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1.
Emerging Contaminants: An Emerging Risk Factor for Diabetes Mellitus.
Niu, H, Xu, M, Tu, P, Xu, Y, Li, X, Xing, M, Chen, Z, Wang, X, Lou, X, Wu, L, et al
Toxics. 2024;(1)
Abstract
Emerging contaminants have been increasingly recognized as critical determinants in global public health outcomes. However, the intricate relationship between these contaminants and glucose metabolism remains to be fully elucidated. The paucity of comprehensive clinical data, coupled with the need for in-depth mechanistic investigations, underscores the urgency to decipher the precise molecular and cellular pathways through which these contaminants potentially mediate the initiation and progression of diabetes mellitus. A profound understanding of the epidemiological impact of these emerging contaminants, as well as the elucidation of the underlying mechanistic pathways, is indispensable for the formulation of evidence-based policy and preventive interventions. This review systematically aggregates contemporary findings from epidemiological investigations and delves into the mechanistic correlates that tether exposure to emerging contaminants, including endocrine disruptors, perfluorinated compounds, microplastics, and antibiotics, to glycemic dysregulation. A nuanced exploration is undertaken focusing on potential dietary sources and the consequential role of the gut microbiome in their toxic effects. This review endeavors to provide a foundational reference for future investigations into the complex interplay between emerging contaminants and diabetes mellitus.
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2.
Ginseng Oligopeptides Improve the Intestinal Physiology and Promote the Antioxidant Capacity of the Gut-on-a-Chip Model.
You, M, Xu, M
Nutrients. 2024;(6)
Abstract
During ageing, the permeability of the intestinal barrier increases, the integrity of the intestinal barrier decreases, and the physiology of intestinal cells changes. Furthermore, intestinal inflammation and excessive oxidative stress are both likely to cause systemic diseases. Ginseng oligopeptides have a positive significant effect in terms of improving human health and delaying ageing, but their role in the ageing of the intestine has not been studied much. In our experiment, we constructed a gut-on-a-chip model and induced senescence of the chip with H2O2 so as to explore the effects of ginseng oligopeptides on the senescent intestine. The experimental results showed that ginseng oligopeptides had no obvious effects on the integrity of the intestine, including the TEER value and the expression of tight junction proteins. However, ginseng oligopeptides might have other positive effects, such as inhibiting excessive cell proliferation, promoting mucin secretion, and increasing the antioxidant capacity of the intestine, to improve intestinal health.
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3.
Lifestyle intervention in children with obesity and nonalcoholic fatty liver disease (NAFLD): study protocol for a randomized controlled trial in Ningbo city (the SCIENT study).
Zhang, PP, Wang, YX, Shen, FJ, Xing, YF, Gu, JY, Li, XY, Jin, H, Jin, SF, Xu, M, Wang, HJ, et al
Trials. 2024;(1):196
Abstract
BACKGROUND The increasing prevalence of childhood obesity has become an urgent public health problem, evidence showed that intervention for childhood obesity bring enormous health benefits. However, an effective individualized intervention strategy remains to be developed, and the accompanying remission of related complications, such as nonalcoholic fatty liver disease (NAFLD), needs to be assessed. This study aimed to develop an m-Health-assisted lifestyle intervention program targeting overweight/obese children and assess its effectiveness on indicators of adiposity and NAFLD. METHODS This is a cluster-randomized controlled trial that conducted in children with overweight/obesity in Ningbo city, Zhejiang Province, China. Students in Grade 3 (8-10 years old) were recruited from six primary schools, with three be randomized to intervention group and three to usual practice group. The intervention program will last for one academic year and consists of health education, dietary guidance, and physical activity reinforcement. This program is characterized by encouraging four stakeholders, including School, Clinic, famIly, and studENT (SCIENT), to participate in controlling childhood obesity, assisted by m-Health technology. Assessments will be conducted at baseline and 3 months, 9 months, 24 months, and 36 months after baseline. The primary outcome will be the differences between the two groups in students' body mass index and fatty liver index at the end of the intervention (9 months after baseline). During the implementation process, quality control methods will be adopted. DISCUSSION The program will test the effectiveness of the m-Health-assisted lifestyle intervention on children with obesity and NAFLD. The results of this study will provide evidence for establishing effective lifestyle intervention strategy aimed at childhood obesity and NAFLD and may help develop guidelines for the treatment of obesity and NAFLD in Chinese children. TRIAL REGISTRATION Clinicaltrials.gov NCT05482191. Registered on July 2022.
