Assuntos
Bilirrubina/metabolismo , Celulose/química , Microesferas , Nanotubos de Carbono/química , Adsorção , Bilirrubina/sangue , Bilirrubina/isolamento & purificação , Humanos , Porosidade , Hidróxido de Sódio/química , Tioureia/química , Água/química
2.
Am J Cardiol ; 134: 69-73, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32892993

RESUMO

Statin therapy is the gold standard for hypercholesterolemia. However, a significant number of patients cannot achieve their target low-density lipoprotein (LDL) levels despite a maximal dose of statin therapy, and some cannot tolerate statins at all. Approval of proprotein convertase subtilisin/kexin type 9 inhibitors has been revolutionary for those patients. However, the need for frequent injections limits patient compliance with their use. Recently, a twice-yearly injection of inclisiran, a small interfering RNA, has been shown to inhibit hepatic synthesis of proprotein convertase subtilisin/kexin type 9. However, patient randomized clinical trial has been underpowered for clinical end points, necessitating a meta-analysis of those trials. The weighted mean difference was used to describe continuous variables, and pooled risk ratios, calculated using a random effects model, were used to describe discrete variables. Data from 3 randomized clinical trials comprising 3,660 patients showed that inclisiran decreased LDL cholesterol levels by 51% (95% Confidence Interval, 48 to 53%; p < 0.001) compared with placebo. It was associated with a 24% lower major adverse cardiovascular events rate (risk ratios = 0.76; 95% Confidence Interval, 0.61 to 0.92). It also significantly decreased total cholesterol by 37%, apolipoprotein B by 41%, and non high-density lipoprotein (HDL) cholesterol by 45% (all p < 0.001). No differences were found in adverse events, abnormalities in liver function tests, or creatine kinase levels between the treatment strategies. However, a mild injection site reaction occurred more frequently in the inclisiran group. In conclusions, in patients with hypercholesterolemia, inclisiran decreased LDL level by 51% without significant adverse effects. Additionally, it was associated with a lower major adverse cardiovascular event rate.


Assuntos
Anticolesterolemiantes/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Reação no Local da Injeção/epidemiologia , RNA Interferente Pequeno/uso terapêutico , Idoso , Alanina Transaminase/metabolismo , Fosfatase Alcalina/metabolismo , Apolipoproteínas B/metabolismo , Aspartato Aminotransferases/metabolismo , Bilirrubina/metabolismo , Doenças Cardiovasculares/mortalidade , Colesterol/metabolismo , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Creatina Quinase/metabolismo , Quimioterapia Combinada , Ezetimiba/uso terapêutico , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/metabolismo , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/epidemiologia
3.
Medicine (Baltimore) ; 99(31): e21332, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756118

RESUMO

Biliary atresia (BA) is a devastating cholestatic disorder of infants that presents during the first several months after birth due to an idiopathic obstruction to the bile flow. Without prompt diagnosis, Kasai portoenterostomy, and deliberate follow-ups, the resulting cholestasis leads to progressive hepatic failure. Oxidative stress is an abnormal phenomenon inside cells or tissues caused by a disturbance in the reactive oxygen species (ROS). We aimed to measure perioperative ROS in BA patients.Data are presented as median (25th, 75th percentiles). We evaluated 15 BA patients (age 55 [48, 69] days) and measured ROS; serum superoxide dismutase (SOD), urinary 8-iso prostaglandin F2α (8-iso-PGF2α) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) preoperatively and 30 days later to compare values with serum liver function tests and histologic grades of liver cholestasis. For compared BA patients, 4 normal subjects as control group (age 55 [27, 75] days) measured ROS and serum liver function tests.In BA patients, the preoperative serum SOD was 6.1 IU/mL (4.7, 7.2), urinary 8-iso-PGF2α was 1969 pg/mg Cre (1697, 2374), and urinary 8-OHdG was 37.1 ng/mg Cre (33.1, 53.7). At the postoperative day 30, the serum SOD was 5.2 IU/mL (4.2, 6.7), urinary 8-iso-PGF2α was 1761 pg/mg Cre (1256, 3036), and urinary 8-OHdG was 42.1 ng/mg Cre (29.65, 72.64). In ROS, there were no significant differences between the 2 periods. In control group, urinary 8-iso-PGF2α was significantly lower than that in preoperative BA patient group. However, other ROS were not significant differences between control group and BA patient group. The concentration of urinary 8-iso-PGF2α was positively correlated with total bilirubin and direct bilirubin levels (preoperatively: r = 0.6921, P = .0042 and r = 0.6639, P = .007, postoperatively: r = 0.6036, P = .0172 and r = 0.6464, P = .0092, respectively). The preoperative ROS were not correlated with histologic grades of liver cholestasis. Various factors such as liver inflammation, lipid malabsorption, and tissue disorders due to jaundice might affect the antioxidant activity and elevated urinary 8-iso-PGF2α. However, at least until 30 days later, urinary 8-OHdG as oxidative DNA damage might persist after the operation whether the cholestasis improved or not.


