RESUMEN
OBJECTIVES: Fear of diabetes and major surgery may prohibit referral of young children severely affected by pancreatitis for total pancreatectomy with islet autotransplant (TPIAT). We evaluated outcomes in our youngest TPIAT recipients, 3 to 8 years of age at surgery. METHODS: Medical records were reviewed for 17 children (9 girls) ages 8 years or younger undergoing TPIAT from 2000 to 2014. Most (14/17) had genetic risk factors for pancreatitis. Since 2006, TPIAT recipients were followed prospectively with health questionnaires including assessments of pain and narcotic use, and scheduled hemoglobin A1c (HbA1c) and mixed-meal tolerance tests (6 mL/kg Boost HP) before surgery, and at regular intervals after. Patients are 1 to 11 years post-TPIAT (median 2.2 years). Data are reported as median (25th, 75th percentile). RESULTS: All had relief of pain, with all 17 patients off narcotics at most recent follow-up. Hospitalization rates decreased from 5.0 hospitalization episodes per person-year of follow-up before TPIAT, to 0.35 episodes per person-year of follow-up after TPIAT. Fourteen (82%) discontinued insulin, higher than the observed insulin independence rate of 41% in 399 patients older than 8 years of age undergoing TPIAT over the same interval (Pâ=â0.004). Median post-TPIAT HbA1c was 5.9% (5.6%, 6.3%), and within patient post-TPIAT mean HbA1c was ≤6.5% for all but 2 patients. CONCLUSIONS: Young children with severe refractory chronic pancreatitis may be good candidates for TPIAT, with high rates of pain relief and insulin independence, and excellent glycemic control in the majority.
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Dolor Abdominal/etiología , Trasplante de Islotes Pancreáticos/métodos , Pancreatectomía/métodos , Pancreatitis Crónica/cirugía , Dolor Abdominal/diagnóstico , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Dimensión del Dolor , Pancreatitis Crónica/complicaciones , Estudios Prospectivos , Trasplante Autólogo , Resultado del TratamientoRESUMEN
NF-κB has an essential role in the initiation and progression of pancreatic cancer and specifically mediates the induction of epithelial-mesenchymal transition and invasiveness. In this study, we demonstrate the importance of activated NF-κB signaling in EMT induction, lymphovascular metastasis, and neural invasion. Modulation of NF-κB activity was accomplished through the specific NF-κB inhibitor (BAY 11-7085), triptolide, and Minnelide treatment, as well as overexpression of IKBα repressor and IKK activator plasmids. In the classical lymphovascular metastatic cascade, inhibition of NF-κB decreased the expression of several EMT transcription factors (SNAI1, SNAI2, and ZEB1) and mesenchymal markers (VIM and CDH2) and decreased in vitro invasion, which was rescued by IKK activation. This was further demonstrated in vivo via BAY 11-7085 treatment in a orthotopic model of pancreatic cancer. In vivo NF-κB inhibition decreased tumor volume; decreased tumor EMT gene expression, while restoring cell-cell junctions; and decreasing overall metastasis. Furthermore, we demonstrate the importance of active NF-κB signaling in neural invasion. Triptolide treatment inhibits Nerve Growth Factor (NGF) mediated, neural-tumor co-culture in vitro invasion, and dorsal root ganglia (DRG) neural outgrowth through a disruption in tumor-neural cross talk. In vivo, Minnelide treatment decreased neurotrophin expression, nerve density, and sciatic nerve invasion. Taken together, this study demonstrates the importance of NF-κB signaling in the progression of pancreatic cancer through the modulation of EMT induction, lymphovascular invasion, and neural invasion.
