Protocatechuic acid supplement alleviates allergic airway inflammation by inhibiting the IL-4Rα-STAT6 and Jagged 1/Jagged2-Notch1/Notch2 pathways in allergic asthmatic mice.

OBJECTIVE AND DESIGN: To clarify the effects of dietary supplementation of protocatechuic acid (PCA) and in-depth mechanisms on allergic asthma in ovalbumin (OVA)-induced mice. MATERIALS: Female BALB/c mice were randomly divided into three groups (n = 10 in each group): control group, OVA-induced allergic asthma group, and OVA plus PCA group. TREATMENT: Dietary supplementation of PCA was achieved by adding 50 mg/kg PCA to AIN 93G diet for 25 days. METHODS: Peripheral blood cells, pulmonary inflammatory cell infiltration, the levels of IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid (BALF), the mRNA levels of Th2-related genes in the lungs, and the protein expressions of the IL-4Rα-STAT6 and the Jagged1/Jagged2-Notch1/Notch2 signaling pathways were measured. RESULTS: Significantly reduced inflammatory cells infiltration and mucosal hypersecretion in the lung tissues, repaired levels of interleukin IL-4, IL-5, and IL-13 in the BALF, and decreased mRNA expression of IL-4, IL-5, and GATA3 were observed in OVA plus PCA group. Moreover, PCA treatment down-regulated the protein levels of IL-4Rα-STAT6 and Jagged1/Jagged2-Notch1/Notch2 signaling pathways. CONCLUSIONS: Dietary supplement of PCA alleviated allergic asthma partly through suppressing the IL-4Rα-STAT6 and Jagged1/Jagged2-Notch1/Notch2 signaling pathways in mice. Our study provided the theoretic basis of PCA used as functional food in preventing allergic asthma.

Early oral nutritional supplement improves COVID-19 outcomes among hospitalized older patients during the Omicron wave.

OBJECTIVES: The effect of and optimal timing for initiating an oral nutritional supplement(ONS) in hospitalized older patients with the Omicron variant infection remain unclear. The aim of this study was to explore the associations between the ONS and clinical outcomes. METHODS: This study used a retrospective cohort design as primary analysis and a case-control design as sensitivity analysis. We collected data from patients with confirmed coronavirus disease 2019 (COVID-19) between April 2022 and June 2022 at Shanghai Fourth People's Hospital, one of the designated medical centers for COVID-19 in Shanghai, China. Patients were identified as ONS users or non-ONS users, with the former defined as early ONS (ONS initiated within 48 h from hospital admission), and late ONS (ONS initiated after 48 h) users. RESULTS: The study included 1181 hospitalized patients ≥60 y of age. The mean age of the cohort was 78 y, and most patients were women (57.7%). Mortalities after propensity-score matching were 1.2% and 4.3% in the ONS group and non-ONS groups, respectively (P = 0.032). Subgroup analysis results showed that median (IQR) hospital length of stay and the median (IQR) length from symptom onset to viral clearance were shorter for the early ONS than for the late ONS group (9 [6-13] d versus 14 [11 -18] d; P < 0.001, and 11 [8-17] d versus 17 [13-22] d; P < 0.001, respectively). The findings from the case-control analysis supported those from the primary analysis. CONCLUSIONS: Early ONS might have significantly lowered risk for in-hospital death, as well as reduce hospital length of stay and days of viral clearance in older patients with COVID-19 during the Omicron wave.

Sleep Duration and Risks of Incident Cardiovascular Disease and Mortality Among People With Type 2 Diabetes.