Assuntos
Atresia Biliar/cirurgia , Espécies Reativas de Oxigênio/sangue , Atresia Biliar/sangue , Bilirrubina/metabolismo , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Feminino , Humanos , Lactente , Testes de Função Hepática , Masculino , Estudos Retrospectivos
4.
Life Sci ; 257: 118032, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32621920

RESUMO

Diabetes mellitus is one of the major global health issues, which is closely related to metabolic dysfunction and the chronic inflammatory diseases. Multiple studies have demonstrated that serum bilirubin is negatively correlated with metabolic syndrome and associated inflammatory diseases, including atherosclerosis, hypertension, etc. However, the roles of bilirubin in metabolic syndrome and associated inflammatory diseases still remain unclear. Here, we explain the role of bilirubin in metabolic syndrome and chronic inflammatory diseases and its therapeutic potential. Understanding the role of bilirubin activities in diabetes may serve as a therapeutic target for the treatment of chronic inflammatory diseases in diabetic patients.


Assuntos
Bilirrubina/metabolismo , Bilirrubina/fisiologia , Síndrome Metabólica/metabolismo , Aterosclerose/sangue , Bilirrubina/sangue , Humanos , Hipertensão/sangue , Síndrome Metabólica/sangue , Síndrome Metabólica/imunologia
7.
Am J Respir Crit Care Med ; 202(7): 996-1004, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32551817

RESUMO

Rationale: Two distinct phenotypes of acute respiratory distress syndrome (ARDS) with differential clinical outcomes and responses to randomly assigned treatment have consistently been identified in randomized controlled trial cohorts using latent class analysis. Plasma biomarkers, key components in phenotype identification, currently lack point-of-care assays and represent a barrier to the clinical implementation of phenotypes.Objectives: The objective of this study was to develop models to classify ARDS phenotypes using readily available clinical data only.Methods: Three randomized controlled trial cohorts served as the training data set (ARMA [High vs. Low Vt], ALVEOLI [Assessment of Low Vt and Elevated End-Expiratory Pressure to Obviate Lung Injury], and FACTT [Fluids and Catheter Treatment Trial]; n = 2,022), and a fourth served as the validation data set (SAILS [Statins for Acutely Injured Lungs from Sepsis]; n = 745). A gradient-boosted machine algorithm was used to develop classifier models using 24 variables (demographics, vital signs, laboratory, and respiratory variables) at enrollment. In two secondary analyses, the ALVEOLI and FACTT cohorts each, individually, served as the validation data set, and the remaining combined cohorts formed the training data set for each analysis. Model performance was evaluated against the latent class analysis-derived phenotype.Measurements and Main Results: For the primary analysis, the model accurately classified the phenotypes in the validation cohort (area under the receiver operating characteristic curve [AUC], 0.95; 95% confidence interval [CI], 0.94-0.96). Using a probability cutoff of 0.5 to assign class, inflammatory biomarkers (IL-6, IL-8, and sTNFR-1; P < 0.0001) and 90-day mortality (38% vs. 24%; P = 0.0002) were significantly higher in the hyperinflammatory phenotype as classified by the model. Model accuracy was similar when ALVEOLI (AUC, 0.94; 95% CI, 0.92-0.96) and FACTT (AUC, 0.94; 95% CI, 0.92-0.95) were used as the validation cohorts. Significant treatment interactions were observed with the clinical classifier model-assigned phenotypes in both ALVEOLI (P = 0.0113) and FACTT (P = 0.0072) cohorts.Conclusions: ARDS phenotypes can be accurately identified using machine learning models based on readily available clinical data and may enable rapid phenotype identification at the bedside.