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Transición Epitelial-Mesenquimal , FN-kappa B/metabolismo , Páncreas/metabolismo , Neoplasias Pancreáticas/metabolismo , Nervios Periféricos/metabolismo , Neoplasias del Sistema Nervioso Periférico/secundario , Transducción de Señal , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular , Línea Celular Tumoral , Técnicas de Cocultivo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Ganglios Espinales/citología , Ganglios Espinales/efectos de los fármacos , Ganglios Espinales/metabolismo , Ganglios Espinales/patología , Humanos , Metástasis Linfática/patología , Metástasis Linfática/prevención & control , Ratones , Ratones Desnudos , Inhibidor NF-kappaB alfa/genética , Inhibidor NF-kappaB alfa/metabolismo , FN-kappa B/antagonistas & inhibidores , Invasividad Neoplásica/patología , Trasplante de Neoplasias , Páncreas/efectos de los fármacos , Páncreas/patología , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Nervios Periféricos/citología , Nervios Periféricos/efectos de los fármacos , Nervios Periféricos/patología , Neoplasias del Sistema Nervioso Periférico/metabolismo , Neoplasias del Sistema Nervioso Periférico/patología , Neoplasias del Sistema Nervioso Periférico/prevención & control , Proteínas Recombinantes/metabolismo , Nervio Ciático/citología , Nervio Ciático/efectos de los fármacos , Nervio Ciático/metabolismo , Nervio Ciático/patología , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND & AIMS: Obesity is associated with an increased risk for pancreatic cancer, but it is unclear whether it affects mortality. We performed a systematic review and meta-analysis to assess the association between premorbid obesity and mortality from pancreatic cancer. METHODS: We performed a systematic search through January 2015 and identified studies of the association between premorbid obesity (at least 1 year prior to pancreatic cancer diagnosis) and pancreatic cancer-related mortality. We estimated summary adjusted hazard ratio (aHR) with 95% confidence interval (CI), comparing data from obese (body mass index [BMI] ≥30 kg/m(2)) and overweight subjects (BMI, 25.0-29.9 kg/m(2)) with those from individuals with a normal BMI (controls) by using random-effects model. RESULTS: We identified 13 studies (including 3 studies that pooled multiple cohorts); 5 studies included only patients with pancreatic cancer, whereas 8 studies evaluated pancreatic cancer-related mortality in cancer-free individuals at inception. In the meta-analysis, we observed increase in pancreatic cancer-related mortality among overweight (aHR, 1.06; 95% CI, 1.02-1.11; I(2) = 0) and obese individuals (aHR, 1.31; 95% CI, 1.20-1.42; I(2) = 43%), compared with controls; the association remained when we analyzed data from only subjects with pancreatic cancer. Each 1 kg/m(2) increase in BMI was associated with 10% increase in mortality (aHR, 1.10; 95% CI, 1.05-1.15) with minimal heterogeneity (I(2) = 0). In the subgroup analysis, obesity was associated with increased mortality in Western populations (11 studies; aHR, 1.32; 95% CI, 1.22-1.42) but not in Asia-Pacific populations (2 studies; aHR, 0.98; 95% CI, 0.76-1.27). CONCLUSIONS: In a systematic review and meta-analysis, we associated increasing level of obesity with increased mortality in patients with pancreatic cancer in Western but not Asia-Pacific populations. Strategies to reduce obesity-induced metabolic abnormalities might be developed to treat patients with pancreatic cancer.
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Obesidad/complicaciones , Obesidad/epidemiología , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/mortalidad , Índice de Masa Corporal , Salud Global , HumanosRESUMEN
BACKGROUND/OBJECTIVES: Total pancreatectomy and islet autotransplant (TP-IAT) is a potential treatment for children with severe refractory chronic pancreatitis. Cultures from the resected pancreas and final islet preparation are frequently positive for microbes. It is unknown whether positive cultures are associated with adverse outcomes in pediatric patients. METHODS: We reviewed the medical records of children (n = 86) who underwent TP-IAT from May 2006-March 2015 with emphasis on demographics, previous pancreatic interventions, culture results, islet yield, hospital days, posttransplant islet function, and posttransplant infections. We compared outcomes in patients with positive (n = 57) and negative (n = 29) cultures. RESULTS: Patients with positive cultures had higher rates of previous pancreas surgery (P = 0.007) and endoscopic retrograde cholangiopancreatography (P < 0.0001). Positive cultures were not associated with posttransplant infections (P = 1.00) or prolonged hospital length of stay (P = 0.29). Patients with positive final islet preparation culture showed increased rates of graft failure at 2 years posttransplant (P = 0.041), but not when adjusted for islet mass transplanted (P = 0.39). CONCLUSIONS: Positive cultures during pediatric TP-IATs do not increase the risk of posttransplant infections or prolong hospital length of stay. Endocrine function depends on islet mass transplanted.
