Nutrients

Osteoarthritis (OA) is a common disorder that can affect any joint in the human body. This study aimed to examine the anti-arthritic properties of high and low doses of grapefruit juice (GFJ), as grapefruit appears to contain anti-inflammatory biochemicals. Forty male Sprague–Dawley rats weighing 170–180 g were divided into five groups. These groups comprised the untreated control group and osteoarthritic (Osteo) rats administered intra-articular injections of Freund’s complete adjuvant (CFA; 0.5 mL; 1 mg/mL) as follows: OA rats administered low doses of GFJ (Osteo+GFJ (low); 5 mL/kg body weight (BW)); OA rats administered high doses of GFJ (Osteo+GFJ (high); 27 mL/kg BW); and OA rats administered diclofenac sodium (Osteo+Diclo) as a reference drug. Injections of CFA induced OA, as indicated by a significant increase in the serum levels of the inflammatory biomarkers C-reactive protein (CRP), interleukin-1β (IL-1β), and (prostaglandin (PGE2), as well as matrix metalloproteinases (MMP-1) and cathepsin K. The synovial levels of glycosaminoglycans (GAGs), tumor necrosis factor (TNF-α), and interleukin 6 (IL-6) also increased, with a concomitant reduction in osteocalcin levels. The administration of either high or low doses of GFJ reduced CRP, IL-1β, PGE2, MMP-1, cathepsin K, and osteocalcin while increasing the synovial levels of GAGs, TNF-α, and IL-6, slowing cartilage degradation and boosting joint function. The results showed comparable histopathological and biochemical responses. A comparison of the treatments showed that high-dose GFJ had a greater chondroprotective effect than low-dose GFJ. Full article

High-grade adult-type diffuse gliomas are the most common and deadliest malignant adult tumors of the central nervous system. Despite the advancements in the multimodality treatment of high-grade adult-type diffuse gliomas, the five-year survival rates still remain poor. The biggest challenge in treating high-grade adult-type diffuse gliomas is the intra-tumor heterogeneity feature of the glioma tumors. Introducing dietary flavonoids to the current high-grade adult-type diffuse glioma treatment strategies is crucial to overcome this challenge, as flavonoids can target several molecular targets. This review discusses the anticancer mechanism of flavonoids (quercetin, rutin, chrysin, apigenin, naringenin, silibinin, EGCG, genistein, biochanin A and C3G) through targeting molecules associated with high-grade adult-type diffuse glioma cell proliferation, apoptosis, oxidative stress, cell cycle arrest, migration, invasion, autophagy and DNA repair. In addition, the common molecules targeted by the flavonoids such as Bax, Bcl-2, MMP-2, MMP-9, caspase-8, caspase-3, p53, p38, Erk, JNK, p38, beclin-1 and LC3B were also discussed. Moreover, the clinical relevance of flavonoid molecular targets in high-grade adult-type diffuse gliomas is discussed with comparison to small molecules inhibitors: ralimetinib, AMG232, marimastat, hydroxychloroquine and chloroquine. Despite the positive pre-clinical results, further investigations in clinical studies are warranted to substantiate the efficacy and safety of the use of flavonoids on high-grade adult-type diffuse glioma patients. Full article

This cross-sectional study aimed to develop and validate a vitamin D food frequency questionnaire (VitD-FFQ) to assess vitamin D intake in Moroccan women of reproductive age. Using the method of triads, the VitD-FFQ was validated against seven-day dietary records (7d-FR) and 25-hydroxyvitamin D (25(OH)D) as a biomarker of vitamin D status in 152 women (aged 18–45 years). Participants’ sun exposure scores (SES) were assessed using a specific questionnaire (SEQ). Predictors of vitamin D status were identified via linear regression models. Several statistical tests were applied to evaluate the criterion validity of the FFQ against two references methods (7d-FR and the biomarker-serum 25(OH)D). Median (Interquartile range) intakes were 7.10 ± 6.95 µg /day and 6.33 ± 5.02 µg/ day, respectively, for VitD-FFQ and 7d-FR. Vitamin D status was mainly determined by SES (R = 0.47) and vitamin D absolute food intakes derived by the VitD-FFQ (R = 0.56), which demonstrated a more significant prediction ability compared to 7d-FR (R = 0.36). An agreement was observed between the VitD-FFQ and 7d-FR (BA index of 3.29%) with no proportional bias (R² = 0.002, p = 0.54). <10% of participants were incorrectly classified, and weighted kappa statistics showed that VitD-FFQ had an acceptable ranking ability compared to the 7d-FR and the biomarker. The validity coefficient for the VitD-FFQ was high: ρQR = 0.90 (95%CI: 0.89–0.92), and a range from 0.46 to 0.90. Adjustment for the participants’ SES and BMI (body mass index) improved the biomarker’s validity coefficient (ρRB 0.63 (95% CI 0.39–0.82). Our results indicate that the VitD-FFQ is valid for estimating absolute vitamin D intake in Moroccan women of reproductive age. Full article

