Explore the vast range of titles available.

The evidence for the beneficial effects of drinking hydrogen-water (HW) is rare. We aimed to investigate the effects of HW consumption on oxidative stress and immune functions in healthy adults using systemic approaches of biochemical, cellular, and molecular nutrition. In a randomized, double-blind, placebo-controlled study, healthy adults (20–59 y) consumed either 1.5 L/d of HW ( n  = 20) or plain water (PW, n  = 18) for 4 weeks. The changes from baseline to the 4th week in serum biological antioxidant potential (BAP), derivatives of reactive oxygen, and 8-Oxo-2′-deoxyguanosine did not differ between groups; however, in those aged ≥ 30 y, BAP increased greater in the HW group than the PW group. Apoptosis of peripheral blood mononuclear cells (PBMCs) was significantly less in the HW group. Flow cytometry analysis of CD4 + , CD8 + , CD20 + , CD14 + and CD11b + cells showed that the frequency of CD14 + cells decreased in the HW group. RNA-sequencing analysis of PBMCs demonstrated that the transcriptomes of the HW group were clearly distinguished from those of the PW group. Most notably, transcriptional networks of inflammatory responses and NF-κB signaling were significantly down-regulated in the HW group. These finding suggest HW increases antioxidant capacity thereby reducing inflammatory responses in healthy adults.

A well-functioning immune system requires balanced immune responses. In vitro studies have shown that plant stanols contribute to restoring the T-helper (Th)1/Th2 ratio when it is imbalanced. However, effects of plant stanols on healthy immune responses are unknown. Therefore, we studied effects of recommended (2·5 g/d) or high (9·0 g/d) plant stanol intakes on the Th1/Th2 cytokine balance in immunologically healthy subjects. In two RCTs, peripheral blood mononuclear cells (PBMCs) were isolated, cultured, and stimulated with 5 µg/ml Phytohemagglutinin-M to study ex vivo cytokine production. In the first study, twenty participants consumed margarines (2·5 g/d plant stanols) or control for three weeks. In the second study, nineteen participants consumed margarines and yogurts (9·0 g/d plant stanols) or control for four weeks. T-cell cytokine concentrations were measured in culture medium and in study 2 a standardized Th1/Th2 index was calculated. Serum lipids and non-cholesterol sterols were also measured. Compliance was confirmed by significant increases in serum total cholesterol (TC)-standardized sitostanol and campestanol levels in both studies. Changes in ex vivo cytokine production and Th1/Th2 index did not differ between intervention and control groups. In the first study, no statistically significant changes were observed in lipid and lipoprotein concentrations. In the second study, LDL cholesterol significantly decreased compared to control (–0·77 (–1·11, –0·42) mmol/l; P < 0·001). Recommended (2·5 g/d) or high (9·0 g/d) intakes of plant stanols did not alter PBMC ex vivo cytokine production in immunologically healthy subjects. This suggests that plant stanols might only affect immune function when Th1/Th2 immune responses are imbalanced.

