Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 106.407
Filtrar
1.
J Environ Qual ; 49(2): 368-377, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33016416

RESUMO

Sorgoleone-358 is an important allelochemical of the oily droplets exuded from root hairs of various species in the Sorghum genus. Due to its hydrophobic nature, sorgoleone-358 can be strongly adsorbed onto soil organic matter, resulting in increased sorgoleone soil persistence. Because of the herbicidal activity of sorgoleone on many small-seeded weeds, concerns have been raised that sorghum residues may have a detrimental effect on emergence of wheat used as a double crop in the southeastern United States. Laboratory experiments were conducted to evaluate root exudate production and its sorgoleone-358 content for 36 cultivated sorghum cultivars as well as eight shattercane [Sorghum bicolor (L.) Moench ssp. arundinaceum (Desv.) de Wet & Harlan] accessions and one johnsongrass [S. halepense (L.) Pers.] accession. Using a capillary growing mat system, root exudate was extracted with dichloromethane and subjected to chromatography analysis to determine sorgoleone-358 content. Root biomass of 7- to 12-d-old seedlings averaged 18.8 mg g-1 seed, and root exudate production ranged from 0.2 and 4.8 mg g-1 root fresh weight (RFW). The amount of sorgoleone produced varied greatly among sorghum accessions. Sorgoleone-358 amount in the root exudate averaged 0.5 mg g-1 RFW and varied from 0.13 to 1.05 mg g-1 for shattercane cultivar S7 and cultivated sorghum cultivar 992123, respectively. Regarding volume of root biomass, sorgoleone-358 levels averaged 0.49 mg g-1 (range, 0.06-1.46 mg g-1 ) for sorghum cultivar AAS3479 and shattercane cultivar S2, respectively. Segregation of commercial sorghum cultivars according to their maturity group did not show any difference in root biomass and dry extract production, but early-maturing cultivars produced on average 18% less sorgoleone-358 compared with medium- and late-maturing cultivars. These results suggest that sorgoleone production may be genetically constitutive because sorghum growing conditions were identical across cultivars.


Assuntos
Sorghum , Benzoquinonas , Lipídeos , Raízes de Plantas , Sudeste dos Estados Unidos
2.
Drugs Today (Barc) ; 56(9): 573-582, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33025951

RESUMO

Bempedoic acid is a new, first-in-class oral ATP-citrate lyase (ACLY) inhibitor that has to be converted to its CoA thioester before it inhibits ACLY. This conversion only occurs in the liver and not in skeletal muscle. This may explain why, unlike the statins, bempedoic acid does not cause myalgia. Bempedoic acid given at a dosage of 180 mg orally once daily produces a highly significant reduction in low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B and importantly also in high-sensitivity C-reactive protein. It has recently been approved by both the Food and Drug Administration (FDA) and the European Commission for use in adult patients with heterozygous familial hypercholesterolemia or atherosclerotic cardiovascular disease who require additional lowering of LDL-C, and for the treatment of adults with primary hypercholesterolemia (heterozygous familial and nonfamilial) or mixed dyslipidemia, respectively.


Assuntos
ATP Citrato (pro-S)-Liase/antagonistas & inibidores , LDL-Colesterol/sangue , Ácidos Dicarboxílicos/uso terapêutico , Ácidos Graxos/uso terapêutico , Lipídeos/sangue , Humanos
3.
Medicine (Baltimore) ; 99(40): e22572, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019469

RESUMO

RATIONALE: Atorvastatin is the most common drug used in therapy for cardiovascular diseases. The most common adverse side effects associated with statins are myopathy and hypertransaminasemia. Here, we report a rare case of gamma glutamyl transpeptidase (GGT) elevation induced by atorvastatin. PATIENT CONCERNS: A 47-year-old male was admitted to our hospital with dyslipidemia, he had been taking pitavastatin 2 mg/day for 2 months. The levels of total cholesterol (265.28 mg/dL) and low-density lipoprotein-cholesterol (LDL) (179.15 mg/dL) were also high. DIAGNOSIS: Blood lipid test showed mixed dyslipidemia. INTERVENTION: Atorvastatin 10 mg/day was given to the patient. OUTCOMES: The patient came back to our hospital for blood tests after 4 weeks. Although no symptoms were detectable, the patient's GGT level was markedly elevated (up to 6-fold over normal level) with less marked increases in alkaline phosphatase (ALP) and alanine aminotransferase (ALT). The serum GGT level returned to normal within 6 weeks of cessation of atorvastatin. LESSONS: This is a case of GGT elevation without hyperbilirubinemia, hypertransaminasemiam, or serum creatine phosphokinase (CPK) abnormalities despite an atorvastatin regimen. This case highlights GGT elevation caused by atorvastatin, a rare but serious condition. Clinicians should be aware of these possible adverse effects and monitor liver function tests in patients on statin therapy.


