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1.
Plant Biol (Stuttg) ; 25(6): 902-914, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37641387

RESUMO

Studies on plant responses to combined abiotic stresses are very limited, especially in major crop plants. The current study evaluated the response of chorismate mutase overexpressor (OxCM) rice line to combined UV light and drought stress. The experiments were conducted in pots in a growth chamber, and data were assessed for gene expression, antioxidant and hormone regulation, flavonoid accumulation, phenotypic variation, and amino acid accumulation. Wild-type (WT) rice had reduced the growth and vigour, while transgenic rice maintained growth and vigour under combined UV light and drought stress. ROS and lipid peroxidation analysis revealed that chorismate mutase (OsCM) reduced oxidative stress mediated by ROS scavenging and reduced lipid peroxidation. The combined stresses reduced biosynthesis of total flavonoids, kaempferol and quercetin in WT plants, but increased significantly in plants with OxCM. Phytohormone analysis showed that SA was reduced by 50% in WT and 73% in transgenic plants, while ABA was reduced by 22% in WT plants but increased to 129% in transgenic plants. Expression of chorismate mutase regulates phenylalanine biosynthesis, UV light and drought stress-responsive genes, e.g., phenylalanine ammonia lyase (OsPAL), dehydrin (OsDHN), dehydration-responsive element-binding (OsDREB), ras-related protein 7 (OsRab7), ultraviolet-B resistance 8 (OsUVR8), WRKY transcription factor 89 (OsWRKY89) and tryptophan synthase alpha chain (OsTSA). Moreover, OsCM also increases accumulation of free amino acids (aspartic acid, glutamic acid, leucine, tyrosine, phenylalanine and proline) and sodium (Na), potassium (K), and calcium (Ca) ions in response to the combined stresses. Together, these results suggest that chorismate mutase expression induces physiological, biochemical and molecular changes that enhance rice tolerance to combined UV light and drought stresses.


Assuntos
Oryza , Oryza/genética , Secas , Espécies Reativas de Oxigênio , Raios Ultravioleta , Aminoácidos , Corismato Mutase , Flavonoides
2.
Circ Cardiovasc Qual Outcomes ; 15(9): e008592, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36065815

RESUMO

BACKGROUND: Care fragmentation is associated with higher rates of infection after durable left ventricular assist device (LVAD) implant. Less is known about the relationship between care fragmentation and total spending, and whether this relationship is mediated by infections. METHODS: Total payments were captured from admission to 180 days post-discharge. Drawing on network theory, a measure of care fragmentation was developed based on the number of shared patients among providers (ie, anesthesiologists, cardiac surgeons, cardiologists, critical care specialists, nurse practitioners, physician assistants) caring for 4,987 Medicare beneficiaries undergoing LVAD implantation between July 2009 - April 2017. Care fragmentation was measured using average path length, which describes how efficiently information flows among network members; longer path length indicates greater fragmentation. Terciles based on the level of care fragmentation and multivariable regression were used to analyze the relationship between care fragmentation and LVAD payments and mediation analysis was used to evaluate the role of post-implant infections. RESULTS: The patient cohort was 81% male, 73% white, 11% Intermacs Profile 1 with mean (SD) age of 63.1 years (11.1). The mean (SD) level of care fragmentation in provider networks was 1.7 (0.2) and mean (SD) payment from admission to 180 days post-discharge was $246,905 ($109,872). Mean (SD) total payments at the lower, middle, and upper terciles of care fragmentation were $250,135 ($111,924), $243,288 ($109,376), and $247,290 ($108,241), respectively. In mediation analysis, the indirect effect of care fragmentation on total payments, through infections, was positive and statistically significant (ß=16032.5, p=0.008). CONCLUSIONS: Greater care fragmentation in the delivery of care surrounding durable LVAD implantation is associated with a higher incidence of infections, and consequently, higher payments for Medicare beneficiaries. Interventions to reduce care fragmentation may reduce the incidence of infections and in turn enhance the value of care for patients undergoing durable LVAD implantation.


