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Age-related changes in energy metabolism in peripheral mononuclear blood cells (PBMCs) and the brains of cognitively healthy seniors.
Silaidos, CV, Reutzel, M, Wachter, L, Dieter, F, Ludin, N, Blum, WF, Wudy, SA, Matura, S, Pilatus, U, Hattingen, E, et al
GeroScience. 2024;(1):981-998
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Abstract
Mitochondrial dysfunction is a hallmark of cellular senescence and many age-related neurodegenerative diseases. We therefore investigated the relationship between mitochondrial function in peripheral blood cells and cerebral energy metabolites in young and older sex-matched, physically and mentally healthy volunteers. Cross-sectional observational study involving 65 young (26.0 ± 0.49 years) and 65 older (71.7 ± 0.71 years) women and men recruited. Cognitive health was evaluated using established psychometric methods (MMSE, CERAD). Blood samples were collected and analyzed, and fresh peripheral blood mononuclear cells (PBMCs) were isolated. Mitochondrial respiratory complex activity was measured using a Clarke electrode. Adenosine triphosphate (ATP) and citrate synthase activity (CS) were determined by bioluminescence and photometrically. N-aspartyl-aspartate (tNAA), ATP, creatine (Cr), and phosphocreatine (PCr) were quantified in brains using 1H- and 31P-magnetic resonance spectroscopic imaging (MRSI). Levels of insulin-like growth factor 1 (IGF-1) were determined using a radio-immune assay (RIA). Complex IV activity (CIV) (- 15%) and ATP levels (- 11%) were reduced in PBMCs isolated from older participants. Serum levels of IGF-1 were significantly reduced (- 34%) in older participants. Genes involved in mitochondrial activity, antioxidant mechanisms, and autophagy were unaffected by age. tNAA levels were reduced (- 5%), Cr (+ 11%), and PCr (+ 14%) levels were increased, and ATP levels were unchanged in the brains of older participants. Markers of energy metabolism in blood cells did not significantly correlate with energy metabolites in the brain. Age-related bioenergetic changes were detected in peripheral blood cells and the brains of healthy older people. However, mitochondrial function in peripheral blood cells does not reflect energy related metabolites in the brain. While ATP levels in PBMCs may be be a valid marker for age-related mitochondrial dysfunction in humans, cerebral ATP remained constant.
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Sex-specific association of visceral and subcutaneous adipose tissue volumes with systemic inflammation and innate immune cells in people living with obesity.
van den Munckhof, ICL, Bahrar, H, Schraa, K, Brand, T, Ter Horst, R, van der Graaf, M, Dekker, HM, Stienstra, R, de Graaf, J, Joosten, LAB, et al
International journal of obesity (2005). 2024;(4):523-532
Abstract
BACKGROUND AND AIMS Obesity predisposes to metabolic and cardiovascular diseases. Adipose tissue inflammation and systemic inflammation contribute to these complications. There are strong sex differences in adipose tissue distribution and in systemic inflammation. Women have more subcutaneous adipose tissue (SAT) and less visceral adipose tissue (VAT) than men. We explored the sex differences in the association between the different adipose compartments and inflammatory markers that are important in cardiometabolic disease pathophysiology. METHODS Single-center observational cohort study with 302 individuals with a BMI ≥ 27 kg/m2. We were unable to acquire MRI data from seven individuals and from another 18 the MRI data were not usable, resulting in 277 people (155 men, 122 women), aged 55-81 years. INTERVENTION We performed the following measurements: abdominal magnetic resonance imaging to measure VAT, and SAT (deep and superficial) volumes; circulating leukocyte counts and cytokine production capacity of peripheral blood mononuclear cells (PBMCs), circulating cytokines, adipokines, and targeted proteomics; abdominal sSAT biopsies for histology and gene expression. RESULTS Only in women, (s)SAT volume was associated with circulating leukocytes, monocytes, and neutrophils. Circulating IL-6 and IL-18BP were associated with SAT volume in women and VAT in men. Several circulating proteins, including monocyte-colony-stimulating factor 1 and hepatocyte growth factor, are associated with sSAT in women and VAT in men. Only in women, SAT volume is associated with SAT expression of inflammatory proteins, including leptin, CD68, TNFα and IL-1α. CONCLUSION In women living with obesity, abdominal SAT volume, especially sSAT, is associated with circulating leukocytes and inflammatory proteins. In men, these parameters mainly show associations with VAT volume. This could be because only in women, sSAT volume is associated with sSAT expression of inflammatory proteins. These findings underscore that future research on adipose tissue in relation to cardiometabolic and cardiovascular disease should take sex differences into account.
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Prevalence and clinicopathological Spectrum of Auto-Immune Liver Diseases & Overlap syndrome.