Assuntos
Atorvastatina/efeitos adversos , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Quinolinas/efeitos adversos , gama-Glutamiltransferase/efeitos dos fármacos , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Atorvastatina/administração & dosagem , Atorvastatina/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dislipidemias/diagnóstico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Suspensão de Tratamento , gama-Glutamiltransferase/sangue
4.
Water Sci Technol ; 82(6): 1120-1130, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33055402

RESUMO

As a byproduct of agriculture, rice bran can be a good alternative carbon source to mass-produce microalgae and increase lipid content. The purpose of this study was to investigate the effects of rice bran extract (RBE) on the mass culture and oil content of microalgae. Various parameters were applied to the growth rate model to explain the dynamics of substrate inhibition and growth of microalgae. The rice bran contains 46.1% of carbohydrates, in which is 38.3% glucose, and is very suitable as a carbon source for microalgae growth. The culture with RBE had a four times higher biomass production than microalgae cultured on Jaworski's medium (JM) with a small amount of 1 g/L. In addition, for RBE, the lipid content was three times higher and saturated fatty acid was 3% lower than were those of JM. According to the above results, when Chlorella vulgaris is cultured using RBE, a high amount of biomass and high lipid content can be obtained with a small amount of RBE. RBE is a discarded waste and has a high content of glucose, so it can be replaced by an organic carbon source to increase microbial biomass growth and lipid content at low cost.


Assuntos
Chlorella vulgaris , Oryza , Agricultura , Biomassa , Carbono , Lipídeos
5.
Nat Commun ; 11(1): 4955, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009385

RESUMO

The light-harvesting-reaction center complex (LH1-RC) from the purple phototrophic bacterium Thiorhodovibrio strain 970 exhibits an LH1 absorption maximum at 960 nm, the most red-shifted absorption for any bacteriochlorophyll (BChl) a-containing species. Here we present a cryo-EM structure of the strain 970 LH1-RC complex at 2.82 Å resolution. The LH1 forms a closed ring structure composed of sixteen pairs of the αß-polypeptides. Sixteen Ca ions are present in the LH1 C-terminal domain and are coordinated by residues from the αß-polypeptides that are hydrogen-bonded to BChl a. The Ca2+-facilitated hydrogen-bonding network forms the structural basis of the unusual LH1 redshift. The structure also revealed the arrangement of multiple forms of α- and ß-polypeptides in an individual LH1 ring. Such organization indicates a mechanism of interplay between the expression and assembly of the LH1 complex that is regulated through interactions with the RC subunits inside.


Assuntos
Cálcio/metabolismo , Microscopia Crioeletrônica , Complexos de Proteínas Captadores de Luz/ultraestrutura , Peptídeos/metabolismo , Fotossíntese , Sequência de Aminoácidos , Bacterioclorofila A/metabolismo , Sítios de Ligação , Chromatiaceae/metabolismo , Detergentes/química , Dimerização , Complexos de Proteínas Captadores de Luz/química , Complexos de Proteínas Captadores de Luz/metabolismo , Lipídeos/química , Peptídeos/química , Quinonas/química
6.
BMC Dermatol ; 20(1): 6, 2020 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-32867747

RESUMO

BACKGROUND: Specific species of ceramides (Cer), major constituents of lipids in the stratum corneum (SC), are decreased and are correlated with SC barrier and water-holding functions in the skin of patients with atopic dermatitis (AD) or psoriasis (Pso). However, possible correlations between Cer subclass ratios and skin properties in barrier-disrupted skin and in healthy skin remain unclear. The objective of this study was to identify a new marker to evaluate skin properties and epidermal differentiation in SC not only in barrier-disrupted skin but also in healthy skin. METHODS: The Cer subclass ratios in the SC of healthy control subjects and in patients with AD or Pso were evaluated. Correlations with candidate markers and facial skin features of healthy Japanese females (20-74 years old, n = 210) were investigated. Variations of markers during epidermal differentiation were studied in human epidermis and in cultured keratinocytes. RESULTS: The ratios of Cer [NP]/[NS], Cer [NH]/[NS], Cer [NP]/[AS], Cer [NH]/[NS], Cer [NDS]/[AS], Cer [AH]/[AS] and Cer [EOP]/[AS] showed significant differences between non-lesional skin of AD patients and normal skin of healthy control subjects, as well as Pso patients and their healthy control subjects. The Cer [NP]/[NS] ratio was correlated with SC functional parameters (transepidermal water loss and capacitance) and with skin appearance (texture, scaling and color) even in the cheek skin of healthy female subjects. The Cer [NP]/[NS] ratio in the SC was approximately 18-times higher than in living keratinocytes, and it increased as they differentiated. CONCLUSIONS: The Cer [NP]/[NS] ratio in the SC is a potential marker for skin properties and epidermal differentiation in barrier-disrupted skin as well as in healthy skin.


