IL-33 Reduces Saturated Fatty Acid Accumulation in Mouse Atherosclerotic Foci

Rheumatology

Objectives Platelets and low-density neutrophils (LDNs) are major players in the immunopathogenesis of SLE. Despite evidence showing the importance of platelet–neutrophil complexes (PNCs) in inflammation, little is known about the relationship between LDNs and platelets in SLE. We sought to characterize the role of LDNs and Toll-like receptor 7 (TLR7) in clinical disease. Methods Flow cytometry was used to immunophenotype LDNs from SLE patients and controls. The association of LDNs with organ damage was investigated in a cohort of 290 SLE patients. TLR7 mRNA expression was assessed in LDNs and high-density neutrophils (HDNs) using publicly available mRNA sequencing datasets and our own cohort using RT-PCR. The role of TLR7 in platelet binding was evaluated in platelet–HDN mixing studies using TLR7-deficient mice and Klinefelter syndrome …

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by inflammation in multiple organs. A few treatments for SLE currently exist, including antimalarials, glucocorticoids, immunosuppressants, and two recently approved antibody agents; however, an unmet medical need remains for SLE. In addition, developing new drugs targeting SLE is a challenge since no specific biomarkers exist for the prediction of disease progression or drug response. A new drug candidate, E6742, is a specific antagonist of the toll-like receptors 7/8. To address the challenges for drug development in SLE, the process of developing E6742 utilizes a unique system of the Japan Agency for Medical Research and Development (AMED), the Cyclic Innovation for Clinical Empowerment (CiCLE) program. In the CiCLE program, a Phase 1 study in healthy adults was completed (NCT04683185) and a Phase 1/2 study in …

Nutrients

The cellular and molecular mechanisms of atherosclerosis are still unclear. Type 2 innate lymphocytes (ILC2) exhibit anti-inflammatory properties and protect against atherosclerosis. This study aimed to elucidate the pathogenesis of atherosclerosis development using atherosclerosis model mice (ApoE KO mice) and mice deficient in IL-33 receptor ST2 (ApoEST2 DKO mice). Sixteen-week-old male ApoE KO and ApoEST2 DKO mice were subjected to an 8-week regimen of a high-fat, high-sucrose diet. Atherosclerotic foci were assessed histologically at the aortic valve ring. Chronic inflammation was assessed using flow cytometry and real-time polymerase chain reaction. In addition, saturated fatty acids (palmitic acid) and IL-33 were administered to human aortic endothelial cells (HAECs) to assess fatty acid metabolism. ApoEST2 DKO mice with attenuated ILC2 had significantly worse atherosclerosis than ApoE KO mice. The levels of saturated fatty acids, including palmitic acid, were significantly elevated in the arteries and serum of ApoEST2 DKO mice. Furthermore, on treating HAECs with saturated fatty acids with or without IL-33, the Oil Red O staining area significantly decreased in the IL-33-treated group compared to that in the non-treated group. IL-33 potentially prevented the accumulation of saturated fatty acids within atherosclerotic foci.

medRxiv

Objectives To evaluate the safety, tolerability, pharmacokinetics (PK), biomarker response, and efficacy of E6742 in a phase 1/2 study in patients with systemic lupus erythematosus (SLE). Methods Two sequential cohorts of SLE patients were enrolled and randomized to 12 weeks of twice-daily treatment with E6742 (100 or 200 mg; n = 8 or 9) or placebo (n = 9). Results The proportion of patients with any treatment-emergent adverse events (TEAEs) was 58.8% in the E6742 group (37.5% for 100 mg; 77.8% for 200 mg) and 66.7% in the placebo group. No Common Terminology Criteria for Adverse Events ≥ Grade 3 TEAEs occurred. PK parameter levels were similar between SLE patients and healthy adults in previous phase 1 studies. The interferon gene signature (IGS) and levels of proinflammatory cytokines (interleukin-1β, interleukin-6, tumor necrosis factor-α) after ex-vivo challenge with a Toll-like receptor 7/8 agonist were immediately decreased by E6742 treatment. Dose-dependent improvements in the British Isles Lupus Assessment Group-based Composite Lupus Assessment response were observed at Week 12 in the E6742 (37.5% for 100 mg; 57.1% for 200 mg) and placebo (33.3%) groups. E6742 also had therapeutic effects on other symptoms, including skin inflammation, arthritis, and levels of anti-double-stranded DNA antibodies and complements. Conclusions E6742 had a favorable safety profile and was well tolerated, with marked IGS responses and sufficient efficacy signals in patients with SLE. These results provide the first clinical evidence to support E6742 in the treatment of SLE, and support larger, longer-term clinical trials.

International Immunology

Transforming growth factor-β-activated kinase 1 (TAK1) plays a pivotal role in innate and adaptive immunity. TAK1 is essential for the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB pathways downstream of diverse immune receptors, including Toll-like receptors (TLRs). Upon stimulation with TLR ligands, TAK1 is activated via recruitment to lysine 63-linked polyubiquitin chain through TAK1-binding proteins (TAB) 2 and TAB3. However, the physiological importance of TAB2 and TAB3 in macrophages is still controversial. A previous study has shown that mouse bone marrow-derived macrophages (BMDMs) isolated from mice double deficient for TAB2 and TAB3 produced tumor necrosis factor (TNF)-α and interleukin (IL)-6 to the similar levels as control wild-type BMDMs in response to TLR ligands such as lipopolysaccharide (LPS) or Pam3CSK4, indicating that TAB2 and …