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4.
Effects of folic acid supplementation on cognitive impairment: A meta-analysis of randomized controlled trials.
Xu, M, Zhu, Y, Chen, J, Li, J, Qin, J, Fan, Y, Ren, P, Hu, H, Wu, W
Journal of evidence-based medicine. 2024;(1):134-144
Abstract
OBJECTIVE With the increasing number of patients with cognitive impairment, nonpharmacological ways to delay cognitive impairment have attracted people's attention, such as lifestyle changes and nutritional supplementation. Folic acid supplementation appears to be a promising treatment option. However, it remains controversial whether folic acid supplementation is effective in delaying adult's cognitive impairment. Therefore, we conducted a meta-analysis to analyze the effects of folic acid supplementation on different cognitive impairments. METHODS We systematically searched PubMed, Web of Science, EMbase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), WanFang and VIP databases for randomized controlled trials on January 22, 2024. The included population comprised those diagnosed with cognitive impairment. We included trials that compared folic acid treatment with placebo, other dosing regimens, or other intervention controls. Conducting quality evaluation of included studies according to the Cochrane Risk of Bias tool. Statistical analyses were performed using Review Manager software. RESULTS Twenty-two trials, including 3604 participants, met inclusion criteria. Compared with controls, the cognitive function of Alzheimer's disease (AD) patients showed improvement with folic acid supplementation: supplementation with < 3 mg (standardized mean differences (SMD) = 0.15, 95% confidence interval (CI) -0.10 to 0.41), and supplementing with ≥ 3 mg folic acid could improve cognitive function in AD patients (SMD = 1.03, 95% CI 0.18 to 1.88). Additionally, it reduced homocysteine (HCY) levels (mean differences (MD) = -4.74, 95% CI -8.08 to -1.39). In mild cognitive impairment (MCI) patients, cognitive function improved with folic acid supplementation: supplementation with > 400 μg (SMD = 0.38, 95% CI 0.13 to 0.63), and supplementation with ≤ 400 μg (SMD = 1.10, 95% CI 0.88 to 1.31). It also reduced HCY levels at intervention ≤ 6 months (MD = -3.93, 95% CI -5.05 to -2.82) and intervention > 6 months (MD = -4.38, 95% CI -5.15 to -3.61). However, supplementing with folic acid did not improve cognitive function in vascular cognitive impairment (VCI) patients, with folic acid supplements < 3 mg (SMD = -0.07, 95% CI -0.23 to -0.08), folic acid supplements ≥ 3 mg (SMD = 0.46, 95% CI -0.57 to 1.49), however, it reduced HCY levels at intervention > 6 months (MD = -5.91, 95% CI -7.13 to -4.69) and intervention ≤ 6 months (MD = -11.15, 95% CI -12.35 to -9.95). CONCLUSIONS Supplement folic acid is beneficial to the cognitive profile of patients with MCI, supplementation with ≥ 3 mg folic acid can improve cognitive function in AD patients.
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5.
Association between the Maternal Mediterranean Diet and Perinatal Outcomes: A Systematic Review and Meta-Analysis.
Xu, J, Wang, H, Bian, J, Xu, M, Jiang, N, Luo, W, Zu, P, Yin, W, Zhu, P
Advances in nutrition (Bethesda, Md.). 2024;(2):100159
Abstract
The Mediterranean diet is a global, well-known healthy dietary pattern. This review aims to synthesize the existing evidence on the relationship between the maternal Mediterranean diet during pregnancy and perinatal outcomes, including randomized controlled trials (RCTs) and cohort studies. PubMed, Web of Science, and the Cochrane Library were searched from inception to 10 March, 2023, supplemented by manual screening. A random-effect model was used to estimate pooled sizes with 95% confidence intervals (CIs) for specific outcomes of interest. Data from 5 RCTs and 18 cohort studies with 107,355 pregnant participants were synthesized. In RCTs, it was observed that the maternal Mediterranean diet significantly reduced the incidence of gestational diabetes mellitus [odds ratio (OR), 0.56; 95% CI: 0.34, 0.93], as well as small for gestational age (0.55; 95% CI: 0.35, 0.88). In cohort studies, the highest adherence score to the maternal Mediterranean diet was inversely associated with a lower risk of various adverse pregnancy outcomes, including gestational diabetes mellitus (OR, 0.82; 95% CI: 0.67, 1.00), pregnancy-induced hypertension (0.73; 95% CI: 0.60, 0.89), pre-eclampsia (0.77; 95% CI: 0.64, 0.93), preterm delivery (0.67; 95% CI: 0.49, 0.91), low birth weight (0.70; 95% CI: 0.64, 0.78), intrauterine growth restriction (0.46; 95% CI: 0.23, 0.91), and increased gestational age at delivery (weighted mean difference, 0.11 wk; 95% CI: 0.03, 0.20). Meta-regression analyses did not identify the adjustment for confounders and geographical location as predictive factors for heterogeneity. The results suggest that adherence to the Mediterranean diet during pregnancy appears to be beneficial for perinatal outcomes. Future, larger, and higher-quality RCTs and cohort studies are warranted to confirm the present findings. PROSPERO registration no.: CRD42023406317.
