-
1.
Targeting dysregulated lipid metabolism for the treatment of Alzheimer's disease and Parkinson's disease: Current advancements and future prospects.
Tong, B, Ba, Y, Li, Z, Yang, C, Su, K, Qi, H, Zhang, D, Liu, X, Wu, Y, Chen, Y, et al
Neurobiology of disease. 2024;:106505
Abstract
Alzheimer's and Parkinson's diseases are two of the most frequent neurological diseases. The clinical features of AD are memory decline and cognitive dysfunction, while PD mainly manifests as motor dysfunction such as limb tremors, muscle rigidity abnormalities, and slow gait. Abnormalities in cholesterol, sphingolipid, and glycerophospholipid metabolism have been demonstrated to directly exacerbate the progression of AD by stimulating Aβ deposition and tau protein tangles. Indirectly, abnormal lipids can increase the burden on brain vasculature, induce insulin resistance, and affect the structure of neuronal cell membranes. Abnormal lipid metabolism leads to PD through inducing accumulation of α-syn, dysfunction of mitochondria and endoplasmic reticulum, and ferroptosis. Great progress has been made in targeting lipid metabolism abnormalities for the treatment of AD and PD in recent years, like metformin, insulin, peroxisome proliferator-activated receptors (PPARs) agonists, and monoclonal antibodies targeting apolipoprotein E (ApoE). This review comprehensively summarizes the involvement of dysregulated lipid metabolism in the pathogenesis of AD and PD, the application of Lipid Monitoring, and emerging lipid regulatory drug targets. A better understanding of the lipidological bases of AD and PD may pave the way for developing effective prevention and treatment methods for neurodegenerative disorders.
-
2.
Cost-Effectiveness of Salt Substitute and Salt Supply Restriction in Eldercare Facilities: The DECIDE-Salt Cluster Randomized Clinical Trial.
Lai, X, Yuan, Y, Wang, H, Zhang, R, Qiao, Q, Feng, X, Jin, A, Li, H, Li, J, Si, L, et al
JAMA network open. 2024;(2):e2355564
-
-
Free full text
-
Abstract
IMPORTANCE Salt substitution has been reported to be a cost-saving sodium reduction strategy that has not yet been replicated in different contexts. OBJECTIVE To estimate the cost-effectiveness of sodium reduction strategies within the DECIDE-Salt trial. DESIGN, SETTING, AND PARTICIPANTS The DECIDE-Salt trial cluster randomized in a 1:1:1:1 ratio 48 eldercare facilities in China into 4 groups for evaluation of 2 sodium reduction strategies for 2 years: 1 with both strategies, 2 with either strategy, and 1 with neither strategy. The trial was conducted from September 25, 2017, through October 24, 2020. INTERVENTIONS The 2 intervention strategies were replacing regular salt with salt substitute and progressively restricting salt supply to kitchens. MAIN OUTCOMES AND MEASURES The main outcomes included per-participant costs of intervention implementation and medical treatments for hypertension and major adverse cardiovascular events (MACEs) against mean reductions in systolic blood pressure, hypertension prevalence, MACE incidence, and mortality. The incremental cost-utility ratio was then assessed as the additional mean cost per quality-adjusted life-year gained. Analyses were conducted separately for each strategy, comparing groups assigned and not assigned the test strategy. Disease outcomes followed the intention-to-treat principle and adopted different models as appropriate. One-way and probabilistic sensitivity analyses were conducted to explore uncertainty, and data analyses were performed between August 13, 2022, and April 5, 2023. RESULTS A total of 1612 participants (1230 males [76.3%]) with a mean (SD) age of 71.0 (9.5) years were enrolled. Replacing regular salt with salt substitute reduced mean systolic blood pressure by 7.14 (95% CI, 3.79-10.48) mm Hg, hypertension prevalence by 5.09 (95% CI, 0.37-9.80) percentage points, and cumulative MACEs by 2.27 (95% CI, 0.09-4.45) percentage points. At the end of the 2-year intervention, the mean cost was $25.95 less for the salt substitute group than the regular salt group due to substantial savings in health care costs for MACEs (mean [SD], $72.88 [$9.11] vs $111.18 [$13.90], respectively). Sensitivity analysis showed robust cost savings. By contrast, the salt restriction strategy did not show significant results. If the salt substitution strategy were rolled out to all eldercare facilities in China, 48 101 MACEs and 107 857 hypertension cases were estimated to be averted and $54 982 278 saved in the first 2 years. CONCLUSIONS AND RELEVANCE The findings of this cluster randomized clinical trial indicate that salt substitution may be a cost-saving strategy for hypertension control and cardiovascular disease prevention for residents of eldercare facilities in China. The substantial health benefit savings in preventing MACEs and moderate operating costs offer strong evidence to support the Chinese government and other countries in planning or implementing sodium intake reduction and salt substitute campaigns. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03290716.