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Contaminación de Medicamentos , Infecciones/etiología , Trasplante de Islotes Pancreáticos/efectos adversos , Soluciones Farmacéuticas/efectos adversos , Adolescente , Autoinjertos , Niño , Preescolar , Colangiopancreatografia Retrógrada Endoscópica , Femenino , Rechazo de Injerto , Humanos , Incidencia , Infecciones/epidemiología , Tiempo de Internación , Masculino , Pancreatectomía , Pruebas de Función Pancreática , Pancreatitis Crónica/metabolismo , Pancreatitis Crónica/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/microbiología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVES: To examine temporal trends in inpatient testicular torsion (TT) treatment and testicular loss (TL), and to identify risk factors for TL using a large nationally representative paediatric cohort, stratified to established high prevalence TT cohorts (neonatal TT [NTT]; age <1 years) and adolescent TT (ATT; age 12-17 years). METHODS: Boys (age ≤17 years, n = 17 478) undergoing surgical exploration for TT were identified within the Nationwide Inpatient Sample (1998-2010). Temporal trends in inpatient TT management (salvage surgery vs orchiectomy) and TL were examined using estimated annual percent change methodology. Multivariable logistic regression models were used to identify risk factors for TL. RESULTS: Teaching hospitals treated 90% of boys with NTT, compared with 55% with ATT (P < 0.001). Of boys with NTT, 85% lost their testis, compared with 35% with ATT (P < 0.001). Inpatient management of NTT declined during the study period, from 7.5/100 000 children in 1998 to 3/100 000 in 2010 (estimated annual percent change -4.95%; P < 0.001). The decrease was similar but less dramatic in ATT. TL patterns did not improve. In adjusted analyses, for NTT, orchiectomy was more likely at teaching hospitals. For ATT, orchiectomy was more likely in children with comorbidities (odds ratio 5.42; P = 0.045), Medicaid coverage or self-pay (P < 0.05) and weekday presentation (P = 0.001). Regional or racial disposition was not associated with TL. CONCLUSIONS: There has been a gradual decrease in inpatient surgical treatment for both NTT and ATT, presumably as a result of increased outpatient and/or non-operative management of these children. Concerningly, TL patterns have not improved; targeted interventions such as parental and adolescent male health education may lead to timely recognition/intervention in children at-risk for ATT. We noted no regional/racial disparities in contrast to earlier studies.
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Orquiectomía , Torsión del Cordón Espermático/cirugía , Adolescente , Niño , Preescolar , Hospitalización , Humanos , Masculino , Orquiectomía/tendencias , Factores de Riesgo , Terapia Recuperativa , Factores de TiempoRESUMEN
Inflammation is considered as one of the major causes for the initiation of various chronic diseases such as asthma, cancer, cardiovascular disease, diabetes, obesity, inflammatory bowel disease, osteoporosis and neurological diseases like Parkinson's disease. Increasing scientific evidence has delineated that inflammatory markers such as TNF-α, IL-1, IL-6, IL-8 and CRP and different transcription factors such as NF-κB and STAT are the major key factors that regulate these inflammatory diseases. Food protein-derived bioactive peptides have been shown to exhibit anti-inflammatory activity by inhibiting or reducing the expression of these inflammatory biomarkers and/or by modulating the activity of these transcription factors. This review aims to discuss various molecular targets and underlying mechanisms of food protein-derived anti-inflammatory peptides and to explore their potential against various chronic inflammatory diseases. © 2015 Society of Chemical Industry.