Nature

The immune system has a critical role in orchestrating tissue healing. As a result, regenerative strategies that control immune components have proved effective 1, 2. This is particularly relevant when immune dysregulation that results from conditions such as diabetes or advanced age impairs tissue healing following injury 2, 3. Nociceptive sensory neurons have a crucial role as immunoregulators and exert both protective and harmful effects depending on the context 4, 5, 6, 7, 8, 9, 10, 11, 12. However, how neuro–immune interactions affect tissue repair and regeneration following acute injury is unclear. Here we show that ablation of the Na V 1.8 nociceptor impairs skin wound repair and muscle regeneration after acute tissue injury. Nociceptor endings grow into injured skin and muscle tissues and signal to immune cells through the neuropeptide calcitonin gene-related peptide (CGRP) during the healing process …

Journal of Experimental & Clinical Cancer Research

BackgroundPancreatitis is known to be an important risk factor for pancreatic ductal adenocarcinoma (PDAC). However, the exact molecular mechanisms of how inflammation promotes PDAC are still not fully understood. Regnase-1, an endoribonuclease, regulates immune responses by degrading mRNAs of inflammation-related genes. Herein, we investigated the role of Regnase-1 in PDAC.MethodsClinical significance of intratumor Regnase-1 expression was evaluated by immunohistochemistry in 39 surgically-resected PDAC patients. The functional role of Regnase-1 was investigated by pancreas-specific Regnase-1 knockout mice and Kras-mutant Regnase-1 knockout mice. The mechanistic studies with gene silencing, RNA immunoprecipitation sequencing (RIP-seq) and immune cell reconstitution were performed in human/mouse PDAC cell lines and a syngeneic orthotopic tumor transplantation model of …

Cardiovascular Research

Aims Microsomal prostaglandin E synthase-1 (mPGES-1)/prostaglandin E2 (PGE2) induces angiogenesis through the prostaglandin E2 receptor (EP1–4). Among immune cells, regulatory T cells (Tregs), which inhibit immune responses, have been implicated in angiogenesis, and PGE2 is known to modulate the function and differentiation of Tregs. We hypothesized that mPGES-1/PGE2-EP signalling could contribute to recovery from ischaemic conditions by promoting the accumulation of Tregs. Methods and results Wild-type (WT), mPGES-1-deficient (mPges-1−/−), and EP4 receptor-deficient (Ep4−/−) male mice, 6–8 weeks old, were used. Hindlimb ischaemia was induced by femoral artery ligation. Recovery from ischaemia was suppressed in mPges-1−/− mice and compared with WT mice. The number of accumulated forkhead box protein P3 (FoxP3)+ cells in ischaemic …

Immunity

Lung infection during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via the angiotensin-I-converting enzyme 2 (ACE2) receptor induces a cytokine storm. However, the precise mechanisms involved in severe COVID-19 pneumonia are unknown. Here, we showed that interleukin-10 (IL-10) induced the expression of ACE2 in normal alveolar macrophages, causing them to become vectors for SARS-CoV-2. The inhibition of this system in hamster models attenuated SARS-CoV-2 pathogenicity. Genome-wide association and quantitative trait locus analyses identified a IFNAR2-IL10RB readthrough transcript, COVID-19 infectivity-enhancing dual receptor (CiDRE), which was highly expressed in patients harboring COVID-19 risk variants at the IFNAR2 locus. We showed that CiDRE exerted synergistic effects via the IL-10-ACE2 axis in alveolar macrophages and functioned as a decoy receptor for type I …

Journal of Clinical Microbiology

Because nontuberculous mycobacterial pulmonary disease is a considerable health burden, a simple and clinically applicable analytical protocol enabling the identification of subspecies and drug-resistant disease is required to determine the treatment strategy. We aimed to develop a simplified workflow consisting only of direct sequencing of mycobacterial growth indicator tube cultures (MGIT-seq). In total, 138 patients were prospectively enrolled between April 2021 and May 2022, and culture-positive MGIT broths were subjected to sequencing using MinION, a portable next-generation sequencer. Sequence analysis was conducted to identify species using core genome multilocus sequence typing and to predict macrolide and amikacin (AMK) resistance based on previously reported mutations in rrl, rrs, and erm(41). The results were compared to clinical tests for species identification and drug susceptibility. A …

Journal of Experimental Medicine

Loss-of-function mutations in the lysosomal nucleoside transporter SLC29A3 cause lysosomal nucleoside storage and histiocytosis: phagocyte accumulation in multiple organs. However, little is known about the mechanism by which lysosomal nucleoside storage drives histiocytosis. Herein, histiocytosis in Slc29a3−/− mice was shown to depend on Toll-like receptor 7 (TLR7), which senses a combination of nucleosides and oligoribonucleotides (ORNs). TLR7 increased phagocyte numbers by driving the proliferation of Ly6Chi immature monocytes and their maturation into Ly6Clow phagocytes in Slc29a3−/− mice. Downstream of TLR7, FcRγ and DAP10 were required for monocyte proliferation. Histiocytosis is accompanied by inflammation in SLC29A3 disorders. However, TLR7 in nucleoside-laden splenic monocytes failed to activate inflammatory responses. Enhanced production of proinflammatory cytokines was …