Assuntos
Aprendizado de Máquina , /classificação , Fatores Etários , Área Sob a Curva , Bicarbonatos/metabolismo , Bilirrubina/metabolismo , Biomarcadores Tumorais , Pressão Sanguínea , Dióxido de Carbono/metabolismo , Creatinina/metabolismo , Humanos , Inflamação , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Análise de Classes Latentes , Contagem de Leucócitos , Mortalidade , Oxigênio/metabolismo , Pressão Parcial , Fenótipo , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Contagem de Plaquetas , Prognóstico , Proteína C/metabolismo , Ventilação Pulmonar , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , /fisiopatologia , Albumina Sérica/metabolismo , Volume de Ventilação Pulmonar , Vasoconstritores/uso terapêutico , Sinais Vitais
8.
Physiol Rev ; 100(3): 1291-1346, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32401177

RESUMO

Bilirubin is the end product of heme catabolism formed during a process that involves oxidation-reduction reactions and conserves iron body stores. Unconjugated hyperbilirubinemia is common in newborn infants, but rare later in life. The basic physiology of bilirubin metabolism, such as production, transport, and excretion, has been well described. However, in the neonate, numerous variables related to nutrition, ethnicity, and genetic variants at several metabolic steps may be superimposed on the normal physiological hyperbilirubinemia that occurs in the first week of life and results in bilirubin levels that may be toxic to the brain. Bilirubin exists in several isomeric forms that differ in their polarities and is considered a physiologically important antioxidant. Here we review the chemistry of the bilirubin molecule and its metabolism in the body with a particular focus on the processes that impact the newborn infant, and how differences relative to older children and adults contribute to the risk of developing both acute and long-term neurological sequelae in the newborn infant. The final section deals with the interplay between the brain and bilirubin and its entry, clearance, and accumulation. We conclude with a discussion of the current state of knowledge regarding the mechanism(s) of bilirubin neurotoxicity.


Assuntos
Bilirrubina/sangue , Bilirrubina/metabolismo , Encéfalo/metabolismo , Mucosa Intestinal/metabolismo , Fígado/metabolismo , Humanos , Recém-Nascido
9.
PLoS One ; 15(3): e0216970, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32119664

RESUMO

Jaundice is a major cause of mortality and morbidity in the newborn. Globally, early identification and home monitoring are significant challenges in reducing the incidence of jaundice-related neurological damage. Smartphone cameras are promising as colour-based screening tools as they are low-cost, objective and ubiquitous. We propose a novel smartphone method to screen for neonatal jaundice by imaging the sclera. It does not rely on colour calibration cards or accessories, which may facilitate its adoption at scale and in less economically developed regions. Our approach is to explicitly address three confounding factors in relating colour to jaundice: (1) skin pigmentation, (2) ambient light, and (3) camera spectral response. (1) The variation in skin pigmentation is avoided by imaging the sclera. (2) With the smartphone screen acting as an illuminating flash, a flash/ no-flash image pair is captured using the front-facing camera. The contribution of ambient light is subtracted. (3) In principle, this permits a device- and ambient-independent measure of sclera chromaticity following a one-time calibration. We introduce the concept of Scleral-Conjunctival Bilirubin (SCB), in analogy with Transcutaneous Bilirubin (TcB). The scleral chromaticity is mapped to an SCB value. A pilot study was conducted in the UCL Hospital Neonatal Care Unit (n = 37). Neonates were imaged using a specially developed app concurrently with having a blood test for total serum bilirubin (TSB). The better of two models for SCB based on ambient-subtracted sclera chromaticity achieved r = 0.75 (p<0.01) correlation with TSB. Ambient subtraction improved chromaticity estimates in proof-of-principle laboratory tests and screening performance within our study sample. Using an SCB decision threshold of 190µmol/L, the sensitivity was 100% (specificity 61%) in identifying newborns with TSB>250µmol/L (area under receiver operating characteristic curve, AUROC, 0.86), and 92% (specificity 67%) in identifying newborns with TSB>205µmol/L (AUROC 0.85). These results are comparable to modern transcutaneous bilirubinometers.