Assuntos
Ceramidas/análise , Dermatite Atópica/patologia , Epiderme/química , Psoríase/patologia , Adulto , Idoso , Biomarcadores/análise , Estudos de Casos e Controles , Diferenciação Celular , Células Cultivadas , Dermatite Atópica/diagnóstico , Epiderme/patologia , Feminino , Humanos , Queratinócitos/química , Queratinócitos/citologia , Lipídeos/análise , Pessoa de Meia-Idade , Psoríase/diagnóstico , Adulto Jovem
7.
Medicine (Baltimore) ; 99(33): e21498, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32871996

RESUMO

Adjuvant chemotherapy may cause alterations in serum lipids in postoperative breast cancer (BC) patients, but the specific alterations caused by different chemotherapy regimens remain unclear. The aim of this study was to investigate the status of serum lipids pre- and post-chemotherapy and to compare the side effects of different chemotherapy regimens on serum lipid.We retrospectively analysed the lipid profiles of 1934 consecutive postoperative BC patients who received one of the following chemotherapy regimens:The levels of triglycerides (TG), total cholesterols (TC), and low-density lipoprotein (LDL-C) were significantly elevated in patients who received chemotherapy regimens above (P < .001). With respect to different chemotherapy regimens, FEC had less side effects on lipid profiles (TG (P = .006), high-density lipoprotein (HDL-C) (P < .001), and LDL-C (P < .001)) than TC regimen and AC-T and EC-T regimen. Also, the incidence of newly diagnosed dyslipidemia after chemotherapy was lower in FEC group than TC group and AC-T and EC-T group (P < .001). Additionally, the magnitude of the alterations in lipid profiles (TG, TC, HDL-C, and LDL-C) was greater in premenopausal patients than that of the postmenopausal patients (P = .004; P < .001; P = .002; P = .003, respectively). Moreover, after adjusting for multiple baseline covariates, anthracycline-plus-taxane-based regimens (AC-T and EC-T) were still statistically associated with a high level of TG (P = .004) and a low level of HDL-C (P = .033) after chemotherapy compared with FEC regimen. Also, body mass index (BMI) > 24 was associated with abnormal lipid profiles (TG, TC, HDL-C, LDL-C) post-chemotherapy compared with BMI ≤ 24 (P < .001; P = .036; P = .012; P = .048, respectively).BC patients receiving chemotherapy may have elevated lipid profiles, and anthracycline-based regimen had less side effects on lipid profiles compared with regimens containing taxane. Therefore, it is necessary to take lipid metabolism into consideration when making chemotherapy decisions and dyslipidemia prevention and corresponding interventions are indispensable during the whole chemotherapy period.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Lipídeos/sangue , Adulto , Idoso , Neoplasias da Mama/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
8.
Cells ; 9(9)2020 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-32899484

RESUMO

Hybrid nanoparticles from lipidic and polymeric components were assembled to serve as vehicles for the transfection of messenger RNA (mRNA) using different portions of the cationic lipid DOTAP (1,2-Dioleoyl-3-trimethylammonium-propane) and the cationic biopolymer protamine as model systems. Two different sequential assembly approaches in comparison with a direct single-step protocol were applied, and molecular organization in correlation with biological activity of the resulting nanoparticle systems was investigated. Differences in the structure of the nanoparticles were revealed by thorough physicochemical characterization including small angle neutron scattering (SANS), small angle X-ray scattering (SAXS), and cryogenic transmission electron microscopy (cryo-TEM). All hybrid systems, combining lipid and polymer, displayed significantly increased transfection in comparison to lipid/mRNA and polymer/mRNA particles alone. For the hybrid nanoparticles, characteristic differences regarding the internal organization, release characteristics, and activity were determined depending on the assembly route. The systems with the highest transfection efficacy were characterized by a heterogenous internal organization, accompanied by facilitated release. Such a system could be best obtained by the single step protocol, starting with a lipid and polymer mixture for nanoparticle formation.


Assuntos
Biopolímeros/química , Lipídeos/química , Nanopartículas/química , RNA Mensageiro/metabolismo , Transfecção/métodos , Animais , Linhagem Celular , Ácidos Graxos Monoinsaturados/química , Feminino , Heparina/química , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Imagem Óptica , Tamanho da Partícula , Compostos de Amônio Quaternário/química , RNA Mensageiro/química
9.
Medicine (Baltimore) ; 99(33): e21566, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872008

RESUMO

Metabolic syndrome (MetS) refers to the pathological state of metabolic disorders in the body's proteins, fats, carbohydrates and other substances. MetS is a systemic metabolic disease. Periodontal disease is also a part of systemic inflammatory diseases. Among Chinese patients with middle-aged and elderly MetS, the periodontal morbidity is very high, which is due to the involvement of inflammatory mediators in the pathogenesis of MetS and periodontal disease. The latter may also be a risk factor for the former's morbidity and promotion of disease progression. At present, there are not many investigations and studies on periodontal examination data and periodontal disease prevalence of patients with MetS. Coal mine workers, especially coal mine underground workers, have different work natures and different working environments. See related report.We will collect the clinical diagnosis and treatment information of the enrolled patients. We will focus on checking the incidence of periodontal disease and recording. Establish a database, check every 10 medical records, and make corrections in time to ensure data accuracy. We will popularize oral hygiene knowledge for the included patients and guide them to brush their teeth correctly and how to use dental floss. We will perform periodontal examination on the patients' teeth by site and record the plaque index, gingival sulcus bleeding index, periodontal pocket exploration depth and other indicators. We will repeat the above inspection items and record in the second and fourth weeks of the experiment.This study will explore the correlation between periodontal disease and MetS of coal mine workers. We aim to clarify the role and mechanism of MetS in the occurrence and development of periodontal diseases, guide the prevention of periodontal diseases, and thus reduce the prevalence of periodontal diseases. TRIAL REGISTRATION:: ClinicalTrials.gov, ChiCTR2000034177, Registered on 27 June 2020.