International Immunopharmacology

Alcaligenes faecalis was previously identified as an intestinal lymphoid tissue-resident commensal bacteria, and our subsequent studies showed that lipopolysaccharide and its core active element (i.e., lipid A) have a potent adjuvant activity to promote preferentially antigen-specific Th17 response and antibody production. Here, we compared A. faecalis lipid A (ALA) with monophosphoryl lipid A, a licensed lipid A–based adjuvant, to elucidate the immunological mechanism underlying the adjuvant properties of ALA. Compared with monophosphoryl lipid A, ALA induced higher levels of MHC class II molecules and costimulatory CD40, CD80, and CD86 on dendritic cells (DCs), which in turn resulted in strong T cell activation. Moreover, ALA more effectively promoted the production of IL-6 and IL-23 from DCs than did monophosphoryl lipid A, thus leading to preferential induction of Th17 and Th1 cells. As underlying …

The EMBO Journal

Tight regulation of Toll‐like receptor (TLR)‐mediated inflammatory responses is important for innate immunity. Here, we show that T‐cell death‐associated gene 51 (TDAG51/PHLDA1) is a novel regulator of the transcription factor FoxO1, regulating inflammatory mediator production in the lipopolysaccharide (LPS)‐induced inflammatory response. TDAG51 induction by LPS stimulation was mediated by the TLR2/4 signaling pathway in bone marrow‐derived macrophages (BMMs). LPS‐induced inflammatory mediator production was significantly decreased in TDAG51‐deficient BMMs. In TDAG51‐deficient mice, LPS‐ or pathogenic Escherichia coli infection‐induced lethal shock was reduced by decreasing serum proinflammatory cytokine levels. The recruitment of 14‐3‐3ζ to FoxO1 was competitively inhibited by the TDAG51‐FoxO1 interaction, leading to blockade of FoxO1 cytoplasmic translocation and thereby …

Periodontitis, which is induced by repeated bacterial invasion and the ensuing immune reactions that follow, is the leading cause of tooth loss. However, studies on immune responses are usually based on gingival tissue, although periodontal tissue is actually comprised of four different components. Here, we have developed a novel model to analyze the pathogenesis of periodontitis with different periodontal tissue components. We have found that the inflammatory response in the peri-root tissues and the expression of interleukin (IL)-6 and nuclear factor κ-Β ligand (RANKL) by Thy-1.2–fibroblasts/stromal cells were prominent during the course of bone destruction. Furthermore, a comprehensive analysis of the initiation phase confirmed these findings while revealing a high level of expression of ST2 (also known as IL33R and encoded by Il1rl1) in the peri-root tissue. Il1rl1 and Il33 deficient mice exhibited exacerbated bone loss in the acute phase of periodontitis, demonstrating the protective role of the IL-33/ST2 axis in acute inflammation. Thus, the findings obtained with this novel model show the crucial role of the peri-root tissue and advance our understanding of the etiology of periodontitis.

Genes to Cells

The RNA‐binding protein (RBP) Regnase‐1 is an endonuclease that regulates immune responses by modulating target mRNA stability. Regnase‐1 degrades a group of inflammation‐associated mRNAs, which contributes to a balanced immune response and helps prevent autoimmune diseases. Regnase‐1 also cleaves its own mRNA by binding stem‐loop (SL) RNA structures in its 3′UTR. To understand how this autoregulation is important for immune responses, we generated mice with a 2‐bp genome deletion in the target SL of the Regnase‐1 3′‐untranslated region (3′UTR). Deletion of these nucleotides inhibited SL formation and limited Regnase‐1‐mediated mRNA degradation. Mutant mice had normal hematopoietic cell differentiation. Biochemically, mutation of the 3′UTR SL increased Regnase‐1 mRNA stability and enhanced both Regnase‐1 mRNA and protein levels in mouse embryonic …

The EMBO Journal

Mitochondrial DNA (mtDNA) leakage into the cytoplasm can occur when cells are exposed to noxious stimuli. Specific sensors recognize cytoplasmic mtDNA to promote cytokine production. Cytoplasmic mtDNA can also be secreted extracellularly, leading to sterile inflammation. However, the mode of secretion of mtDNA out of cells upon noxious stimuli and its relevance to human disease remain unclear. Here, we show that pyroptotic cells secrete mtDNA encapsulated within exosomes. Activation of caspase‐1 leads to mtDNA leakage from the mitochondria into the cytoplasm via gasdermin‐D. Caspase‐1 also induces intraluminal membrane vesicle formation, allowing for cellular mtDNA to be taken up and secreted as exosomes. Encapsulation of mtDNA within exosomes promotes a strong inflammatory response that is ameliorated upon exosome biosynthesis inhibition in vivo. We further show that monocytes …

Hepatology

Conclusions:Our study identified that IL‐33 is pro‐regenerative in a noninjurious model of liver resection. The underlying mechanism involved IL‐33/ST2‐induced increase of serotonin release from enterochromaffin cells to portal blood and subsequent HTR2A/p70S6K activation in hepatocytes by serotonin. The findings implicate the potential of targeting the IL‐33/ST2/serotonin pathway to reduce the risk of post‐hepatectomy liver failure and small‐for‐size syndrome.