Varadarajan, A, Rastogi, A, Maiwall, R, Bihari, C, Thomas, S, Sood, V, Shasthry, SM
Indian journal of pathology & microbiology. 2024;(1):107-114
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Abstract
AIMS: Autoimmune liver diseases (AILD) represent a spectrum of related yet distinct immune-mediated disorders. The literature on the prevalence of these AILDs in Indian population is scarce. This study aims to assess the prevalence and clinicopathological spectrum of various AILDs especially the overlap syndrome. MATERIALS AND METHODS A 10-year (2011-2020) cross-sectional, retrospective observational study of histological proven cases of AILD was conducted. Clinical, demographic, and laboratory parameters were retrieved. Two pathologists independently reviewed the liver biopsies and reassessed 18 histopathological parameters. RESULTS During the study period, 17664 liver biopsies were received, out of which 1060 (6%) biopsies of AILD were identified. After exclusion, we had 721 cases which revealed a distribution of autoimmune hepatitis (AIH)-64.7%, primary biliary cholangitis (PBC)-14.8%, primary sclerosing cholangitis (PSC)-7.6%, overlap AIH-PBC 11%, and overlap AIH-PSC 1.7%. AIH patients had significantly higher prevalence for severe lobular inflammation (27%, P ≤ 0.001), several lobular plasma cells (37%, P ≤ 0.001), central perivenulitis (30%, P ≤ 0.001), hepatic rosettes (51%, P ≤ 0.001), and necrosis (35.5%, P ≤ 0.001), while PBC patients had significantly higher frequency of florid duct lesions (11.2%, P ≤ 0.001), duct loss (83.17%, P ≤ 0.001), bile duct damage (76.6%, P ≤ 0.001), and periportal copper deposits (19.6%, P ≤ 0.001). Overlap AIH-PBC group had the highest proportion of severe portal inflammation (27.5%, P ≤ 0.001), prominent portal plasma cells (75%, P ≤ 0.001), moderate interface activity (53.7%, P ≤ 0.001), Mallory-Denk bodies (27.5%, P ≤ 0.001), and periportal cholate stasis (25%, P ≤ 0.001). CONCLUSION Prevalence of biopsy-proven AILDs in our study cohort is 6%. AIH (64.7%) is the most common AILD followed by PBC (14.8%). Overlap syndrome (AIH-PBC) showed prevalence of 11%.
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Adaptive immune responses to two-dose COVID-19 vaccine series in healthy Canadian adults ≥ 50 years: a prospective, observational cohort study.
Gaultier, GN, McMillan, B, Poloni, C, Lo, M, Cai, B, Zheng, JJ, Baer, HM, Shulha, HP, Simmons, K, Márquez, AC, et al
Scientific reports. 2024;(1):8926
Abstract
To evaluate immune responses to COVID-19 vaccines in adults aged 50 years and older, spike protein (S)-specific antibody concentration, avidity, and function (via angiotensin-converting enzyme 2 (ACE2) inhibition surrogate neutralization and antibody dependent cellular phagocytosis (ADCP)), as well as S-specific T cells were quantified via activation induced marker (AIM) assay in response to two-dose series. Eighty-four adults were vaccinated with either: mRNA/mRNA (mRNA-1273 and/or BNT162b2); ChAdOx1-S/mRNA; or ChAdOx1-S/ChAdOx1-S. Anti-S IgG concentrations, ADCP scores and ACE2 inhibiting antibody concentrations were highest at one-month post-second dose and declined by four-months post-second dose for all groups. mRNA/mRNA and ChAdOx1-S/mRNA schedules had significantly higher antibody responses than ChAdOx1-S/ChAdOx1-S. CD8+ T-cell responses one-month post-second dose were associated with increased ACE2 surrogate neutralization. Antibody avidity (total relative avidity index) did not change between one-month and four-months post-second dose and did not significantly differ between groups by four-months post-second dose. In determining COVID-19 correlates of protection, a measure that considers both antibody concentration and avidity should be considered.
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The Distinct Regulation of the Vitamin D and Aryl Hydrocarbon Receptors in COVID-19.
Robak, O, Kastner, MT, Voill-Glaninger, A, Viveiros, A, Steininger, C
Nutrients. 2024;(5)
Abstract
(1) Background: SARS-CoV-2 affects several immune pathways, including the vitamin D (VDR) and the aryl hydrocarbon receptor pathways (AhR). The aim of the study was the evaluation of the VDR and AhR pathways in the blood of COVID-19 patients with regard to the severity of disease. (2) Methods: Observational, single-center, case-control design. A total of 240 samples were selected for exploration. Patients who tested negative for SARS-CoV-2 but suffered from other respiratory infections (ORIs) served as a control group. (3) Results: VDR-specific mRNA in the blood of patients with mild symptoms (131.2 ± 198.6) was significantly upregulated relative to the VDR expression of the ORI group (23.24 ± 42.60; p < 0.0001); however, VDR expression of critically ill patients showed an impaired upregulation (54.73 ± 68.34; p < 0.001). CYP27B1 expression was not significantly regulated during SARS-CoV-2 infection. There was a downregulation of VDR and CYP27B1 compared to survivors. There was no significant difference in 25(OH)-vitamin D3 levels between critically ill patients with regard to survival (24.3 ± 9.4 vs. 27.1 ± 11.3; p = 0.433). (4) Conclusion: The VDR and AhR pathways are distinctively regulated in patients suffering from COVID-19 depending on the severity of disease. A combination treatment of antiviral drugs and vitamin D substitution should be evaluated for potentially improved prognosis in COVID-19.