The novel term metabolic dysfunction-associated fatty liver disease (MAFLD), which has been proposed to describe the major cause of hepatic disease, pinpoints the coexistence of multiple metabolic disturbances and liver steatosis, giving rise to different phenotypic manifestations. Within the psychoneuroendocrineimmunological (PNEI) network that regulates body–mind interactions, the stress response plays a pervasive role by affecting metabolic, hormonal, immune, and behavioral balance. In this perspective, we focus on chronic psychosocial stress and high levels of cortisol to highlight their role in MAFLD pathogenesis and worsening. From a PNEI perspective, considering the stress response as a therapeutic target in MAFLD allows for simultaneously influencing multiple pathways in the development of MAFLD, including dysmetabolism, inflammation, feeding behaviors, gut–liver axis, and dysbiosis, with the hope of better outcomes. Full article

Ecological studies showed correlations between a shift toward animal-protein-rich diets and longer life-expectancy; however, only a few studies examined individual-level association of protein source and mortality risks using appropriate iso-caloric substitution models adjusted for total energy intake. We used EPIC-Heidelberg (European Prospective Investigation into Cancer and nutrition) to create iso-caloric substitution models and determined relative all-cause, cardiovascular and cancer mortality hazards associated with dietary intake of animal protein and other macronutrients, employing Cox proportional hazard models. For comparison with other studies, we also synthesized evidence from a systematic review relating animal protein intake to mortality risk from seven prospective cohort studies in the USA, Europe and Japan. Substitution of 3% of total energy from animal protein for fat (saturated, mono-unsaturated) and carbohydrate (simple, complex) was associated with all-cause mortality (Hazard Ratios [HR] from 1.05 to 1.11), mostly driven by cardiovascular mortality (HR from 1.13 to 1.15). Independently of animal protein, substituting poly-unsaturated fat for saturated fat increased cancer-related mortality risk by 12 percent. The systematic review largely corroborated our findings. Overall, higher proportions of dietary energy from animal protein, combined with low energy intake from either carbohydrate sub-types or dietary fats, increases all-cause and cardiovascular mortality risks, but not cancer-related mortality. Full article

There has been an increasing interest in the consumption of halophytes as a healthy food in the last few years. Salicornia ramosissima is a seasonal Mediterranean halophyte with an interesting profile of bioactive compounds, including more than 60 identified polyphenols with a broad range of biological activities. Accumulating evidence supports the role of dietary polyphenols in the prevention of cardiovascular diseases, such as stroke. Stroke is the second cause of death worldwide and it is estimated that a substantial proportion of stroke incidence and recurrence may be prevented by healthier dietary patterns. Here, we have grouped the phenolic acids and flavonoids identified in S. ramosissima and reviewed their potential protective effect on brain ischemia, which are mostly related to the reduction of oxidative stress and inflammation, the inhibition of cell death pathways and their role in the preservation of the vascular function. Despite the fact that most of these compounds have been reported to be neuroprotective through multiple mechanisms, human studies are still scarce. Given the safe profile of polyphenols identified in S. ramosissima, this halophyte plant could be considered as a source of bioactive compounds for the nutraceutical industry. Full article