Journal of Investigative Dermatology

The relationship between chronic inflammation and carcinogenesis has been controversial, despite known clinical evidence such as development of squamous cell carcinoma (SCC) from chronic skin ulcer. We previously demonstrated that a ribonuclease Regnase-1 (Reg1) in keratinocytes, played a down-modulator of skin inflammation in a cross-regulatory fashion with proinflammatory signals. Here, we addressed whether Reg1 had a protective role in skin carcinogenesis. The two-stage carcinogenesis protocol allowed keratinocyte-specific Reg1 KO mice (K5. Cre+ Reg1 fl/fl: Reg1-cKO) mice developed 10 or more papillomas and several SCCs per head, while almost no tumor emerged in controls (Reg1 fl/fl). By repeated exposure to ultraviolet B irradiation, Reg1-cKO mice showed marked acanthosis and atypical epidermis resembling solar keratosis at much earlier timing compared with controls. These data …

Infection of the lungs with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via the angiotensin I converting enzyme 2 (ACE2) receptor induces a type of systemic inflammation known as a cytokine storm. However, the precise mechanisms involved in severe coronavirus disease 2019 (COVID-19) pneumonia are unknown. Here, we show that interleukin-10 (IL-10) changed normal alveolar macrophages into ACE2-expressing M2c-type macrophages that functioned as spreading vectors for SARS-CoV-2 infection. The depletion of alveolar macrophages and blockade of IL-10 attenuated SARS-CoV-2 pathogenicity. Furthermore, genome-wide association and quantitative trait locus analyses identified novel mRNA transcripts in human patients, COVID-19 infectivity enhancing dual receptor (CiDRE), which has unique synergistic effects within the IL-10-ACE2 system in M2c-type macrophages. Our results demonstrate that alveolar macrophages stimulated by IL-10 are key players in severe COVID-19. Collectively, CiDRE expression levels are potential risk factors that predict COVID-19 severity, and CiDRE inhibitors might be useful as COVID-19 therapies.

Nutrients

Our study harnesses the power of natural language processing (NLP) to explore the relationship between dietary patterns and metabolic health outcomes among Korean adults using data from the Seventh Korea National Health and Nutrition Examination Survey (KNHANES VII). Using Latent Dirichlet Allocation (LDA) analysis, we identified three distinct dietary patterns: “Traditional and Staple”, “Communal and Festive”, and “Westernized and Convenience-Oriented”. These patterns reflect the diversity of dietary preferences in Korea and reveal the cultural and social dimensions influencing eating habits and their potential implications for public health, particularly concerning obesity and metabolic disorders. Integrating NLP-based indices, including sentiment scores and the identified dietary patterns, into our predictive models significantly enhanced the accuracy of obesity and dyslipidemia predictions. This improvement was consistent across various machine learning techniques—XGBoost, LightGBM, and CatBoost—demonstrating the efficacy of NLP methodologies in refining disease prediction models. Our findings underscore the critical role of dietary patterns as indicators of metabolic diseases. The successful application of NLP techniques offers a novel approach to public health and nutritional epidemiology, providing a deeper understanding of the diet–disease nexus. This study contributes to the evolving field of personalized nutrition and emphasizes the potential of leveraging advanced computational tools to inform targeted nutritional interventions and public health strategies aimed at mitigating the prevalence of metabolic disorders in the …

Nutrients

The programme aimed to improve selected cardiometabolic risk (CMR) variables using a nutritional intervention among farmers who reported hypertensive disorders as hindrances during agricultural activities. The intervention had two case controls (n = 103) [experimental group-EG (n = 53) and control group-CG (n = 50)] which were tracked and whose blood pressure measurements, dietary intake, blood indices for cholesterol concentration and glucose levels from pre- and post-intervention surveys after the baseline survey (n = 112) were analysed. The interval for data collection was 12 weeks (±120 days) after five legume varieties were consumed between 3 and 5 times a day, and servings were not <125 g per at least three times per week. Sixty-five per cent of farmers were above 60 years old, with mean age ranges of 63.3 (SD ± 6.3) years for women and 67.2 (SD ± 6.7) for men. The post-intervention survey revealed that EG blood results indicated nutrient improvement with p <= 0.05 for blood glucose (p = 0.003) and cholesterol (p = 0.001) as opposed to the CG. A trend analysis revealed that cholesterol (p = 0.033) and systolic blood pressure (SBP); (p = 0.013) were statistically significant when comparing genders for all study phases. Interventions focusing on legumes can improve hypertension and cardiovascular disease and fast-track the achievement of SGDs 3 and 12 through community-based programmes.

Nutrients

Background Alzheimer’s disease (AD) and Parkinson’s disease (PD) are multifactorial neurodegenerative disorders that are mostly treated with drugs inhibiting key enzymes of cholinergic and aminergic neurotransmission, such as acetyl and butyryl cholinesterase (AChE, BuChE) or monoamine oxidases (MAO)-A/B, and of Aβ 1–40 aggregation. Diet plant components with multitarget functions are promising compounds in the prevention of AD and PD. Our aim was to identify neuroprotective compounds from Annurca apple polyphenol extract (AFPE). Methods AFPE was fractionated by gel filtration, and the eluted peaks were subjected to chemical analyses (i.e., RP-HPLC and mass spectrometry), determination of inhibitory enzyme activity and cell effects by MTT, and morphology assays. Results In AFPE, we identified thaumatin-like protein 1a, belonging to the pathogenesis-related protein (PR) family. This protein showed the best inhibitory activity on AChE, MAO-A (IC50 = 5.53 µM and 1.71 µM, respectively), and Aβ 1–40 fibril aggregation (IC50 = 9.16 µM), compared to AFPE and other polyphenol-containing fractions. Among the latter, Peak 4 reverted Aβ fibril formation (IC50 = 104.87 µM). Moreover, thaumatin-like protein 1a protected AGS and MKN-28 cells from serum-deprivation-induced stress conditions. Conclusions We showed that AFPE exerted neuroprotective functions not only through its polyphenols but also through thaumatin-like protein 1a, which acted like a multitarget molecule.