OBJECTIVE: People with type 2 diabetes may have insufficient or prolonged sleep that could accelerate cardiovascular disease (CVD) onset, but existing evidence from prospective studies has been limited. We examined the association of sleep duration with CVD incidence and mortality in this high-risk population. RESEARCH DESIGN AND METHODS: This prospective study included 18,876 participants with type 2 diabetes in the UK Biobank who were free of CVD and cancer at baseline. Habitual sleep duration was obtained using a baseline questionnaire. Cox proportional hazards regression models were used to examine the association between sleep duration and CVD events. RESULTS: During an average follow-up of 11.0-12.0 years, we documented 2,570 incident cases of atherosclerotic cardiovascular disease (ASCVD) and 598 CVD deaths. Compared with sleeping for 7 h/day, the multivariable-adjusted hazard ratios of ≤5 and ≥10 h/day were 1.26 (95% CI 1.08, 1.48) and 1.41 (1.16, 1.70) for incident ASCVD, 1.22 (0.99, 1.50) and 1.16 (0.88, 1.52) for coronary artery disease, 1.70 (1.23, 2.35) and 2.08 (1.44, 3.01) for ischemic stroke, 1.02 (0.72, 1.44) and 1.45 (1.01, 2.10) for peripheral artery disease, and 1.42 (1.02, 1.97) and 1.85 (1.30, 2.64) for CVD mortality. Similar results were observed in most sensitivity analyses that aimed to address potential reverse causation and in the joint analyses of sleep duration and metabolic control or diabetes severity status. CONCLUSIONS: Short and long sleep durations were independently associated with increased risks of CVD onset and death among people with type 2 diabetes.

Betanin Dose-Dependently Ameliorates Allergic Airway Inflammation by Attenuating Th2 Response and Upregulating cAMP-PKA-CREB Pathway in Asthmatic Mice.

Allergic asthma is a refractory disease that affects hundreds of millions of people worldwide. Betanin is a natural plant-derived nutrient and possesses health-promoting properties. The effects of betanin on allergic asthma remain unknown. Herein, the effects and mechanisms of betanin on allergic asthma were explored in ovalbumin (OVA)-induced BALB/c mice. Betanin in doses of 0, 20, 60, and 180 mg/kg was applied. Peripheral inflammatory cells, IgE, pulmonary pathology, T cell subsets, cytokine levels, protein expressions of the cAMP-PKA-CREB/CREM pathway, and gut microbial profile were measured. The 60 and 180 mg/kg/day betanin doses significantly downregulated IgE, eotaxin, eosinophil infiltration, mucus hyperproduction, and Th2. A 180 mg/kg/day betanin dose also significantly reduced percentages of Th17, Tc17, and Tc2 and Th2- and Th17-signature cytokines and upregulated the cAMP-PKA-CREB pathway. Additionally, 20 mg/kg/day betanin altered the gut microbial profile. In conclusion, betanin dose-dependently alleviated allergic asthma and upregulated the cAMP-PKA-CREB pathway in mice. This study provides a novel nutritional strategy to treat allergic asthma.

Tetrahydrocurcumin alleviates allergic airway inflammation in asthmatic mice by modulating the gut microbiota.

Dietary factors can reshape the gut microbiota and consequently affect disease progression. We previously reported that tetrahydrocurcumin (THC), the major active metabolite of curcumin (Cur), could ameliorate allergic inflammation in asthmatic mice. Herein, we aimed to investigate whether THC or Cur exerts anti-inflammatory effects on allergic asthma via modulating gut microbiota. Ovalbumin (OVA)-induced asthmatic mice were treated with Cur or THC, and the gut microbiota profiles were analyzed by 16S rRNA sequencing. Fecal microbiota transplantation (FMT) from Cur- or THC-fed donor mice was administered to OVA-induced asthmatic mice. Nasal symptoms and inflammation patterns of lungs and colons were evaluated in control, OVA-induced and Cur-or THC-treated mice. Both Cur and THC treatment could alter the compositions of the gut microbiota in asthmatic mice, characterized by a significant decrease in the ratio of Firmicutes to Bacteroidetes; Cur or THC supplementation also reduced the relative abundances of pro-inflammatory bacteria, e.g., Proteobacteria, Intestinimonas, Unidentified-Ruminococcaceae, and Lachnospiraceae, in OVA-induced mice. The relative abundances of Unidentified-Ruminococcaceae, Romboutsia, Intestinimonas, Akkermansia, and Mucispirillum were positively associated with the levels of Th2-related factors in asthmatic mice upon Cur or THC treatment. Moreover, THC-FMT showed better preventive effects than Cur-FMT on the development of allergic inflammation in OVA-induced mice, resulting in a reduction in symptoms and Th2-mediated inflammation in both lung and colon tissues. The results reveal that Cur- or THC-mediated alleviation of airway allergic inflammation is dependent on gut microbiota modulation. THC-induced gut microbiota may have therapeutic potential for asthma treatment.

