Ezetimibe increases resistance to oxidative stress and extends lifespan mimicking dietary restriction in Caenorhabditis elegans

Ezetimibe is an approved drug for lowering plasma LDL (low-density lipoprotein) level via inhibition of cholesterol absorption. Derivatives of ezetimibe reduce inflammatory response and oxidative stress. In the present study, we investigated the effect of dietary supplementation with ezetimibe in response to environmental stressors and found that ezetimibe increases resistance to oxidative stress and ultraviolet irradiation. Ezetimibe also significantly extended lifespan accompanying reduced fertility, which is a common trade-off for longevity in C. elegans. Cellular level of reactive oxygen species was increased and the expression of stress-responsive genes, hsp-16.2 and sod-3, was induced by dietary supplementation with ezetimibe, suggesting a hormetic effect on oxidative stress response and lifespan. Ezetimibe also significantly prevented amyloid beta-induced toxicity and completely reversed increased mortality by high-glucose diet. Nuclear localization of DAF-16 required for the prevention of amyloid beta-induced toxicity was enhanced by ezetimibe supplementation. Lifespan assay using known long-lived mutants, age-1, clk-1, and eat-2, revealed that lifespan extension by ezetimibe specifically overlapped with that of eat-2 mutants, which are genetic models of dietary restriction. Effect of ezetimibe on lifespan of worms fed with diluted bacteria suggested that ezetimibe mimics the effect of dietary restriction on lifespan. These findings suggest that ezetimibe exhibits anti-oxidative and anti-aging effects through hormesis and works as a dietary-restriction mimetic on lifespan extension.

Progress of Research on Dietary Restriction Behavior and its Influencing Factors in Patients With Inflammatory Bowel Disease / 胃肠病学

Inflammatory bowel disease (IBD) is of unknown cause and is not yet curable. Scientific diet has positive implication for disease treatment, control, and remission. However, IBD patients commonly have dietary restriction behavior, there is lack of specific assessment tools for dietary restriction in IBD, and dietary restriction hazards are numerous and the influencing factors are complex. This article reviewed the progress of research on dietary restriction behavior and its influencing factors in patients with IBD.

Latent class analysis of dietary restraint in mother-adolescent dyads / Análisis de clases latentes de restricción alimentaria en díadas madre-adolescente

ABSTRACT The objectives of this study were to identify adolescent profiles based on their dietary restraint behavior. A sample of 470 mothers with one child between 10 and 17 years of age were surveyed in Chile. Questionnaires included the Revised Restraint Scale, Satisfaction with Life Scale, Satisfaction with Food-related Life scale, Satisfaction with Family Life scale and the Adapted Healthy Eating Index. The results of the Latent Class Analysis yielded two classes: dieters and non-dieters. Dieters had a higher mean age, higher proportion of overweight and obesity and lower scores on the satisfaction with life and food-related life. Families from the dieters class had a lower frequency of family dinners. Their mothers had higher weight fluctuation and rates of obesity. The results suggest that interventions aimed at reducing overweight/obesity and dietary restraint in adolescents and intended to improve adolescent subjective well-being must include both the mother and the adolescent, regardless of sex.

RESUMEN Los objetivos de este estudio fueron identificar perfiles de adolescentes basados en su comportamiento de restricción alimentaria. Se encuestó a una muestra de 470 madres con un hijo entre 10 y 17 años en Chile. Los cuestionarios incluyeron la Escala Revisada de Restricción, la Escala de Satisfacción con la Vida, la Escala de Satisfacción con la Alimentación, la Escala de Satisfacción con la Vida Familiar y el Índice de Alimentación Saludable Adaptado. Los resultados del análisis de clases latentes arrojaron dos tipos: dietantes y no dietantes. Los dietantes tuvieron una edad media más alta, mayor proporción de sobrepeso y obesidad y puntuaciones más bajas en la satisfacción con la vida y con la alimentación. Las familias de los dietantes tuvieron una menor frecuencia de cenas familiares. Sus madres tuvieron una mayor fluctuación de peso y tasas de obesidad. Los resultados sugieren que las intervenciones dirigidas a reducir la obesidad/sobrepeso y la restricción alimentaria en adolescentes y destinadas a mejorar el bienestar subjetivo de los adolescentes deben incluir tanto a la madre como al adolescente, independientemente del género.

Is There Any Necessity to Prescribe Consumption of Walnuts Cooked by Different Processing Techniques to Patients With Walnut Allergy?