Nutrients

There is a growing interest in studies involving carbohydrate (CHO) manipulation and subsequent adaptations to endurance training. This study aimed to analyze whether a periodized carbohydrate feeding strategy based on a daily training session has any advantages compared to a high-carbohydrate diet in well-trained cyclists. Seventeen trained cyclists (VO2peak = 70.8 ± 6.5 mL·kg−1·min−1) were divided into two groups, a periodized (PCHO) group and a high-carbohydrate (HCHO) group. Both groups performed the same training sessions for five weeks. In the PCHO group, 13 training sessions were performed with low carbohydrate availability. In the HCHO group, all sessions were completed following previous carbohydrate intake to ensure high pre-exercise glycogen levels. In both groups, there was an increase in the maximal lactate steady state (MLSS) (PCHO: 244.1 ± 29.9 W to 253.2 ± 28.4 W; p = 0.008; HCHO: 235.8 ± 21.4 W to 246.9 ± 16.7 W; p = 0.012) but not in the time to exhaustion at MLSS intensity. Both groups increased the percentage of muscle mass (PCHO: p = 0.021; HCHO: p = 0.042) and decreased the percent body fat (PCHO: p = 0.021; HCHO: p = 0.012). We found no differences in carbohydrate or lipid oxidation, heart rate, and post-exercise lactate concentration. Periodizing the CHO intake in well-trained cyclists during a 5-week intervention did not elicit superior results to an energy intake-matched high-carbohydrate diet in any of the measured outcomes.

Nutrients

Unhealthy dietary habits play a key role in the pathogenesis of nephrolithiasis (NL). The aims of this case–control study were to evaluate (i) the adherence to the Mediterranean Diet (MD) and the dietary salt intake in stone-forming patients (SF), (ii) the relationship occurring between MD adherence, salt intake and NL-related metabolic risk factors in SF, and (iii) the impact of combined high MD adherence and low salt intake on NL susceptibility. From 1 January 2018 to 31 December 2019, we recruited all SF consecutively referred to the Extracorporeal Shock Wave Lithotripsy (ESWL) center of Federico II University, and at least two control subjects without a personal history of NL, age-, sex-, and body mass index-matched to SF (NSF). All study participants were interviewed using the validated MEDI-LITE and MINISAL questionnaires. In an SF subgroup, the NL-related metabolic risk factors were also evaluated. SF showed a lower MD adherence and a higher salt intake compared with NSF. The NL susceptibility decreased by 36% [OR: 0.64 (0.59–0.70); p < 0.01] for each point of increase in MEDI-LITE score, while it increased by 13% [OR: 1.13 (1.03–1.25); p = 0.01] for each point of increase in MINISAL score. The SF prevalence was higher among subjects showing combined low MD adherence and high salt intake. In SF, the MEDI-LITE score directly correlated with 24 h-citraturia, whereas the MINISAL score directly correlated with urinary sodium and uric acid excretion. In conclusion, high MD adherence and low salt intake are associated with a reduced NL susceptibility, both separately and in combination.

Nutrients

The cellular and molecular mechanisms of atherosclerosis are still unclear. Type 2 innate lymphocytes (ILC2) exhibit anti-inflammatory properties and protect against atherosclerosis. This study aimed to elucidate the pathogenesis of atherosclerosis development using atherosclerosis model mice (ApoE KO mice) and mice deficient in IL-33 receptor ST2 (ApoEST2 DKO mice). Sixteen-week-old male ApoE KO and ApoEST2 DKO mice were subjected to an 8-week regimen of a high-fat, high-sucrose diet. Atherosclerotic foci were assessed histologically at the aortic valve ring. Chronic inflammation was assessed using flow cytometry and real-time polymerase chain reaction. In addition, saturated fatty acids (palmitic acid) and IL-33 were administered to human aortic endothelial cells (HAECs) to assess fatty acid metabolism. ApoEST2 DKO mice with attenuated ILC2 had significantly worse atherosclerosis than ApoE KO mice. The levels of saturated fatty acids, including palmitic acid, were significantly elevated in the arteries and serum of ApoEST2 DKO mice. Furthermore, on treating HAECs with saturated fatty acids with or without IL-33, the Oil Red O staining area significantly decreased in the IL-33-treated group compared to that in the non-treated group. IL-33 potentially prevented the accumulation of saturated fatty acids within atherosclerotic foci.

Nutrients

(1) Background: The elderly suffer from functional constipation (FC), whose causes are not fully known, but nutritional factors may play a role. The aim of the present study was to assess the effect of a low FODMAP diet supplemented with L-tryptophan (TRP) on its metabolism and symptoms of functional constipation in elderly patients. (2) Methods: This study included 40 people without abdominal complaints (Group I, controls) and 60 patients with FC, diagnosed according to the Rome IV Criteria (Group II). Two groups were randomly selected: Group IIA (n = 30) was qualified for administration of the low FODMAP diet, and the diet of patients of Group IIB (n = 30) was supplemented with 1000 mg TRP per day. The severity of abdominal symptoms was assessed with an abdominal pain index ranging from 1 to 7 points (S-score). The concentration of TRP and its metabolites, 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), and 3-indoxyl sulfate (3-IS) in urine were determined using the LC-MS/MS method. (3) Results: In Group II, 5-HIAA concentration in urine was lower, and KYN and 3-IS concentrations were higher than in the control group. A negative correlation was found between the S-score and urinary concentration of 5-HIAA (p < 0.001), and 3-IS concentration was positively correlated with the S-score. However, the correlation between the S-score and 3-IS concentration was negative (p < 0.01). After a dietary intervention, 5-HIAA concentration increased in both groups, and the severity of symptoms decreased, but the decrease was more pronounced in Group IIB. (4) Conclusion: A low FODMAP diet supplemented with L-tryptophan has …