Assuntos
Carvão Mineral , Síndrome Metabólica/epidemiologia , Mineradores/estatística & dados numéricos , Doenças Periodontais/epidemiologia , Adulto , Glicemia , Pressão Sanguínea , Índice de Massa Corporal , China/epidemiologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Higiene Bucal , Índice Periodontal , Prevalência , Fatores de Risco , Fumar/epidemiologia , Adulto Jovem
10.
N Engl J Med ; 383(14): 1317-1327, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32865373

RESUMO

BACKGROUND: Evolocumab, a fully human monoclonal antibody directed against proprotein convertase subtilisin-kexin type 9, is widely used in adult patients to lower low-density lipoprotein (LDL) cholesterol levels. Its effects in pediatric patients with heterozygous familial hypercholesterolemia are not known. METHODS: We conducted a 24-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of evolocumab in pediatric patients with heterozygous familial hypercholesterolemia. Patients 10 to 17 years of age who had received stable lipid-lowering treatment for at least 4 weeks before screening and who had an LDL cholesterol level of 130 mg per deciliter (3.4 mmol per liter) or more and a triglyceride level of 400 mg per deciliter (4.5 mmol per liter) or less were randomly assigned in a 2:1 ratio to receive monthly subcutaneous injections of evolocumab (420 mg) or placebo. The primary end point was the percent change in LDL cholesterol level from baseline to week 24; key secondary end points were the mean percent change in LDL cholesterol level from baseline to weeks 22 and 24 and the absolute change in LDL cholesterol level from baseline to week 24. RESULTS: A total of 157 patients underwent randomization and received evolocumab (104 patients) or placebo (53 patients). At week 24, the mean percent change from baseline in LDL cholesterol level was -44.5% in the evolocumab group and -6.2% in the placebo group, for a difference of -38.3 percentage points (P<0.001). The absolute change in the LDL cholesterol level was -77.5 mg per deciliter (-2.0 mmol per liter) in the evolocumab group and -9.0 mg per deciliter (-0.2 mmol per liter) in the placebo group, for a difference of -68.6 mg per deciliter (-1.8 mmol per liter) (P<0.001). Results for all secondary lipid variables were significantly better with evolocumab than with placebo. The incidence of adverse events that occurred during the treatment period was similar in the evolocumab and placebo groups. CONCLUSIONS: In this trial involving pediatric patients with familial hypercholesterolemia, evolocumab reduced the LDL cholesterol level and other lipid variables. (Funded by Amgen; HAUSER-RCT ClinicalTrials.gov number, NCT02392559.).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticolesterolemiantes/uso terapêutico , LDL-Colesterol/sangue , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Pró-Proteína Convertase 9/antagonistas & inibidores , Adolescente , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticolesterolemiantes/efeitos adversos , Criança , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Heterozigoto , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/genética , Lipídeos/sangue , Masculino , Resultado do Tratamento
11.
PLoS Med ; 17(9): e1003302, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32915777

RESUMO

BACKGROUND: A number of epidemiological and genetic studies have attempted to determine whether levels of circulating lipids are associated with risks of various cancers, including breast cancer (BC). However, it remains unclear whether a causal relationship exists between lipids and BC. If alteration of lipid levels also reduced risk of BC, this could present a target for disease prevention. This study aimed to assess a potential causal relationship between genetic variants associated with plasma lipid traits (high-density lipoprotein, HDL; low-density lipoprotein, LDL; triglycerides, TGs) with risk for BC using Mendelian randomization (MR). METHODS AND FINDINGS: Data from genome-wide association studies in up to 215,551 participants from the Million Veteran Program (MVP) were used to construct genetic instruments for plasma lipid traits. The effect of these instruments on BC risk was evaluated using genetic data from the BCAC (Breast Cancer Association Consortium) based on 122,977 BC cases and 105,974 controls. Using MR, we observed that a 1-standard-deviation genetically determined increase in HDL levels is associated with an increased risk for all BCs (HDL: OR [odds ratio] = 1.08, 95% confidence interval [CI] = 1.04-1.13, P < 0.001). Multivariable MR analysis, which adjusted for the effects of LDL, TGs, body mass index (BMI), and age at menarche, corroborated this observation for HDL (OR = 1.06, 95% CI = 1.03-1.10, P = 4.9 × 10-4) and also found a relationship between LDL and BC risk (OR = 1.03, 95% CI = 1.01-1.07, P = 0.02). We did not observe a difference in these relationships when stratified by breast tumor estrogen receptor (ER) status. We repeated this analysis using genetic variants independent of the leading association at core HDL pathway genes and found that these variants were also associated with risk for BCs (OR = 1.11, 95% CI = 1.06-1.16, P = 1.5 × 10-6), including locus-specific associations at ABCA1 (ATP Binding Cassette Subfamily A Member 1), APOE-APOC1-APOC4-APOC2 (Apolipoproteins E, C1, C4, and C2), and CETP (Cholesteryl Ester Transfer Protein). In addition, we found evidence that genetic variation at the ABO locus is associated with both lipid levels and BC. Through multiple statistical approaches, we minimized and tested for the confounding effects of pleiotropy and population stratification on our analysis; however, the possible existence of residual pleiotropy and stratification remains a limitation of this study. CONCLUSIONS: We observed that genetically elevated plasma HDL and LDL levels appear to be associated with increased BC risk. Future studies are required to understand the mechanism underlying this putative causal relationship, with the goal of developing potential therapeutic strategies aimed at altering the cholesterol-mediated effect on BC risk.