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Antiinflamatorios no Esteroideos/farmacología , Análisis de los Alimentos , Inflamación/tratamiento farmacológico , Proteínas/farmacología , Antiinflamatorios no Esteroideos/química , Enfermedad Crónica , Humanos , Proteínas/químicaRESUMEN
Despite significant progress in diagnostics and therapeutics, over 50 thousand patients die from colorectal cancer annually. Hence, there is urgent need for new lines of treatment. Triptolide, a natural compound isolated from the Chinese herb Tripterygium wilfordii, is effective against multiple cancers. We have synthesized a water soluble analog of triptolide, named Minnelide, which is currently in phase I trial against pancreatic cancer. The aims of the current study were to evaluate whether triptolide/Minnelide is effective against colorectal cancer and to elucidate the mechanism by which triptolide induces cell death in colorectal cancer. Efficacy of Minnelide was evaluated in subcutaneous xenograft and liver metastasis model of colorectal cancer. For mechanistic studies, colon cancer cell lines HCT116 and HT29 were treated with triptolide and the effect on viability, caspase activation, annexin positivity, lactate dehydrogenase release, and cell cycle progression was evaluated. Effect of triptolide on E2F transcriptional activity, mRNA levels of E2F-dependent genes, E2F1- retinoblastoma protein (Rb) binding, and proteins levels of regulator of G1-S transition was also measured. DNA binding of E2F1 was evaluated by chromatin immunoprecipitation assay. Triptolide decreased colon cancer cell viability in a dose- and time-dependent fashion. Minnelide markedly inhibited the growth of colon cancer in the xenograft and liver metastasis model of colon cancer and more than doubles the median survival of animals with liver metastases from colon cancer. Mechanistically, we demonstrate that at low concentrations triptolide induces apoptotic cell death but at higher concentrations it induces cell cycle arrest. Our data suggest that triptolide is able to induce G1 cell cycle arrest by inhibiting transcriptional activation of E2F1. Our data also show that triptolide downregulates E2F activity by potentially modulating events downstream of DNA binding. Therefore, we conclude that Triptolide and Minnelide are effective against colon cancer in multiple pre-clinical models.
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Antineoplásicos Alquilantes/farmacología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Neoplasias del Colon/metabolismo , Diterpenos/farmacología , Factores de Transcripción E2F/metabolismo , Fenantrenos/farmacología , Animales , Apoptosis/efectos de los fármacos , Neoplasias del Colon/genética , Compuestos Epoxi/farmacología , Femenino , Células HCT116 , Células HT29 , Humanos , Ratones Desnudos , Organofosfatos/farmacología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: To examine racial disparities in end-of-life (EOL) care among black and white patients dying of prostate cancer (PCa). METHODS: Relying on the SEER-Medicare database, 3789 patients who died of metastatic PCa between 1999 and 2009 were identified. Information was assessed regarding diagnostic care, therapeutic interventions, hospitalizations, intensive care unit (ICU) admissions, and emergency department visits in the last 12 months, 3 months, and 1 month of life. Logistic regression tested the relationship between race and the receipt of diagnostic care, therapeutic interventions, and high-intensity EOL care. RESULTS: Overall, 729 patients (19.24%) were black. In the 12-months preceding death, laboratory tests (odds ratio [OR], 0.51; 95% CI, 0.36-0.72), prostate-specific antigen test (OR, 0.54; 95% CI, 0.43-0.67), cystourethroscopy (OR, 0.71; 95% CI, 0.56-0.90), imaging procedure (OR, 0.58; 95% CI, 0.41-0.81), hormonal therapy (OR, 0.53; 95% CI, 0.44-0.65), chemotherapy (OR, 0.59; 95% CI, 0.48-0.72), radiotherapy (OR, 0.74; 95% CI, 0.61-0.90), and office visit (OR, 0.38; 95% CI, 0.28-0.50) were less frequent in black versus white patients. Conversely, high-intensity EOL care, such as ICU admission (OR, 1.27; 95% CI, 1.04-1.58), inpatient admission (OR, 1.49; 95% CI, 1.09-2.05), and cardiopulmonary resuscitation (OR, 1.72; 95% CI, 1.40-2.11), was more frequent in black versus white patients. Similar trends for EOL care were observed at 3-month and 1-month end points. CONCLUSIONS: Although diagnostic and therapeutic interventions are less frequent in black patients with end-stage PCa, the rate of high-intensity and aggressive EOL care is higher in these individuals. These disparities may indicate that race plays an important role in the quality of care for men with end-stage PCa.