Assuntos
Infecção Hospitalar , Insuficiência Cardíaca , Coração Auxiliar , Cirurgiões , Assistência ao Convalescente , Idoso , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Atenção à Saúde , Feminino , Humanos , Masculino , Análise de Mediação , Medicare , Pessoa de Meia-Idade , Alta do Paciente , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos/epidemiologia
3.
ESMO Open ; 7(3): 100484, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35576696

RESUMO

BACKGROUND: A comprehensive analysis of peripheral immune cell phenotypes and tumor immune-gene expression profiles in locally advanced pancreatic cancer patients treated with neoadjuvant chemotherapy in a phase II clinical trial was carried out. METHODS: Patients were treated with neoadjuvant modified folinic acid, fluorouracil, irinotecan hydrochloride, oxaliplatin (mFOLFIRINOX) followed by surgery and adjuvant gemcitabine at the Asan Medical Center. Correlations between survival outcomes and baseline peripheral immune cells and their changes during preoperative chemotherapy were analyzed. Patients who had surgery were divided into two groups according to achievement of disease-free survival >10 months (achieved versus failed). Differential expression and pathway analysis of immune-related genes were carried out using the Nanostring platform, and immune cells within the tumor microenvironment were compared by immunohistochemistry. RESULTS: Forty-four patients were treated in the phase II clinical trial. Higher baseline CD14+CD11c+HLA-DR+ monocytes (P = 0.044) and lower Foxp3+CD4+ T cells (P = 0.02) were associated with poor progression-free survival of neoadjuvant mFOLFIRINOX. During the preoperative chemotherapy, PD-1 T cells significantly decreased (P = 0.0110). Differential expression and pathway analysis of immune-genes from the resected tumor after neoadjuvant treatment revealed transforming growth factor-ß pathway enrichment and higher expression of MARCO (adjusted P < 0.05) associated with early recurrence. Enrichment of the Th1 pathway and higher peritumoral CD8+ T cells (P = 0.0103) were associated with durable disease-free survival from surgery (>10 months) following neoadjuvant mFOLFIRINOX. CONCLUSIONS: Our results identify potential immune biomarkers for locally advanced pancreatic cancer and provide insights into pancreatic cancer immunity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Pancreáticas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Irinotecano/farmacologia , Irinotecano/uso terapêutico , Leucovorina/farmacologia , Leucovorina/uso terapêutico , Oxaliplatina/farmacologia , Oxaliplatina/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Fenótipo , Transcriptoma , Microambiente Tumoral
4.
Br Poult Sci ; 63(2): 211-217, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34309442

RESUMO

1. Mineral excretion is an issue in the poultry industry. The use of micro minerals in nano form can increase bioavailability and decrease excretion rate. However, information concerning the bioavailability of nano manganese (Mn) in broiler chicks is limited.2. This experiment studied the influences of hot-melt extrusion (HME)-processed manganese sulphate on body weight gain, Mn bioavailability, nutrient digestibility and meat quality in broiler chicks fed a corn-soybean meal-based diet as a starter and grower phase. A total of 700 birds (Ross 308, 1-day-old) were randomly placed in 35 cages (20 birds per cage). The broiler chicks were fed one of seven experimental diets, which consisted of a control (without supplemental Mn), different levels of MnSO4 (IN-Mn60; 60, 120, and 200 mg/kg), or HME MnSO4 (HME-Mn; 60, 120, and 200 mg/kg).3. There was an increased serum Mn content in broilers fed diet supplemented with HME-Mn. In the grower phase, increased dietary Mn levels elevated the concentrations in the serum, liver, and tibia. There were increases in the excreta Mn content of broilers fed increasing levels. The supplementation of HME-Mn showed a lower percentage of abdominal fat compared with the IN-Mn treatment diets. Supplementation with HME-Mn decreased intramuscular fat compared with the diets supplemented with IN-Mn. The supplementation of HME-Mn decreased the thiobarbituric acid reactive substances (TBARS) at d 6 of age. The HME-Mn source showed a greater decrease in TBARS compared with the IN-Mn treatment.4. In conclusion, HME processing increased bioavailability and could be used as an environmentally friendly method to facilitate lower levels of Mn in the diet of broiler chickens.