Coenzyme Q10 attenuates platelet integrin αIIbß3 signaling and platelet hyper-reactivity in ApoE-deficient mice.

Coenzyme Q10 (CoQ10) exists in a wide variety of foods and has promising cardiovascular benefits. However, its effects on platelets and integrin αIIbß3 signaling during atherosclerosis have not been previously explored. Here, apolipoprotein E-deficient (ApoE-/-) mice were fed a standard diet, high-fat diet (HFD) or CoQ10-supplemented HFD for 12 weeks. We found that CoQ10 supplementation in ApoE-/- mice significantly alleviated formation of HFD-induced atherosclerotic lesions, and attenuated platelet hyper-aggregation and granule secretion, including CD62P, CD63 and CD40 ligand (CD40L) expression and platelet factor-4, ß-thromboglobulin and activation normal T cell expressed and secreted (CCL5) release. CoQ10 supplementation decreased soluble fibrinogen and JON/A binding to αIIbß3 on activated platelets, indicating that αIIbß3-mediated inside-out signaling was attenuated. Additionally, CoQ10 down-regulated platelet αIIbß3 outside-in signaling including decreasing phosphorylation of the ß3 intracellular tail, cellular and sarcoma tyrosine-protein kinase (c-Src), and myosin light chain (MLC), and consistently attenuating platelet spreading and clot retraction. Importantly, platelet-monocyte aggregation that was primarily mediated by αIIbß3 and can be blocked using an αIIbß3-specific antagonist tirofiban was also markedly diminished by CoQ10. Thus, CoQ10 supplementation attenuates platelet hyper-reactivity via down-regulating both αIIbß3 inside-out and outside-in signaling, which may play important preventive roles in atherothrombosis.

Cyanidin-3-O-ß-glucoside attenuates allergic airway inflammation by modulating the IL-4Rα-STAT6 signaling pathway in a murine asthma model.

Cyanidin-3-O-ß-glucoside (Cy-3-g), a typical and abundant monomer of anthocyanins, exhibits a variety of biological activities, such as anti-atherosclerosis, anti-obesity, and anticancer effects. However, to date little is known about its effects on asthma. This study aimed to investigate the efficacy of dietary Cy-3-g on allergic asthma in an animal model. BALB/c mice were sensitized and challenged with ovalbumin (OVA) to induce allergic asthma. The pathological changes of the lung tissues, type 2 helper (Th2)-associated cytokine production in bronchoalveolar lavage fluid (BALF), and the interleukin 4 receptor alpha (IL-4Rα)-signal transducer and activator of transcription 6 (STAT6) signaling pathway activities were assessed. We found that Cy-3-g significantly inhibited OVA-induced inflammatory cell infiltration and mucus hyper-production in lung tissues, reduced the production of interleukin 4 (IL-4), interleukin 5 (IL-5) and interleukin 13 (IL-13) in BALF. Furthermore, Cy-3-g effectively suppressed OVA-induced up-regulation of the IL-4Rα-STAT6 signaling pathway activity of the lung tissues. These results demonstrated that dietary Cy-3-g could attenuate allergic airway inflammation in a murine asthma model, and Cy-3-g might be used as an agent for asthma prevention and/or treatment in the future.