The present study focused on identifying the usual methods of cooking walnuts in order to investigate changes in walnut allergen activity caused by cooking and evaluated the allergenic changes in walnut proteins within raw, dry-fried and boiled walnuts. Previous studies have reported a decrease in the allergen activity of walnut by thermal processing methods, which are not used in Korean kitchens, such as dry-frying and boiling. In Korea, Walnuts are consumed with rice and usually boiled and stir-fried with seasoning. Thus, the present study clarified the protein bands corresponding to raw walnuts and confirmed that the patterns of each walnut protein differ depending on cooking methods. This concern may be a very crucial point to understand the other tree nuts allergy as well as walnut allergy. The results of the present study differ from those of previous studies performed in Europe, although further studies with older participants are needed in order to draw more definite conclusions on lipid transfer protein (LTP). The other crucial point is that the findings of the present study support existing findings that the allergenic components of walnut have varying antigenicity depending on cooking methods. The allergenic components of walnut identified using diagnostic tests for walnut allergic patients could be reduced in walnuts cooked by different processing techniques. The allergenic components of walnut have varying allergen activity depending on cooking methods. Therefore, the allergenic components of walnuts identified using diagnostic tests for walnut allergic patients could allow physicians to prescribe consumption of walnuts cooked by different processing techniques to patients with walnut allergy.

Avaliação do controle da expressão gênica de citocinas pró inflamatórias mediado pela IL-10. Participação da IL-10 na modulação da resposta inflamatória exercida pela glutamina e na restrição alimentar / Proinflammatory cytokines gene expression control mediated by IL-10. Participation of IL-10 on inflammatory response exerted by glutamine and dietary restriction

O desenvolvimento de uma resposta imune adequada é um processo extremamente importante para a manutenção da homeostase do organismo. Uma série de processos são desencadeados a partir do primeiro contato com micro-organismos patógenos até a efetivação da resposta imune de memória. Todos esses processos envolvem a participação e a complexa atuação de mediadores como as citocinas inflamatórias e também citocinas regulatórias, que exercerão efeitos controlando o processo inflamatório. Diversos mecanismos moleculares, subjacentes à resposta inflamatória, ainda não estão totalmente compreendidos, como por exemplo o controle da expressão de genes inflamatórios exercido pela IL-10. Os processos envolvidos na resposta inflamatória são mantidos às custas do consumo de nutrientes, dentre eles podemos destacar o aminoácido glutamina, que atua em nível molecular, fornecendo nitrogênio para a formação do material genético e fonte energética para determinadas células do sistema imunológico como os macrófagos. Portanto, neste trabalho, investigamos os efeitos da IL-10 na modificação de nucleossomos, evidenciando o papel dessa citocina em regular a expressão de genes inflamatórios em macrófagos. Avaliamos também a função da glutamina, modulando a expressão de RNAm de citocinas inflamatórias e regulatórias dessas células. E por último, desenvolvemos um modelo de restrição alimentar em camundongos, nos quais avaliamos os efeitos desse modelo considerando-se alguns aspectos hematológicos e estudamos as alterações na resposta inflamatória em células esplênicas e do peritônio, bem como avaliamos a suplementação de glutamina in vitro na produção das citocinas (IL-12, TNF-alfa, IL-10) e a expressão do fator de transcrição NFkB. Os resultados compilados mostraram que a IL-10 leva a uma rápida redução da acetilação de nucleossomos, modulando a arquitetura da cromatina de genes inflamatórios como a IL-12. A glutamina modula a expressão de citocinas inflamatórias, regulando positivamente a expressão de IL-10 e Interferon beta. E a restrição alimentar induz a redução de citocinas proinflamatórias (IL-12 e TNF-α), influenciadas pelo aumento da produção de IL-10 e finalmente a suplementação com glutamina não interfere nesses parâmetros nas células peritoneiais e esplênicas do grupo submetido à restrição alimentar. Conclusão: a IL-10 modula a expressão gênica através da modificação de nucleossomos em macrófagos derivados da medula; a glutamina modula a expressão de IL-10 inibindo a resposta inflamatória, e a restrição alimentar modula alguns aspectos hematológicos e possui propriedades anti-inflamatórias.