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Negro o Afroamericano/estadística & datos numéricos , Disparidades en Atención de Salud/etnología , Neoplasias de la Próstata/terapia , Cuidado Terminal/estadística & datos numéricos , Población Blanca/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Antineoplásicos Hormonales/uso terapéutico , Reanimación Cardiopulmonar/estadística & datos numéricos , Técnicas de Laboratorio Clínico/estadística & datos numéricos , Cuidados Críticos/estadística & datos numéricos , Cistoscopía/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Medicare , Visita a Consultorio Médico/estadística & datos numéricos , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/etnología , Radioterapia/estadística & datos numéricos , Programa de VERF , Cuidado Terminal/tendencias , Factores de Tiempo , Estados UnidosRESUMEN
BACKGROUND: Obesity is associated with poor surgical outcomes and disparity in access-to-care. There is a lack of quality data on the effect of body mass index (BMI) on perioperative outcomes. Accordingly, we sought to determine the procedure specific, independent-effect of BMI on 30-day perioperative outcomes in patients undergoing major surgery. METHODS: Participants included individuals undergoing one of 16 major surgery (cardiovascular, orthopedic, oncologic; n = 141,802) recorded in the ACS-NSQIP (2005-2011). Outcomes evaluated included complications, blood transfusion, length-of-stay (LOS), re-intervention, readmission, and perioperative mortality. Multivariable-regression models assessed the independent-effect of BMI on outcomes. RESULTS: Nearly, 74 % of patients had a BMI disturbance; the majority being overweight (35.3 %) or obese (29.8 %). Morbidly obese patients constituted a small but significant proportion of the patients (5.7 %; n = 8067). In adjusted-analyses, morbidly obese patients had significantly increased odds of wound complications in 15 of the examined procedures, of renal complications after 6-procedures, of thromboembolism after 5-procedures, of pulmonary, septic and UTI complications after 2-procedures, and of cardiovascular complications after CABG. Conversely, obese/overweight patients, except for increased odds of wound complications after select procedures, had significantly decreased odds of perioperative mortality, prolonged-LOS and blood transfusion relative to normal BMI patients after 4, 8, and 9 of the examined procedures. CONCLUSIONS: The prevalence of BMI derangements in surgical patients is high. The effect of BMI on outcomes is procedure specific. Patients with BMI between 18.5 and 40-kg/m(2) at time of surgery fare equally well with regard to complications and mortality. However, morbidly obese patients are at-risk for postsurgical complications and targeted preoperative-optimization may improve outcomes and attenuate disparity in access-to-care.
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Índice de Masa Corporal , Sobrepeso/complicaciones , Procedimientos Quirúrgicos Operativos/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Transfusión Sanguínea/estadística & datos numéricos , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Obesidad Mórbida/complicaciones , Obesidad Mórbida/epidemiología , Sobrepeso/epidemiología , Complicaciones Posoperatorias/epidemiología , Mejoramiento de la Calidad , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
There is growing interest in using functional foods or nutraceuticals for the prevention and treatment of hypertension or high blood pressure. Although numerous preventive and therapeutic pharmacological interventions are available on the market, unfortunately, many patients still suffer from poorly controlled hypertension. Furthermore, most pharmacological drugs, such as inhibitors of angiotensin-I converting enzyme (ACE), are often associated with significant adverse effects. Many bioactive food compounds have been characterized over the past decades that may contribute to the management of hypertension; for example, bioactive peptides derived from various food proteins with antihypertensive properties have gained a great deal of attention. Some of these peptides have exhibited potent in vivo antihypertensive activity in both animal models and human clinical trials. This review provides an overview about the complex pathophysiology of hypertension and demonstrates the potential roles of food derived bioactive peptides as viable interventions targeting specific pathways involved in this disease process. This review offers a comprehensive guide for understanding and utilizing the molecular mechanisms of antihypertensive actions of food protein derived peptides.
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Antihipertensivos/farmacología , Hipertensión/tratamiento farmacológico , Fragmentos de Péptidos/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Animales , Antihipertensivos/uso terapéutico , Caseínas/farmacología , Caseínas/uso terapéutico , Proteínas en la Dieta/farmacología , Proteínas en la Dieta/uso terapéutico , Humanos , Hipertensión/etiología , Fragmentos de Péptidos/uso terapéuticoRESUMEN
The present study delved into the chemical composition, antioxidant, and anti-inflammatory properties of three dry edible beans: Black (BL), Great Northern (GN), and Pinto (PN). The beans were soaked, cooked, and subjected to in vitro gastrointestinal (GI) digestion. BL bean exhibited significantly higher gastric (42%) and intestinal (8%) digestion rates. Comparative assessment of soluble GI-digested fractions (<3 kDa) revealed that the GN bean exhibited the highest abundance of dipeptides (P < 0.05). The BL bean fraction displayed a 4-fold increase in tripeptides (P < 0.05). Both BL and PN bean fractions are high in essential free amino acids, flavonols, and derivatives of hydroxybenzoic acid when compared to the GN bean. All the beans exhibited the ability to mitigate TNF-α-induced pro-inflammatory signaling; however, the BL bean fraction was the most effective at lowering AAPH-induced oxidative stress in HT-29 cells, followed by the GN bean (P < 0.05). In contrast, a low antioxidant effect was observed with PN beans.