Assuntos
Galinhas , Manganês , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Disponibilidade Biológica , Dieta/veterinária , Suplementos Nutricionais , Carne
5.
Ann Oncol ; 32(3): 368-374, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33278599

RESUMO

BACKGROUND: Adjuvant chemotherapy and chemoradiotherapy are some of the standards of care for gastric cancer (GC). The Adjuvant chemoRadioTherapy In Stomach Tumors (ARTIST) 2 trial compares two adjuvant chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II or III, node-positive GC. PATIENTS AND METHODS: The ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens: oral S-1 (40-60 mg twice daily 4 weeks on/2 weeks off) for 1 year, S-1 (2 weeks on/1 week off) plus oxaliplatin 130 mg/m2 every 3 weeks (SOX) for 6 months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to surgery type (total or subtotal gastrectomy), pathologic stage (II or III), and Lauren histologic classification (diffuse or intestinal/mixed). The primary endpoint was disease-free survival (DFS) at 3 years; a reduction of 33% in the hazard ratio (HR) for DFS with SOX or SOXRT, when compared with S-1, was considered clinically meaningful. The trial is registered at clinicaltrials.gov (NCT0176146). RESULTS: A total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively. Median follow-up period was 47 months, with 178 DFS events observed. Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively. HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 versus SOX, 0.692 (P = 0.042) and S-1 versus SOXRT, 0.724 (P = 0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971; P = 0.879). Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable. CONCLUSIONS: In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2 gastrectomy.


Assuntos
Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Quimioterapia Adjuvante , Intervalo Livre de Doença , Fluoruracila/uso terapêutico , Humanos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Oxaliplatina/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia
6.
Ecology ; 101(3): e02946, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31840224

RESUMO

Resource availability in agricultural landscapes has been disturbed for many organisms, including pollinator species. Abundance and diversity in flower availability benefit bee populations; however, little is known about which of protein or carbohydrate resources may limit their growth and reproductive performance. Here, we test the hypothesis of complementary resource limitation using a supplemental feeding approach. We applied this assumption with bumble bees (Bombus terrestris), assuming that colony growth and reproductive performance should depend on the continuous supply of carbohydrates and proteins, through the foraging for nectar and pollen, respectively. We placed wild-caught bumble bee colonies along a landscape gradient of seminatural habitats, and monitored the colonies' weight, foraging activity, and reproductive performance during the whole colony cycle. We performed supplemental feeding as an indicator of landscape resource limitation, using a factorial design consisting of the addition of sugar water (carbohydrate, supplemented or not) crossed by pollen (protein, supplemented or not). Bumble bee colony dynamics showed a clear seasonal pattern with a period of growth followed by a period of stagnation. Higher abundance of seminatural habitats resulted in reducing the proportion of pollen foragers relative to all foragers in both periods, and in improving the reproductive performance of bumble bees. Interestingly, the supplemental feeding of sugar water positively affected the colony weight during the stagnation period, and the supplemental feeding of pollen mitigated the landscape effect on pollen collection investment. Single and combined supplementation of sugar water and pollen increased the positive effect of seminatural habitats on reproductive performance. This study reveals a potential colimitation in pollen and nectar resources affecting foraging behavior and reproductive performance in bumble bees, and indicates that even in mixed agricultural landscapes with higher proportions of seminatural habitats, bumble bee populations face resource limitations. We conclude that the seasonal management of floral resources must be considered in conservation to support bumble bee populations and pollination services in farmlands.


