世界生物化学杂志:英文版(电子版)最新文献

Choline supports phospholipid synthesis, membrane integrity, neurotransmission, verylowdensity lipoprotein export, and one-carbon/epigenetic pathways, yet most United States adults fall short of adequate intake. Fatty liver is now viewed as a mitochondrial-centric metabolic-inflammatory disorder; ethanol and excess linoleic acid (LA) can magnify bioenergetic stress when choline is insufficient to sustain phosphatidylcholine/phosphatidylethanolamine. This narrative review examines whether optimized choline delivery, alongside reduced exposure to mitochondrial toxicants, offers a rational therapeutic approach. Low choline intake associates with higher liver fat and aminotransferases. In rodents, choline deficiency combined with ethanol or LA lowers mitochondrial membrane potential, limits β-oxidation, and promotes steatosis and inflammation. Advanced formulations-especially citicoline-demonstrate favorable absorption and tissue choline delivery and may lessen trimethylamine-N-oxide formation versus free choline salts. Early, small human studies suggest that choline repletion, together with curtailed ethanol or dietary LA, can reduce intrahepatic triglyceride content and improve insulin sensitivity, though large randomized trials are lacking. Framing fatty liver as nutrition-modifiable mitochondrial toxicosis highlights correctable choline insufficiency when the liver is burdened by ethanol or excess LA. A dual strategy-using higher-bioavailability, gutmicrobial trimethylamineNoxide-sparing choline forms and mitigating mitochondrial toxicants-targets core bioenergetic defects, may reverse early steatosis, and warrants testing in adequately powered clinical trials.

Obesity is a major contributor to metabolic dysfunction, and its impact on pancreatic health has garnered increasing attention. Macrophages, as key regulators of inflammation and metabolism, play a central role in mediating obesity-induced pancreatic damage. In obese individuals, excessive lipid accumulation and chronic low-grade inflammation drive the infiltration and polarization of macrophages within the pancreas. These macrophages, particularly the pro-inflammatory Macrophage, pro-inflammatory phenotype (M1) phenotype, secrete cytokines such as C-C motif ligand 2 (CCL2) and transforming growth factor beta (TGF-β), which disrupt pancreatic β-cell function and impair insulin secretion. Conversely, anti-inflammatory Macrophage, anti-inflammatory phenotype (M2) macrophages contribute to tissue repair but may also promote fibrotic changes under prolonged metabolic stress. Pancreatic macrophages are activated under high-fat diet conditions, promoting inflammation and impairing β-cell function through the SUCLA2-HIF-1α axis and mechanistic Target of Rapamycin Complex 1 (mTORC1)/PD-1 pathway, thereby establishing a self-perpetuating "metabolic-immunosuppressive" vicious cycle. Targeted intervention strategies against macrophages-such as SUCLA2 inhibitors can ameliorate metabolic dysregulation. Meanwhile, exosome-mediated interorgan communication [e.g., via microRNA-155 (miR-155) and miR-30a] offers novel insights for multi-system synergistic therapies. Understanding the mechanisms by which macrophages mediate metabolic dysregulation in the pancreas under obese conditions provides critical insights into the pathogenesis of obesity-related pancreatic disorders.

Pentadecanoic acid (C15:0) is an odd-chain fatty acid, the β-oxidation of which yields propionyl-CoA that replenishes succinyl-CoA and tricarboxylic acid cycle flux; higher circulating levels are associated with reduced type 2 diabetes, cardiovascular disease, metabolic dysfunction-associated steatotic liver disease, and mortality. Summarize the cellular and molecular mechanisms underlying these associations. A comprehensive literature search (2000-2025) identified studies of C15:0's mechanistic actions in vitro and in vivo, and multi-omics studies focused on receptor binding, signaling cascades, gene expression, and comparative pharmacology. C15:0 is a dual partial peroxisome proliferator-activated receptor α/δ agonist. It activates AMP-activated protein kinase, suppresses mechanistic target of rapamycin, and selectively inhibits histone deacetylase 6. It augments succinate-driven complex II respiration, preserves mitochondrial membrane potential, limits reactive oxygen species, and attenuates interleukin-6 (IL-6) - triggered Janus kinase 2/signal transducer and activator of transcription 3 and nuclear factor kappa B p65 signaling, lowering monocyte chemoattractant protein-1, tumor necrosis factor-alpha, and IL-6. Across the BioMAP^® human-primarycell platform - which tests 12 distinct primary human cell systems such as endothelial cells, fibroblasts, macrophages, and T-cells - C15:0 (17 µM) produced statistically significant changes in 36 mechanistically diverse biomarkers. This broad, multi-pathway modulation mirrors the phenotype produced by metformin and rapamycin, yet occurred with no detectable cytotoxicity, paralleling metformin and rapamycin with negligible cytotoxicity. C15:0 engages receptor targets that converge on enhanced lipid oxidation, cellular energetics, and inflammation resolution. Although prospective clinical outcomes are still lacking, the pleiotropic mechanism profile positions C15:0 as a potentially unique nutraceutical or adjunct therapeutic candidate. Further research is warranted to confirm its clinical impacts, optimize dosing, and clarify long-term safety as an essential fatty acid supporting metabolic and immune homeostasis.