COVID-19 vaccine supply shortages are causing concerns about compromised immunity in some countries as the interval between the first and second dose becomes longer. Conversely, countries with no supply constraints are considering administering a third dose. We assessed the persistence of immunogenicity after a single dose of ChAdOx1 nCoV-19 (AZD1222), immunity after an extended interval (44–45 weeks) between the first and second dose, and response to a third dose as a booster given 28–38 weeks after the second dose. In this substudy, volunteers aged 18–55 years who were enrolled in the phase 1/2 (COV001) controlled trial in the UK and had received either a single dose or two doses of 5 × 1010 viral particles were invited back for vaccination. Here we report the reactogenicity and immunogenicity of a delayed second dose (44–45 weeks after first dose) or a third dose of the vaccine (28–38 weeks after second dose). Data from volunteers aged 18–55 years who were enrolled in either the phase 1/2 (COV001) or phase 2/3 (COV002), single-blinded, randomised controlled trials of ChAdOx1 nCoV-19 and who had previously received a single dose or two doses of 5 × 1010 viral particles are used for comparison purposes. COV001 is registered with ClinicalTrials.gov, NCT04324606, and ISRCTN, 15281137, and COV002 is registered with ClinicalTrials.gov, NCT04400838, and ISRCTN, 15281137, and both are continuing but not recruiting. Between March 11 and 21, 2021, 90 participants were enrolled in the third-dose boost substudy, of whom 80 (89%) were assessable for reactogenicity, 75 (83%) were assessable for evaluation of antibodies, and 15 (17%) were assessable for T-cells responses. The two-dose cohort comprised 321 participants who had reactogenicity data (with prime-boost interval of 8–12 weeks: 267 [83%] of 321; 15–25 weeks: 24 [7%]; or 44–45 weeks: 30 [9%]) and 261 who had immunogenicity data (interval of 8–12 weeks: 115 [44%] of 261; 15–25 weeks: 116 [44%]; and 44–45 weeks: 30 [11%]). 480 participants from the single-dose cohort were assessable for immunogenicity up to 44–45 weeks after vaccination. Antibody titres after a single dose measured approximately 320 days after vaccination remained higher than the titres measured at baseline (geometric mean titre of 66·00 ELISA units [EUs; 95% CI 47·83–91·08] vs 1·75 EUs [1·60–1·93]). 32 participants received a late second dose of vaccine 44–45 weeks after the first dose, of whom 30 were included in immunogenicity and reactogenicity analyses. Antibody titres were higher 28 days after vaccination in those with a longer interval between first and second dose than for those with a short interval (median total IgG titre: 923 EUs [IQR 525–1764] with an 8–12 week interval; 1860 EUs [917–4934] with a 15–25 week interval; and 3738 EUs [1824–6625] with a 44–45 week interval). Among participants who received a third dose of vaccine, antibody titres (measured in 73 [81%] participants for whom samples were available) were significantly higher 28 days after a third dose (median total IgG titre: 3746 EUs [IQR 2047–6420]) than 28 days after a second dose (median 1792 EUs [IQR 899–4634]; Wilcoxon signed rank test p=0·0043). T-cell responses were also boosted after a third dose (median response increased from 200 spot forming units [SFUs] per million peripheral blood mononuclear cells [PBMCs; IQR 127–389] immediately before the third dose to 399 SFUs per milion PBMCs [314–662] by day 28 after the third dose; Wilcoxon signed rank test p=0·012). Reactogenicity after a late second dose or a third dose was lower than reactogenicity after a first dose. An extended interval before the second dose of ChAdOx1 nCoV-19 leads to increased antibody titres. A third dose of ChAdOx1 nCoV-19 induces antibodies to a level that correlates with high efficacy after second dose and boosts T-cell responses. UK Research and Innovation, Engineering and Physical Sciences Research Council, National Institute for Health Research, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research Oxford Biomedical Research Centre, Chinese Academy of Medical Sciences Innovation Fund for Medical Science, Thames Valley and South Midlands NIHR Clinical Research Network, AstraZeneca, and Wellcome.

There is an urgent need to better understand the pathophysiology of Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2, which has infected more than three million people worldwide 1 . Approximately 20% of patients with COVID-19 develop severe disease and 5% of patients require intensive care 2 . Severe disease has been associated with changes in peripheral immune activity, including increased levels of pro-inflammatory cytokines 3 , 4 that may be produced by a subset of inflammatory monocytes 5 , 6 , lymphopenia 7 , 8 and T cell exhaustion 9 , 10 . To elucidate pathways in peripheral immune cells that might lead to immunopathology or protective immunity in severe COVID-19, we applied single-cell RNA sequencing (scRNA-seq) to profile peripheral blood mononuclear cells (PBMCs) from seven patients hospitalized for COVID-19, four of whom had acute respiratory distress syndrome, and six healthy controls. We identify reconfiguration of peripheral immune cell phenotype in COVID-19, including a heterogeneous interferon-stimulated gene signature, HLA class II downregulation and a developing neutrophil population that appears closely related to plasmablasts appearing in patients with acute respiratory failure requiring mechanical ventilation. Importantly, we found that peripheral monocytes and lymphocytes do not express substantial amounts of pro-inflammatory cytokines. Collectively, we provide a cell atlas of the peripheral immune response to severe COVID-19. Single-cell transcriptomic analysis identifies changes in peripheral immune cells in seven hospitalized patients with COVID-19, including HLA class II downregulation, a heterogeneous interferon-stimulated gene signature and low pro-inflammatory cytokine gene expression in monocytes and lymphocytes.