The development of an appropriate immune response is an important process to the organism's homeostatic maintenance. A series of processes are triggered upon the very first contact with pathogens, up to the immunological memory establishment. These processes implicate in the participation of complex mediators, such as inflammatory and regulatory cytokines that will control the inflammatory process. Some mechanisms underlying the inflammatory response are not totally understood, the control of inflammatory genes exerted by IL-10 is an example. The processes involved in the inflammatory response are kept with nutrients expense, among these nutrients we can highlight the amino acid glutamine. It acts in a molecular level, supplying nitrogen to genetic material formation and as an energy supply for immune cells such as macrophages. Thus, we investigated the IL-10 effects on nucleosome modifications evidencing this cytokine role regulating inflammatory genes expression in macrophages. We also evaluated glutamine functions modulating inflammatory and regulatory cytokines mRNA expression on these cells. Ultimately, we developed a dietary restriction animal model where we evaluated it's effects on selected haematological aspects, analyzing the alteration in the inflammatory response of splenic and peritoneal cells. We also evaluated in vitro glutamine supplementation assessing cytokines production (IL-12, TNF-α, and IL-10) and the expression of NFkB transcription factor. The compiled results a expressive reduction in nucleosome acetylation modifying the chromatin architecture of inflammatory genes such as IL-12 and IL-6. Glutamine modulates inflammatory cytokines gene expression upregulating the expression of IL-10 and interferon beta. The dietary restriction reduces proinflammatory cytokines production (IL-12 and TNF-α), these results are influenced by the upregulated IL-10 production, glutamine supplementation have no effect on these parameters in the dietary restriction group. In conclusion, we can infer that IL-10 modulates gene expression trough nucleosome modification in bone marrow derived macrophages, glutamine has a potential effect on IL-10 expression, inhibiting the inflammatory response and dietary restriction modifies hematological parameters, presenting anti-inflammatory properties.

Avaliação do controle da expressão gênica de citocinas pró inflamatórias mediado pela IL-10. Participação da IL-10 na modulação da resposta inflamatória exercida pela glutamina e na restrição alimentar / Proinflammatory cytokines gene expression control mediated by IL-10. Participation of IL-10 on inflammatory response exerted by glutamine and dietary restriction

O desenvolvimento de uma resposta imune adequada é um processo extremamente importante para a manutenção da homeostase do organismo. Uma série de processos são desencadeados a partir do primeiro contato com micro-organismos patógenos até a efetivação da resposta imune de memória. Todos esses processos envolvem a participação e a complexa atuação de mediadores como as citocinas inflamatórias e também citocinas regulatórias, que exercerão efeitos controlando o processo inflamatório. Diversos mecanismos moleculares, subjacentes à resposta inflamatória, ainda não estão totalmente compreendidos, como por exemplo o controle da expressão de genes inflamatórios exercido pela IL-10. Os processos envolvidos na resposta inflamatória são mantidos às custas do consumo de nutrientes, dentre eles podemos destacar o aminoácido glutamina, que atua em nível molecular, fornecendo nitrogênio para a formação do material genético e fonte energética para determinadas células do sistema imunológico como os macrófagos. Portanto, neste trabalho, investigamos os efeitos da IL-10 na modificação de nucleossomos, evidenciando o papel dessa citocina em regular a expressão de genes inflamatórios em macrófagos. Avaliamos também a função da glutamina, modulando a expressão de RNAm de citocinas inflamatórias e regulatórias dessas células. E por último, desenvolvemos um modelo de restrição alimentar em camundongos, nos quais avaliamos os efeitos desse modelo considerando-se alguns aspectos hematológicos e estudamos as alterações na resposta inflamatória em células esplênicas e do peritônio, bem como avaliamos a suplementação de glutamina in vitro na produção das citocinas (IL-12, TNF-alfa, IL-10) e a expressão do fator de transcrição NFkB. Os resultados compilados mostraram que a IL-10 leva a uma rápida redução da acetilação de nucleossomos, modulando a arquitetura da cromatina de genes inflamatórios como a IL-12. A glutamina modula a expressão de citocinas inflamatórias, regulando positivamente a expressão de IL-10 e Interferon beta. E a restrição alimentar induz a redução de citocinas proinflamatórias (IL-12 e TNF-α), influenciadas pelo aumento da produção de IL-10 e finalmente a suplementação com glutamina não interfere nesses parâmetros nas células peritoneiais e esplênicas do grupo submetido à restrição alimentar. Conclusão: a IL-10 modula a expressão gênica através da modificação de nucleossomos em macrófagos derivados da medula; a glutamina modula a expressão de IL-10 inibindo a resposta inflamatória, e a restrição alimentar modula alguns aspectos hematológicos e possui propriedades anti-inflamatórias