Assuntos
Neoplasias da Mama/genética , Lipídeos/análise , Lipídeos/sangue , Adulto , Neoplasias da Mama/metabolismo , Colesterol/análise , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Análise da Randomização Mendeliana/métodos , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Triglicerídeos/sangue
12.
Medicine (Baltimore) ; 99(38): e22032, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957320

RESUMO

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a metabolic disease with widespread concern in the world. It has the characteristics of high incidence rate and high disability rate, which seriously affects economic and social development. large dose herb Rhizoma Coptidis (Huanglian) and Scutellaria (Huangqin) or compound prescription contain large dose Huanglian and Huanglian for treatment of T2DM has already been confirmed. However, due to the lack of evidence, there is no specific method or suggestion, so it is necessary to carry out systematic evaluation on Coptidis and Scutellaria and provide effective evidence for further research. METHODS AND ANALYSIS: The following databases will be searched from their inception to June 2020: Electronic database includes PubMed, Embase, Cochrane Library, Web of Science, Nature, Science online, Chinese Biomedical Database WanFang, VIP medicine information, and China National Knowledge Infrastructure. Primary outcomes: fasting blood-glucose (FBG), 2 Hours Postprandial Blood Glucose (2hPBG), Glycosylated hemoglobin A1c (HbA1c). additional outcomes: Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), triglycerides (TG), total serum cholesterol (TC). Data will be extracted by 2 researchers independently, risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. All data analysis will be conducted by data statistics software Review Manager V.5.3. and Stata V.12.0. RESULTS: The results of this study will systematically evaluate the effectiveness and safety of large dose Huanglian and Huangqin intervention for people with T2DM. CONCLUSION: The systematic review of this study will summarize the current published evidence of large dose Huanglian and Huangqin for the treatment of T2DM, which can further guide the promotion and application of it. ETHICS AND DISSEMINATION: This study is a systematic review, the outcomes are based on the published evidence, so examination and agreement by the ethics committee are not required in this study. We intend to publish the study results in a journal or conference presentations. OPEN SCIENCE FRAMEWORK (OSF) REGISTRATION NUMBER: July 21, 2020. osf.io/b6r3z. (https://osf.io/b6r3z).


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Scutellaria , Glicemia , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Hemoglobina A Glicada , Estilo de Vida Saudável , Humanos , Hipoglicemiantes/uso terapêutico , Lipídeos/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
13.
Medicine (Baltimore) ; 99(38): e22036, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957321

RESUMO

Studies about the effects of metabolically healthy obesity on cardiovascular disease (CVD) have yielded conflicting results. These heterogeneous results could be due to the limited usefulness of BMI in measuring general adiposity, as body mass index (BMI) does not accurately reflect body composition. This study aimed to evaluate the effect of body shape on CVD outcomes across different obesity phenotypes, and to provide an explanation for the heterogeneous effects of metabolically healthy obese (MHO) phenotype on CVD.We analyzed data from the Korean Genome and Epidemiology Study, a population-based cohort study conducted between 2001 and 2012. We divided the participants into 4 groups: metabolically healthy non-obese (MHNO), MHO, metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO). To assess body shape, we calculated the z-score of the log-transformed a body shape index (LBSIZ). We computed Pearson correlation coefficients to examine the association of LBSIZ with muscle mass index, percentage of total fat mass (%Total FM), and percentage of abdominal fat mass (%Abdominal FM). We also used Cox proportional hazards regression to evaluate the effect of LBSIZ on CVD events according to the obesity phenotypes.A total of 9460 participants were assessed in this study. The incidence of CVD was 8.53 cases per 1000 person-year. LBSIZ showed strong positive correlation with %Total FM and %Abdominal FM, but negative correlation with muscle mass index. In Cox regression, MHO individuals did not show increased risk of CVD compared with MHNO individuals (hazard ratio [HR], 1.29; 95% confidence interval [CI], 0.96-1.73). However, MHO individuals in the 3rd (HR, 2.40; 95% CI, 1.28-4.51) and 4th (HR, 3.67; 95% CI, 1.99-6.74) quarters of LBSIZ showed significantly higher risk of CVD compared with MHNO individuals in the 1st quarter of LBSIZ. Moreover, LBSIZ showed a linear relationship with CVD among MHO individuals.While the MHO individuals showed similar CVD risk to the MHNO individuals, CVD risk increases with LBSIZ among the MHO individuals. LBSIZ appears to be a useful measure for CVD risk assessment in clinical practice and epidemiologic studies, especially for MHO patients.