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SCOPE: There is a lack of research comparing how different protein isolates influence the microbiome, especially when carbohydrate (CHO) availability is varied. The objective is to determine changes in gut microbiota composition and function during fermentation of digested protein isolates under high and low CHO conditions. METHODS AND RESULTS: Protein isolates from beef, egg white, milk, pea, and soy are subjected to in vitro digestion and fermentation with human fecal microbiota. Under low CHO conditions, the microbiota is primarily proteolytic with decreased concentrations of peptides and increased variance among microbial taxa and production of ammonia and branched chain fatty acids by the microbiota. Milk protein not only results in the highest production of butyrate and p-hydroxyphenylacetate but also has high concentrations of deleterious fermentation metabolites. Amino acid composition of the protein isolates is significantly correlated with abundances of many microbial taxa and metabolites, but the correlations are stronger in the low CHO medium. CONCLUSION: This study shows that low CHO conditions increase proteolytic fermentation and result in increased differences in microbiota response to protein isolates. It also showed that amino acid composition is highly associated with microbiota composition and function especially under low CHO conditions.
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Heces , Fermentación , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/fisiología , Microbioma Gastrointestinal/efectos de los fármacos , Animales , Heces/microbiología , Aminoácidos/metabolismo , Carbohidratos de la Dieta/metabolismo , Femenino , Proteínas en la Dieta/metabolismo , Adulto , MasculinoRESUMEN
Plant-based proteins, in particular pulse proteins, have grown in popularity worldwide. Germination, or sprouting, is an effective method to release peptides and other dietary compounds. However, the combination of germination and gastrointestinal digestion in enhancing the release of dietary compounds with potential health-beneficial biological activity has yet to be entirely elucidated. The present study illustrates the impact of germination and gastrointestinal digestion on the release of dietary compounds with antioxidant activity from chickpeas (Cicer arietinum L.). Germination up to 3 days (D0 to D3) increased the peptide content by denaturing chickpea storage proteins and increased the degree of hydrolysis (DH) in the gastric phase. The antioxidant activity was measured at three different dosages (10, 50, and 100 µg/mL) and compared between D0 and D3 on human colorectal adenocarcinoma cells (HT-29). A significant increase in antioxidant activity was observed in the D3 germinated samples in all three tested dosages. Further analysis identified 10 peptides and 7 phytochemicals differentially expressed between the D0 and D3 germinated samples. Among the differentially expressed compounds, 3 phytochemicals (2',4'-dihydroxy-3,4-dimethoxychalcone, isoliquiritigenin 4-methyl ether, and 3-methoxy-4,2',5'-trihydroxychalcone) and 1 peptide (His-Ala-Lys) were identified only in the D3 samples, indicating their potential contribution towards the observed antioxidant activity.
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Radiofrequency (RF) assisted thermal processing can significantly enhance the gel firmness of egg white powder compared to the traditional hot room (HR) processing. Thus, the present study aims to delineate the impact of RF processing on the proteins' structure and bio-functional properties of egg white protein gels. The secondary protein conformations of egg white proteins exhibited no significant alteration upon RF-assisted thermal processing over traditional HR processing. In-vitro gastrointestinal (GI) digestion of egg white gels demonstrated that the RF processing did not compromise the accessibility of digestive proteases despite a more robust gel network. Peptides from the GI digest of egg white gel showed that Ovalbumin and Ovotransferrin were the parent proteins of most of the unique peptides generated, and minor structural differences accounted for these peptides. The bioavailability of the egg protein-derived peptides remains unaffected after RF processing without compromising the viability and integrity of the GI epithelial cells.