Background: Behavioral programs are needed for prevention and treatment of NAFLD and the effectiveness of a web-based intervention (WBI) is similar to a standard group-based intervention (GBI) on liver disease biomarkers. Objective: We aimed to test the long-term effectiveness of both programs on diabetes incidence, a common outcome in NAFLD progression. Methods: 546 NAFLD individuals (212 WBI, 334 GBI) were followed up to 60 months with regular 6- to 12-month hospital visits. The two cohorts differed in several socio-demographic and clinical data. In the course of the years, the average BMI similarly decreased in both cohorts, by 5% or more in 24.4% and by 10% or more in 16.5% of cases available at follow-up. After excluding 183 cases with diabetes at entry, diabetes was newly diagnosed in 48 cases during follow-up (31 (16.6% of cases without diabetes at entry) in the GBI cohort vs. 17 (9.7%) in WBI; p = 0.073). Time to diabetes was similar in the two cohorts (mean, 31 ± 18 months since enrollment). At multivariable regression analysis, incident diabetes was significantly associated with prediabetes (odds ratio (OR) 4.40; 95% confidence interval (CI) 1.97–9.81; p < 0.001), percent weight change (OR 0.57; 95% CI 0.41–0.79; p < 0.001) and higher education (OR 0.49; 95% CI 0.27–0.86; p = 0.014), with no effect of other baseline socio-demographic, behavioral and clinical data, and of the type of intervention. The importance of weight change on incident diabetes were confirmed in a sensitivity analysis limited to individuals who completed the follow-up. Conclusion: In individuals with NAFLD, WBI is as effective as GBI on the pending long-term risk of diabetes, via similar results on weight change. Full article

Compared with non-Indigenous populations, Indigenous populations experience worse health across many outcomes, including non-communicable diseases, and they are three times more likely to live in extreme poverty. The objectives were to identify (1) the content, implementation, and duration of the intervention; (2) the evaluation designs used; (3) the outcomes reported; and (4) the enablers and the challenges. Using the PRISMA-ScR guidelines, a search of research databases and grey literature was conducted. Seven studies met the inclusion criteria. Papers reported on acceptability, nutrition knowledge, fruit and vegetable intake, self-efficacy, motivation, and preference concerning fruit and vegetable, diet, and gardening. No study measured all outcomes. All papers reported on acceptability, whether implicitly or explicitly. The evaluation used mostly pre- and post-intervention assessments. The effect of gardening on nutrition and gardening knowledge and fruit and vegetable intake was inconclusive, and was related to a general lack of robust evaluations. Applying the He Pikinga Waiora Framework, however, revealed strong evidence for community engagement, cultural centeredness, integrated knowledge translation and systems thinking in increasing the acceptability and feasibility of gardening in Indigenous communities. Despite environmental challenges, the evidence signaled that gardening was an acceptable intervention for the Indigenous communities. Full article

Aging-related gut microbiota dysbiosis initiates gut inflammation and microbiota dysbiosis, which induce the occurrence of psychiatric disorders including dementia. The alleviation of gut microbiota dysbiosis by probiotics is suggested to be able to alleviate psychiatric disorders including cognitive impairment (CI). Therefore, to understand how probiotics could alleviate CI, we examined the effects of anti-inflammatory Lactobacillus gasseri NK109 and its supplement (NS, mixture of NK109 and soybean embryo ethanol extract) on cognitive function in aged (Ag), 5XFAD transgenic (Tg), or mildly cognition-impaired adult fecal microbiota (MCF)-transplanted mice. Oral administration of NK109 or NS decreased CI-like behaviors in Ag mice. Their treatments suppressed TNF-α and p16 expression and NF-κB-activated cell populations in the hippocampus and colon, while BDNF expression was induced. Moreover, they partially shifted the β-diversity of gut microbiota in Ag mice to those of young mice: they decreased Bifidobacteriaceae, Lactobacillaceae, and Helicobacteriaceae populations and increased Rikenellaceae and Prevotellaceae populations. Oral administration of NK109 or NS also reduced CI-like behaviors in Tg mice. Their treatments induced BDNF expression in the hippocampus, decreased hippocampal TNF-α and Aβ expression and hippocampal and colonic NF-κB-activated cell populations. NK109 and NS partially shifted the β-diversity of gut microbiota in Tg mice: they decreased Muribaculaceae and Rhodospiraceae populations and increased Helicobacteriaceae population. Oral administration of NK109 or NS decreased MCF transplantation-induced CI-like behaviors in mice. NK109 and NS increased hippocampal BDNF expression, while hippocampal and colonic TNF-α expression and NF-κB-activated cell populations decreased. These findings suggest that dementia can fluctuate the gut microbiota composition and NK109 and its supplement NS can alleviate CI with systemic inflammation by inducing BDNF expression and suppressing NF-κB activation and gut microbiota dysbiosis. Full article