Assuntos
Icterícia Neonatal/diagnóstico , Triagem Neonatal , Esclera/patologia , Smartphone , Bilirrubina/metabolismo , Cor , Túnica Conjuntiva/metabolismo , Feminino , Humanos , Recém-Nascido , Masculino , Curva ROC
10.
BMC Pregnancy Childbirth ; 20(1): 162, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32171284

RESUMO

BACKGROUND: Early diagnosis is important to lower the mortality rate of acute fatty liver of pregnancy (AFLP). The Swansea criteria is commonly used to diagnose AFLP, but some terms could only be reached when symptoms and signs have progressed, or are not efficient in clinical practice. Therefore, it is necessary to select cost effective tests to simplify and facilitate early suspicion of acute fatty liver of pregnancy. METHODS: This is a retrospective study of 28,800 medical records at the Second Xiangya Hospital from 2009 to 2015, including 41 patients with AFLP and 172 other diseases that could show similar symptoms to AFLP. The evaluated variables included past history of liver diseases, blood pressure, gastrointestinal symptoms, blood count, liver function test, coagulation function test and blood sugar test. The sensitivity, specificity, positive predict value and negative predict value were calculated for models in diagnosing AFLP. RESULTS: The significant variables associated with AFLP included gastrointestinal symptoms, blood pressure > 140/90 mmHg, aminotransferase> 42 IU/l, total bilirubin> 0.8 mg/dl, total bilirubin acid> 10.0 µmol/L, activated partial prothrombin time(APTT) > 34 s, prothrombin time(PT) > 14 s, white blood cells> 11 *106/l and blood sugar< 72 mg/dl. Gastrointestinal symptoms +aminotransferase +bilirubin +bile acid +APTT/PT showed 97.6% sensitivity and 97.1% specificity to diagnose AFLP. Adding blood pressure, blood sugar or white blood cells decreased the accuracy of the statistical model. CONCLUSIONS: Application of a statistical model including maternal symptoms, biochemical and haematological parameters has high diagnostic accuracy for earlier identification of AFLP. However, this finding needs to be tested in another cohort to determine whether this statistical model has the same performance.


Assuntos
Diagnóstico Precoce , Fígado Gorduroso/diagnóstico , Complicações na Gravidez/diagnóstico , Adulto , Ácidos e Sais Biliares/metabolismo , Bilirrubina/metabolismo , Estudos de Casos e Controles , Fígado Gorduroso/sangue , Fígado Gorduroso/metabolismo , Feminino , Humanos , Testes de Função Hepática , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/metabolismo , Tempo de Protrombina , Estudos Retrospectivos , Sensibilidade e Especificidade
11.
Protein J ; 39(2): 145-151, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32096074

RESUMO

Biofluorescence has been found to be an increasingly widespread phenomenon in the ocean. The reclusive Caribbean chlopsid eel, Kaupichthys hyoproroides displays bright green fluorescence in its native marine environment. We have previously shown the fluorescence to be attributed to a fluorescent fatty acid-binding protein, Chlopsid FP, part of a larger family of fluorescent fatty acid-binding proteins, including the homologous UnaG. All require the addition of exogenous bilirubin for fluorescence. Here, we report the generation of a series of point mutants, and deletions that result in the quenching of fluorescence in Chlopsid FP. In addition, we report the binding constants of bilirubin to Chlopsid FP and mutants, measured by fluorescence titration. This study provides key insights into the potential mechanism of fluorescence in this class of fluorescent fatty acid-binding proteins.


Assuntos
Bilirrubina/metabolismo , Enguias , Proteínas de Ligação a Ácido Graxo/genética , Fluorescência , Proteínas Luminescentes/genética , Animais , Proteínas de Ligação a Ácido Graxo/metabolismo , Ligação Proteica , Deleção de Sequência
12.
Oncology ; 98(5): 295-302, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32097925