Nutrients

The programme aimed to improve selected cardiometabolic risk (CMR) variables using a nutritional intervention among farmers who reported hypertensive disorders as hindrances during agricultural activities. The intervention had two case controls (n = 103) [experimental group-EG (n = 53) and control group-CG (n = 50)] which were tracked and whose blood pressure measurements, dietary intake, blood indices for cholesterol concentration and glucose levels from pre- and post-intervention surveys after the baseline survey (n = 112) were analysed. The interval for data collection was 12 weeks (±120 days) after five legume varieties were consumed between 3 and 5 times a day, and servings were not <125 g per at least three times per week. Sixty-five per cent of farmers were above 60 years old, with mean age ranges of 63.3 (SD ± 6.3) years for women and 67.2 (SD ± 6.7) for men. The post-intervention survey revealed that EG blood results indicated nutrient improvement with p <= 0.05 for blood glucose (p = 0.003) and cholesterol (p = 0.001) as opposed to the CG. A trend analysis revealed that cholesterol (p = 0.033) and systolic blood pressure (SBP); (p = 0.013) were statistically significant when comparing genders for all study phases. Interventions focusing on legumes can improve hypertension and cardiovascular disease and fast-track the achievement of SGDs 3 and 12 through community-based programmes.

Nutrients

Vitamin D3 synthesis in human skin is initiated by solar ultraviolet radiation (UVR) exposure of precursor 7-dehydrocholesterol (7DHC), but influence of age on the early stage of vitamin D3 metabolism is uncertain. We performed a prospective standardised study in healthy ambulant adults aged ≥65 and ≤40 years examining (1) if baseline skin 7DHC concentration differs between younger and older adults and (2) the impact of older age on serum vitamin D3 response to solar simulated UVR. Eleven younger (18–40 years) and 10 older (65–89 years) adults, phototype I–III, received low-dose UVR (95% UVA, 5% UVB, 1.3 SED) to ~35% of the body surface area. Biopsies were taken for 7DHC assay from unexposed skin, skin immediately and 24 h post-UVR, and blood sampled at baseline, 24 h and 7 d post-UVR for vitamin D3 assay. Samples were analysed by HPLC-MS/MS. Baseline skin 7DHC (mean ± SD) was 0.22 ± 0.07 and 0.25 ± 0.08 µg/mg in younger versus older adults (no significant difference). Baseline serum vitamin D3 concentration was 1.5 ± 1.5 and 1.5 ± 1.7 nmol/L in younger versus older adults, respectively, and showed a significant increase in both groups post-UVR (no significant differences between age groups). Thus, skin 7DHC concentration was not a limiting factor for vitamin D3 production in older relative to younger adults. This information assists public health guidance on sun exposure/vitamin D nutrition, with particular relevance to the growing populations of healthy ambulant adults ≥65 years.

Nutrients

A Crataegus Extract Mixture (CEM) is a combination of extracts from Crataegus pinnatifida leaves and Citrus unshiu peels, well-known herbs used for treating obesity and dyslipidemia. We aimed to investigate the efficacy and safety of a CEM on the body fat and lipid profiles in overweight adults. A 12-week, randomized, double-blind, placebo-controlled, parallel-group trial was conducted on 105 subjects aged 20–60 years with body mass indexes between 25 and 30 kg/m2. Eligible subjects were randomly assigned in a 1:1:1 ratio to receive either a high dose of the CEM (400 mg tid), a low dose of the CEM (280 mg tid), or a placebo. Body fat was evaluated using dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), and anthropometric measurements. The blood lipid and adipokine profiles were measured before and after the administration. After 12 weeks, the reductions in the fat percentages measured by DXA and BIA were significantly greater in the CEM groups than in the placebo group. The CEM also significantly decreased the body weights, body mass indexes, and blood leptin levels. An additional per-protocol analysis revealed that the high dose of the CEM also lowered the blood levels of triglycerides and very low-density lipoprotein cholesterol. No adverse events occurred after the CEM treatment. Our results suggest that CEMs are safe and effective for reducing the body fat and body weight and regulating the blood lipid and leptin levels in overweight or mildly obese individuals.

Nutrients

The prevalence and correlates of food insecurity—the unavailability of food and limited access to it—have not been adequately considered among transgender women (TW), particularly alongside other health-related conditions burdening this population, such as HIV infection. This study examined the prevalence and correlates of food insecurity among TW. Between 2018 and 2020, 1590 TW in the Eastern and Southern U.S. completed a multi-site baseline assessment (socio-behavioral survey and HIV testing). Descriptive statistics were calculated and multivariable Poisson models with robust error variance were used to estimate prevalence ratios and 95% confidence intervals for correlates of food insecurity (dichotomized as sometimes-to-always vs. seldom-to-never running out of food). Eighteen percent of TW were living with HIV and nearly half of participants (44%) reported food insecurity. Correlates of food insecurity included being Black, multiracial, or another race/ethnicity; having < college education, low income, unstable housing, and high anticipated discrimination; and a history of sex work and sexual violence (all p < 0.05). Food insecurity was highly prevalent among TW. Current programs to provide food support do not adequately meet the needs of TW. HIV pr evention and care programs may benefit from addressing food insecurity.

