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Thus, targeting NFATc4 can be a novel therapeutic approach for preventing HFrD induced- IR and renal injury.The application of lipidomics, after genomics, proteomics and metabolomics, offered largely opportunities to illuminate the entire spectrum of lipidome based on a quantitative or semi-quantitative level in a biological system. When combined with advances in proteomics and metabolomics high-throughput platforms, lipidomics provided the opportunity for analyzing the unique roles of specific lipids in complex cellular processes. Abnormal lipid metabolism was demonstrated to be greatly implicated in many human lifestyle-related diseases. In this review, we focused on lipidomic applications in brain injury disease, cancer, metabolic disease, cardiovascular disease, respiratory disease and infectious disease to discover disease biomarkers and illustrate biochemical metabolic pathways. We also discussed the analytical techniques, future perspectives and potential problems of lipidomic applications. The application of lipidomics in disease biomarker discovery provides the opportunity for gaining novel insights into biochemical mechanism.Serogroup A meningococcal epidemics have been a recurrent public health problem, especially in resource-poor countries of Africa. Recently, the administration in mass vaccination campaigns of a single dose of the monovalent meningococcal conjugate vaccine, MenAfriVac, to the 1-29 year-old population of sub-Saharan Africa has prevented epidemics of meningitis caused by serogroup A Neisseria meningitidis. This strategy has also been shown to provide herd protection of the non-vaccinated population. Development of meningococcal conjugate vaccines covering other serogroups and enhanced use of the pneumococcal and Haemophilus influenzae type b conjugate vaccines must be pursued to fully control bacterial meningitis in sub-Saharan Africa.

Consuming 30g of nuts/day is recommended to reduce chronic disease. However, nut consumption appears far from ideal among several populations. A potential strategy to increase consumption is to add nuts to a staple, for example, bread. Whether the health benefits and acceptability of nuts persist in this form is currently unknown. Thus, we examined the effects of consuming three nut-enriched breads on postprandial glycaemia, satiety, gastrointestinal tolerance, dietary intakes, and acceptance.

In this controlled, crossover study, 32 participants were randomly allocated to receive one of four breads for 8days each. Three breads contained either 30g of finely sliced hazelnuts, 30g semi-defatted hazelnut flour, or 15g of each (amounts per 120g bread) and were compared with a control nut-free bread. Blood glucose response was measured over 120min, along with ratings of gastrointestinal discomfort. Ipatasertib in vitro Appetite ratings and diet diaries were completed during each treatment period.

Area under the blood glucose curve was significantly lower for the nut breads compared to the control bread (all P<0.001), with no significant differences between the nut breads (all P≥0.130). There were no significant differences in satiety (all P≥0.135) or gastrointestinal symptoms (all P≥0.102) between the breads. Acceptance was highest for the finely sliced hazelnut bread. Furthermore, consuming hazelnut-enriched bread improved diet quality, increasing monounsaturated fat, vitamin E, and dietary fibre intakes.

Bread appears to be an effective and acceptable vehicle for increasing nut consumption, resulting in improved postprandial glycaemia and diet profiles. Long-term studies are now required.

Bread appears to be an effective and acceptable vehicle for increasing nut consumption, resulting in improved postprandial glycaemia and diet profiles. Long-term studies are now required.

The objective of this study was to determine the effect of feeding a maternal diet supplemented with docosahexaenoic acid (DHA) while also containing adequate amounts of arachidonic acid on immune system development and function in suckled offspring and lactating rats.

Sprague-Dawley dams were randomized to one of the two nutritionally adequate experimental diets 24-48h prior to parturition control diet (N=12, 0% DHA) or high DHA diet (N=8, 0.9% DHA of total fatty acids). Diets were fed throughout the lactating/suckling period (21days), and then, dams and pups were terminated, and immune cell phenotypes and cytokine production by mitogen- or ovalbumin-stimulated splenocytes were measured.

Feeding dams a high DHA diet resulted in a higher proportion of 183n-3, 225n-3 and 226n-3 found in pup's stomach content (breast milk; P<0.01). Feeding the high DHA diet had no impact on growth parameters or the ex vivo cytokine production by mitogen-stimulated splenocytes in both dams and pups. There was a higher proportion of OX12+CD80+ cells and a lower production of TGF-β by splenocytes after ovalbumin stimulation in pups from dams fed the DHA diet (both P<0.05) while maintaining a similar IL-2 production. LPS-stimulated splenocytes from dams fed the high DHA diet produced more TNF-α versus control diet (P<0.05).

Overall, our results suggest that DHA supplementation in the maternal diet does not change the immune response to mitogens but positively affects the activation of B cells as well as the response to a potential food antigen upon challenge in suckled offspring.

Overall, our results suggest that DHA supplementation in the maternal diet does not change the immune response to mitogens but positively affects the activation of B cells as well as the response to a potential food antigen upon challenge in suckled offspring.

Excessive fat intake induces obesity and causes cardiac injury. Intracellular degradation process involving destruction of long-lived proteins and organelles maintains homeostasis for cells under stress. The purpose of this study was to explore the relation of high-fat diet (HFD)-induced cardiac injury and intracellular degradation process with regard to autophagy and ER stress.

