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Optimized strategy among diet, exercise, and pharmacological interventions for nonalcoholic fatty liver disease: A network meta-analysis of randomized controlled trials.
Wang, H, Ma, Q, Chen, Y, Luo, L, Ye, J, Zhong, B
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2024
Abstract
BACKGROUND Emerging treatment methods, including exercise, diet, and drugs, for nonalcoholic fatty liver disease have been proposed. However, the differences in their efficacy have not been determined. We aimed to compare the effects of these treatments excluding surgery via a systematic review and network meta-analysis of randomized controlled trials. DATA SOURCE The data sources included PubMed, Embase, Web of Science and Cochrane up to February 1st, 2023. The endpoints consisted of body mass index (BMI), serum markers of metabolism and liver injury markers, liver fat content, and stiffness. RESULTS A total of 174 studies with 10,183 patients were included in this meta-analysis. In terms of improving BMI, Pan-agonist of peroxisome proliferator-activated receptors (PPAR) is the best treatment with the highest SUCRA (surface under the cumulative ranking) of 84.8% (mean = -3.40, 95% CI -5.55, -1.24) by the comparative effectiveness ranking. GLP-1 (glucagon-like peptide-1) has the best effect in improving the liver fat content based on the MRI-PDFF, steatosis score (SUCRA 99.7%, mean = -2.19, 95% CI -2.90, -1.48) and ballooning score (SUCRA 61.2%, mean = -0.82, 95% CI -4.46, 2.83). CONCLUSIONS Pan-agonist of PPAR was the most efficacious regimen in lowering BMIs, whereas GLP-1R agonists achieved the highest efficacy of steatosis improvement in this network meta-analysis.
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Deciphering mitochondrial dysfunction: Pathophysiological mechanisms in vascular cognitive impairment.
He, Y, He, T, Li, H, Chen, W, Zhong, B, Wu, Y, Chen, R, Hu, Y, Ma, H, Wu, B, et al
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2024;:116428
Abstract
Vascular cognitive impairment (VCI) encompasses a range of cognitive deficits arising from vascular pathology. The pathophysiological mechanisms underlying VCI remain incompletely understood; however, chronic cerebral hypoperfusion (CCH) is widely acknowledged as a principal pathological contributor. Mitochondria, crucial for cellular energy production and intracellular signaling, can lead to numerous neurological impairments when dysfunctional. Recent evidence indicates that mitochondrial dysfunction-marked by oxidative stress, disturbed calcium homeostasis, compromised mitophagy, and anomalies in mitochondrial dynamics-plays a pivotal role in VCI pathogenesis. This review offers a detailed examination of the latest insights into mitochondrial dysfunction within the VCI context, focusing on both the origins and consequences of compromised mitochondrial health. It aims to lay a robust scientific groundwork for guiding the development and refinement of mitochondrial-targeted interventions for VCI.
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Treatment of obesity and metabolic-associated fatty liver disease with a diet or orlistat: A randomized controlled trial.
Feng, X, Lin, Y, Zhuo, S, Dong, Z, Shao, C, Ye, J, Zhong, B
The American journal of clinical nutrition. 2023;117(4):691-700
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Plain language summary
Metabolic-associated fatty liver disease (MAFLD) is characterised by excessive lipid accumulation in hepatocytes. Weight management by the treatment to target strategy through lifestyle intervention remains the primary approach for MAFLD treatment. The aim of this study was to compare the efficacy of a conventional energy-restricted diet (the control group), orlistat, and an experimental diet in the Asian population with obesity and MAFLD. This study was a prospective, open-label, monocentric randomised controlled study. Participants (n = 118) were randomly assigned to the control (n = 39), orlistat (n = 40), or experimental diet (n = 39) groups at a 1:1:1 allocation. Results showed that: - orlistat and the experimental diet were superior to lifestyle intervention in ameliorating liver steatosis [fatty liver]. - the experimental diet had an advantage over lifestyle intervention when patients adhered to the diet. - orlistat was superior to the experimental diet and lifestyle modifications in decreasing liver fat content. Authors conclude that more multicentre, large-scale, prospective studies are needed to verify the long-term efficacy and safety of the experimental diet and orlistat treatment in subjects with MAFLD.
Abstract
BACKGROUND Losing weight by lifestyle interventions is the first-line treatment for metabolic-associated fatty liver disease (MAFLD) but is limited by low compliance. OBJECTIVES This study aimed to compare the effects of orlistat or an experimental high-protein/lower-carbohydrate diet with a control diet in Asian patients with obesity and MAFLD. METHODS A total of 118 Asian patients with obesity and MAFLD confirmed with MRI-based proton density fat fraction with Dixon sequence were enrolled and allocated to the control group, the orlistat group, or the experimental diet group for 24 wk. The primary endpoint was the relative change in liver fat content (LFC) assessed by MRI-based proton density fat fraction. RESULTS A total of 118 subjects with obesity and MAFLD were randomly assigned to the control group (n = 39), the orlistat group (n = 40), or the experimental diet group (n = 39). All 3 groups demonstrated improvement in liver steatosis at wk 24. The absolute decrease in LFC in the orlistat group was 9.1% and 5.4% in the experimental diet group, both significantly higher than that in the control group (P < 0.05). The relative reduction in LFC was 30.2% in the experimental diet group, which was significantly higher than the 12.2% observed in the control group (P = 0.01). CONCLUSIONS Orlistat and the experimental diet group reduced liver steatosis compared to the control group. This trial was registered at Chinese Clinical Trial Registry (ChiCTR-1900027172). http://www.chictr.org.cn.