Assuntos
Composição Corporal/fisiologia , Doenças Cardiovasculares/epidemiologia , Obesidade Metabolicamente Benigna/epidemiologia , Obesidade Metabolicamente Benigna/patologia , Adiposidade , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Glicemia , Índice de Massa Corporal , Pesos e Medidas Corporais , Fumar Cigarros/epidemiologia , Feminino , Comportamentos Relacionados com a Saúde , Nível de Saúde , Humanos , Incidência , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Fenótipo , Modelos de Riscos Proporcionais , República da Coreia/epidemiologia , Fatores de Risco , Fatores Socioeconômicos
14.
Nat Commun ; 11(1): 4830, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32973134

RESUMO

Non-invasively probing metabolites within single live cells is highly desired but challenging. Here we utilize Raman spectro-microscopy for spatial mapping of metabolites within single cells, with the specific goal of identifying druggable metabolic susceptibilities from a series of patient-derived melanoma cell lines. Each cell line represents a different characteristic level of cancer cell de-differentiation. First, with Raman spectroscopy, followed by stimulated Raman scattering (SRS) microscopy and transcriptomics analysis, we identify the fatty acid synthesis pathway as a druggable susceptibility for differentiated melanocytic cells. We then utilize hyperspectral-SRS imaging of intracellular lipid droplets to identify a previously unknown susceptibility of lipid mono-unsaturation within de-differentiated mesenchymal cells with innate resistance to BRAF inhibition. Drugging this target leads to cellular apoptosis accompanied by the formation of phase-separated intracellular membrane domains. The integration of subcellular Raman spectro-microscopy with lipidomics and transcriptomics suggests possible lipid regulatory mechanisms underlying this pharmacological treatment. Our method should provide a general approach in spatially-resolved single cell metabolomics studies.


Assuntos
Melanoma/metabolismo , Metabolômica/métodos , Microscopia/métodos , Análise Espectral Raman/métodos , Apoptose , Linhagem Celular Tumoral , Ácidos Graxos/metabolismo , Humanos , Gotículas Lipídicas , Metabolismo dos Lipídeos , Lipidômica , Lipídeos , Ácido Oleico , Estearoil-CoA Dessaturase/metabolismo , Transcriptoma
15.
Crit Care Resusc ; 22(3): 227-236, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32900329

RESUMO

OBJECTIVE: The systemic inflammatory response syndrome (SIRS) is a dysregulated response that contributes to critical illness. Adjunctive acetylsalicylic acid (ASA) treatment may offer beneficial effects by increasing the synthesis of specialised proresolving mediators (a subset of polyunsaturated fatty acid-derived lipid mediators). DESIGN: Pilot, feasibility, multicentre, double-blind, randomised, placebo-controlled trial. SETTING: Four interdisciplinary intensive care units (ICUs) in Australia. PARTICIPANTS: Critically ill patients with SIRS. INTERVENTIONS: ASA 100 mg 12-hourly or placebo, administered within 24 hours of ICU admission and continued until ICU day 7, discharge or death, whichever came first. MAIN OUTCOME MEASURES: Interleukin-6 (IL-6) serum concentration at 48 hours after randomisation and, in a prespecified subgroup of patients, serum lipid mediator concentrations measured by mass spectrometry. RESULTS: The trial was discontinued in December 2017 due to slow recruitment and after the inclusion of 48 patients. Compared with placebo, ASA did not decrease IL-6 serum concentration at 48 hours. In the 32 patients with analysis of lipid mediators, low-dose ASA increased the concentration of 15-hydroxyeicosatetraenoic acid, a proresolving precursor of lipoxin A4, and reduced the concentration of the proinflammatory cytochrome P-dependent mediators 17-HETE (hydroxyeicosatetraenoic acid), 18-HETE and 20-HETE. In the eicosapentaenoic acid pathway, ASA significantly increased the concentration of the anti-inflammatory mediators 17,18-DiHETE (dihydroxyeicosatetraenoic acid) and 14,15-DiHETE. CONCLUSIONS: In ICU patients with SIRS, low-dose ASA did not significantly alter serum IL-6 concentrations, but it did affect plasma concentrations of certain lipid mediators. The ability to measure lipid mediators in clinical samples and to monitor the effect of ASA on their levels unlocks a potential area of biological investigation in critical care. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN 12614001165673).