Assuntos
Pólen , Polinização , Animais , Abelhas , Ecossistema , Comportamento Alimentar , Néctar de Plantas , Reprodução
8.
Brain Res Bull ; 138: 106-111, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28625784

RESUMO

To determine the effects of auditory stimulus on skin conductance (SC) in infants with severe neonatal abstinence syndrome (NAS) that required morphine treatment (MT) compared with NAS infants that did not require morphine treatment (non-MT). We prospectively enrolled opiate-exposed term infants without polysubstance exposure. Skin conductance responses to an auditory stimulus (ringing a bell for 3s) near the time of discharge were obtained. Skin conductance was measured before, during, and after the stimulus. Non-parametric tests were used to determine between group and within phase differences. Infants were off MT at the time of SC measurement in response to an auditory stimulus. In a 2-group comparison of MT vs. non-MT infants, there was significantly higher SC responsivity to an auditory stimulus (p <0.05) in the MT group as compared with the non-MT group near discharge. The mean +SE peak morphine dose was 0.85+0.20mg/kg/day in the MT group. The mean Length of Stay (LOS) was 32 vs. 7 (p <0.05) days respectively, for the MT vs. the non-MT group. Our preliminary data suggest that in infants with severe NAS symptoms, higher sympathetic arousal in response to an auditory stimulus persists at discharge, underscoring the need for ongoing evaluation and specialized care at home.


Assuntos
Estimulação Acústica/métodos , Sistema Nervoso Autônomo/efeitos dos fármacos , Resposta Galvânica da Pele/efeitos dos fármacos , Morfina/uso terapêutico , Entorpecentes/uso terapêutico , Síndrome de Abstinência Neonatal/tratamento farmacológico , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Idade Gestacional , Humanos , Lactente , Masculino , Síndrome de Abstinência Neonatal/fisiopatologia , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/fisiopatologia
9.
J Dairy Sci ; 100(10): 7788-7792, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28803022

RESUMO

Ginseng marc, a by-product of the extraction of fresh ginseng, is known to have bioactive compounds, but is frequently discarded as agriculture waste. The objectives of our study were to assess the antioxidative activity of fermented ginseng marc extract using Lactobacillus plantarum KCCM 11613P and to evaluate antibacterial activity of fermented milk with added ginseng marc extract during fermentation. After 24 h of fermentation of ginseng marc extract, the viable cell number was increased to 7.7 ± 0.1 log cfu/mL, and the pH and total titratable acidity were 4.2 ± 0.4 and 0.6% lactic acid, respectively. The total phenolic and flavonoid contents of fermented ginseng marc extract increased by 32.4 and 23.3%, respectively. Higher antioxidative activity of fermented ginseng marc extract was obtained in the ß-carotene bleaching, ferric-reducing ability of plasma, and ferric thiocyanate assays than the 1,1-diphenyl-2-picrylhydrazy assay. However, the 1,1-diphenyl-2-picrylhydrazy scavenging effect decreased due to lowered pH. During production of fermented milk with ginseng, inhibition rate of Staphylococcus aureus and Escherichia coli were 9.7 and 2.3%, respectively. The present study shows the possibilities of Lactobacillus plantarum KCCM 11613P used as a fermentation strain and ginseng marc used as a functional supplement in milk.


Assuntos
Antibacterianos/farmacologia , Produtos Fermentados do Leite/microbiologia , Escherichia coli O157/efeitos dos fármacos , Lactobacillus plantarum , Leite/microbiologia , Panax/química , Extratos Vegetais/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Animais , Fermentação
11.
Angew Chem Int Ed Engl ; 56(3): 733-737, 2017 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-27966822

RESUMO

A strategy for the preparation of homogeneous antibody-drug conjugates (ADCs) containing multiple payloads has been developed. This approach utilizes sequential unmasking of cysteine residues with orthogonal protection to enable site-specific conjugation of each drug. In addition, because the approach utilizes conjugation to native antibody cysteine residues, it is widely applicable and enables high drug loading for improved ADC potency. To highlight the benefits of ADC dual drug delivery, this strategy was applied to the preparation of ADCs containing two classes of auristatin drug-linkers that have differing physiochemical properties and exert complementary anti-cancer activities. Dual-auristatin ADCs imparted activity in cell line and xenograft models that are refractory to ADCs comprised of the individual auristatin components. This work presents a facile method for construction of potent dual-drug ADCs and demonstrates how delivery of multiple cytotoxic warheads can lead to improved ADC activities. Lastly, we anticipate that the conditions utilized herein for orthogonal cysteine unmasking are not restricted to ADCs and can be broadly utilized for site-specific protein modification.