Background: Alzheimer's disease is a neurodegenerative dementia characterized by accumulation of β-amyloid plaques, tau hyperphosphorylation, and neuroinflammation. Recent research has highlighted a potential relationship between chronic oral infections and neurodegeneration, particularly the involvement of Porphyromonas gingivalis (P. gingivalis), a key pathogen in periodontitis. Experimental mouse models have been used to explore how P. gingivalis products contribute to neuroinflammatory and degenerative processes. However, a comprehensive synthesis of these findings is lacking. This systematic review evaluates the role of P. gingivalis-derived factors in triggering Alzheimer's-like pathology, with an emphasis on bacterial products and host immune responses. We hypothesize that P. gingivalis products exacerbate neuroinflammation and pathology in mouse models of Alzheimer's disease.

Aim: To link gingival P. gingivalis bacteria-associated products with the onset and progression of Alzheimer's disease-like pathology in mouse models.

Methods: This systematic review followed the 2020 PRISMA guidelines. A comprehensive search was conducted in five databases (PubMed, Scopus, ScienceDirect, Sage, SpringerLink) for original studies between 2014 and 2024. Studies included mouse models to evaluate the effect of P. gingivalis or its products on Alzheimer's-like pathologies. Exclusion criteria were in vitro, human, or review studies. Twenty-three studies met the inclusion criteria. Bacterial components and activated host factors were extracted, categorized, and analyzed using narrative synthesis and descriptive statistics.

Results: In 24 studies, lipopolysaccharides (54.84%) and gingipains (25.81%) were the most frequently reported P. gingivalis products. These factors activated toll-like receptors (TLR2/TLR4), microglia, and astrocytes, increasing levels of interleukin 1 beta, tumor necrosis factor-alpha, and other proinflammatory cytokines. The host response included β-amyloid accumulation, Tau hyperphosphorylation, and changes in blood-brain barrier permeability. Glial cells were the most frequently mentioned host factors (n = 15), followed by proteins (n = 13) and cytokines (n = 11). These interactions promoted cognitive impairment, synaptic dysfunction, and neurodegeneration in mouse models, supporting a role for P. gingivalis in Alzheimer's-like pathology.

Conclusion: P. gingivalis products induce neuroinflammatory responses and Alzheimer's-like pathology in mouse models, supporting their role as contributors to neurodegeneration and potential targets for preventive strategies.

Background: Neurodegeneration refers to the progressive loss of neurons, affecting both their structure and function. It is driven by synaptic dysfunction, disruptions in neural networks, and the accumulation of abnormal protein variants. Endoplasmic reticulum (ER) stress, caused by the accumulation of misfolded or unfolded protein, is a major contributor to neurodegeneration. Dithiothreitol (DTT) is a widely used redox reagent that disrupts the oxidative protein folding environment, inducing ER stress and leading to the imbalance in protein homeostasis can activate stress response pathway, potentially contributing to neurodegenerative processes. Caenorhabditis elegans (C. elegans) is a widely used model organism for studying neurodegeneration due to its well-mapped nervous system, approximately one-third of neuron cells in their body, complete genome sequenced, and conserved stress response pathway.

Aim: To study the neurodegeneration in C. elegans caused by DTT-induced ER stress, assessed by behavioral, molecular, and lifespan changes.

Methods: C. elegans were cultured on nematode growth medium plates with OP50, and ER stress was induced using DTT. Effects were assessed via behavioral assays such as locomotion, chemotaxis, lifespan assay, and molecular studies.