Umbilical cord blood-derived mononuclear cell (UCB-MNC) transplants improve recovery in animal spinal cord injury (SCI) models. We transplanted UCB-MNCs into 28 patients with chronic complete SCI in Hong Kong (HK) and Kunming (KM). Stemcyte Inc. donated UCB-MNCs isolated from human leukocyte antigen (HLA ≥4:6)-matched UCB units. In HK, four patients received four 4-μl injections (1.6 million cells) into dorsal entry zones above and below the injury site, and another four received 8-μl injections (3.2 million cells). The eight patients were an average of 13 years after C5-T10 SCI. Magnetic resonance diffusion tensor imaging of five patients showed white matter gaps at the injury site before treatment. Two patients had fiber bundles growing across the injury site by 12 months, and the rest had narrower white matter gaps. Motor, walking index of SCI (WISCI), and spinal cord independence measure (SCIM) scores did not change. In KM, five groups of four patients received four 4-μl (1.6 million cells), 8-μl (3.2 million cells), 16-μl injections (6.4 million cells), 6.4 million cells plus 30 mg/kg methylprednisolone (MP), or 6.4 million cells plus MP and a 6-week course of oral lithium carbonate (750 mg/day). KM patients averaged 7 years after C3-T11 SCI and received 3–6 months of intensive locomotor training. Before surgery, only two patients walked 10 m with assistance and did not need assistance for bladder or bowel management before surgery. The rest could not walk or do their bladder and bowel management without assistance. At about a year (41–87 weeks), WISCI and SCIM scores improved: 15/20 patients walked 10 m (p = 0.001) and 12/20 did not need assistance for bladder management (p = 0.001) or bowel management (p = 0.002). Five patients converted from complete to incomplete (two sensory, three motor; p = 0.038) SCI. We conclude that UCB-MNC transplants and locomotor training improved WISCI and SCIM scores. We propose further clinical trials.

Nutrients, including bioactive natural compounds, have been demonstrated to affect key metabolic processes implicated in tumor growth and progression, both in preclinical and clinical trials. Although the application of precision nutrition as a complementary approach to improve cancer treatments is still incipient in clinical practice, the development of powerful \"omics\" techniques has opened new possibilities for delivering nutritional advice to cancer patients. Precision nutrition may contribute to improving the plasticity and function of antitumor immune responses. Herein, we present the results of a randomized, prospective, longitudinal, double-blind, and parallel clinical trial (NCT05080920) in cancer patients to explore the immune-metabolic effects of a bioactive formula based on diterpenic phenols from rosemary, formulated with bioactive alkylglycerols (Lipchronic WO/2017/187000). The trial involved cancer patients, including those with lung cancer (LC), colorectal cancer (CRC), and breast cancer (BC), undergoing chemotherapy, targeted biological therapy, and/or immunotherapy. The main readouts of the study were the analysis of Lip on systemic inflammation, hemogram profile, anthropometry, lipid and glucose profiles, and tolerability. Additionally, a deep immune phenotyping of peripheral blood mononuclear cells (PBMCs) was performed to identify the functional effects of Lip on key mediators of the immune system. Lip was well tolerated. The lung cancer subgroup of patients showed a reduction in biomarkers of systemic inflammation, including the neutrophil-to-lymphocyte ratio (NLR). Furthermore, modulation of key players in the immune system associated with the experimental treatment Lip compared to the control placebo (Pla) treatment was revealed, with particularities among the distinct subgroups of patients. Our results encourage further research to apply molecular nutrition-based strategies as a complementary tool in the clinical management of cancer patients, particularly in the current era of novel immunotherapies. ClinicalTrials.gov, identifier NCT05080920.

The gut microbiota regulates T cell functions throughout the body. We hypothesized that intestinal bacteria impact the pathogenesis of multiple sclerosis (MS), an autoimmune disorder of the CNS and thus analyzed the microbiomes of 71 MS patients not undergoing treatment and 71 healthy controls. Although no major shifts in microbial community structure were found, we identified specific bacterial taxa that were significantly associated with MS. Akkermansia muciniphila and Acinetobacter calcoaceticus, both increased in MS patients, induced proinflammatory responses in human peripheral blood mononuclear cells and in monocolonized mice. In contrast, Parabacteroides distasonis, which was reduced in MS patients, stimulated antiinflammatory IL-10–expressing human CD4⁺CD25⁺ T cells and IL-10⁺FoxP3⁺ Tregs in mice. Finally, microbiota transplants from MS patients into germ-free mice resulted in more severe symptoms of experimental autoimmune encephalomyelitis and reduced proportions of IL-10⁺ Tregs compared with mice “humanized” with microbiota from healthy controls. This study identifies specific human gut bacteria that regulate adaptive autoimmune responses, suggesting therapeutic targeting of the microbiota as a treatment for MS.