Assuntos
Aminobenzoatos/química , Anticorpos Monoclonais/química , Antineoplásicos/química , Cisteína/química , Imunoconjugados/química , Oligopeptídeos/química , Sistemas de Liberação de Medicamentos , Conformação Molecular
12.
Poult Sci ; 96(3): 710-716, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-27697932

RESUMO

The use of chlorella as an immune stimulant to enhance nonspecific host defense mechanisms or as an antimicrobial to inhibit bacterial growth has been reported. Thus, the aim of the present study was to clarify the effect of recombinant chlorella supplementation on growth performance, meat quality, and the blood profile, excreta microflora, and nutrient digestibility in broilers. A total of 375 one-day-old ROSS 308 broilers (male and female) were allotted to 5 dietary treatments using 5 cages with 15 chicks per cage. Treatments were: 1) NC, basal diet supplemented with 1.0% E. coli fermented liquor (EFL); 2) PC1, 0.2% EFL with chlorella; 3) PC2, 1.0% EFL with chlorella; 4) T1, 0.2% EFL with chlorella (anti-viral); and 5) T2, 1.0% EFL with chlorella (anti-viral). The broilers in the T2 treatment groups showed higher body weight gain (BGW) by 2.55% (P < 0.01) and lower feed conversion ratio (FCR) by 2.75% (P < 0.05) compared with those fed the control NC treatment group. Moreover, the blood contents of blood urea nitrogen (BUN), creatinine, and IgA in the broilers of the T2 treatment group were significantly increased by 28.12, 23.07, and 29.72%, respectively -more than those found in the broilers of the NC treatment group (P < 0.01). In contrast, the LDL/C in the blood from the animals in the T2 treatment group was significantly decreased by 23.23% - more than that in the blood from the NC broilers (P < 0.05). Based on these results, we suggest that the dietary supplementation of broilers with recombinant chlorella could improve their growth performance, increase the concentration of IgA and apparently metabolizable nitrogen in the blood, and decrease ammonia emissions. Therefore, our findings have important implications for the effect of recombinant chlorella supplementation through increasing the concentration of IgA and the level of metabolizable nitrogen.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Galinhas/fisiologia , Chlorella , Suplementos Nutricionais , Digestão/fisiologia , Fezes/microbiologia , Carne/normas , Ração Animal/análise , Animais , Galinhas/sangue , Galinhas/crescimento & desenvolvimento , Galinhas/microbiologia , Chlorella/química , Chlorella/genética , Dieta/veterinária , Suplementos Nutricionais/análise , Feminino , Masculino , Carne/análise , Distribuição Aleatória , Anticorpos de Cadeia Única
13.
Climacteric ; 19(6): 574-580, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27763802

RESUMO

OBJECTIVES: The purpose of this clinical trial was to evaluate the effectiveness of a natural extract from Schisandra chinensis for relief of various menopausal symptoms. METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted from January 1, 2014 until January 13, 2015. We recruited women between the ages of 40 and 70 years who complained of menopausal symptoms measured by the Kupperman Index (KI). Patients were randomly assigned to treatment with either an extract from Schisandra chinensis (BMO-30) or placebo. They received the treatment for 6 weeks and were followed for 12 weeks. The primary endpoint was the mean interval change in KI score from baseline to week 12. Secondary measures included laboratory studies and the Menopause Rating Scale (MRS) score for sexual and bladder problems. RESULTS: Forty-one patients were considered eligible for enrolment, and 36 completed the study. After screening and randomization, patients were categorized into the placebo group (n = 18) and the BMO-30 group (n = 18). Total KI scores were significantly lower in the BMO-30 group than in the placebo group when evaluated with respect to group and time (p = 0.042). CONCLUSIONS: BMO-30 from Schisandra chinensis can be a safe and effective complementary medicine for menopausal symptoms, especially for hot flushes, sweating, and heart palpitations.