Results: DTT exposure led to a significant decline in locomotion and chemotaxis response, indicating neurotoxicity. A reduction in lifespan was observed, suggesting an overall impact on health. Molecular analysis confirmed ER stress activation. DTT-induced ER stress negatively affects C. elegans, leading to behavioral impairments and molecular alterations associated with neurodegeneration.

Conclusion: These findings establish C. elegans as a potential model for studying ER stress-mediated neurotoxicity and its implications in neurodegenerative diseases.

Background: Chemotherapy-induced cardiotoxicity is a significant complication in cancer therapy, limiting treatment efficacy and worsening patient outcomes. Recent studies have implicated the gut microbiome and its key metabolites, such as short-chain fatty acids (SCFAs) and trimethylamine-N-oxide (TMAO), in mediating inflammation, oxidative stress, and cardiac damage. The gut-heart axis is increasingly recognized as a pivotal pathway linking microbiota dysregulation to chemotherapy-related cardiac dysfunction.

Aim: To systematically review existing evidence on the role of gut microbiome alterations in chemotherapy-induced cardiotoxicity and evaluate emerging microbiome-based therapeutic strategies aimed at mitigating cardiovascular risk in cancer patients.

Methods: A systematic literature search was conducted in PubMed, Scopus, and Web of Science for studies published between January 2013 and December 2024. Studies were included if they examined chemotherapy-induced cardiotoxicity in relation to gut microbiota composition, microbial metabolites (e.g., SCFAs, TMAO), or microbiome-targeted interventions. Selection followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data extraction focused on microbiota alterations, mechanistic pathways, cardiac outcomes, and quality assessments using standardized risk-of-bias tools.

Results: Eighteen studies met the inclusion criteria. Chemotherapy was consistently associated with gut dysbiosis characterized by reduced SCFA-producing bacteria and increased TMAO-producing strains. This imbalance contributed to gut barrier disruption, systemic inflammation, and oxidative stress, all of which promote myocardial damage. SCFA depletion weakened anti-inflammatory responses, while elevated TMAO levels exacerbated cardiac fibrosis and dysfunction. Preclinical studies showed promising cardioprotective effects from probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation, though human data remain limited.

Conclusion: Gut microbiome dysregulation plays a crucial role in the development of chemotherapy-induced cardiotoxicity. Altered microbial composition and metabolite production trigger systemic inflammation and cardiac injury. Microbiome-targeted therapies represent a promising preventive and therapeutic approach in cardio-oncology, warranting further clinical validation through well-designed trials.

Background: Botulinum toxin (BoNT) is a bacterial poison that acts by blocking the release of acetylcholine-containing vesicles at the neuromuscular junction. Notably, a mild amount of BoNT is known to exert therapeutic benefits against various diseases, including migraine, movement disorders, anxiety and neurocognitive deficits. BoNT treatment appears to increase platelet count in circulation. Therefore, BoNT treatment may be associated with the regulation of blood coagulation upon haemorrhagic events. However, the effects of BoNT on the degree of bleeding and clotting events have not yet been determined.

Aim: To investigate the effect of BoNT on the bleeding parameters and blood coagulation events in experimental mice.

Methods: A group of 7-8-month-old mice was intramuscularly injected with a mild single dose of BoNT. After a month of BoNT injection, animals were subjected to tail bleeding assay, assessment of clotting time, and degree of platelet aggregation in comparison with the control group.

Results: Results revealed that BoNT injection significantly reduced blood loss and bleeding time in experimental aging mice upon tail tip transection. Moreover, the blood samples collected from the BoNT-treated mice showed enhanced platelet aggregation and intense formation of the fibrin clot compared to the control. This study indicates a putative therapeutic value of BoNT in mitigating bleeding episodes, possibly through its platelet-enhancing property.

Conclusion: BoNT treatment effectively facilitates blood coagulation. Upon further validation, this approach can be translated to treat traumatic blood vessel injuries, haemorrhagic diseases, and bleeding complications associated with surgical procedures.