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6.
Reprogramming of lipid metabolism in the tumor microenvironment: a strategy for tumor immunotherapy.
Wu, Y, Pu, X, Wang, X, Xu, M
Lipids in health and disease. 2024;(1):35
Abstract
Lipid metabolism in cancer cells has garnered increasing attention in recent decades. Cancer cells thrive in hypoxic conditions, nutrient deficiency, and oxidative stress and cannot be separated from alterations in lipid metabolism. Therefore, cancer cells exhibit increased lipid metabolism, lipid uptake, lipogenesis and storage to adapt to a progressively challenging environment, which contribute to their rapid growth. Lipids aid cancer cell activation. Cancer cells absorb lipids with the help of transporter and translocase proteins to obtain energy. Abnormal levels of a series of lipid synthases contribute to the over-accumulation of lipids in the tumor microenvironment (TME). Lipid reprogramming plays an essential role in the TME. Lipids are closely linked to several immune cells and their phenotypic transformation. The reprogramming of tumor lipid metabolism further promotes immunosuppression, which leads to immune escape. This event significantly affects the progression, treatment, recurrence, and metastasis of cancer. Therefore, the present review describes alterations in the lipid metabolism of immune cells in the TME and examines the connection between lipid metabolism and immunotherapy.
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7.
A SCYL2 gene from Oryza sativa is involved in phytosterol accumulation and regulates plant growth and salt stress.
Xu, M, Ni, Y, Tu, Y, Wang, Y, Zhang, Z, Jiao, Y, Zhang, X
Plant science : an international journal of experimental plant biology. 2024;:112062
Abstract
Rice is a crucial food for humans due to its high nutritional value. Phytosterols, essential components of the plant membrane lipid bilayer, play a vital role in plant growth and contribute significantly to lipid-lowering, antitumor, and immunomodulation processes. In this study, SCY1-like protein kinases 2 (SCYL2) was found to be closely related to the accumulation of phytosterols. The levels of campesterol, stigmasterol, and β-sitosterol significantly increased in transgenic rice seeds, husks, and leaves, whereas there was a considerable reduction in scyl2 plants. Subsequent investigations revealed the crucial role of SCYL2 in plant development. Mutations in this gene led to stunted plant growth while overexpressing OsSCYL2 in Arabidopsis and rice resulted in larger leaves, taller plants, and accelerated development. When subjected to salt stress, Arabidopsis plants overexpressed OsSCYL2 showed significantly higher germination rates than wild-type plants. Similarly, transgenic rice seedlings displayed better growth than both ZH11 and mutant plants, exhibiting lower malondialdehyde (MDA) content and higher peroxidase (POD), and catalase (CAT) activities. Conversely, scyl2 plants exhibited more yellow leaves or even death. These findings suggested that OsSCYL2 proteins might be involved in phytosterols synthesis and play an important role during plant growth and development. This study provides a theoretical basis for developing functional rice.
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8.
Polarizable Additive with Intermediate Chelation Strength for Stable Aqueous Zinc-Ion Batteries.