Adequate dietary intake during the lactation period is important for breast milk components, postpartum recovery, and physical and mental health. This study aimed to clarify the psychosocial experiences related to dietary behavior around one month postpartum among Japanese lactating women. Semi-structured interviews were conducted with 18 women between February and June 2022 in Osaka, Japan. The data were analyzed using qualitative descriptive approaches. Four core categories were identified. All participants had a [desire to have healthy meals for themselves or their families] to improve their postpartum health, regain their pre-pregnancy body shape, produce sufficient and good-quality breast milk, and keep their families healthy. Some participants, who had [subjective difficulties in getting information on diet and preparing meals] due to insufficient or complicated information and viewing meal preparation as a burden, used [services and support regarding their postpartum diet] to alleviate these difficulties. They had [postpartum-specific appetite and dietary views], including an increased appetite triggered by breastfeeding and postpartum stress and the effects of the dietary changes during pregnancy. Some of these psychosocial experiences were influenced by Japanese traditional customs in the postpartum period and familiar food preferences in the Japanese. Healthcare professionals should consider these experiences when providing tailored dietary guidance. Full article

Methyl cedryl ether (MCE) is a derivative of cedrol and is widely used as a fragrance compound. The aim of this study was to evaluate the preventative effects of MCE on obesity and related metabolic syndromes and to delineate the mechanisms from the perspective of gut microbiota and white adipose tissues (WAT) transcriptomic profiles. Five-week-old male C57BL/6J mice were randomly assigned into 3 groups and fed with chow diet, high-fat diet (HFD), or HFD supplemented with 0.2% (w/w) MCE for 13 weeks. We found that MCE significantly reduced body weight, inhibited adipocyte hypertrophy, and ameliorated hepatic steatosis under HFD conditions. MCE dietary supplementation downregulated the expression of adipogenesis genes (FAS and C/EBPα) and upregulated the mRNA levels of thermogenesis genes (PGC-1α, PRDM16, UCP1, Cidea, Cytc, and COX4) in epididymal WAT. 16S rRNA sequencing revealed that MCE improved gut microbiota dysbiosis in HFD-fed mice, as manifested by the alteration of strains associated with obesity. Further transcriptome analysis of WAT indicated that MCE dramatically changed the gene expression profiles. Our results demonstrate the anti-obesity effect of MCE under HFD conditions, highlighting the nutraceutical potential of MCE for preventing obesity. Full article

Conventional dietary assessment methods are based predominately on Western models which lack Aboriginal and Torres Strait Islander knowledges, methodologies, and social and cultural contextualisation. This review considered dietary assessment methods used with Aboriginal and Torres Strait Islander populations and assessed their applicability. Four electronic databases and grey literature were searched with no time limit applied to the results. Screening, data extraction and quality appraisal were undertaken independently by two reviewers. Out of 22 studies, 20 were conducted in rural/remote settings, one in an urban setting, and one at the national population level. The most frequently used and applicable dietary assessment method involved store data. Weighed food records and food frequency questionnaires had low applicability. Modifications of conventional methods were commonly used to adapt to Indigenous practices, but few studies incorporated Indigenous research methodologies such as yarning. This highlights an opportunity for further investigation to validate the accuracy of methods that incorporate qualitative yarning-based approaches, or other Indigenous research methodologies, into quantitative data collection. The importance of developing validated dietary assessment methods that are appropriate for this population cannot be understated considering the high susceptibility to nutrition-related health conditions such as malnutrition, overweight or obesity, diabetes, and cardiovascular disease. Full article