Nutrients

Metabolic syndrome (MetS) is associated with cardiovascular risk factors, such as insulin resistance, dyslipidaemia, hypertension and abdominal obesity. Given the growing need to investigate food supplements with positive health effects, this study was aimed at testing the benefits of a specific supplement for people with MetS. Fifty-eight subjects with MetS and T2DM or impaired glucose tolerance assuming metformin, were randomly assigned to take a food supplement of glucomannan, D-chiro-inositol, Cinnamomum zeylanicum blume and inulin at a daily fixed dose of 4 g orally for four months. Body weight, waist circumference, plasma lipid profile (total cholesterol, LDL, HDL and triglyc-erides), plasma glycaemic profile and visceral adiposity index (VAI) were measured at baseline and after four months of supplementation. After 16 weeks, in subjects with T2DM or insulin resistance who took the supplement (+ metformin), there was a significant reduction in body weight and BMI (p < 0.0001), serum insulin (p < 0.05) and the HOMA index (p < 0.01), as well as in the lipaemic pattern, with a significant improvement in total serum cholesterol (p < 0.005), triglycerides (p < 0.03) and LDL (p < 0.02). Our study shows that the food supplement tested is a valid and safe alternative therapeutic approach in the management of MetS and all its resulting risk factors, as its efficacy has been demonstrated across anthropometric, glucose, lipid and hepatic parameters.

Nutrients

Diet quality may be an important modifiable risk factor for mental health disorders. However, these findings have been inconsistent, particularly in older adults. We explored the independent associations between adherence to a Mediterranean diet (MedDiet) and severity of symptoms related to depression, anxiety and stress in older adults from Australia. This was a cross-sectional analysis of older Australians ≥ 60 years. MedDiet adherence was assessed using the Mediterranean Diet Adherence Screener (MEDAS), and the Depression, Anxiety and Stress Scale (DASS−21) was used to assess the severity of negative emotional symptoms. A total of n = 294 participants were included in the final analyses (70.4 ± 6.2 years). Adherence to a MedDiet was inversely associated with the severity of anxiety symptoms (β = −0.118; CI: −0.761, −0.012; p = 0.043) independent of age, gender, BMI, physical activity, sleep, cognitive risk and ability to perform activities of daily living. Furthermore, MedDiet adherence was inversely associated with symptoms of stress (β = −0.151; CI: −0.680, −0.073; p = 0.015) independent of age, gender, BMI, physical activity and sleep. However, no relationship between MedDiet adherence and depressive symptoms was observed. We showed that adherence to a MedDiet is inversely associated with the severity of symptoms related to anxiety and stress but not depression. Exploring these findings with the use of longitudinal analyses and robust clinical trials are needed to better elucidate these findings in older adults.

Nutrients

Reporting key dietary indicators from sales data can help us guide store decision makers in developing effective store policy to support healthier customer purchases. We aimed to develop a web-based reporting tool of key dietary indicators from sales data to support health-promoting policy and practice in stores in geographically remote Aboriginal and Torres Strait Islander communities. Tool development included identifying key dietary indicators (informed by sales data from 31 stores), community consultation (19 Aboriginal and Torres Strait Islander store directors and two store managers) and a web-build. Tool evaluation involved feedback interviews with stakeholders (25 store managers and two nutritionists). Key dietary indicators aligned with Australian Dietary Guideline food groupings and recommendations. An online portal for accessing and customising reports was built. Stakeholder feedback indicated that the strengths of the reports were the visuals, ease of interpretation, providing information that was not currently available and potential to increase capacity to support healthy food retailing. Difficulties were defining healthiness classification with alignment to other nutrition guidelines used and ensuring reports reached relevant store decision makers. This tool may be valuable to support store decision makers in identifying and prioritising nutrition issues and optimising the health-enabling attributes of stores.

Nutrients

The COVID-19 pandemic and related restrictions have significantly impacted the quality of life of society in many countries in various aspects. The purpose of this study was to examine how the COVID-19 pandemic affected the consumption of meat and fish in society in Poland as well as the factors that determined these changes. The cross-sectional study was conducted using an original online questionnaire between 8th and 18th of April 2020. The subjects were selected randomly. The target population were adults living in Poland. The inclusion criterion for the study was the age of at least 18 years and consent to selfless participation in the study. Communication via social media such as Facebook or Instagram was used to enroll more participants from different socio-demographic subgroups. The questionnaire was divided into two parts—the first part contained questions about sex, age, body mass, body height, residence, level of education, and occupation, and the second part consisted of specific questions about the consumption frequency of different kinds of meat during the COVID-19 lockdown period (in comparison to the time before the pandemic). A total of 3888 people took part in the study including 84.54% women, with an average age of 30.17 ± 9.22 years. The frequency of poultry consumption increased, while for pork, beef, ham and other meat products as well as fish and seafood it declined. The factors that influenced the change in dietary patterns during the lockdown related to the COVID-19 pandemic included age, body mass index, gender, place of residence, and type of work performed. However, no relationship was found …

Nutrients

Caffeine (CAF) has been shown to be an effective ergogenic aid in enhancing sports performance, including vertical jump (VJ), sprint, balance, agility, and freestyle swimming performance (FSP). However, whether acute CAF supplementation improves FSP in moderately trained female swimmers has not been well documented. Therefore, this study aimed to investigate the effects of CAF intake on vertical jump, balance, auditory reaction time (ART), and swimming performance in female swimmers. In a double-blind, cross-over design, eight moderately trained female swimmers (age: 21.3±1.4 years, height: 161.2±7.1 cm, body mass: 56.3±6.7 kg, body mass index (BMI): 21.9±1.3 kg/m2, and habitual CAF intake: 246.4±111.4 mg/day) ingested caffeine (CAF)(6 mg/kg) or a placebo (PLA) 60 min before completing VJ, balance, ART, and 25/50 m FSP. CAF supplementation resulted in a significantly lower time both in 25m (p= 0.032) and 50m (p= 0.033) FSP. However, CAF resulted in no significant difference in VJ, ART, and RPE (p> 0.05). Balance test results showed a non-significant moderate main effect (d= 0.58). In conclusion, CAF seems to reduce time in shortdistance swimming performances, which could be the determinant of success considering the total time of the race. Thus, we recommend coaches and practitioners incorporate CAF into swimmers’ nutrition plans before competitions, which may meet the high performance demands.