RESUMO

BACKGROUND/AIM: Few studies have examined the details of nutritional status in patients with unresectable hepatocellular carcinoma (u-HCC) undergoing systemic chemotherapy with lenvatinib. We evaluated the prognostic/predictive value of nutritional status using Onodera's prognostic nutritional index (O-PNI) for overall survival among patients with u-HCC treated with lenvatinib. METHODS: Three-hundred and seventy-five u-HCC patients treated with lenvatinib were enrolled (median age 72 years; Child-Pugh class A/B/C: n = 312/60/3; BCLC stage A/B/C/D: n = 2/159/212/2). We examined median survival time (MST) and time to progression (TTP) in all patients (n = 375), prognosis according to the O-PNI (high/low: >40/≤40) in 298 patients with lymphocyte findings, and the prognostic/predictive values of Child-Pugh stage, albumin-bilirubin (ALBI)/modified ALBI (mALBI) grade, and O-PNI for Chemotherapy grade (OPNIC grade 1/2/3: O-PNI >40/≤40 to >36/≤36). RESULTS: The MST and TTP were 16.6 and 8.0 months, respectively. The MST and TTP according to the O-PNI (>40/≤40) were "not reached" (NR)/12.4 months (p < 0.001) and 10.0/6.1 months (p = 0.012), respectively. There was a good correlation noted between ALBI score and O-PNI (r = -0.939, p < 0.001). The predictive value of the O-PNI for mALBI grade 2a was 36.0 (specificity/sensitivity = 0.894/0.942; area under the curve [AUC] = 0.978), while that for mALBI grade 1 was 39 (specificity/sensitivity = 0.920/0.929; AUC = 0.972), which was very similar to a high O-PNI. The MST analyzed with the OPNIC in the 298 patients was NR/16.2/10.4 months for OPNIC grade 1/2/3 (p < 0.001), respectively, and the c-index was 0.632, the same as that for mALBI grade (0.632), while that for Child-Pugh class was 0.571. CONCLUSIONS: OPNIC grading might have a potential for easy substitution of mALBI grading. A good nutritional status (OPNIC grade 1) or mALBI grade 1 is the best indication for lenvatinib use, while with an OPNIC grade 3, lenvatinib might be not suitable.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Idoso , Bilirrubina/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Feminino , Humanos , Estimativa de Kaplan-Meier , Testes de Função Hepática/métodos , Neoplasias Hepáticas/metabolismo , Masculino , Avaliação Nutricional , Prognóstico , Albumina Sérica Humana/metabolismo
13.
Am J Pathol ; 190(4): 830-843, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32035059

RESUMO

The molecular mechanisms of prostate inflammation are unclear. We hypothesized that heme oxygenase 1 (HMOX1; HO-1), an enzyme responsible for degradation of heme to carbon monoxide, bilirubin, and iron, is an important regulator of inflammation and epithelial responses in the prostate. Injection of non-uropathogenic Escherichia coli (MG1655 strain) or phosphate-buffered saline into the urethra of mice led to increased numbers of CD45+ leukocytes and mitotic markers (phosphorylated histone H3 and phosphorylated ERK1/2) in the prostate glands. Leukocyte infiltration was elevated in the prostates harvested from mice lacking HO-1 in myeloid compartment. Conversely, exogenous carbon monoxide (250 ppm) increased IL-1ß levels and suppressed cell proliferation in the prostates. Carbon monoxide did not affect the number of infiltrating CD45+ cells in the prostates of E. coli- or phosphate-buffered saline-treated mice. Interestingly, immunomodulatory effects of HO-1 and/or carbon monoxide correlated with early induction of the long-chain acyl-CoA synthetase 1 (ACSL1). ACSL1 levels were elevated in response to E. coli treatment, and macrophage-expressed ACSL1 was in part required for controlling of IL-1ß expression and prostate cancer cell colony growth in soft agar. These results suggest that HO-1 and/or carbon monoxide might play a distinctive role in modulating prostate inflammation, cell proliferation, and IL-1ß levels in part via an ACSL1-mediated pathway.


Assuntos
Infecções por Escherichia coli/complicações , Heme Oxigenase-1/metabolismo , Heme/metabolismo , Inflamação/imunologia , Metabolismo dos Lipídeos/imunologia , Proteínas de Membrana/metabolismo , Próstata/imunologia , Animais , Bilirrubina/metabolismo , Monóxido de Carbono/metabolismo , Proliferação de Células , Coenzima A Ligases/genética , Coenzima A Ligases/metabolismo , Escherichia coli/imunologia , Infecções por Escherichia coli/microbiologia , Heme Oxigenase-1/genética , Inflamação/metabolismo , Inflamação/microbiologia , Inflamação/patologia , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Próstata/metabolismo , Próstata/microbiologia , Próstata/patologia , Transdução de Sinais
14.
Pak J Biol Sci ; 23(2): 150-158, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31944074