The development of an appropriate immune response is an important process to the organism's homeostatic maintenance. A series of processes are triggered upon the very first contact with pathogens, up to the immunological memory establishment. These processes implicate in the participation of complex mediators, such as inflammatory and regulatory cytokines that will control the inflammatory process. Some mechanisms underlying the inflammatory response are not totally understood, the control of inflammatory genes exerted by IL-10 is an example. The processes involved in the inflammatory response are kept with nutrients expense, among these nutrients we can highlight the amino acid glutamine. It acts in a molecular level, supplying nitrogen to genetic material formation and as an energy supply for immune cells such as macrophages. Thus, we investigated the IL-10 effects on nucleosome modifications evidencing this cytokine role regulating inflammatory genes expression in macrophages. We also evaluated glutamine functions modulating inflammatory and regulatory cytokines mRNA expression on these cells. Ultimately, we developed a dietary restriction animal model where we evaluated it's effects on selected haematological aspects, analyzing the alteration in the inflammatory response of splenic and peritoneal cells. We also evaluated in vitro glutamine supplementation assessing cytokines production (IL-12, TNF-α, and IL-10) and the expression of NFkB transcription factor. The compiled results a expressive reduction in nucleosome acetylation modifying the chromatin architecture of inflammatory genes such as IL-12 and IL-6. Glutamine modulates inflammatory cytokines gene expression upregulating the expression of IL-10 and interferon beta. The dietary restriction reduces proinflammatory cytokines production (IL-12 and TNF-α), these results are influenced by the upregulated IL-10 production, glutamine supplementation have no effect on these parameters in the dietary restriction group. In conclusion, we can infer that IL-10 modulates gene expression trough nucleosome modification in bone marrow derived macrophages, glutamine has a potential effect on IL-10 expression, inhibiting the inflammatory response and dietary restriction modifies hematological parameters, presenting anti-inflammatory properties

Dietary Restriction Reduces Blood Lipids and Ameliorates Liver Function of Mice with Hyperlipidemia / 华中科技大学学报（医学）（英德文版）

Dietary restriction (DR) can delay senescence,prolong lifespan of mammals and improve their learning-memory activity.The purpose of the study was to explore the effects of DR on hypolipidemic action and liver function of mice with hyperlipidemia.To investigate these effects,hyperlipidemia mouse models were established with high-fat diet (HFD) (34％ of energy),then randomly divided into HFD group,DR30％ group and DR50％ group.Mice in DR30％ and DR50％ group were respectively supplied with HFD as much as about 70％ and 50％ of the consumption of HFD in the mice of HFD group.Rats in control group were fed routinely.After DR for 5 weeks,the average body weight,liver weight,liver index,serum lipids and glucose levels in both DR groups decreased significantly as compared with the HFD group (P＜0.05 or P＜0.01),so did alanine aminotransferase (ALT),aspartate aminotransferase (AST),lactate dehydrogenase (LDH) levels and the ratio of LDL-C/HDL-C in the DR50％ group (P＜0.05 or P＜0.01).Histopathology examination of liver tissues further proved ameliorative effect of DR on liver function.Western blotting showed that DR significantly increased the expression of silent mating type information regulation 2 homolog 1 (SIRT1) in liver and adipose,while notably decreased the expression of peroxisome proliferators-activated receptors-gamma (PPARγ) in adipose (P＜0.05 or P＜0.01).The increase of SIRT1 and decrease of PPARγ may be a mechanism by which DR reduces blood lipids and ameliorates liver function.

Dietary restriction enhancesγ-aminobutyric acid and brain derived neurotrophic factor expression in the visual cortex of the cat / 解剖学报

Objective To explore the effect of DR on the expression of inhibitory neurotransmitter ,γ-aminobutyric acid ( GABA) and brain derived neurotrophic factor ( BDNF) in the primary visual cortex of young cats .Methods Totally 6 cats were wsed in this study . Nissl staining was used for cortical layer identification and cell counting . Immunohistochemical techniques were utilized to label GABA-and BDNF-positive neurons .Sections were observed under an Olympus light microscope and photographed with a digital camera .The cell density and absorbance of immunoreactivity were measured with Image-Pro Express 6.0 softwares .Results Our results showed that the mean density of Nissl-stained neurons in the primary visual cortex ( V1) of the DR group showed no significant difference from that of the control group . However , the mean density of GABA-immunoreactive neurons in each cortical layer of V 1 in DR cats was significantly higher than that in control cats .The mean immunoreactive intensity of GABA-positive neurons , as indicated by the average absorbance , increased significantly in DR cats relative to control ones . Accompanied with the elevation of GABA expression, DR enhanced BDNF expression in V1, as indicated by an increased mean density of BDNF-positive neurons and BDNF-immunoreactive average absorbance in DR cats relative to controls .Conclusion These results indicate that dietary restriction leads to a concurrent expression upregulation of GABA and BDNF , which may likely compensate for brain functional degradation during senescence and thus delay aging process .