-
3.
Biological roles of soil microbial consortium on promoting safe crop production in heavy metal(loid) contaminated soil: A systematic review.
Wang, N, Wang, X, Chen, L, Liu, H, Wu, Y, Huang, M, Fang, L
The Science of the total environment. 2024;:168994
Abstract
Heavy metal(loid) (HM) pollution of agricultural soils is a growing global environmental concern that affects planetary health. Numerous studies have shown that soil microbial consortia can inhibit the accumulation of HMs in crops. However, our current understanding of the effects and mechanisms of inhibition is fragmented. In this review, we summarise extant studies and knowledge to provide a comprehensive view of HM toxicity on crop growth and development at the biological, cellular and the molecular levels. In a meta-analysis, we find that microbial consortia can improve crop resistance and reduce HM uptake, which in turn promotes healthy crop growth, demonstrating that microbial consortia are more effective than single microorganisms. We then review three main mechanisms by which microbial consortia reduce the toxicity of HMs to crops and inhibit HMs accumulation in crops: 1) reducing the bioavailability of HMs in soil (e.g. biosorption, bioaccumulation and biotransformation); 2) improving crop resistance to HMs (e.g. facilitating the absorption of nutrients); and 3) synergistic effects between microorganisms. Finally, we discuss the prospects of microbial consortium applications in simultaneous crop safety production and soil remediation, indicating that they play a key role in sustainable agricultural development, and conclude by identifying research challenges and future directions for the microbial consortium to promote safe crop production.
-
4.
Susceptibility of Cd availability in microplastics contaminated paddy soil: Influence of ferric minerals and sulfate reduction.
Wang, Y, Tang, L, Chen, J, Joseph, A, Wu, Y, Rene, ER, Tang, J, Zhu, N, Wang, P
Journal of hazardous materials. 2024;:133343
Abstract
The combined contamination of cadmium (Cd) and microplastics (MPs) in paddy soil always occurred, while its influence on Cd availability remained unclear. This study investigated the Cd availability in Cd-MPs co-contaminated paddy soil in consideration of both ferric minerals and sulfate reduction under flooding conditions. The presence of MPs resulted in a higher Cd releasing risk, as represented by the increase in the available Cd and decrease in Fe-Mn oxide-bound Cd contents, especially on the 7th and 14th days based on the sequential extraction results. MPs facilitated the formation of Fe-organic ligands, which accelerated the reductive dissolution of iron minerals but decreased the amounts of amorphous iron minerals due to the release of dissolved organic substances into pore water. Furthermore, MPs promoted the relative abundance of sulfate-reducing bacteria (such as Streptomyces and Desulfovibrio genera), thus increasing the contents of reductive S species, which was advantageous to the co-precipitation of Fe, S, and Cd on the surface of MPs based on our experimental and statistical results. Taken together, both iron and sulfate reduction under anaerobic conditions played a critical role in Cd mobilization in Cd-MPs co-contaminated paddy fields.
-
5.
The role of NLRP3 inflammasome in aging and age-related diseases.
Liang, R, Qi, X, Cai, Q, Niu, L, Huang, X, Zhang, D, Ling, J, Wu, Y, Chen, Y, Yang, P, et al
Immunity & ageing : I & A. 2024;(1):14
Abstract
The gradual aging of the global population has led to a surge in age-related diseases, which seriously threaten human health. Researchers are dedicated to understanding and coping with the complexities of aging, constantly uncovering the substances and mechanism related to aging like chronic low-grade inflammation. The NOD-like receptor protein 3 (NLRP3), a key regulator of the innate immune response, recognizes molecular patterns associated with pathogens and injury, initiating an intrinsic inflammatory immune response. Dysfunctional NLRP3 is linked to the onset of related diseases, particularly in the context of aging. Therefore, a profound comprehension of the regulatory mechanisms of the NLRP3 inflammasome in aging-related diseases holds the potential to enhance treatment strategies for these conditions. In this article, we review the significance of the NLRP3 inflammasome in the initiation and progression of diverse aging-related diseases. Furthermore, we explore preventive and therapeutic strategies for aging and related diseases by manipulating the NLRP3 inflammasome, along with its upstream and downstream mechanisms.
-
6.