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Anti-spike antibody durability after SARS-CoV-2 vaccination in adolescent solid organ transplant recipients.
McAteer, J, Kalluri, DD, Abedon, RR, Qin, CX, Auerbach, SR, Charnaya, O, Danziger-Isakov, LA, Ebel, NH, Feldman, AG, Hsu, EK, et al
Pediatric transplantation. 2024;(1):e14671
Abstract
BACKGROUND Adolescent solid organ transplant recipients (aSOTRs) who received three doses of the COVID-19 mRNA vaccine experience high seroconversion rates and antibody persistence for up to 3 months. Long-term antibody durability beyond this timeframe following three doses of the SARS-CoV-2 mRNA vaccine remains unknown. We describe antibody responses 6 months following the third vaccine dose (D3) of the BNT162b2 mRNA vaccination among aSOTRs. METHODS Participants in a multi-center, observational cohort who received the third dose of the vaccine were analyzed for antibodies to the SARS-CoV-2 spike protein receptor-binding domain (Roche Elecsys anti-SARS-CoV-2-S positive: ≥0.8, maximum: >2500 U/mL). Samples were collected at 1-, 3-, and 6-months post-D3. Participants were surveyed at each timepoint and at 12-months post-D3. RESULTS All 34 participants had positive anti-RBD antibody titers 6 months post-D3. Variations in titers occurred between 3 and 6 months post-D3, with 8/28 (29%) having decreased antibody levels at 6 months compared to 3 months and 2/28 (7%) reporting increased titers at 6 months. The remaining 18/28 (64%) had unchanged antibody titers compared to 3-month post-D3 levels. A total of 4/34 (12%) reported breakthrough infection within 6 months and 3/32 (9%) reported infection after 6-12 months following the third dose of the SARS-CoV-2 mRNA vaccine. CONCLUSIONS The results suggest that antibody durability persists up to 6 months following three doses of the SARS-CoV-2 mRNA in aSOTRs. Demography and transplant characteristics did not differ for those who experienced antibody weaning. Breakthrough infections did occur, reflecting immune-evasive nature of novel variants such as Omicron.
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Association between oxidative balance score and rheumatoid arthritis in female: a cross-sectional study.
La, R, Zhou, L, Yin, Y, Lu, L, Li, L, Jiang, D, Huang, L, Wu, Q
BMC women's health. 2024;(1):225
Abstract
OBJECTIVE Although oxidative stress is a recognized factor of inflammation, the correlation between oxidative balance score (OBS), a biomarker indicating the balance of oxidation and antioxidant, and rheumatoid arthritis (RA), an immune system disease that tends to occur in women, remains unexplored. Hence, the aim of this study was to investigate the potential association between OBS and RA in women. METHODS Observational surveys were performed by employing information extracted from the National Health and Nutrition Examination Survey (NHANES) for the period 2007-2018. Various statistical techniques were employed to investigate the association between OBS and RA, encompassing multivariable logistic regression analysis, subgroup analyses, smooth curve fitting, and threshold effect analysis. RESULTS The study included 8219 female participants, including 597 patients with RA. The results showed that higher Total OBS (TOBS) significantly correlated with lower RA prevalence in the entirely modified model [odd ratio (OR) = 0.968; 95% confidence interval (CI) = 0.952 to 0.984; P = 0.0001]. Dietary OBS (DOBS) and lifestyle OBS (LOBS) also negatively correlated with RA. This association was remarkably consistent across TOBS subgroups by age, race, education level, family poverty-to-income ratio (PIR), hypertension and diabetes. Smooth curve fitting and threshold effect analysis also revealed the linear relationship between OBS and RA. CONCLUSIONS Overall, OBS was negatively associated with RA in female. This study suggested that an antioxidant diet and lifestyle may be promising measures to prevent RA in female.
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Demographic and clinical characteristics of patients with zinc deficiency: analysis of a nationwide Japanese medical claims database.