Molecular Links between Caloric Restriction and Sir2/SIRT1 Activation

Ageing is the most significant risk factor for a range of prevalent diseases, including cancer, cardiovascular disease, and diabetes. Accordingly, interventions are needed for delaying or preventing disorders associated with the ageing process, i.e., promotion of healthy ageing. Calorie restriction is the only nongenetic and the most robust approach to slow the process of ageing in evolutionarily divergent species, ranging from yeasts, worms, and flies to mammals. Although it has been known for more than 80 years that calorie restriction increases lifespan, a mechanistic understanding of this phenomenon remains elusive. Yeast silent information regulator 2 (Sir2), the founding member of the sirtuin family of protein deacetylases, and its mammalian homologue Sir2-like protein 1 (SIRT1), have been suggested to promote survival and longevity of organisms. SIRT1 exerts protective effects against a number of age-associated disorders. Caloric restriction increases both Sir2 and SIRT1 activity. This review focuses on the mechanistic insights between caloric restriction and Sir2/SIRT1 activation. A number of molecular links, including nicotinamide adenine dinucleotide, nicotinamide, biotin, and related metabolites, are suggested to be the most important conduits mediating caloric restriction-induced Sir2/SIRT1 activation and lifespan extension.

Dietary restriction prevents diabetogenic effect of streptozotocin in mice.

The beneficial role of dietary restriction (DR) was studied in streptozotocin (STZ)-induced diabetes in mice. The DR mice exhibited the lower blood glucose (mg/dl) level as compared to ad libitum (AL) fed ones. After 3 months’ DR, STZ treatment to both AL and DR mice showed significant (p<0.001) elevation of the blood glucose level in AL-fed mice, while a lower level of glucose was maintained in DR-fed mice. The ability of maintaining a low blood glucose level in STZ-treated DR mice indicated that STZ might have been ineffective from its action on beta cells of pancreas by long-term DR. Thus, these findings suggested that DR may be an important tool for preventing the diabetic conditions. However, further studies are required to know the mechanism(s) of DR protection against diabetogenic action of STZ in experimental animals.

Survey on Dietary Restrictions for Neutropenic Patients / 종양간호학회지

PURPOSE: This survey was aimed to examine the current dietary restrictions practices for neutropenic patients among hospitals with 500 and more beds. METHODS: Self-administered questionnaires were sent to 100 head or charge nurses of oncology or hemato-oncology wards by mail during October 2009, and 51 questionnaires were returned. The data were analyzed with descriptive statistics using SPSS (WIN version 12.0). RESULTS: Of the hospitals surveyed, 47.1% (n=24) had guidelines on the dietary restrictions, and 80.4% (n=41) placed patients with neutropenia on restricted diets. The major decisional criteria of the dietary restriction was absolute neutrophil count (30.5%) and cooking status (29.2%). The most commonly restricted foods were raw fish or fresh meat (98.0%), uncooked intestine (98.0%), raw eggs (98.0%), draught beer (96.1%), and fresh fruits or vegetables (86.3%). CONCLUSION: The results showed variation in pattern of dietary restrictions and lower rate of guideline among hospitals, so that the need for the standard dietary restriction guideline is high. However, the role of diet in the development of infection in neutropenic patients is still unclear, which makes it difficult to establish dietary restriction guideline. Therefore, additional research are required to identify the relationship between dietary factors and infections.

INFLUENCE OF DIETARY RESTRICTION ON THE EXPRESSION OF INSULIN SIGNALING GENES IN MOUSE EPIDIDYMIS FAT PAD / 营养学报

Objective:To study the influence of dietary restriction on the expression of insulin signaling pathway genes in mouse adipose tissue. Method:Twenty four C57BL/6 male mice of 2 w age were subjected to either AL (ad libitum) or DR (dietary restriction, 40% from AL) randomly until sacrificed.Then the epididymis fat pads were weighed, and their insulin signaling gene expression was detected by Oligo Insulin Signaling Pathway Microarray (SuperArray), and two of the differentially expressed genes, NPY and AKT3 were validated by Real Time PCR. Results:Dietary restriction significantly reduced the weight of epididymis fat pads and 31 (20 up, 11 down regulation) of 96 insulin signaling pathway genes were differentially expressed. The results of Microarray coincided with that of Real Time PCR. Conclusion:The differential regulation on the expressions of insulin signaling pathway gene may be the important molecular basis of dietary restriction.