Assuntos
Menopausa , Extratos Vegetais/uso terapêutico , Schisandra/química , Adulto , Idoso , Terapias Complementares , Método Duplo-Cego , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Fogachos/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Fitoterapia , Placebos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/efeitos adversos , Qualidade de Vida , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Inquéritos e Questionários , Sudorese , Resultado do Tratamento
14.
Biotech Histochem ; 91(5): 377-85, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27149303

RESUMO

Autologous disc cell implantation, growth factors and gene therapy appear to be promising therapies for disc regeneration. Unfortunately, the replicative lifespan and growth kinetics of human nucleus pulposus (NP) cells related to host age are unclear. We investigated the potential relations among age, replicative lifespan and growth rate of NP cells, and determined the age range that is suitable for cell-based biological therapies for degenerative disc diseases. We used NP tissues classified by decade into five age groups: 30s, 40s, 50s, 60s and 70s. The mean cumulative population doubling level (PDL) and population doubling rate (PDR) of NP cells were assessed by decade. We also investigated correlations between cumulative PDL and age, and between PDR and age. The mean cumulative PDL and PDR decreased significantly in patients in their 60s. The mean cumulative PDL and PDR in the younger groups (30s, 40s and 50s) were significantly higher than those in the older groups (60s and 70s). There also were significant negative correlations between cumulative PDL and age, and between PDR and age. We found that the replicative lifespan and growth rate of human NP cells decreased with age. The replicative potential of NP cells decreased significantly in patients 60 years old and older. Young individuals less than 60 years old may be suitable candidates for NP cell-based biological therapies for treating degenerative disc diseases.


Assuntos
Terapia Biológica , Degeneração do Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/terapia , Disco Intervertebral/patologia , Núcleo Pulposo/patologia , Regeneração/fisiologia , Adulto , Fatores Etários , Idoso , Terapia Biológica/métodos , Feminino , Humanos , Disco Intervertebral/metabolismo , Masculino , Pessoa de Meia-Idade
15.
Int J Biol Macromol ; 85: 522-9, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26778161

RESUMO

Although the peel of the hallabong (Citrus sphaerocarpa) fruit is rich in polysaccharides, which are valuable dietary ingredients for human health, it is normally wasted. The present study aimed to utilize the peel waste and identify properties it may have against breast cancer metastasis. Hallabong peel extract containing crude polysaccharides was fractionated by gel permeation chromatography to produce four different polysaccharide fractions (HBE-I, -II, -III, and -IV). The HBE polysaccharides significantly blocked tube formation of human umbilical vein vascular endothelial cells (HUVECs), at a concentration of 12.5 or 25 µg/mL. Tube formation appeared to be more sensitive to HBE-II than to other HBE polysaccharides. HBE-II also inhibited breast cancer cell migration, through downregulation of matrix metalloproteinase-9 (MMP-9) in MDA-MB-231 triple-negative breast cancer cells. Therefore, inhibition of tube formation and MMP-9-mediated migration observed in HUVEC and MDA-MB-231 cells, respectively, are likely to be important therapeutic targets in triple-negative breast cancer metastasis.


Assuntos
Inibidores da Angiogênese/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Citrus/química , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Inibidores da Angiogênese/química , Inibidores da Angiogênese/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Neoplasias da Mama , Carboidratos/química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Peso Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Polissacarídeos/química , Polissacarídeos/isolamento & purificação
16.
J Eur Acad Dermatol Venereol ; 30(5): 783-8, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26551044