Immunosenescence is an important factor in the impaired immune response in older adults and plays a significant role in the development of biological aging. Targeting immunosenescence could present a novel pharmacological approach to mitigating aging and age-related diseases. We aimed to investigate the effect of N-acetylcysteine (NAC) and vitamin D (Vit-D) on the senescence of peripheral blood mononuclear cells (PBMCs). This randomized clinical trial was conducted on older adults with Vit-D deficiency. Eligible participants were randomly assigned to one of four groups to receive either (A) 1000 IU of Vit-D daily (D1) (B), 1000 IU of Vit-D plus 600 mg of NAC daily (D1N) (C), 5000 IU of Vit-D daily (D5), or (D) 5000 IU of Vit-D plus 600 mg of NAC daily (D5N) for 8 weeks. Senescence-associated beta-galactosidase (SA-β-gal) staining, expression of senescence-related genes, and serum inflammatory factors were measured at baseline and after 8 weeks. After the intervention, supplementation with D5N and D5 significantly downregulated , interleukin-6 ( ), and tumor necrosis factor-α ( ) expression and decreased SA-β-gal activity compared to the D1 group. Additionally, co-administration of NAC with 1000 IU of Vit-D significantly downregulated transcripts in PBMCs compared to Vit-D 1000 IU alone. No significant differences were observed between the groups in serum IL-6, C-reactive protein (CRP), or the neutrophil-to-lymphocyte ratio (NLR) after the intervention. The loading dose of Vit-D significantly attenuates senescence in PBMCs of older adults. However, co-administration of NAC with both the standard and loading doses of Vit-D further enhances these beneficial effects. https://irct.behdasht.gov.ir, identifier IRCT20230508058120N1.

The infusion of coronavirus disease 2019 (COVID-19) patients with mesenchymal stem cells (MSCs) potentially improves clinical symptoms, but the underlying mechanism remains unclear. We conducted a randomized, single-blind, placebo-controlled (29 patients/group) phase II clinical trial to validate previous findings and explore the potential mechanisms. Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay ( P  = 0.0198) and less time required for symptoms remission ( P  = 0.0194) than those who received placebo. Based on chest images, both severe and critical patients treated with MSCs showed improvement by day 7 ( P  = 0.0099) and day 21 ( P  = 0.0084). MSC-treated patients had fewer adverse events. MSC infusion reduced the levels of C-reactive protein, proinflammatory cytokines, and neutrophil extracellular traps (NETs) and promoted the maintenance of SARS-CoV-2-specific antibodies. To explore how MSCs modulate the immune system, we employed single-cell RNA sequencing analysis on peripheral blood. Our analysis identified a novel subpopulation of VNN2 + hematopoietic stem/progenitor-like (HSPC-like) cells expressing CSF3R and PTPRE that were mobilized following MSC infusion. Genes encoding chemotaxis factors — CX3CR1 and L-selectin — were upregulated in various immune cells. MSC treatment also regulated B cell subsets and increased the expression of costimulatory CD28 in T cells in vivo and in vitro. In addition, an in vivo mouse study confirmed that MSCs suppressed NET release and reduced venous thrombosis by upregulating kindlin-3 signaling. Together, our results underscore the role of MSCs in improving COVID-19 patient outcomes via maintenance of immune homeostasis.

Genome-wide association studies have identified thousands of genetic variants that are associated with disease 1 . Most of these variants have small effect sizes, but their downstream expression effects, so-called expression quantitative trait loci (eQTLs), are often large 2 and celltype-specific 3 – 5 . To identify these celltype-specific eQTLs using an unbiased approach, we used single-cell RNA sequencing to generate expression profiles of ~25,000 peripheral blood mononuclear cells from 45 donors. We identified previously reported cis-eQTLs, but also identified new celltype-specific cis-eQTLs. Finally, we generated personalized co-expression networks and identified genetic variants that significantly alter co-expression relationships (which we termed ‘co-expression QTLs’). Single-cell eQTL analysis thus allows for the identification of genetic variants that impact regulatory networks. Single-cell RNA sequencing (scRNA-seq) of ~25,000 peripheral blood mononuclear cells from 45 donors identifies new celltype-specific cis-eQTLs and genetic variants that significantly alter co-expression relationships (‘co-expression QTLs’).