Nutrients

The causes and conditions of displacement often increase the vulnerability of migrant and refugee populations to food insecurity, alongside other material hardships. We aimed to examine the multidimensional aspects and patterns of food insecurity and other material hardships in a cross-sectional sample of 6221 Venezuelan refugees and migrants in urban Colombia using a latent class analysis. Using multinomial and logistic regression models, we investigated the demographic and migratory experiences associated with identified classes and how class membership is associated with multiple health outcomes among Venezuelan refugees and migrants, respectively. Approximately two thirds of the sample was comprised cisgender women, and the participants had a median age of 32 years (IQR: 26–41). Four heterogeneous classes of food insecurity and material hardships emerged: Class 1—low food insecurity and material hardship; Class 2—high food insecurity and material hardship; Class 3—high income hardship with insufficient food intake; and Class 4—income hardship with food affordability challenges. Class 2 reflected the most severe food insecurity and material hardships and had the highest class membership; Venezuelans with an irregular migration status were almost 1.5 times more likely to belong to this class. Food insecurity and material hardship class membership was independently associated with self-rated health, mental health symptoms, and recent violence victimization and marginally associated with infectious disease outcomes (laboratory-confirmed HIV and/or syphilis infection). Social safety nets, social protection …

Nutrients

We aimed to investigate the association of a sustainable diet with a long-term reduction in waist circumference (WC) while identifying novel biomarkers for WC reduction (WCR). The participants were recruited initially during 2004–2013 in a large hospital-based cohort, and the followup measurements were conducted during 2012–2016. The 65,611 adults aged 45–75 were categorized into WC-loss (n= 22,290) and WC-gain (n= 43,321). Each study investigated demographic, anthropometric, biochemical, genetic, and dietary factors. The modified Healthy Eating Index (MHEI), dietary patterns, and glycemic index were calculated from a validated semi-quantitative food frequency questionnaire. Novel biomarkers influencing WC reduction were identified using machine learning approaches. A WCR was inversely associated with metabolic syndrome (MetS) risk and its components. Daily energy intake did not differ between those with and without WCR. However, MHEI, which represents diet quality, demonstrated a positive association with WCR. Among various dietary patterns, the Asian-style balanced diet (ABD), including more fermented soybeans and less restricted salt than the Diet Approach to Stop Hypertension, was positively associated with WCR. However, an inverse association was observed between the diet that was high in noodle and processed meat consumption and that which was high in rice consumption. However, the PRS for abdominal obesity did not significantly interrupt WCR. The receiver operating characteristic curve in the prediction model for WCR was about 0.86. The biomarkers in the models included MetS components …

Nutrients

This study aimed to analyze the placebo effect associated with caffeine ingestion on running performance. Methods Thirteen recreationally trained males in long-distance running (age: 38.5 ± 11.9 years, 11.0 ± 8.8 years of running experience) performed a 6 min time trial test in each experimental condition (caffeine-informed/placebo ingested (placebo) and non-ingested (control)) separated by 7 days. The total distance covered was measured, and partial times of each 400 m were used to analyze the pacing strategy. Heart rate and kinematic variables were recorded for each split. In addition, the rate of perceived exertion and prevalence of caffeine side effects was measured using questionnaires. Results Placebo ingestion improved running performance in the 6 min time trial test (1668 ± 139 m placebo vs. 1642 ± 158 m control, t = 2.49; p = 0.03; moderate ES = 0.69), while pacing, heart rate, RPE, and kinematic variables were similar between conditions (p > 0.05 in all cases). Minor side effects were reported. Conclusions Beliefs of caffeine ingestion can improve running performance at speeds around maximal aerobic speed in recreationally trained runners without affecting pacing strategy so this “nutritional” strategy could be useful in competition scenarios. As a practical application, recreationally trained runners could improve ≈5 s in 1500 m or mile competitions.

Nutrients

Food addiction (FA) and disordered eating behaviors related to obesity are gaining attention in clinical and research fields. The modified Yale Food Addiction Scale 2.0 (mYFAS2. 0) is the gold standard questionnaire to measure FA, while another tool is the Measure of Eating Compulsivity 10 (MEC10). Discriminant validity is present when two measures of similar but distinct constructs show a correlation that is low enough for the factors to be regarded as distinct. However, the discriminant validity of these measures has never been tested. Through a cross-sectional study design, 717 inpatients (females: 56.20%, age: 53.681±12.74) with severe obesity completed the MEC10, Binge Eating Scale (BES), and mYFAS2. 0. A structural equation model (SEM) was fitted, freely estimating latent correlations with 95% confidence intervals (95% CI). The results confirmed the scales’ excellent psychometric properties. Importantly, latent factor correlations between MEC10 and mY-FAS2. 0 (est= 0.783, 95% CI [0.76, 0.80]) supported their discriminant validity. In contrast, the latent correlation of MEC10 and BES (est= 0.86, 95% CI [0.84, 0.87]) exceeded the recommended thresholds, indicating the absence of discriminant validity and suggesting a potential overlap, consistent with previous evidence. In conclusion, MEC10 demonstrates excellent psychometric properties but is more a measure of BED and not FA.