RESUMO

BACKGROUND AND OBJECTIVE: The evidence for safe consumption of chili pepper to gain health benefits is insufficient as high doses reported to cause gastric erosion. The objective of this study was to investigate the contribution of red chili pepper ethanol extract (RCEE) to weight loss in high fat dieted female albino Wistar rats while monitoring adverse effects of high dose consumption. MATERIALS AND METHODS: Body weight gain, lipid profile, oxidative stress parameters, liver, kidney and thyroid biochemical functions were determined in addition to histopathological examination of liver and kidney to determine biological effects of 2 ingested concentrations of red chili pepper extract (5 and 10 mg). RESULTS: Red chili pepper ethanol extract (RCEE) showed anti-obesity potentials and hypolipidemic effects through decreased levels of total cholesterol (T.Ch), low density lipoprotein (LDL), triglycerides (TG) and very low density lipoprotein (VLDL) reached 25, 55, 45 and 45%, respectively, in parallel with increased high density lipoprotein (HDL) levels by 22.6%. The antioxidative potentials of RCEE were pronounced through significant increases in glutathione peroxidase (GPx) and catalase (CAT) activities (346.43 mU mL-1 and 15.33 U L-1 in group 2, respectively). Histological examination of liver and kidney showed adverse results but that did not significantly reflect on their functional biochemical parameters. CONCLUSION: Results introduced scientific evidence that red chili pepper possesses functional pharmacological properties but the excessive consumption induces liver and kidney damage.


Assuntos
Peso Corporal/efeitos dos fármacos , Capsicum/química , Dieta Hiperlipídica , Ganho de Peso/efeitos dos fármacos , Administração Oral , Animais , Antioxidantes/farmacologia , Bilirrubina/metabolismo , Catalase/metabolismo , Feminino , Radicais Livres , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Lipoproteínas HDL/metabolismo , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Glândula Tireoide/metabolismo
15.
Nat Commun ; 11(1): 273, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31937765

RESUMO

We introduce UnaG as a green-to-dark photoswitching fluorescent protein capable of high-quality super-resolution imaging with photon numbers equivalent to the brightest photoswitchable red protein. UnaG only fluoresces upon binding of a fluorogenic metabolite, bilirubin, enabling UV-free reversible photoswitching with easily controllable kinetics and low background under Epi illumination. The on- and off-switching rates are controlled by the concentration of the ligand and the excitation light intensity, respectively, where the dissolved oxygen also promotes the off-switching. The photo-oxidation reaction mechanism of bilirubin in UnaG suggests that the lack of ligand-protein covalent bond allows the oxidized ligand to detach from the protein, emptying the binding cavity for rebinding to a fresh ligand molecule. We demonstrate super-resolution single-molecule localization imaging of various subcellular structures genetically encoded with UnaG, which enables facile labeling and simultaneous multicolor imaging of live cells. UnaG has the promise of becoming a default protein for high-performance super-resolution imaging.


Assuntos
Bilirrubina/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Imagem Individual de Molécula/métodos , Fluorescência , Cinética , Ligantes , Luz , Microscopia de Fluorescência , Processos Fotoquímicos , Ligação Proteica
16.
Res Vet Sci ; 129: 90-95, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31954319

RESUMO

This study aims to evaluate the effect of the presence of food and the material used in a panel of biomarkers in saliva of horses. For the food effect study, clean saliva was incubated with a known amount of food consisting of oats, hay or grass. Significant changes were observed when saliva was incubated with oats for total protein (P = .050) and phosphorus (P = .008), with grass for total protein (P = .037), salivary alpha-amylase (sAA, P = .018), total esterase (TEA, P = .018), butyrilcholinesterase (BChE, P = .037), adenosine deaminase (ADA, P = .037), and total bilirubin (P = .018), and with hay for sAA (P = .018), phosphorus (P = .037), γ-glutamyl transferase (gGT, P = .004), and creatine kinase (CK, P = .016). For the material-based collection study, saliva using a sponge and a cotton role at the same time were collected and compared. Lower values were obtained in clean saliva collected with cotton role compared to sponge for sAA (P = .030), TEA (P = .034), BChE (P = .003), gGT (P = .002) and cortisol (P < .001) In conclusion, the presence of food and the material used for its collection, can influence the results obtained when analytes are measured in saliva of horses.