This study aimed to investigate the association between the plant-based diet index (PDI) score and T2D risk among residents of Shanxi Province, China, and explore whether the association was influenced by different levels of cardiovascular risk. A total of 50,694 participants aged 35–75 years were recruited between 2017 and 2019, and they were further divided into the high cardiovascular risk population (HCRP; n = 17,255) and the non-high cardiovascular risk population (non-HCRP; n = 33,439). The PDI was calculated based on food frequency from a food frequency questionnaire (FFQ). Incident T2D was defined based on elevated plasma glucose (≥7 mmol/L) or hypoglycemic medicine use. We investigated the association of the PDI andT2D risk using a two-level generalized estimating equation and restricted cubic splines model. The results showed that quartile 4 of the PDI indicated significantly reduced T2D risk in the total population (OR: 0.83; 95% CI: 0.75–0.92), HCRP (OR: 0.80; 95% CI: 0.71–0.91), and non-HCRP (OR: 0.80; 95% CI: 0.74–0.87) compared with corresponding quartile 1 (OR = 1). In stratified analysis, the negative associations between PDI and T2D risk were stronger in the total population with the elderly (age > 60 years), BMI < 24, and men, and in the non-HCRP with men and BMI 24–28, and in the HCRP with the elderly and BMI < 24 than those with corresponding subgroups (p_interaction < 0.05). Linear curves were observed for the total population and non-HCRP, but an L-shaped association was observed for the HCRP. Therefore, our results suggest that higher PDI scores may effectively attenuate the T2D risk in the Chinese population and non-HCRP, and a beneficial association of PDI with T2D risk was observed in the HCRP at a certain threshold level. Longitudinal studies and intervention trials are required to validate our study findings. Full article

Background: Studies on the association between solute, nutrition and fluid intakes and mortality and later kidney function in critically ill acute kidney injury (AKI) patients receiving continuous veno-venous hemodialysis (CVVHD) are scarce. Methods: Altogether, 471 consecutive critically ill AKI patients receiving CVVHD in the research intensive care unit (ICU) were recruited in this single-center, retrospective study. Results: The median age was 66 (58–74) years, and 138 (29.3%) were female. The 90-day and one-year mortalities were 221 (46.9%) and 251 (53.3%), respectively. After adjusting for age, sex, Acute Physiology and Chronic Health Evaluation II (APACHE) score, coronary artery disease, immunosuppression, ICU care duration, mechanical ventilation requirement, vasopressor requirement and study time period, the cumulative daily intake of potassium, chloride, sodium, phosphate, calcium, glucose, lipids and water was associated with one-year mortality in separate multivariable cox proportional hazards models. In a sensitivity analysis excluding patients who died within the first three days of ICU care, the daily intake of chloride (hazard ratio (HR) 1.001, confidence interval (CI) 95% 1.000–1.003, p = 0.032), sodium (HR 1.001, CI 95% 1.000–1.002, p = 0.031) and calcium (HR 1.129, CI 95% 1.025–1.243, p = 0.014) remained independently associated with mortality within one-year in the respective, similarly adjusted multivariable cox analyses. The cumulative daily intake of chloride, sodium, calcium and water was independently associated with the estimated glomerular filtration rate (eGFR) at 90 days follow-up in separate substantially adjusted multivariable cox proportional hazards models. Conclusion: The cumulative daily intake of chloride, sodium and calcium is associated with mortality and daily chloride, sodium, calcium and water intake is associated with follow-up eGFR in critically ill patients with CVVHD-treated AKI. Full article

This study tested the hypothesis that the increases in salivary and plasma [NO₂⁻] after dietary NO₃⁻ supplementation would be greater when oral temperature and pH were independently elevated, and increased further when oral temperature and pH were elevated concurrently. Seven healthy males (mean ± SD, age 23 ± 4 years) ingested 70 mL of beetroot juice concentrate (BR, which provided ~6.2 mmol NO₃⁻) during six separate laboratory visits. In a randomised crossover experimental design, salivary and plasma [NO₃⁻] and [NO₂⁻] were assessed at a neutral oral pH with a low (T_Lo-pH_Norm), intermediate (T_Mid-pH_Norm), and high (T_Hi-pH_Norm) oral temperature, and when the oral pH was increased at a low (T_Lo-pH_Hi), intermediate (T_Mid-pH_Hi), and high (T_Hi-pH_Hi) oral temperature. Compared with the T_Mid-pH_Norm condition (976 ± 388 µM), the mean salivary [NO₂⁻] 1–3 h post BR ingestion was higher in the T_Mid-pH_Hi (1855 ± 423 µM), T_Hi-pH_Norm (1371 ± 653 µM), T_Hi-pH_Hi (1792 ± 741 µM), T_Lo-pH_Norm (1495 ± 502 µM), and T_Lo-pH_Hi (2013 ± 662 µM) conditions, with salivary [NO₂⁻] also higher at a given oral temperature when the oral pH was increased (p < 0.05). Plasma [NO₂⁻] was higher 3 h post BR ingestion in the T_Mid-pH_Hi, T_Hi-pH_Hi, and T_Lo-pH_Hi conditions, but not the T_Lo-pH_Norm and T_Hi-pH_Norm conditions, compared with T_Mid-pH_Norm (p < 0.05). Therefore, despite ingesting the same NO₃⁻ dose, the increases in salivary [NO₂⁻] varied depending on the temperature and pH of the oral cavity, while the plasma [NO₂⁻] increased independently of oral temperature, but to a greater extent at a higher oral pH. Full article