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Transcription factor E4F1 as a regulator of cell life and disease progression.
Sun, S, Zhong, B, Zeng, X, Li, J, Chen, Q
Science advances. 2023;(39):eadh1991
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Abstract
E4F transcription factor 1 (E4F1), a member of the GLI-Kruppel family of zinc finger proteins, is now widely recognized as a transcription factor. It plays a critical role in regulating various cell processes, including cell growth, proliferation, differentiation, apoptosis and necrosis, DNA damage response, and cell metabolism. These processes involve intricate molecular regulatory networks, making E4F1 an important mediator in cell biology. Moreover, E4F1 has also been implicated in the pathogenesis of a range of human diseases. In this review, we provide an overview of the major advances in E4F1 research, from its first report to the present, including studies on its protein domains, molecular mechanisms of transcriptional regulation and biological functions, and implications for human diseases. We also address unresolved questions and potential research directions in this field. This review provides insights into the essential roles of E4F1 in human health and disease and may pave the way for facilitating E4F1 from basic research to clinical applications.
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Ferroptosis landscape in prostate cancer from molecular and metabolic perspective.
Liang, J, Liao, Y, Wang, P, Yang, K, Wang, Y, Wang, K, Zhong, B, Zhou, D, Cao, Q, Li, J, et al
Cell death discovery. 2023;(1):128
Abstract
Prostate cancer is a major disease that threatens men's health. Its rapid progression, easy metastasis, and late castration resistance have brought obstacles to treatment. It is necessary to find new effective anticancer methods. Ferroptosis is a novel iron-dependent programmed cell death that plays a role in various cancers. Understanding how ferroptosis is regulated in prostate cancer will help us to use it as a new way to kill cancer cells. In this review, we summarize the regulation and role of ferroptosis in prostate cancer and the relationship with AR from the perspective of metabolism and molecular pathways. We also discuss the feasibility of ferroptosis in prostate cancer treatment and describe current limitations and prospects, providing a reference for future research and clinical application of ferroptosis.
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Phosphorylation Modification Force Field FB18CMAP Improving Conformation Sampling of Phosphoproteins.
Song, G, Zhong, B, Zhang, B, Rehman, AU, Chen, HF
Journal of chemical information and modeling. 2023;(5):1602-1614
Abstract
Phosphorylation of proteins plays an important regulatory role at almost all levels of cellular organization. Molecular dynamics (MD) simulation is a promising tool to reveal the mechanism of how phosphorylation regulates many key biological processes at the atomistic level. MD simulation accuracy depends on force field precision, while the current force fields for phospho-amino acids have resulted in notable inconsistency with experimental data. Here, a new force field parameter (named FB18CMAP) is generated by fitting against quantum mechanics (QM) energy in aqueous solution with φ/ψ dihedral potential-energy surfaces optimized using CMAP parameters. MD simulations of phosphorylated dipeptides, intrinsically disordered proteins (IDPs), and ordered (folded) proteins show that FB18CMAP can mimic NMR observables and structural characteristics of phosphorylated dipeptides and proteins more accurately than the FB18 force field. These findings suggest that FB18CMAP performs well in both the simulation of ordered and disordered states of phosphorylated proteins.
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Proteome-wide 3D structure prediction provides insights into the ancestral metabolism of ancient archaea and bacteria.
Zhao, W, Zhong, B, Zheng, L, Tan, P, Wang, Y, Leng, H, de Souza, N, Liu, Z, Hong, L, Xiao, X
Nature communications. 2022;(1):7861
Abstract
Ancestral metabolism has remained controversial due to a lack of evidence beyond sequence-based reconstructions. Although prebiotic chemists have provided hints that metabolism might originate from non-enzymatic protometabolic pathways, gaps between ancestral reconstruction and prebiotic processes mean there is much that is still unknown. Here, we apply proteome-wide 3D structure predictions and comparisons to investigate ancestorial metabolism of ancient bacteria and archaea, to provide information beyond sequence as a bridge to the prebiotic processes. We compare representative bacterial and archaeal strains, which reveal surprisingly similar physiological and metabolic characteristics via microbiological and biophysical experiments. Pairwise comparison of protein structures identify the conserved metabolic modules in bacteria and archaea, despite interference from overly variable sequences. The conserved modules (for example, middle of glycolysis, partial TCA, proton/sulfur respiration, building block biosynthesis) constitute the basic functions that possibly existed in the archaeal-bacterial common ancestor, which are remarkably consistent with the experimentally confirmed protometabolic pathways. These structure-based findings provide a new perspective to reconstructing the ancestral metabolism and understanding its origin, which suggests high-throughput protein 3D structure prediction is a promising approach, deserving broader application in future ancestral exploration.
