MICROBIAL PATHOGENESIS
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2024
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IF 3.3
Xiaoye Cheng,Yijin Jiang,Xu Zhao,Nana Ma,Xiangzhen Shen
Lactate has been increasingly recognized for its role in diseases progression, necessitating a deeper understanding of its metabolic processes and regulatory mechanisms. This study aimed to evaluate the impact of lipopolysaccharide (LPS) on lactate accumulation in bovine mammary epithelial cells (BMECs) and to elucidate the underlying regulatory mechanisms. Further optimization of LPS treatment points was achieved by assessing the content of key glycolytic enzymes-hexokinases (HK), pyruvate kinase (PK) and pyruvate dehydrogenase (PDH)-as well as the expression levels of HK2, pyruvate dehydrogenase kinase4 (PDK4) and lactate dehydrogenase (LDHA). Our results indicate that LPS can promote intracellular glycolysis and inhibits pyruvate synthesis, thereby increasing lactate content. BMECs were cultured and divided into a control group (CON) and an LPS-stimulated group (10 μg/mL for 6 h, LPS group). LPS was found to upregulate expression levels of HIF-1α and MCT1, suggesting a role for HIF-1α and MCT1 in cellular glucose metabolism. To explore the effect of HIF-1α on lactate accumulation, BMECs were stimulated with a HIF-1α inducer (COCL 2 ) and HIF-1α inhibitor (DMBPA). COCL 2 was observed to promote lactate accumulation, while DMBPA inhibited it. Additionally, modulation of HIF-1α expression influenced the expression of MCT1, which is a crucial transporter for extracellular lactate influx. To investigate the specific impact of MCT1 on intracellular lactate, we utilized overexpression plasmids and small interfering RNA to modulate MCT1 expression. The findings indicate that while MCT1 expression alone does not affect intracellular lactate levels, it does modulate the changes induced by LPS. In conclusion, our study suggests that LPS regulates lactate accumulation in BMECs through the HIF-1α/MCT1 pathway, providing insights into the metabolic dysregulation associated with LPS-induced stress in dairy cattle.
研究领域:
动物科学
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细胞生物学
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代谢学
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乳品科学
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PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2026
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IF 5.6
Shu-Li Wei,Ying Yang,Cong-Cong Wang,Xue-Min Li,Yuan-Wei Li,Xiao-Li Li,Yang Zhou,Tong Du,Ru-Tao Liu,Ying Liu,Bing Yang,Rui-Sheng Duan,Peng Zhang,Chun-Lin Yang
MCT1 is highly expressed by activated and germinal center B cells. • Targeting MCT1 suppressed humoral response and autoimmunity. • Targeting MCT1 inhibited B cell survival by modulating NAD(H) redox state. Immunometabolism has garnered significant attention due to its essential roles in regulating B cell activation, proliferation and differentiation. Monocarboxylate transporters (MCTs), a family of solute carrier transporters responsible for lactate transport across biological membranes, have been shown to play a pivotal role in immune responses across various immune cell types. However, the expression and functional significance of MCTs in B cells remain poorly understood. In this study, we demonstrated that germinal center B cells and activated B cells exhibit elevated levels of MCT1 expression. Pharmacologically blocking MCT1 with AZD3965 inhibited both T-cell dependent and independent humoral response and ameliorated autoimmunity in the experimental autoimmune myasthenia gravis. Mechanically, MCT1 blockade led to the accumulation of intracellular lactate, which in turn suppressed NAD + regeneration, thereby inhibiting B cell activation and survival. Taken together, these findings suggest that MCT1 might be a potential therapeutical target in antibody-mediate autoimmune disease. Download: Download high-res image (95KB) Download: Download full-size image
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高影响因子
Nature Communications
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2025
·Vol. 16
·期 1
·10551
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IF 15.7
Meng Qingcai,Li Chengxi,Cai Yuping,Chen Ying,Chen Xiaoqing,Wang Xin,Zhang Biling,Zhang Yue,Liu Feng,Chen Meixin
Itaconate accumulates in macrophages upon bacterial infection, and manifests antibacterial activity. Convincing evidence substantiates that itaconate is transported across the plasma membrane and vacuolar membrane, but the molecular bases underlying bidirectional transport of itaconate across membranes and its effects on intracellular bacterial replication are less known. Here, we identify MCT1 and MCT4 as bidirectional transporters of itaconate. In addition to modulating itaconate concentration as transporters at the plasma membrane, MCT1 and MCT4 function as itaconate transporters at Salmonella -containing vacuole (SCV). Upon Salmonella infection, MCT1 and MCT4 transport itaconate into SCV facilitated by RAB32. Itaconate is also secreted out of cells through MCT1 and MCT4 as the infection persists. The suppression of MCT1 and MCT4-dependent itaconate secretion increases the overall concentration of itaconate and the proportion of itaconate-targeted Salmonella intracellularly, consequently inhibiting Salmonella replication. Our study thus offers valuable insights into itaconate transport during bacterial infection and provides proof of principle for the development of itaconate-dependent therapeutic strategies.