HFD feeding for 24weeks induced hyperglycemia, hyperlipidemia, and cardiac hypertrophy in adult male C57BL/6 mice. In the heart, PARP cleavage, an indicator of apoptosis, levels of LC3-II and p62, indicators of autophagy, and CHOP, indicator of ER stress, were increased. A palmitate-treated cardiomyoblast (H9C2) cell culture was examined to explore how HFD induced myocardial injury. Excessive palmitate (400μM) treatment induced apoptosis and increased the number of autophagosomes and acid vacuoles of H9C2 cells. Besides, it elevated the expression of LC3-II, p62, and PARP cleavage. Induction of autophagy by rapamycin ameliorated palmitate-induced apoptosis, while inhibition of autophagy by 3-methyladenine or LC3 siRNA exacerbated palmitate-induced apoptosis. Palmitate treatment also induced CHOP expression which is associated with ER stress.

HFD can cause cardiac injury by induction of apoptosis which is associated with autophagy dysregulation and ER stress. In addition, autophagy deficiency augments cardiac apoptosis, suggesting that autophagy serves as a pro-survival role in lipotoxic condition.

HFD can cause cardiac injury by induction of apoptosis which is associated with autophagy dysregulation and ER stress. In addition, autophagy deficiency augments cardiac apoptosis, suggesting that autophagy serves as a pro-survival role in lipotoxic condition.

This study aimed to determine whether fenugreek seed powder could reduce the glycemic response and glycemic index (GI) when added to buns and flatbreads.

In a randomised, controlled crossover trial, ten healthy human subjects (five men, five women) were given 50g glucose (reference food, twice); buns (0 and 10% fenugreek seed powder); and flatbreads (0 and 10% fenugreek seed powder) on six different occasions. Finger prick capillary blood samples were collected at 0, 15, 30, 45, 60, 90 and 120min after the start of the meal. The palatability of the test meals was scored using Likert scales.

The incremental areas under the glucose curve value of buns and flatbreads with 10% fenugreek (138±17mmol×min/L; 121±16mmol×min/L) were significantly lower than those of 0% fenugreek bun and flatbreads (227±15mmol×min/L; 174±14mmol×min/L, P=<0.01). Adding 10% fenugreek seed powder reduced the GI of buns from 82±5 to 51±7 (P<0.01) and to the GI of flatbread from 63±4 to 43±5 (P<0.01).

These results suggest that replacing 10% of refined wheat flour with fenugreek seed powder significantly reduces the glycemic response and the GI of buns and flatbreads. Thus, fenugreek powder may be a useful functional ingredient to reduce postprandial glycemia.

These results suggest that replacing 10 % of refined wheat flour with fenugreek seed powder significantly reduces the glycemic response and the GI of buns and flatbreads. Thus, fenugreek powder may be a useful functional ingredient to reduce postprandial glycemia.Alpha-1 antitrypsin deficiency is linked with an increased risk of suffering from lung emphysema. This discovery from the 1960s led to the development of the protease-antiprotease (im)balance hypothesis Overshooting protease concentrations, especially high levels of elastase were deemed to have an destructive effect on lung tissue. Consequently, it was postulated that efficient elastase inhibitors could alleviate the situation in patients. However, despite intensive drug discovery efforts, even five decades later, no neutrophil elastase inhibitors are available for a disease-modifying treatment of (cardio)pulmonary diseases such as chronic obstructive pulmonary disease. Here, we critically review the attempts to develop effective human neutrophil elastase inhibitors while strongly focussing on recent developments. On purpose and with perspective distortion we focus on recent developments. One aim of this review is to classify the known HNE inhibitors into several generations, according to their binding modes. In general, there seem to be three major challenges in the development of suitable elastase inhibitors (1) assuring sufficient potency, (2) securing selectivity, and (3) achieving metabolic stability especially under pathophysiological conditions. Impressive achievements have been made since 2001 with the identification of potent nonreactive, reversible small molecule inhibitors. The most modern inhibitors bind HNE via an induced fit with a frozen bioactive conformation that leads to a significant boost in potency, selectivity, and stability ('pre-adaptive pharmacophores'). These 5th generation inhibitors might succeed in re-establishing the protease-antiprotease balance in patients for the first time.The bioactivity of nitroimidazole in Tc-99m-labeled 2-nitroimidazole, a traditional solid tumor hypoxia-imaging agent for single photon emission computed tomography (SPECT), is reduced by the presence of large ligand and metallic radionuclide, exhibiting lower tumor-to-nontumor ratios. In an effort to solve this general problem, a pretargeting strategy based on click chemistry (strain-promoted cyclooctyne-azide cycloaddition) was applied. The functional click synthons were synthesized as pretargeting components an azide group linked to 2-nitroimidazole (2NIM-Az) serves for tumor hypoxia-targeting and azadibenzocyclooctyne conjugated with monoamine monoamide dithiol ligand (AM) functions as radiolabeling and binding group to azides in vivo. 2NIM-triazole-MAMA was obtained from in vitro click reaction with a reaction rate constant of 0.98M(-1)s(-1). AM and 2NIM-triazole-MAMA were radiolabeled with Tc-99m. The hypoxia-pretargeting biodistribution was studied in Kunming mice bearing S180 tumor; (99m)Tc-AM and (99m)Tc-triazole-2NIM were used as blank control and conventional control.

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