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Balanced Force Field ff03CMAP Improving the Dynamics Conformation Sampling of Phosphorylation Site.
Zhong, B, Song, G, Chen, HF
International journal of molecular sciences. 2022;(19)
Abstract
Phosphorylation plays a key role in plant biology, such as the accumulation of plant cells to form the observed proteome. Statistical analysis found that many phosphorylation sites are located in disordered regions. However, current force fields are mainly trained for structural proteins, which might not have the capacity to perfectly capture the dynamic conformation of the phosphorylated proteins. Therefore, we evaluated the performance of ff03CMAP, a balanced force field between structural and disordered proteins, for the sampling of the phosphorylated proteins. The test results of 11 different phosphorylated systems, including dipeptides, disordered proteins, folded proteins, and their complex, indicate that the ff03CMAP force field can better sample the conformations of phosphorylation sites for disordered proteins and disordered regions than ff03. For the solvent model, the results strongly suggest that the ff03CMAP force field with the TIP4PD water model is the best combination for the conformer sampling. Additional tests of CHARMM36m and FB18 force fields on two phosphorylated systems suggest that the overall performance of ff03CMAP is similar to that of FB18 and better than that of CHARMM36m. These results can help other researchers to choose suitable force field and solvent models to investigate the dynamic properties of phosphorylation proteins.
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Evaluation of bioremediation and detoxification potentiality for papermaking black liquor by a new isolated thermophilic and alkali-tolerant Serratia sp. AXJ-M.
An, X, Zhong, B, Chen, G, An, W, Xia, X, Li, H, Lai, F, Zhang, Q
Journal of hazardous materials. 2021;:124285
Abstract
There is a great need for efficiently treating papermaking black liquor because it can seriously pollute both soil and water ecosystems. In this study, the Plackett-Burman (PB) experimental design combined with response surface methodology (RSM) was used for improving the biodegradation efficiency of lignin by a new isolated thermophilic and alkali-tolerant strain Serratia sp. AXJ-M, and the results showed that a biodegradation efficiency of 70.5% was achieved under optimal culture conditions. The bacterium with ligninolytic activities significantly decreased target the parameters (color 80%, lignin 60%, phenol 95%, BOD 80% and COD 80%). The control and treated samples were analyzed by gas chromatography-mass spectrometer (GC-MS), which showed that the concentrations of a majority of low-molecular-weight compounds were decreased after biological treatment. Furthermore, toxicological, genotoxicity and phytotoxicity studies have supported the detoxification by the bacterium of black liquor. Finally, the genome sequence of the thermophilic, alkali-tolerant and lignin-degrading bacterium AXJ-M was completed, and the genetic basis of the thermophilic and alkali-resistant properties of AXJ-M was preliminarily revealed. The dyp-type peroxidase was first reported to have the potential to catalyze lignin degradation structurally. These findings suggest that Serratia sp. AXJ-M may be potentially useful for bioremediation applications for papermaking black liquor.
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Low levels of low-density lipoprotein cholesterol and cognitive decline.
Hua, R, Ma, Y, Li, C, Zhong, B, Xie, W
Science bulletin. 2021;(16):1684-1690
Abstract
The relationship between low levels of serum low-density lipoprotein cholesterol (LDL-C) and subsequent cognitive decline remains unclear. The present study aimed to evaluate the longitudinal association between low LDL-C levels and cognition decline in the context of the current aggressive guideline-recommended targets (LDL-C levels less than 55 mg/dL for individuals at very high risk of cardiovascular events, and less than 70 mg/dL for high risk individuals). Data from wave 13 (2016) to wave 14 (2018) of the Health and Retirement Study (HRS) were utilized. LDL-C concentrations measured at wave 13 were categorized into 5 levels, reflecting currently recommended values for lipid lowering treatment. Of 7129 included participants (mean age: 69.0 ± 9.9 years, 60.3% female), we found that compared to participants with LDL-C levels of 70.0-99.9 mg/dL, those with LDL-C levels of <55 mg/dL had significantly slower 2-year decline rates in global cognitive function (0.244 point/year; 95% confidence interval (CI): 0.065-0.422; P = 0.008), working memory (0.068 point/year; 95% CI: 0.004-0.133; P = 0.038), and borderline significantly in episodic memory (0.155 point/year; 95% CI: -0.004-0.315; P = 0.057). Similarly, significantly slower decline rates were observed in those with LDL-C levels of 55.0-69.9 mg/dL. The present study demonstrated that compared with LDL-C levels 70.0-99.9 mg/dL, low LDL-C levels (<70 mg/dL, especially <55 mg/dL) were associated with significantly slower cognitive decline in population-based setting. Future randomized controlled trials are warranted to ascertain the safety and benefit of current aggressive guideline-recommended targets on cognitive function.