研究领域:
免疫学
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微生物学
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细胞生物学
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传染病学
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PubMed
高影响因子
Foods
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2025
·Vol. 14
·期 1
·101
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IF 5.1
Run Yu,Haimeng Zhang,Rui Chen,Yangzhuo Lin,Jingxuan Xu,Ziyang Fang,Yuehang Ru,Chenhan Fan,Guoqing Wu
Alzheimer’s disease (AD) is marked by impaired cognitive functions, particularly in learning and memory, owing to complex and diverse mechanisms. Methionine restriction (MR) has been found to exert a mitigating effect on brain oxidative stress to improve AD. However, the bidirectional crosstalk between the gut and brain through which MR enhances learning and memory in AD, as well as the effects of fecal microbiota transplantation (FMT) from MR mice on AD mice, remains underexplored. In this study, APP/PS1 double transgenic AD mice were used and an FMT experiment was conducted. 16S rRNA gene sequencing, targeted metabolomics, and microbial metabolite short-chain fatty acids (SCFAs) of feces samples were analyzed. The results showed that MR reversed the reduction in SCFAs induced by AD, and further activated the free fatty acid receptors, FFAR2 and FFAR3, as well as the transport protein MCT1, thereby signaling to the brain to mitigate inflammation and enhance the learning and memory capabilities. Furthermore, the FMT experiment from methionine-restricted diet mouse donors showed that mice receiving FMT ameliorated Alzheimer’s learning and memory ability through SCFAs. This study offers novel non-pharmaceutical intervention strategies for AD prevention.
研究领域:
神经科学
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微生物学
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肠脑轴
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代谢组学
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PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICAL RESEARCH
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2026
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IF 4.8
Ziyu Wang,Hongyang Wang,Qinghai Wang,Tao Huang,Chen Guo,Jianlei Ji,Zhen Dong,Yanwei Cao
Glycolysis plays a critical role in regulatory T cells (Tregs), which are frequently exploited by tumor cells, as Treg survival depends on glycolytic activity to suppress antitumor immunity. However, the precise effects of glycolysis on Treg proliferation and differentiation remain incompletely understood. Monocarboxylate transporters (MCTs) are pivotal regulators of glycolytic flux. In this study, we investigated how MCT1 inhibition modulates Treg metabolism and function, and the potential implications for tumor immunotherapy. Silencing MCT1 in human primary Tregs using siRNA disrupted glycolysis, leading to G0/G1 cell cycle arrest, increased apoptosis, and ATP depletion. Integrated metabolomic and transcriptomic analyses identified the ABC transporter pathway as the most significantly altered, with coordinated changes in key genes (ABCA1, ABCB10, ABCC9, etc.) and the metabolite adenosine. Validation using The Cancer Genome Atlas (TCGA) acute myeloid leukemia cohort demonstrated that high expression of the ABC transporter gene ABCC9 is associated with improved overall survival (hazard ratio = 0.45, p < 0.001). These findings indicate that MCT1 inhibition is associated with alterations in the ABC transporter pathway, which may correlate with changes in Treg metabolism and the tumor immune microenvironment. Collectively, this work highlights metabolic reprogramming of Tregs as a novel therapeutic target for cancer immunotherapy.
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PubMed
高影响因子
ELECTROPHORESIS
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2025
·Vol. 46
·期 21
·1576-1587
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IF 2.5
Tao Huang,Chunsu Liang,Xiaomei Ling
High-performance capillary electrophoresis (CE) has been widely applied in the analysis of organic acids, especially monocarboxylic acids (MAs), but no studies on the CE analysis of dissociated states of MAs have been reported. Here, 15 MAs were analyzed by the newly developed universal interface-induced current detector (IICRD). Two current signal peaks were observed in current electrophoretograms (CR-EGs), whereas only one peak with low sensitivity can be obtained by diode array detector (DAD). The current signal peaks of MAs were accurately identified by adding a charge-neutral marker and calculating by p K a . The qualitative analysis indicated that the two current signal peaks of MAs were charge-neutral forms [MA ± ] and monovalent anions [MA − ] in order. Quantitative analysis showed that CE-IICRD can enhance the sensitivity of MA analytes to 40 µM in limit of detection (LOD), with a linear range from 10 −6 to 10 −2 M. Furthermore, interactions between different dissociated states of MAs and monocarboxylate transporter 1 (MCT1) were studied by combined application of nonimmobilized cell CE (NICCE) method for the first time. The binding kinetic parameters and mole number of MCT1 on cell membranes can also be obtained. Besides, competitive binding experiments proved that BAY-8002 (MCT1-specific inhibitor) and lactic acid shared the same binding site. CE-IICRD provides a new method to reveal the interaction between different dissociated forms of MAs or other biomolecules and essential receptors.