RESUMO

BACKGROUND: Surgical excision is conventionally regarded as the treatment of choice for nodular basal cell carcinoma (nBCC), and methyl aminolevulinate photodynamic therapy (MAL-PDT) has relatively low efficacy for nBCC. However, Er:YAG ablative fractional laser (AFL)-primed MAL-PDT (Er:YAG AFL-PDT) may offer enhanced efficacy for nBCC, especially thin nBCC (thickness ≤2 mm). OBJECTIVE: We compared Er:YAG AFL-PDT with conventional MAL-PDT for thin facial nBCC in Korean patients. METHODS: Thirty-nine patients (42 lesions) with primary, histologically proven thin nBCCs were randomized to Er:YAG AFL-PDT (single session, n = 20) or conventional MAL-PDT (two sessions, 7 days apart, n = 19). Efficacy, recurrence rate, cosmetic outcomes and safety were assessed 1 week, 3 months and 12 months after the last treatment. RESULTS: Three months after the final treatment, overall complete response rates were 84.2% with Er:YAG AFL-PDT and 50% with MAL-PDT (P = 0.026). The recurrence rate was significantly lower with Er:YAG AFL-PDT (6.3%) than with MAL-PDT (55.6%) at 12 months (P = 0.006). Er:YAG AFL-PDT and MAL-PDT did not differ significantly with respect to cosmetic outcomes or safety. CONCLUSIONS: Er:YAG AFL-PDT can be used as an alternative treatment option for patients who have thin nBCC and are not suitable for surgical treatment.


Assuntos
Ácido Aminolevulínico/análogos & derivados , Carcinoma Basocelular/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Idoso , Ácido Aminolevulínico/uso terapêutico , Feminino , Seguimentos , Humanos , Lasers de Estado Sólido , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
17.
Hum Exp Toxicol ; 35(5): 501-10, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26187900

RESUMO

The second-generation selective 5-HT2 receptor antagonists and reuptake inhibitors (SARIs) class antidepressants are known to have fewer cardiovascular side effects than the older ones. However, several case reports showed that trazodone, one of the second-generation SARIs, induces QT prolongation, cardiac arrhythmia, and ventricular tachycardia. Although these clinical cases suggested trazodone-induced cardiotoxicity, the toxicological actions of trazodone on cardiac action potentials (APs) beyond the human ether-a-go-go related gene (hERG) remain unclear. To elucidate the cellular mechanism for the adverse cardiac effects of trazodone, we investigated its effects on cardiac APs and ion channels using whole-cell patch clamp techniques in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and transiently transfected human embryonic kidney cells (HEK293) with cardiac ion channel complementary DNA. Trazodone dose-dependently decreased the maximum upstroke velocity (Vmax) and prolonged the AP duration, inducing early after depolarizations at 3 and 10 µM that triggered ventricular arrhythmias in hiPSC-CMs. Trazodone also inhibited all of the major ion channels (IKr, IKs, INa, and ICa), with an especially high inhibitory potency on hERG. These data indicate that the prolonged AP duration and decreased Vmax due to trazodone are mainly the result of hERG and sodium ion inhibition, and its inhibitory effects on cardiac ion channels can be exhibited in hiPSC-CMs.


Assuntos
Potenciais de Ação/efeitos dos fármacos , Antidepressivos de Segunda Geração/toxicidade , Canal de Potássio ERG1/antagonistas & inibidores , Miócitos Cardíacos/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/toxicidade , Trazodona/toxicidade , Cardiotoxicidade , Técnicas de Cultura de Células , Relação Dose-Resposta a Droga , Canal de Potássio ERG1/genética , Células HEK293 , Humanos , Canal de Potássio KCNQ1/antagonistas & inibidores , Canal de Potássio KCNQ1/genética , Miócitos Cardíacos/metabolismo , Técnicas de Patch-Clamp , Canais de Potássio de Abertura Dependente da Tensão da Membrana/antagonistas & inibidores , Canais de Potássio de Abertura Dependente da Tensão da Membrana/genética , Transfecção
18.
Neurogastroenterol Motil ; 27(6): 787-95, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25807997

RESUMO

BACKGROUND: The beneficial effect of biofeedback therapy (BFT) over a period of more than 2 years has not been studied in a large group of patients. The aim of this study was to evaluate the long-term efficacy of BFT for dyssynergic defecation (DD). METHODS: We evaluated the results for 347 consecutive constipated patients with DD who underwent BFT for a median of five sessions between 2004 and 2009. Initial responses were assessed immediately after the completion of BFT. A responder was defined as a subject with at least a three-point improvement from before to after BFT on an 11-point global bowel satisfaction (GBS) scale, or a two-point improvement if the baseline GBS was more than six points. The probability of remaining a responder was estimated by non-parametric maximum likelihood estimation. KEY RESULTS: The initial response rate to BFT was 72.3% (n = 251), Parkinson's disease and higher baseline GBS scores were associated with initial non-response. The long-term efficacy of BFT was analyzed in 103 patients who were followed up for more than 6 months; the initial effects of BFT were maintained in 85 of the patients (82.5%) during a median of 44 months of follow-up (IQR = 12-68). The probability of remaining a responder was 60% at 2 years, and 58% at 5 years. CONCLUSIONS & INFERENCES: The efficacy of BFT is maintained for more than 2 years after BFT in a considerable proportion of constipated patients with DD. BFT is effective and durable treatment for managing DD.