Yokokawa, H, Morita, Y, Hamada, I, Ohta, Y, Fukui, N, Makino, N, Ohata, E, Naito, T
Scientific reports. 2024;(1):2791
Abstract
Zinc deficiency, affecting more than 2 billion people globally, poses a significant public health burden due to its numerous unfavorable effects, such as impaired immune function, taste and smell disorders, pneumonia, growth retardation, visual impairment, and skin disorders. Despite its critical role, extensive large-scale studies investigating the correlation between patient characteristics and zinc deficiency still need to be completed. We conducted a retrospective, cross-sectional observational study using a nationwide Japanese claims database from January 2019 to December 2021. The study population included 13,100 patients with available serum zinc concentration data, excluding individuals under 20 and those assessed for zinc concentrations after being prescribed zinc-containing medication. Significant associations with zinc deficiency were noted among older adults, males, and inpatients. Multivariate analysis, adjusting for age and sex, indicated significant associations with comorbidities, including pneumonitis due to solids and liquids with an adjusted Odds Ratio (aOR) of 2.959; decubitus ulcer and pressure area (aOR 2.403), sarcopenia (aOR 2.217), COVID-19 (aOR 1.889), and chronic kidney disease (aOR 1.835). Significant association with medications, including spironolactone (aOR 2.523), systemic antibacterials (aOR 2.419), furosemide (aOR 2.138), antianemic preparations (aOR 2.027), and thyroid hormones (aOR 1.864) were also found. These results may aid clinicians in identifying patients at risk of zinc deficiency, potentially improving care outcomes.
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Differential expression of TOB/BTG family members in patients with plaque psoriasis: cross-sectional study.
Barrera-Ochoa, CA, Fonseca-Camarillo, G, Vega-Memije, ME, Furuzawa-Carballeda, J, Uriarte-Ruiz, K, Fernández-Camargo, DA, Yamamoto-Furusho, JK
Immunologic research. 2024;(2):234-241
Abstract
TOB/BTG is a family of antiproliferative proteins that play an important role in the regulation of immune responses, acting as lymphocyte activators and macrophage-mediated cytotoxicity. No previous studies have explored their role in patients with psoriasis. The aim of this study was to characterize the expression of TOB/BTG family and their co-localization in skin from patients with psoriasis. This is an exploratory, observational, and cross-sectional study that included 24 plaque psoriasis patients and 15 controls. Gene expression of TOB/BTG family was determinate by RT-PCR. Protein products of TOB/BTG were evaluated by immunohistochemistry and compared with control skin tissues. Holm-Sidak's multiple comparisons test was performed. TOB/BTG family mRNA levels and protein expression were significantly decreased in psoriatic skin tissue compared to non-inflammatory control skin tissue. Double-positive cell TOB1/2, BTG1,2 and BTG4/CD16 expressions were found in normal control skin tissues through epidermis and dermis (p < 0.001) and lesser percentage in patients with mild, almost absent in moderate-severe plaque psoriasis. This is the first report of the TOB/BTG family gene and protein expression in skin tissues by a CD16 + subpopulation in plaque psoriasis. TOB/BTG family protein might represent a new therapeutic target among immune-mediated inflammatory diseases.
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Depression heightened the association of the systemic immune-inflammation index with all-cause mortality among osteoarthritis patient.
Wang, S, Xiao, W, Duan, Z, Fu, Y, Fang, J, Xu, T, Yang, D, Li, G, Guan, Y, Zhang, Y
Journal of affective disorders. 2024;:239-246
Abstract
BACKGROUND Systemic immune-inflammatory index (SII) has been recognized as a novel inflammatory indicator in numerous diseases. It remains unknown how SII affects all-cause mortality among patients with osteoarthritis (OA). In this prospective cohort study, we intended to examine the relationship of SII with all-cause mortality among OA populations and assess the interaction between depression and SII. METHODS Data was collected from National Health and Nutrition Examination Survey (NHANES) in 2005-2018. The National Death Index (NDI) provided vital status records. Multivariable Cox regression analyses with cubic spines were applied to estimate the association between SII and all-cause and CVD mortality. Stratified analysis and interaction tests assessed the interaction of SII and depression on all-cause mortality. RESULTS In total 3174 OA adults were included. The lowest quartile Q1 (HR:1.44, 95%CI:1.02-2.04) and highest quartile Q4 (HR:1.44, 95%CI:1.02-2.04) of SII presented a higher risk of death compared with those in second quartile Q2 (Ref.) and third quartile Q3 (HR:1.23, 95%CI:0.89-1.68. Restricted cubic splines analysis revealed a U-shaped association of SII with all-cause mortality, the inflection points were 412.93 × 109/L. The interaction test observed a more significant relationship of SII with all-cause mortality in depression patients than in non-depression patients, indicating that depression can modify this association. LIMITATIONS First, the observational study design failed to make causal inferences. Second, the baseline SII cannot reflect the long-term level of inflammation. Finally, there may be potential bias. CONCLUSION SII was U-shaped associated with all-cause mortality in OA patients, and this association was significantly heightened by depression.