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Conalbúmina , Proteínas del Huevo , Ondas de Radio , Ovalbúmina , HuevosRESUMEN
γ-Glutamyl peptides (γ-GPs) are a group of peptides naturally found in various food sources. The unique γ-bond potentially enables them to resist gastrointestinal digestion and offers high stability in vivo with a longer half-life. In recent years, these peptides have caught researchers' attention due to their ability to impart kokumi taste and elicit various physiological functions via the allosteric activation of the calcium-sensing receptor (CaSR). This review discusses the various food sources of γ-glutamyl peptides, different synthesis modes, allosteric activation of CaSR for taste perception, and associated multiple biological functions they can exhibit, with a special emphasis on their role in modulating chronic inflammation concerning cardiovascular health.
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Péptidos , Receptores Sensibles al Calcio , Humanos , Inflamación , Péptidos/química , Gusto/fisiología , Percepción del GustoRESUMEN
BACKGROUND: Delayed distal esophageal reconstruction with nonsupercharged jejunum is an option when gastric conduit is not available. This study aimed to describe a single-center experience with distal esophageal reconstruction with retrosternal Roux-en-Y esophagojejunostomy (RYEJ) and compare perioperative outcomes with retrosternal gastric pull-up (GP). METHODS: An Institutional Review Board-exempt retrospective chart review was conducted of patients who underwent esophagostomy closure by the retrosternal route at the University of Minnesota Medical Center (Minneapolis, MN) from January 2009 to July 2019. Patients with colonic conduits were excluded. The study compared patients with RYEJ with a contemporary cohort of patients who underwent GP. The anatomic criteria for RYEJ were the absence of a gastric conduit and an esophageal remnant that reached the sternomanubrial joint. Patient characteristics, anastomotic leak and stricture rate, postoperative complications, hospital length of stay, 30-day readmission, and 90-day mortality were recorded. Statistical analysis was performed using the Fisher exact test and the Wilcoxon rank-sum test with a significance level at P ≤.05. RESULTS: A total of 9 patients underwent RYEJ, and 10 patients had GP. Previous esophageal adenocarcinoma was more common in the RYEJ group (n = 5) compared with the GP group (n = 0) (P = .01). Patient demographics and comorbidities were comparable between the groups. No differences were found in all end points, including operating time, estimated blood loss, anastomotic leak or stricture rate, Clavien-Dindo class III to IV complications, hospital length of stay, or mortality. CONCLUSIONS: Retrosternal RYEJ without microvascular augmentation is a safe alternative for esophagostomy closure in patients with adequate esophageal length when the stomach is not available. The nonsupercharged jejunum can safely reach the level of the sternomanubrial joint.
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Laparoscopía , Neoplasias Gástricas , Anastomosis en-Y de Roux , Anastomosis Quirúrgica , Fuga Anastomótica/cirugía , Constricción Patológica/cirugía , Gastrectomía , Humanos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/cirugía , Estudios Retrospectivos , Neoplasias Gástricas/cirugíaRESUMEN
Three novel peptides, IQW, IRW and LKP, were predicted in our previous study in the thermolysin-pepsin ovotransferrin hydrolysate. The aims of the present study were to purify the peptides, and determine if the predicted peptides purified from the hydrolysate would have the same activity as the synthetic ones. We also determined the stability of the peptides under simulated gastrointestinal condition. IQW, IRW and LKP were then successfully purified from crude ovotransferrin hydrolysate through multi-step chromatographic purification comprising of cation exchange chromatography followed by three-step reverse-phase high performance liquid chromatography (RP-HPLC), and their sequences were analysed by UPLC-MS/MS. Our results showed that their activities were comparable to the synthetic ones. Simulated gastrointestinal incubation showed that IRW was degraded into a dipeptide of IR and a free amino acid of W by pancreatin, LKP was degraded into a dipeptide of KP and a free amino acid of L by mucosal peptidase, while IQW was stable against the digestive enzymes.
