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Item Effect of nicotine on cariogenic virulence of Streptococcus mutans(Springer, 2016-11) Li, Mingyun; Huang, Ruijie; Zhou, Xuedong; Qiu, Wei; Xu, Xin; Gregory, Richard L.; Department of Biomedical and Applied Sciences, IU School of DentistryNicotine has well-documented effects on the growth and colonization of Streptococcus mutans. This study attempts to investigate the effects of nicotine on pathogenic factors of S. mutans, such as the effect on biofilm formation and viability, expression of pathogenic genes, and metabolites of S. mutans. The results demonstrated that addition of nicotine did not significantly influence the viability of S. mutans cells. The biofilms became increasingly compact as the concentrations of nicotine increased. The expression of virulence genes, such as ldh and phosphotransferase system (PTS)-associated genes, was upregulated, and nlmC was upregulated significantly, while ftf was downregulated. The lactate concentration of S. mutans grown in 1 mg/mL of nicotine was increased up to twofold over either biofilm or planktonic cells grown without nicotine. Changes in the metabolites involved in central carbon metabolism from sucrose indicated that most selected metabolites were detectable and influenced by increased concentrations of nicotine. This study demonstrated that nicotine can influence the pathogenicity of S. mutans and may lead to increased dental caries through the production of more lactate and the upregulation of virulence genes.Item Independent and joint associations of cardiometabolic multimorbidity and depression on cognitive function: findings from multi-regional cohorts and generalisation from community to clinic(Elsevier, 2024-09-12) Zhao, Xuhao; Xu, Xiaolin; Yan, Yifan; Lipnicki, Darren M.; Pang, Ting; Crawford, John D.; Chen, Christopher; Cheng, Ching-Yu; Venketasubramanian, Narayanaswamy; Chong, Eddie; Blay, Sergio Luis; Lima-Costa, Maria Fernanda; Castro-Costa, Erico; Lipton, Richard B.; Katz, Mindy J.; Ritchie, Karen; Scarmeas, Nikolaos; Yannakoulia, Mary; Kosmidis, Mary H.; Gureje, Oye; Ojagbemi, Akin; Bello, Toyin; Hendrie, Hugh C.; Gao, Sujuan; Guerra, Ricardo Oliveira; Auais, Mohammad; Gomez, José Fernando; Rolandi, Elena; Davin, Annalisa; Rossi, Michele; Riedel-Heller, Steffi G.; Löbner, Margit; Roehr, Susanne; Ganguli, Mary; Jacobsen, Erin P.; Chang, Chung-Chou H.; Aiello, Allison E.; Ho, Roger; Sanchez-Juan, Pascual; Valentí-Soler, Meritxell; Del Ser, Teodoro; Lobo, Antonio; De-la-Cámara, Concepción; Lobo, Elena; Sachdev, Perminder S.; Xu, Xin; Cohort Studies of Memory in an International Consortium (COSMIC); Psychiatry, School of MedicineBackground: Cardiometabolic multimorbidity (CMM) and depression are often co-occurring in older adults and associated with neurodegenerative outcomes. The present study aimed to estimate the independent and joint associations of CMM and depression on cognitive function in multi-regional cohorts, and to validate the generalizability of the findings in additional settings, including clinical. Methods: Data harmonization was performed across 14 longitudinal cohort studies within the Cohort Studies of Memory in an International Consortium (COSMIC) group, spanning North America, South America, Europe, Africa, Asia, and Australia. Three external validation studies with distinct settings were employed for generalization. Participants were eligible for inclusion if they had data for CMM and were free of dementia at baseline. Baseline CMM was defined as: 1) CMM 5, ≥2 among hypertension, hyperlipidemia, diabetes, stroke, and heart disease and 2) CMM 3 (aligned with previous studies), ≥2 among diabetes, stroke, and heart disease. Baseline depression was primarily characterized by binary classification of depressive symptom measurements, employing the Geriatric Depression Scale and the Center for Epidemiological Studies-Depression scale. Global cognition was standardized as z-scores through harmonizing multiple cognitive measures. Longitudinal cognition was calculated as changes in global cognitive z-scores. A pooled individual participant data (IPD) analysis was utilized to estimate the independent and joint associations of CMM and depression on cognitive outcomes in COSMIC studies, both cross-sectionally and longitudinally. Repeated analyses were performed in three external validation studies. Findings: Of the 32,931 older adults in the 14 COSMIC cohorts, we included 30,382 participants with complete data on baseline CMM, depression, and cognitive assessments for cross-sectional analyses. Among them, 22,599 who had at least 1 follow-up cognitive assessment were included in the longitudinal analyses. The three external studies for validation had 1964 participants from 3 multi-ethnic Asian older adult cohorts in different settings (community-based, memory clinic, and post-stroke study). In COSMIC studies, each of CMM and depression was independently associated with cross-sectional and longitudinal cognitive function, without significant interactions between them (Ps > 0.05). Participants with both CMM and depression had lower cross-sectional cognitive performance (e.g. β = -0.207, 95% CI = (-0.255, -0.159) for CMM5 (+)/depression (+)) and a faster rate of cognitive decline (e.g. β = -0.040, 95% CI = (-0.047, -0.034) for CMM5 (+)/depression (+)), compared with those without either condition. These associations remained consistent after additional adjustment for APOE genotype and were robust in two-step random-effects IPD analyses. The findings regarding the joint association of CMM and depression on cognitive function were reproduced in the three external validation studies. Interpretation: Our findings highlighted the importance of investigating age-related co-morbidities in a multi-dimensional perspective. Targeting both cardiometabolic and psychological conditions to prevent cognitive decline could enhance effectiveness.