Xia, Y, Tong, R, Zhang, J, Xu, M, Shao, G, Wang, H, Dong, Y, Wang, CA
Nano-micro letters. 2024;(1):82
Abstract
Aqueous zinc-ion batteries are promising due to inherent safety, low cost, low toxicity, and high volumetric capacity. However, issues of dendrites and side reactions between zinc metal anode and the electrolyte need to be solved for extended storage and cycle life. Here, we proposed that an electrolyte additive with an intermediate chelation strength of zinc ion-strong enough to exclude water molecules from the zinc metal-electrolyte interface and not too strong to cause a significant energy barrier for zinc ion dissociation-can benefit the electrochemical stability by suppressing hydrogen evolution reaction, overpotential growth, and dendrite formation. Penta-sodium diethylene-triaminepentaacetic acid salt was selected for such a purpose. It has a suitable chelating ability in aqueous solutions to adjust solvation sheath and can be readily polarized under electrical loading conditions to further improve the passivation. Zn||Zn symmetric cells can be stably operated over 3500 h at 1 mA cm-2. Zn||NH4V4O10 full cells with the additive show great cycling stability with 84.6% capacity retention after 500 cycles at 1 A g-1. Since the additive not only reduces H2 evolution and corrosion but also modifies Zn2+ diffusion and deposition, highlyreversible Zn electrodes can be achieved as verified by the experimental results. Our work offers a practical approach to the logical design of reliable electrolytes for high-performance aqueous batteries.
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9.
Population Pharmacokinetic/Pharmacodynamic Analysis of the Glucokinase Activator PB201 in Healthy Volunteers and Patients with Type 2 Diabetes Mellitus: Facilitating the Clinical Development of PB201 in China.
Song, L, Cao, F, Niu, S, Xu, M, Liang, R, Ding, K, Lin, Z, Yao, X, Liu, D
Clinical pharmacokinetics. 2024;(1):93-108
Abstract
PB201 is an orally active, partial glucokinase activator targeting both pancreatic and hepatic glucokinase. As the second glucokinase activator studied beyond phase I, PB201 has demonstrated promising glycemic effects as well as favorable pharmacokinetic (PK) and safety profiles in patients with type 2 diabetes mellitus (T2DM). This study aims to develop a population PK/pharmacodynamic (PD) model for PB201 using the pooled data from nine phase I/II clinical trials conducted in non-Chinese healthy volunteers and a T2DM population and to predict the PK/PD profile of PB201 in a Chinese T2DM population. We developed the PK/PD model using the non-linear mixed-effects modeling approach. All runs were performed using the first-order conditional estimation method with interaction. The pharmacokinetics of PB201 were well fitted by a one-compartment model with saturable absorption and linear elimination. The PD effects of PB201 on reducing the fasting plasma glucose and glycosylated hemoglobin levels in the T2DM population were described by indirect response models as stimulating the elimination of fasting plasma glucose, where the production of glycosylated hemoglobin was assumed to be stimulated by fasting plasma glucose. Covariate analyses revealed enhanced absorption of PB201 by food and decreased systemic clearance with ketoconazole co-administration, while no significant covariate was identified for the pharmacodynamics. The population PK model established for non-Chinese populations was shown to be applicable to the Chinese T2DM population as verified by the PK data from the Chinese phase I study. The final population PK/PD model predicted persistent and dose-dependent reductions in fasting plasma glucose and glycosylated hemoglobin levels in the Chinese T2DM population receiving 50/50 mg, 100/50 mg, and 100/100 mg PB201 twice daily for 24 weeks independent of co-administration of metformin. Overall, the proposed population PK/PD model quantitatively characterized the PK/PD properties of PB201 and the impact of covariates on its target populations, which allows the leveraging of extensive data in non-Chinese populations with the limited data in the Chinese T2DM population to successfully supported the waiver of the clinical phase II trial and facilitate the optimal dose regimen design of a pivotal phase III study of PB201 in China.
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10.
Endothelial dysfunction of syphilis: Pathogenesis.
Liu, Z, Zhang, X, Xiong, S, Huang, S, Ding, X, Xu, M, Yao, J, Liu, S, Zhao, F
Journal of the European Academy of Dermatology and Venereology : JEADV. 2024
Abstract
Treponema pallidum is the causative factor of syphilis, a sexually transmitted disease (STD) characterized by perivascular infiltration of inflammatory cells, vascular leakage, swelling and proliferation of endothelial cells (ECs). The endothelium lining blood and lymphatic vessels is a key barrier separating body fluids from host tissues and is a major target of T. pallidum. In this review, we focus on how T. pallidum establish intimate interactions with ECs, triggering endothelial dysfunction such as endothelial inflammation, abnormal repairment and damage of ECs. In addition, we summarize that migration and invasion of T. pallidum across vascular ECs may occur through two pathways. These two mechanisms of transendothelial migration are paracellular and cholesterol-dependent, respectively. Herein, clarifying the relationship between T. pallidum and endothelial dysfunction is of great significance to provide novel strategies for diagnosis and prevention of syphilis, and has a great potential prospect of clinical application.