Assuntos
Aspirina/administração & dosagem , Estado Terminal , Citocinas/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Austrália , Método Duplo-Cego , Estudos de Viabilidade , Humanos , Interleucina-6/sangue , Lipídeos , Resultado do Tratamento
16.
Medicine (Baltimore) ; 99(35): e21722, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871891

RESUMO

BACKGROUND: In recent years, the role of vitamin D (VD) as a protective factor in cardiovascular disease has been recognized. Thus, there is a need to study the effect of vitamin D supplementation in the control of different cardiovascular risk factors and metabolic syndrome, especially in young populations where few studies have been conducted. METHODS: Pilot study of a randomized, parallel two-arm, triple-blind clinical controlled trial in 150 adolescents and young adults in the city of Bucaramanga-Colombia. The intervention group will receive 1000 IU of VD and the control group 200 IU of VD daily for 15 weeks. The main outcomes are: serum calcifediol levels (25(OH) D), body mass index and lipid profile; secondary outcomes are complementary to the previous ones (skin folds, waist-hip ratio). Other variables will be analyzed such as assessment of dietary intake, physical activity, sun exposure, cigarette and tobacco consumption and compliance with VD supplementation. DISCUSSION: This study is innovative since there is little evidence from clinical trials in adolescents and young adults; similar studies are not known in our context. The results of this study may facilitate the recommendation of oral vitamin D supplementation in the population of interest. In addition, it is a low-cost and easy-to-apply intervention that could contribute to the formulation and implementation of health policies. TRIAL REGISTRATION: NCT04377386.


Assuntos
Índice de Massa Corporal , Calcifediol/sangue , Lipídeos/sangue , Vitamina D/administração & dosagem , Vitaminas/administração & dosagem , Administração Oral , Adolescente , Colômbia , Suplementos Nutricionais , Método Duplo-Cego , Humanos , Projetos Piloto , Ensaios Clínicos Controlados Aleatórios como Assunto , Pregas Cutâneas , Relação Cintura-Quadril , Adulto Jovem
17.
Medicine (Baltimore) ; 99(35): e21574, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871873

RESUMO

The prevalence of the metabolic syndrome (MS) is increasing in China, but there are disparities between urban and rural populations, and across different regions.To examine the prevalence and risk factors of MS in the rural area of Qianjiang (Southwest China).From March 2016 to June 2018, 6 townships in the Qianjiang District of Chongqing Municipality were selected for a cross-sectional study of the residents in rural areas. Demographics and medical history were collected using a questionnaire. Anthropometry and blood pressure were obtained by physical examination. Blood lipids, fasting plasma glucose, and 2-h postprandial glucose were measured.A total of 2949 (1067 males and 1882 females) were included. The mean age was 63.8 ±â€Š10.7 years. The prevalence of MS in the study population was 16.8% (496/2949). The prevalence of MS was 7.4% in men, 22.2% in women, 15.7% in Han, 18.1% in Tujia, and 14.8% in Miao. According to age, the prevalence of MS was 10.6%, 17.0%, and 18.3% in the 30-50, 50-69, and ≥ 70 years groups. The multivariable analysis showed that female sex (OR = 33.36, 95%CI: 17.0-65.53), dyslipidemia (OR = 4.71, 95%CI: 1.73-12.82), kidney diseases (OR = 2.32, 95%CI: 1.37-3.94), waistline (OR = 1.39, 95%CI: 1.33-1.46), high-density lipoprotein cholesterol (OR = 0.12, 95%CI: 0.06-0.23), triglycerides (OR = 1.52, 95%CI: 1.31-1.76), alanine aminotransferase (OR = 0.98, 95%CI: 0.97-1.00), γ-glutamyltransferase (OR = 1.00, 95%CI: 1.00-1.01), and glycated hemoglobin (OR = 1.31, 95%CI: 1.08-1.59) were independently associated with MS.The prevalence of MS was 16.8% in Qianjiang. Female sex, kidney diseases, alanine aminotransferase, and γ-glutamyltransferase were independent risk factors for MS.


Assuntos
Síndrome Metabólica/sangue , Síndrome Metabólica/epidemiologia , População Rural/tendências , Idoso , Alanina Transaminase/sangue , Antropometria , Glicemia/análise , Pressão Sanguínea/fisiologia , China/epidemiologia , HDL-Colesterol/sangue , Estudos Transversais , Dislipidemias/epidemiologia , Jejum/sangue , Feminino , Humanos , Nefropatias/epidemiologia , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fatores Sexuais , Triglicerídeos/sangue , gama-Glutamiltransferase/sangue
18.
Nat Commun ; 11(1): 4576, 2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917905