Plants are an indispensable cornerstone of sustainable global food supply. While immense progress has been made in decoding the genomes of crops in recent decades, the composition of their proteomes, the entirety of all expressed proteins of a species, is virtually unknown. In contrast to the model plant Arabidopsis thaliana, proteomic analyses of crop plants have often been hindered by the presence of extreme concentrations of secondary metabolites such as pigments, phenolic compounds, lipids, carbohydrates or terpenes. As a consequence, crop proteomic experiments have, thus far, required individually optimized protein extraction protocols to obtain samples of acceptable quality for downstream analysis by liquid chromatography tandem mass spectrometry (LC-MS/MS). In this article, we present a universal protein extraction protocol originally developed for gel-based experiments and combined it with an automated single-pot solid-phase-enhanced sample preparation (SP3) protocol on a liquid handling robot to prepare high-quality samples for proteomic analysis of crop plants. We also report an automated offline peptide separation protocol and optimized micro-LC-MS/MS conditions that enables the identification and quantification of ~10,000 proteins from plant tissue within 6 h of instrument time. We illustrate the utility of the workflow by analyzing the proteomes of mature tomato fruits to an unprecedented depth. The data demonstrate the robustness of the approach which we propose for use in upcoming large-scale projects that aim to map crop tissue proteomes. Full article

The dysbiosis of intestinal microbiota and their metabolites is linked to the occurrence and development of metabolic syndrome. Although fructose has been proven to be associated with worsened mucus in the colon, its mechanism remains unclear. In this study, we evaluated the relatively low intake of sucrose and fructose in the experimental colitis of Sprague Dawley rats by investigating the microbiome and metabolome. Results showed that sucrose and fructose significantly reduced body weight, colon length and increased inflammation infiltration in colon. Sucrose and fructose worsen colon functions by inhibiting the expression of tight junction (TJ) protein ZO-1 and increasing the level of lipopolysaccharide neoandrographolide (LPS) in plasma, while fructose was more significant. Furthermore, sucrose and fructose significantly changed the composition of gut microbiota characterized by decreasing Adlercreutzia, Leuconostoc, Lactococcus and Oscillospira and increasing Allobaculum and Holdemania along with reducing histidine, phenylalanine, arginine, glycine, aspartic acid, serine, methionine valine, alanine, lysine, isoleucine, leucine, threonine, tryptophan, tyrosine, proline, citrulline, 4-hydroxyproline and gamma amino butyric acid (GABA). Metabolome results showed that fructose may aggravate experimental colitis symptoms by inducing amino metabolism dysbiosis in the colon. These findings suggested that fructose worsened colitis by manipulating the crosstalk between gut microbiota and their metabolites. Full article

Measures of cardiovascular health (CVH) assessed by a combination of behavioral and biological factors has shown protective associations with all-cause mortality. The mechanisms underlying these associations have not been fully elucidated. In this study, we characterized the plasma proteomics profile of CVH and tested whether specific proteins mediated the associations between CVH and all-cause mortality in participants of the InCHIANTI study. Of the 1301 proteins tested, 92 proteins were associated with CVH (22 positively, 70 negatively). Proteins most strongly associated with CVH included leptin (LEP), fatty acid binding protein 3 (FABP3), Angiopoietin-2 (ANGPT2), and growth-differential factor 15 (GDF15). Of the 92 CVH-associated proteins, 33 proteins significantly mediated the associations between CVH and all-cause mortality, with percent mediation ranging from 5 to 30%. The most significant mediating proteins were GDF15 and insulin-like growth factor 2 (IGFBP2). Proteins associated with better CVH were enriched for proteins that reflect the suppression of the complement coagulation and GH/IGF pathways. Full article