Assuntos
Ração Animal/análise , Contaminação de Alimentos , Cavalos , Saliva/química , Adenosina Desaminase/química , Adenosina Desaminase/metabolismo , Animais , Bilirrubina/química , Bilirrubina/metabolismo , Biomarcadores/química , Biomarcadores/metabolismo , Carboxilesterase/química , Carboxilesterase/metabolismo , Colinesterases/química , Colinesterases/metabolismo , Dieta/veterinária , Proteínas na Dieta/química , Proteínas na Dieta/metabolismo , Feminino , Humanos , Hidrocortisona , Masculino , Fósforo/química , Fósforo/metabolismo , alfa-Amilases/química , alfa-Amilases/metabolismo
17.
ACS Appl Mater Interfaces ; 12(5): 5462-5475, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31927945

RESUMO

Islet transplantation has been considered the most promising therapeutic option with the potential to restore the physiological regulation of blood glucose concentrations in type 1 diabetes treatment. However, islets suffer from oxidative stress and nonspecific inflammation in the early stage of transplantation, which attributed to the leading cause of islet graft failure. Our previous study reported that bilirubin exerted antioxidative and anti-inflammatory effects on hypothermic preserved islets, which inspire us to utilize bilirubin to address the survival issue of grafted islets. However, the application of bilirubin for islet transplantation is limited by its poor solubility and fast clearance. In this study, we designed a supramolecular carrier (PLCD) that could improve the solubility of bilirubin and slowly release bilirubin to protect islets after cotransplantation. PLCD was synthesized by conjugating activated ß-cyclodextrin (ß-CD) to the side chain of ε-polylysine (PLL) and acted as a carrier to load bilirubin via host-guest interactions. The constructed bilirubin supramolecular system (PLCD-BR) significantly improved the solubility and prolonged the action time of bilirubin. In vitro results confirmed that PLCD-BR coculture substantially enhanced the resistance of islets to excessive oxidative stress and proinflammatory stimulation and maximumly maintained the islet function. In vivo, PLCD could prolong drug duration at the transplant site, and the localized released bilirubin could protect the islets from oxidative stress and suppress the production of inflammatory cytokines. Crucially, islet transplantation with PLCD-BR significantly extended the stable blood glucose time of diabetic mice and produced a faster glucose clearance compared to those cotransplanted with free bilirubin. Additionally, immunohistochemical analysis showed that PLCD-BR had superior antioxidative and anti-inflammatory abilities and beneficial effects on angiogenesis. These findings demonstrate that the PLCD-BR has great potentials to support successful islet transplantation.


Assuntos
Anti-Inflamatórios/química , Bilirrubina/metabolismo , Estresse Oxidativo , Polilisina/química , beta-Ciclodextrinas/química , Animais , Anti-Inflamatórios/farmacologia , Bilirrubina/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/terapia , Concentração de Íons de Hidrogênio , Inflamação/metabolismo , Inflamação/prevenção & controle , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , Transplante das Ilhotas Pancreáticas , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Células RAW 264.7 , Fator de Necrose Tumoral alfa/metabolismo
18.
Biomed Pharmacother ; 123: 109744, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31862475

RESUMO

BACKGROUND: Bilirubin has been involved in the process of ageing and the pathology of ageing-related diseases. Circulating bilirubin is mainly derived from the clearance of disintegrated erythrocytes in the blood. However, the change of serum bilirubin level and its regulation during ageing and in ageing-related diseases remain to be elucidated. METHODS: A retrospective study was conducted by analyzing the blood cell test results and liver function results of 14,049 healthy research subjects at the Physical Examination Center and 2052 patients with various types of cardiovascular diseases (CVD) at the Department of Cardiology in Renmin Hospital of Wuhan University. Spearman correlation analysis and linear-regression analysis were used for correlation studies. Differences between male and female were investigated. RESULTS: Whereas the erythrocyte counts continuously decreased along with age, the proportion of aged erythrocytes was significantly increased in both male and female. The level of total circulating bilirubin was positively correlated with age and erythrocyte counts. The increase of bilirubin was associated with the increased morphological deviation of erythrocytes during ageing. Compared with health controls, the level of circulating bilirubin in CVD patients was significantly decreased consistent with the decline of erythrocyte counts and hemoglobin. CONCLUSIONS: Ageing may be accompanied by an increased ageing rate of erythrocytes, which contributes to the ageing-related decline of erythrocyte counts. Both erythrocyte counts and the proportion of aged erythrocytes coordinately might determine the circulating level of bilirubin during ageing. In CVD, the decline of circulating bilirubin may be largely attributed to concurrent anemia.


Assuntos
Bilirrubina/sangue , Bilirrubina/metabolismo , Doenças Cardiovasculares/metabolismo , Envelhecimento Eritrocítico , Eritrócitos/metabolismo , Adulto , Idoso , Feminino , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade
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