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高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2025
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IF 5.4
Hongdong Song,Yaqiong Chen,Ruihan Huang,Xiao Guan
To enhance the oral bioavailability and hypoglycemic effect of insulin, we developed a novel bilayer liposome delivery system in this study. The outer layer of this system was decorated with propanoic acid-functionalized chitosan (CS/PA) to improve gastrointestinal stability and facilitate intestinal targeting of mono-carboxylate transporter protein 1 (MCT1). We encapsulated insulin in this newly developed delivery system. The CS/PA coating significantly enhanced the protective effect of liposomes on insulin in the gastrointestinal environment. Experiments using Caco-2 cells and ligated intestinal loops showed that IN-LIP-CS/PA facilitated insulin absorption and increased intestinal permeability. Importantly, MCT1-mediated energy-dependent endocytosis played a crucial role in the absorption process. Additionally, endocytosis of IN-LIP-CS/PA was mediated through clathrin, lipid raft, caveolin, and macropinocytosis. Furthermore, the endoplasmic reticulum and Golgi apparatus were mainly involved in the intracellular transport of IN-LIP-CS/PA. The combination of MCT1-mediated endocytosis and the intracellular transport pathways may help IN-LIP-CS/PA avoid lysosomal degradation, thereby improving the intracellular transport efficiency of insulin. In vivo studies demonstrated that IN-LIP-CS/PA achieved a significantly better hypoglycemic effect. These findings suggested that the newly developed bilayer liposome delivery system holds promise as an effective platform for the oral delivery of insulin.
研究领域:
药剂学
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药物递送系统
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生物化学
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纳米技术
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生物物理学
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高影响因子
THERIOGENOLOGY
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2024
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IF 2.4
Xiu-Li Zhang,Zhi-Yong An,Gao-Jie Lu,Tuo Zhang,Cheng-Wei Liu,Meng-Qi Liu,Qing-Xin Wei,Lin-Hu Quan,Jin-Dan Kang
Oocytes and embryos are highly sensitive to environmental stress in vivo and in vitro. During in vitro culture, many stressful conditions can affect embryo quality and viability, leading to adverse clinical outcomes such as abortion and congenital abnormalities. In this study, we found that valeric acid (VA) increased the mitochondrial membrane potential and ATP content, decreased the level of reactive oxygen species that the mitochondria generate, and thus improved mitochondrial function during early embryonic development in pigs. VA decreased expression of the autophagy-related factors LC3B and BECLIN1 . Interestingly, VA inhibited expression of autophagy-associated phosphorylation-adenosine monophosphate-activated protein kinase (p-AMPK), phosphorylation-UNC-51-like autophagy-activated kinase 1 (p-ULK1, Ser555), and ATG13, which reduced apoptosis. Short-chain fatty acids (SCFAs) can signal through G-protein-coupled receptors on the cell membrane or enter the cell directly through transporters. We further show that the monocarboxylate transporter 1 (MCT1) was necessary for the effects of VA on embryo quality, which provides a new molecular perspective of the pathway by which SCFAs affect embryos. Importantly, VA significantly inhibited the AMPK-ULK1 autophagic signaling pathway through MCT1, decreased apoptosis, increased expression of embryonic pluripotency genes, and improved embryo quality.
研究领域:
生殖生物学
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分子生物学
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细胞生物学
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PubMed
高影响因子
ACS Applied Materials & Interfaces
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2021
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IF 9.229
Ying Zhang,Jingjing Li,Shengxi Zhang,Weixiang Li,Jin Ouyang,Na Na
Accurate discrimination of inflammations and cancers as well as differential inhibition of cancers are significant for early diagnoses and timely treatments. Nanoparticles have become new modalities for diagnosis and therapy. However, they are still challenged by the efficient delivery of multiple reagents into living cells, discriminating multisignals without any interference, and differential treatments of different diseases. Here, multifunctional spiky topological nanocapsules (STNs) are prepared for the discrimination and differential inhibition of inflammation and cancer. With unique spiky hollow architectures, STNs’ advantages including excellent loading capacity, enhanced cellular uptake, DNAs’ protection against degradation, target-controlled drug release, and efficient endo-/lysosome escape are demonstrated. Therefore, sequential detection of inflammation-related miR-155 (by external modified hairpin DNAs) and the cancer target of monocarboxylate transporter 1 (MCT1) (by internal loaded pH-sensitive carbon dots and MCT1 inhibitor–AZD3965) are achieved. Furthermore, the release of AZD3965 from the cavities of STNs is controlled by the miR-155 amount (first target). Therefore, the released drug of AZD3965 realizes the stage-dependent differential treatment of diseases via cellular acidosis induced by MCT1 inhibition. Via in vivo evaluations of normal, inflammatory, and liver cancer cells/mice, as well as the efficient inhibition of tumor growth, the possibility of STN-based discrimination and differential treatment is confirmed. This would encourage new strategies for multidiagnosis and differential treatment of early-stage cancer.
研究领域:
纳米技术
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生物医学工程
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癌症研究
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炎症研究
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药物递送系统
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DOI
PubMed
高影响因子
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