Assuntos
Ataxia/terapia , Biorretroalimentação Psicológica/métodos , Constipação Intestinal/terapia , Idoso , Canal Anal , Estudos de Coortes , Defecação , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Manometria , Pessoa de Meia-Idade , Reto , Estudos Retrospectivos , Resultado do Tratamento
19.
Water Sci Technol ; 70(1): 136-43, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25026591

RESUMO

The uranium(VI) adsorption efficiency of non-living biomass of brown algae was evaluated in various adsorption experimental conditions. Several different sizes of biomass were prepared using pretreatment and surface-modification steps. The kinetics of uranium uptake were mainly dependent on the particle size of the prepared Laminaria japonica biosorbent. The optimal particle size, contact time, and injection amount for the stable operation of the wastewater treatment process were determined. Spectroscopic analyses showed that uranium was adsorbed in the porous inside structure of the biosorbent. The ionic diffusivity in the biomass was the dominant rate-limiting factor; therefore, the adsorption rate was significantly increased with decrease of particle size. From the results of comparative experiments using the biosorbents and other chemical adsorbents/precipitants, such as activated carbons, zeolites, and limes, it was demonstrated that the brown algae biosorbent could replace the conventional chemicals for uranium removal. As a post-treatment for the final solid waste reduction, the ignition treatment could significantly reduce the weight of waste biosorbents. In conclusion, the brown algae biosorbent is shown to be a favorable adsorbent for uranium(VI) removal from radioactive wastewater.


Assuntos
Biomassa , Laminaria/metabolismo , Urânio/isolamento & purificação , Poluentes Radioativos da Água/isolamento & purificação , Adsorção , Biodegradação Ambiental , Carbono/química , Difusão , Íons , Cinética , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Resíduos Radioativos , Eliminação de Resíduos/métodos , Soluções , Propriedades de Superfície , Temperatura , Fatores de Tempo , Purificação da Água/métodos
20.
J Environ Pathol Toxicol Oncol ; 33(1): 33-43, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24579808

RESUMO

The purpose of this study was to assess the protective effects of an ethanol extract derived from the red alga Gracilaria bursa-pastoris (Gmelin) Silva (GBE) on ultraviolet B (UVB)-irradiated human HaCaT keratinocytes. GBE exhibited scavenging activity against intracellular reactive oxygen species that were induced by either hydrogen peroxide or UVB radiation. In addition, both the superoxide anion and the hydroxyl radical were scavenged by GBE in cell-free systems. GBE absorbed light in the UVB range (280-320 nm) of the electromagnetic spectrum and lessened the extent of UVB-induced oxidative damage to cellular lipids, proteins, and DNA. Finally, GBE-treated keratinocytes showed a reduction in UVB-induced apoptosis, as exemplified by fewer apoptotic bodies. These results suggest that GBE exerts cytoprotective actions against UVB-stimulated oxidative stress by scavenging ROS and absorbing UVB rays, thereby attenuating injury to cellular constituents and preventing cell death.


Assuntos
Gracilaria , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Extratos Vegetais/uso terapêutico , Raios Ultravioleta/efeitos adversos , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Fragmentação do DNA/efeitos dos fármacos , Fragmentação do DNA/efeitos da radiação , Humanos , Radical Hidroxila/metabolismo , Queratinócitos/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos da radiação , Extratos Vegetais/farmacologia , Carbonilação Proteica/efeitos dos fármacos , Carbonilação Proteica/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Superóxidos/metabolismo
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