Osteoporosis and Primary Biliary Cholangitis: A Trans-ethnic Mendelian Randomization Analysis.
Wu, Y, Qian, Q, Liu, Q, Wang, R, Pu, X, Li, Y, Zhang, H, You, Z, Miao, Q, Xiao, X, et al
Clinical reviews in allergy & immunology. 2024
Abstract
Osteoporosis is a major clinical problem in many autoimmune diseases, including primary biliary cholangitis (PBC), the most common autoimmune liver disease. Osteoporosis is a major cause of fracture and related mortality. However, it remains unclear whether PBC confers a causally risk-increasing effect on osteoporosis. Herein, we aimed to investigate the causal relationship between PBC and osteoporosis and whether the relationship is independent of potential confounders. We performed bidirectional Mendelian randomization (MR) analyses to investigate the association between PBC (8021 cases and 16,489 controls) and osteoporosis in Europeans (the UK Biobank and FinnGen Consortium: 12,787 cases and 726,996 controls). The direct effect of PBC on osteoporosis was estimated using multivariable MR analyses. An independent replication was conducted in East Asians (PBC: 2495 cases and 4283 controls; osteoporosis: 9794 cases and 168,932 controls). Trans-ethnic meta-analysis was performed by pooling the MR estimates of Europeans and East Asians. Inverse-variance weighted analyses revealed that genetic liability to PBC was associated with a higher risk of osteoporosis in Europeans (OR, 1.040; 95% CI, 1.016-1.064; P = 0.001). Furthermore, the causal effect of PBC on osteoporosis persisted after adjusting for BMI, calcium, lipidemic traits, and sex hormones. The causal relationship was further validated in the East Asians (OR, 1.059; 95% CI, 1.023-1.096; P = 0.001). Trans-ethnic meta-analysis confirmed that PBC conferred increased risk on osteoporosis (OR, 1.045; 95% CI, 1.025-1.067; P = 8.17 × 10-6). Our data supports a causal effect of PBC on osteoporosis, and the causality is independent of BMI, calcium, triglycerides, and several sex hormones.
-
7.
NAD+-A Hub of Energy Metabolism in Heart Failure.
Wu, Y, Pei, Z, Qu, P
International journal of medical sciences. 2024;(2):369-375
Abstract
Heart failure is a condition where reduced levels of adenosine triphosphate (ATP) affect energy supply in myocardial cells. Nicotinamide adenine dinucleotide (NAD+) plays a crucial role as a coenzyme for electron transfer in energy metabolism. Decreased NAD+ levels in myocardial cells lead to inadequate ATP production and increased susceptibility to heart failure. Researchers are exploring ways to increase NAD+ levels to alleviate heart failure. Targets such as sirtuin2 (sirt2), sirtuin3 (sirt3), Poly (ADP-ribose) polymerase (PARP), and diastolic regulatory proteins are being investigated. NAD+ supplementation has shown promise, even in heart failure with preserved ejection fraction (HFpEF). By focusing on NAD+ as a central component of energy metabolism, it is possible to improve myocardial activity, heart function, and address energy deficiency in heart failure.
-
8.
Exposures to drinking water disinfection byproducts and kidney function in Chinese women.
Li, CR, Deng, YL, Miao, Y, Zhang, M, Zeng, JY, Liu, XY, Wu, Y, Li, YJ, Liu, AX, Zhu, JQ, et al
Environmental research. 2024;:117925
Abstract
BACKGROUND Disinfection byproducts (DBPs), the ubiquitous contaminants in drinking water, have been shown to impair renal function in experimental studies. However, epidemiological evidence is sparse. OBJECTIVE To investigate exposures to DBPs in associations with renal function among women. METHODS A total of 920 women from December 2018 to January 2020 were abstracted from the Tongji Reproductive and Environmental (TREE) Study, an ongoing cohort study in Wuhan, China. Urine samples were gathered at baseline recruitment and analyzed for dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) as biomarkers of DBP exposures. Serum uric acid (UA), creatinine, and estimated glomerular filtration rate (eGFR) were measured as indicators of renal function. Multivariate linear regression and restricted cubic spline (RCS) models were conducted to assess urinary DCAA and TCAA concentrations in associations with renal function indicators. Stratified analyses by age and body mass index (BMI) were also performed. RESULTS We found null evidence of urinary TCAA in associations with renal function indicators. However, elevated urinary DCAA tertiles were related to decreased eGFR (β = -1.78%, 95% CI: 3.21%, -0.36%, comparing the upper vs. lower tertile; P for trend = 0.01). This inverse association still existed when urinary DCAA concentration was treated as a continuous variable, and the dose-response relationship was linear based on the RCS model (P for overall association = 0.002 and P for non-linear associations = 0.44). In the stratified analyses, we found an association of urinary DCAA concentration with decreased UA level among women <30 years but an association with increased UA level among women ≥30 years (P for interaction = 0.04). CONCLUSION Urinary DCAA but not TCAA was associated with impaired renal function among women undergoing assisted reproductive technology.