RESUMEN
The present study analyzed the transepithelial transport of the dietary anti-inflammatory peptide, γ-glutamyl valine (γ-EV). γ-EV is naturally found in dry edible beans. Our previous study demonstrated the anti-inflammatory potency of γ-EV against vascular inflammation at a concentration of 1mM, and that it can transport with the apparent permeability coefficient (Papp) of 1.56 × 10-6 ± 0.7 × 10-6 cm/s across the intestinal Caco-2 cells. The purpose of the current study was to explore whether the permeability of the peptide could be enhanced and to elucidate the mechanism of transport of γ-EV across Caco-2 cells. The initial results indicated that γ-EV was nontoxic to the Caco-2 cells up to 5 mM concentration and could be transported across the intestinal cells intact. During apical-to-basolateral transport, a higher peptide dose (5 mM) significantly (p < 0.01) enhanced the transport rate to 2.5 × 10-6 ± 0.6 × 10-6 cm/s. Cytochalasin-D disintegrated the tight-junction proteins of the Caco-2 monolayer and increased the Papp of γ-EV to 4.36 × 10-6 ± 0.16 × 10-6 cm/s (p < 0.001), while theaflavin 3'-gallate and Gly-Sar significantly decreased the Papp (p < 0.05), with wortmannin having no effects on the peptide transport, indicating that the transport route of γ-EV could be via both PepT1-mediated and paracellular.
Asunto(s)
Antiinflamatorios/metabolismo , Dipéptidos/metabolismo , Mucosa Intestinal/metabolismo , Transporte Biológico , Células CACO-2 , Células Cultivadas , Humanos , Péptidos/metabolismoRESUMEN
Food processing can alter protein structure, modulate enzyme accessibility, and therefore the release of bioactive peptides. Thus, processing techniques, boiling, high-pressure processing (HPP), and a combination of both, were compared for their efficiency to release antioxidant peptides after alcalase hydrolysis of Great Northern Beans (GNBs). The oxygen radical absorbance capacity (ORAC) indicated that boiled hydrolysates had the highest antioxidant activity (370.9 ± 43.8 µmol TEAC/g). Mass spectrometry-based analysis suggested that di- and tri-peptide expression were significantly altered among the three treatments, and either Ile, Leu, Phe, and Arg containing peptides potentially contributed toward the enhanced antioxidant activity. Furthermore, the total phenolic content of the HPP-treated hydrolysate was higher than the other two treatments, with ferulic acid being the most prominent phenolic compound present in the bean hydrolysates. This study indicates that thermal processing such as boiling is more effective in modulating the release of antioxidant peptides. PRACTICAL APPLICATIONS: Common beans (Phaseolus vulgaris), such as Great Northern Beans (GNBs) are one of the major pulse crops in the United States. Storage proteins in beans can release peptides with biological activities after enzymatic hydrolysis. However, processing conditions can modulate the release of peptides. The present study is primarily focused on comparing the two processing methods, boiling and HPP, and their combination for the generation of peptides with potential antioxidant activity in alcalase-digested GNBs. Data from the study suggest that thermal treatment such as boiling is more effective in modulating the release of peptides from alcalase hydrolysate of GNBs with antioxidant activity. This is particularly important because over different cultures around the world, boiling is the most widely used processing method for the cooking of beans, and hence, these data also ensure that boiling is the most effective method in getting the most beneficial effects from the consumption of beans.
Asunto(s)
Phaseolus , Antioxidantes/farmacología , Fenoles , Hidrolisados de Proteína , SubtilisinasRESUMEN
Hen breed, diet enrichment, cooking methods, and gastrointestinal (GI) digestion modulates the bioaccessibility of the bioactive compounds in eggs, but their synergistic role in modulating bioactivity is still unclear. The present study evaluates the effect of hen breed, diet enrichment, and GI digestion on the cooked whole egg-derived peptides in-vitro antioxidant and antihypertensive activities. Standard and enriched whole eggs from White Leghorn (WLH) and Rhode Island Red (RIR) hens were boiled or fried and subjected to GI digestion. Antioxidant activity was measured through oxygen radical absorbance capacity (ORAC) and gastrointestinal epithelial cell-based assays, and the antihypertensive capacity by in-vitro Angiotensin-I Converting Enzyme (ACE) inhibition assay. WLH fried standard egg hydrolysate showed a high ORAC antioxidant activity but failed to show any significant antioxidant effect in the cell-based assay. No significant differences were observed in the antihypertensive activity, although enriched samples tended to have a higher ACE-inhibitory capacity. The peptide profile explained the antioxidant capacities based on antioxidant structural requirements from different peptide fractions, while previously reported antihypertensive peptides were found in all samples. The study validates the importance of physiologically relevant models and requires future studies to confirm mechanisms that yield bioactive compounds in whole egg hydrolysates.