The canonical signaling of interferon gamma (IFN-γ) through the Janus kinase 1 and 2-signal transducer and activator of transcription 1 (STAT1) axis leads to the expression of several interferon-stimulated genes (ISGs), which have diverse effects depending on the cellular context. In glioblastoma, a highly aggressive primary brain tumor in adults, elements of IFN-γ canonical signaling are deregulated, resulting in the overexpression of STAT1-target ISGs associated with tumor progression. This mini-review highlights key ISGs, including STAT1, interferon regulatory factor 1, programmed death-ligand 1, indoleamine 2,3-dioxygenase 1, and interferon-stimulated gene 15, involved in the pathology of glioblastoma. These genes may serve as valuable biomarkers and have therapeutic potential for targeting IFN-γ signaling in this malignancy.

Background: Gestational diabetes mellitus (GDM) is a metabolic disorder causing hyperglycemia during pregnancy. Insulin resistance and decreased insulin secretion are linked to altered lipid metabolism that leads to progression of GDM. CD36 is a membrane glycoprotein involved in lipid metabolism and insulin sensitivity. Studies indicate that the CD36 gene is substantially linked to type 2 diabetes mellitus (T2DM) and could also influence GDM susceptibility. Insulin resistance and decreased insulin secretion are the hallmarks of T2DM, which is thought to have a similar genetic pathophysiology in GDM.

Aim: To investigate the impact of CD36 gene polymorphisms [rs1761667 (G/A) and rs75326924 (C/T)] and mRNA expression in GDM women.

Methods: The case-control study involved a total of 400 pregnant women, (200 healthy controls and 200 GDM cases). The study of CD36 gene polymorphisms G/A (rs1761667) and C/T (rs75326924)) were determined by polymerase chain reaction-restriction fragment length polymorphism. The mRNA expression study of CD36 gene was analyzed by quantitative polymerase chain reaction/quantitative real-time polymerase chain reaction followed by statistical analysis done using GraphPad Prism8 software (ver. 8.0).

Results: The study revealed statistically significant association (P < 0.05) in anthropometric/biochemical parameters (age, gestational age, body mass index, fasting prandial glucose, post-prandial glucose, triglyceride, low-density lipoprotein) between GDM cases and healthy controls. CD36 G/A(rs1761667) and CD36 C/T (rs75326924) polymorphisms were significantly associated with GDM cases. The heterozygous genotypes (GA and CT) of both variants showed significant association (P = 0.0001 and P = 0.0025, odds ratio = 2.683 and 2.022 respectively). Allele frequency of 'T' allele in CD36 C/T (rs75326924) polymorphism was also found to be significant (P = 0.0046). CD36 gene was upregulated in individuals with GDM as compared to healthy controls (P = 0.0001). However, the upregulation of gene expression was not significantly associated with the genotypes of CD36 G/A (rs1761667) and CD36 C/T (rs75326924) polymorphisms.

Conclusion: Heterozygous genotypes GA and CT of CD36 gene variants and expression are linked to GDM, potentially serving as predictive biomarkers for GDM susceptibility; further exploration needed in diverse ethnic communities.

Background: Fruits of Gardenia jasminoides (G. jasminoides) have extremely high medicinal value. However, the quality and traits of the plants vary significantly based on their provenances. In addition, the behaviour of the known bioactive components, such as geniposide and crocin, has been the primary focus of the research on G. jasminoides. However, the identification of unknown bioactive components and their metabolomics remains underexplored. Therefore, analysing the metabolic differences between gardenias from different sources is essential to provide a comprehensive theoretical basis for the evaluation of G. jasminoides and germplasm resource identification.

Aim: To systematically evaluate the morphology, secondary metabolites, typical active ingredients, and antioxidant activity of wild G. jasminoides fruits.

Methods: Gardenia fruits were collected from different provenances. Metabolites were identified via ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The metabolic differences were compared using hierarchical cluster analysis (HCA). The antioxidant capacity was evaluated using 2,2-diphenyl-1-picrylhydrazyl radical scavenging assays and ferric reducing antioxidant power assays, and its correlation with typical active ingredients was analysed.

Results: A total of 444 and 240 metabolites were identified using UPLC-MS/MS in positive and negative ion modes, respectively. The HCA results of the flavonoids indicated that the higher content of flavonoids was in the fruits from Lukou. The differential analysis of metabolites in fruits from Shaoyang, Miluo and Lukou showed that the fruit from Miluo had the highest upregulated differential metabolites.

Conclusion: The metabolic characteristics of the Ningxiang and Xiangxi extracts were similar, while those of Lukou, Miluo and Shaoyang extracts differed significantly.