-
9.
Joint Exposure to Ambient Air Pollutants, Genetic Risk, and Ischemic Stroke: A Prospective Analysis in UK Biobank.
Li, P, Wang, Y, Tian, D, Liu, M, Zhu, X, Wang, Y, Huang, C, Bai, Y, Wu, Y, Wei, W, et al
Stroke. 2024;(3):660-669
Abstract
BACKGROUND Our primary objective was to assess the association between joint exposure to various air pollutants and the risk of ischemic stroke (IS) and the modification of the genetic susceptibility. METHODS This observational cohort study included 307 304 British participants from the United Kingdom Biobank, who were stroke-free and possessed comprehensive baseline data on genetics, air pollutant exposure, alcohol consumption, and dietary habits. All participants were initially enrolled between 2006 and 2010 and were followed up until 2022. An air pollution score was calculated to assess joint exposure to 5 ambient air pollutants, namely particulate matter with diameters equal to or <2.5 µm, ranging from 2.5 to 10 µm, equal to or <10 µm, as well as nitrogen oxide and nitrogen dioxide. To evaluate individual genetic risk, a polygenic risk score for IS was calculated for each participant. We adjusted for demographic, social, economic, and health covariates. Cox regression models were utilized to estimate the associations between air pollution exposure, polygenic risk score, and the incidence of IS. RESULTS Over a median follow-up duration of 13.67 years, a total of 2476 initial IS events were detected. The hazard ratios (95% CI) of IS for per 10 µg/m3 increase in particulate matter with diameters equal to or <2.5 µm, ranging from 2.5 to 10 µm, equal to or <10 µm, nitrogen dioxide, and nitrogen oxide were 1.73 (1.33-2.14), 1.24 (0.88-1.70), 1.13 (0.89-1.33), 1.03 (0.98-1.08), and 1.04 (1.02-1.07), respectively. Furthermore, individuals in the highest quintile of the air pollution score exhibited a 29% to 66% higher risk of IS compared with those in the lowest quintile. Notably, participants with both high polygenic risk score and air pollution score had a 131% (95% CI, 85%-189%) greater risk of IS than participants with low polygenic risk score and air pollution score. CONCLUSIONS Our findings suggested that prolonged joint exposure to air pollutants may contribute to an increased risk of IS, particularly among individuals with elevated genetic susceptibility to IS.
-
10.
Serum electrolyte concentrations and risk of atrial fibrillation: an observational and mendelian randomization study.
Wu, Y, Kong, XJ, Ji, YY, Fan, J, Ji, CC, Chen, XM, Ma, YD, Tang, AL, Cheng, YJ, Wu, SH
BMC genomics. 2024;(1):280
Abstract
BACKGROUND Atrial fibrillation (AF) is a prevalent arrhythmic condition resulting in increased stroke risk and is associated with high mortality. Electrolyte imbalance can increase the risk of AF, where the relationship between AF and serum electrolytes remains unclear. METHODS A total of 15,792 individuals were included in the observational study, with incident AF ascertainment in the Atherosclerosis Risk in Communities (ARIC) study. The Cox regression models were applied to calculate the hazard ratio (HR) and 95% confidence interval (CI) for AF based on different serum electrolyte levels. Mendelian randomization (MR) analyses were performed to examine the causal association. RESULTS In observational study, after a median 19.7 years of follow-up, a total of 2551 developed AF. After full adjustment, participants with serum potassium below the 5th percentile had a higher risk of AF relative to participants in the middle quintile. Serum magnesium was also inversely associated with the risk of AF. An increased incidence of AF was identified in individuals with higher serum phosphate percentiles. Serum calcium levels were not related to AF risk. Moreover, MR analysis indicated that genetically predicted serum electrolyte levels were not causally associated with AF risk. The odds ratio for AF were 0.999 for potassium, 1.044 for magnesium, 0.728 for phosphate, and 0.979 for calcium, respectively. CONCLUSIONS Serum electrolyte disorders such as hypokalemia, hypomagnesemia and hyperphosphatemia were associated with an increased risk of AF and may also serve to be prognostic factors. However, the present study did not support serum electrolytes as causal mediators for AF development.