RESUMO

Endosome maturation depends on membrane contact sites (MCSs) formed between endoplasmic reticulum (ER) and endolysosomes (LyLEs). The mechanism underlying lipid supply for this process and its pathophysiological relevance remains unclear, however. Here, we identify PDZD8-the mammalian ortholog of a yeast ERMES subunit-as a protein that interacts with protrudin, which is located at ER-LyLE MCSs. Protrudin and PDZD8 promote the formation of ER-LyLE MCSs, and PDZD8 shows the ability to extract various lipids from the ER. Overexpression of both protrudin and PDZD8 in HeLa cells, as well as their depletion in mouse primary neurons, impairs endosomal homeostasis by inducing the formation of abnormal large vacuoles reminiscent of those apparent in spastin- or REEP1-deficient neurons. The protrudin-PDZD8 system is also essential for the establishment of neuronal polarity. Our results suggest that protrudin and PDZD8 cooperatively promote endosome maturation by mediating ER-LyLE tethering and lipid extraction at MCSs, thereby maintaining neuronal polarity and integrity.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Endossomos/fisiologia , Metabolismo dos Lipídeos , Neurônios/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Modelos Animais de Doenças , Retículo Endoplasmático/metabolismo , Feminino , Células HEK293 , Células HeLa , Humanos , Lipídeos , Lipossomos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Camundongos Knockout , Mitocôndrias , Domínios Proteicos , Proteômica , Proteínas Recombinantes , Saccharomyces cerevisiae/metabolismo , Proteínas de Transporte Vesicular/genética
19.
Medicine (Baltimore) ; 99(37): e22171, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925785

RESUMO

The correlations between retinal vessel distribution, anterior chamber depth (ACD) and other myopic eye structural parameters remains elusive. This study aims to investigate retinal vasculature and eye structure correlations in healthy and myopic eyes of Chinese young adults.In this cross-sectional study, 181 eyes (97 adults) were recruited. Macular and peripapillary vasculature was quantified by optical coherence tomography angiography. Correlations between retinal vasculature and eye structure were analyzed using multivariable linear regression.There were significant differences in ACD, spherical equivalent, axial length (AL), superficial macular vascular density (MVD), peripapillary vascular density (PVD) and circumference of foveal avascular zone (FAZ) among emmetropia, low-myopia, moderate-myopia, and high-myopia groups (both P < 0.05). Furthermore, ACD had significant positive correlation with AL and FAZ, but negative correlation with PVD. MVD also had a negative correlation with AL (beta = -0.247, P < .001). In addition, there was a significant negative correlation between circumference of the FAZ and spherical equivalent as well as central subfield thickness (beta = -0.20, P = .005; beta = -0.334, P < .001, respectively).The degree of myopia affected ACD, MVD, PVD, and circumference of the FAZ in eyes of young healthy adults. Meanwhile, ACD has a positive, while retinal vascular system measurements have a negative correlation with increasing severity of myopia.


Assuntos
Olho/irrigação sanguínea , Olho/patologia , Miopia/patologia , Vasos Retinianos/patologia , Adolescente , Adulto , Fatores Etários , Glicemia , Capilares/patologia , Estudos Transversais , Feminino , Humanos , Lipídeos/sangue , Masculino , Estudos Prospectivos , Índice de Gravidade de Doença , Fatores Sexuais , Tomografia de Coerência Óptica , Adulto Jovem
20.
Medicine (Baltimore) ; 99(37): e22202, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925796

RESUMO

Metabolic syndrome (MetS), mainly caused by intra-abdominal fat (IAF) accumulation, is an important risk factor for cardiovascular disease. The prevalence of MetS increases rapidly after the age of 40 years, and it is presumed that there is a substantial proportion of MetS in younger age groups. However, the association of IAF with MetS in adults aged 20 to 30 years has not been fully investigated.This study aimed to determine the prevalence of MetS and to verify whether IAF accumulation is associated with other MetS-related metabolic disorders including dyslipidemia, high blood pressure, and high blood glucose among the Japanese population in their 20s.In this cross-sectional study, IAF area (IAFA) and MetS-related metabolic parameters were evaluated in university students in their 20s (n = 1822, 21.5 ±â€Š1.5 years). IAFA was measured using a non-invasive device, DUALSCAN, which can be readily measured through the dual impedance method. The participants were divided into four groups according to IAFA: 0-49.9, 50-74.9, 75-99.9, and ≥100 cm.MetS was prevalent in 3.3% and 0.0% of the males and females, respectively, according to the Japanese criteria of MetS. The sex- and lifestyle-adjusted odds ratios (ORs) for the three metabolic component levels of Mets were elevated in the larger IAFA groups compared to the smallest IAFA group, according to the level of IAFA. The levels particularly increased in participants with abdominal obesity, defined by both, IAFA and waist circumference rather than by waist circumference alone.IAF accumulation was significantly associated with MetS-related metabolic disorders in young adults. An evaluation of IAFA may contribute to the early prediction of the risk of developing MetS in the future.


Assuntos
Síndrome Metabólica/epidemiologia , Obesidade Abdominal/epidemiologia , Glicemia , Pressão Sanguínea , Índice de Massa Corporal , Pesos e Medidas Corporais , Estudos Transversais , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Gordura Intra-Abdominal/fisiopatologia , Estilo de Vida , Lipídeos/sangue , Masculino , Fatores Sexuais , Circunferência da Cintura , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA