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1.
J Hazard Mater ; 446: 130697, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36599277

RESUMO

Biological nitrogen fixation (BNF) driven by diazotrophs is a major means of increasing available nitrogen (N) in paddy soil, in addition to anthropogenic fertilization. However, the influence of long-term polychlorinated biphenyl (PCB) contamination on the diazotrophic community and nitrogen fixation in paddy soil is poorly understood. In this study, samples were collected from paddy soil subjected to > 30 years of PCB contamination, and the soil diazotrophic community and N2 fixation rate were evaluated by Illumina MiSeq sequencing and acetylene reduction assays, respectively. The results indicated that high PCB contamination increased diazotrophic abundance and the N2 fixation rate, and altered diazotrophic community structure in the paddy soil. The random forest model demonstrated that the ß-diversity of the diazotrophic community was the most significant predictor of the N2 fixation rate. Structure equation modeling identified a specialized keystone diazotrophic ecological cluster, predominated by Bradyrhizobium, Desulfomonile, and Cyanobacteria, as the key driver of N2 fixation. Overall, our findings indicated that long-term PCB contamination enhanced the N2 fixation rate by altering diazotrophic community abundance and structure, which may deepen our understanding of the ecological function of diazotrophs in organic-contaminated soil.


Assuntos
Bifenilos Policlorados , Solo , Solo/química , Fixação de Nitrogênio , Microbiologia do Solo , Nitrogênio/análise
2.
Molecules ; 28(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36615651

RESUMO

Salmonella enteritidis (SE) is an important factor causing foodborne disease, and electrochemical sensors have drawn much attention for SE prevention and detection due to their many advantages. A renewable electrochemical sensor using specially designed locked nucleic acids (LNA) as linkers for the detection of SE was proposed to improve the reusability and reproducibility of biosensors. One end of the LNA was designed as an anchor to attach to modified electrodes through the sulfhydryl group; the other end was used to match with a short segment of SE aptamers, which will allow for the convenient renewal of occupied aptamers by raising the temperature. Results revealed that the manufactured biosensor had good stability, reproducibility, and selectivity in addition to a linear range of 6 × 101-6 × 105 CFU/mL and a limit of detection (LOD) of 20.704 CFU/mL. The recovery rate of SE for the real sample varied from 98.84% to 134.82% without exceeding 16.27% in the relative standard deviation (RSD). The proposed biosensor appears to be a promising tool for foodborne pathogen detection.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Penaeidae , Animais , Salmonella enteritidis/genética , Reprodutibilidade dos Testes , Aptâmeros de Nucleotídeos/genética , Limite de Detecção , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos
3.
Angew Chem Int Ed Engl ; : e202218146, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36594710

RESUMO

The stereodivergent synthesis of allene compounds bearing α,ß-adjacent central chiralities has been realized via the Pd/Cu-catalyzed dynamic kinetic asymmetric alkylation of racemic allenylic esters. The matched reactivity of bimetallic catalytic system enables the challenging reaction of racemic aryl-substituted allenylic acetates with sterically crowded aldimine esters smoothly under mild reaction conditions. Various chiral non-natural amino acids bearing a terminal allenyl group are easily synthesized in high yields and with excellent diastereo- and enantioselectivities (up to >20 : 1 dr, >99 % ee). Importantly, all four stereoisomers of the product can be readily accessed by switching the configurations of the two chiral metal catalysts. Furthermore, the easy interconversion between the uncommon η3 -butadienyl palladium intermediate featuring a weak C=C/Pd coordination bond and a stable Csp2 -Pd bond is beneficial for the dynamic kinetic asymmetric transformation process (DyKAT).

4.
Mikrochim Acta ; 190(2): 57, 2023 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-36652031

RESUMO

Au-Fe3O4 multifunctional nanoparticles (NPs) were synthesized and integrated with lateral flow immunoassay (LFIA) for dual-mode detection of Salmonella typhimurium. The Au-Fe3O4 NPs not only combined excellent local surface plasmon resonance characteristics and superparamagnetic properties, but also exhibited good photothermal effect. In the detection, antibody-conjugated Au-Fe3O4 NPs first captured S. typhimurium from complex matrix, which was then loaded on the LFIA strip and trapped by the T-line. By observing the color bands with the naked eyes, qualitative detection was performed free of instrument. By measuring the photothermal signal, quantification was achieved with a portable infrared thermal camera. The introduction of magnetic separation achieved the enrichment and purification of target bacteria, thus enhancing the detection sensitivity and reducing interference. This dual-mode LFIA achieved a visual detection limit of 5 × 105 CFU/mL and a photothermal detection limit of 5 × 104 CFU/mL. Compared with traditional Au-based LFIA, this dual-mode LFIA increased the detection sensitivity by 2 orders of magnitude and could be directly applied to unprocessed milk sample. Besides, this dual-mode LFIA showed good reproducibility and specificity. The intra-assay and inter-assay variation coefficients were 3.0% and 7.9%, and with this dual-mode LFIA, other bacteria hardly produced distinguishable signals. Thus, the Au-Fe3O4 NPs-based LFIA has potential to increase the efficiency of pandemic prevention and control. Au-Fe3O4 nanoparticle proved to be a promising alternative reporter for LFIA, achieving multifunctions: target purification, target enrichment, visual qualitation, and instrumental quantification, which improved the limitations of traditional LFIA.


Assuntos
Nanopartículas Metálicas , Nanopartículas Multifuncionais , Salmonella typhimurium , Colorimetria , Reprodutibilidade dos Testes , Imunoensaio
5.
Int J Mol Sci ; 24(2)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36674985

RESUMO

Colorectal cancer (CRC) is a major health burden worldwide due to its high morbidity, mortality, and complex etiology. Fusobacterium nucleatum (Fn), a Gram-negative anaerobe found in 30% of CRC patients, promotes CRC carcinogenesis, metastasis, and chemoresistance. Effective antimicrobial treatment is an unmet need for the rising CRC burden. Antimicrobial peptides (AMPs) represent a new class of antimicrobial drugs. In our previous study, we did the structure-activity study of Jelleine-I (J-I) and identified several halogenated J-I derivatives Cl-J-I, Br-J-I, and I-J-I. To determine whether those J-I derivatives can be a new therapy for bacterial-associated CRC, here we tested the antibacterial activities of these AMPs against Fn and their effects on CRC development. We found that Br-J-I showed the highest anti-Fn activity and Br-J-I may target membrane-associated FadA for Fn membrane disruption. More importantly, Fn promoted the growth of CRC cells-derived xenograft tumors. Br-J-I suppressed Fn load, colon inflammation, and Fn-induced CRC growth. Of note, Br-J-I induced better anti-CRC effects than common antibiotic metronidazole and Br-J-I sensitized the cancer-killing effect of chemotherapy drug 5-fluorouracil. These results suggest that Br-J-I could be considered as an adjunctive agent for CRC treatment and AMPs-based combination treatment is a new strategy for CRC in the future.


Assuntos
Anti-Infecciosos , Colite , Neoplasias Colorretais , Humanos , Fusobacterium nucleatum , Neoplasias Colorretais/etiologia , Carcinogênese , Colite/complicações
6.
Virulence ; : 2171636, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36694280

RESUMO

Haemophilus parasuis (H. parasuis) causes exudative inflammation, implying endothelial dysfunction during pathogen infection. However, so far, the molecular mechanism of endothelial dysfunction caused by H. parasuis has not been clarified. By using the transwell-based cell co-culture system, we demonstrate that knocking out resistin in porcine alveolar macrophages (PAMs) dramatically attenuated endothelial monolayer damage caused by H. parasuis. The resistin secreted by PAMs inhibited the expression of the tight junction proteins claudin-5 and occludin rather than the adherens junction protein VE-cadherin in co-cultured porcine aortic endothelial cells (PAECs). Furthermore, we demonstrate that resistin regulated claudin-5 and occludin expression and monolayer PAEC permeability in an LKB1/AMPK/mTOR pathway-dependent manner. Additionally, we reveal that the outer membrane lipoprotein gene lppA in H. parasuis induced resistin expression in PAMs, as deleting lppA reduced resistin expression in H. parasuis-infected PAMs, causing a significant change in LKB1/AMPK/mTOR pathway activity in co-cultured PAECs, thereby restoring tight junction protein levels and endothelial monolayer permeability. Thus, we postulate that the H. parasuis lppA gene enhances resistin production in PAMs, disrupting tight junctions in PAECs and causing endothelial barrier dysfunction. These findings elucidate the pathogenic mechanism of exudative inflammation caused by H. parasuis for the first time and provide a more profound angle of acute exudative inflammation caused by bacteria.

7.
Arch Toxicol ; 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36695871

RESUMO

T-2 toxin is a worldwide problem for feed and food safety, leading to livestock and human health risks. The objective of this study was to explore the mechanism of T-2 toxin-induced small intestine injury in broilers by integrating the advanced microbiomic, metabolomic and transcriptomic technologies. Four groups of 1-day-old male broilers (n = 4 cages/group, 6 birds/cage) were fed a control diet and control diet supplemented with T-2 toxin at 1.0, 3.0, and 6.0 mg/kg, respectively, for 2 weeks. Compared with the control, dietary T-2 toxin reduced feed intake, body weight gain, feed conversion ratio, and the apparent metabolic rates and induced histopathological lesions in the small intestine to varying degrees by different doses. Furthermore, the T-2 toxin decreased the activities of glutathione peroxidase, thioredoxin reductase and total antioxidant capacity but increased the concentrations of protein carbonyl and malondialdehyde in the duodenum in a dose-dependent manner. Moreover, the integrated microbiomic, metabolomic and transcriptomic analysis results revealed that the microbes, metabolites, and transcripts were primarily involved in the regulation of nucleotide and glycerophospholipid metabolism, redox homeostasis, inflammation, and apoptosis were related to the T-2 toxin-induced intestinal damage. In summary, the present study systematically elucidated the intestinal toxic mechanisms of T-2 toxin, which provides novel ideas to develop a detoxification strategy for T-2 toxin in animals.

8.
Phys Chem Chem Phys ; 25(5): 4332-4339, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36689259

RESUMO

Environmental pollution and the shortage of drinking water are the challenges that mankind is facing. Solar interface evaporation technology has been demonstrated as an important method for producing clean water, but its application to sewage still faces problems, mainly manifested in solubility and oily pollutants. Therefore, an evaporator device contains a superhydrophobic Bi2WO6 felt floating layer, a filter paper hydrophilic layer, and a copper foam/CuO photothermal layer, of which the water contact angle of the superhydrophobic felt can reach 159°. The floating layer not only has the ability to adsorb n-hexane but the Rh B degradation can also be realized under indoor/outdoor light conditions. The carrier life of Bi2WO6 is 28.8 ns. A copper foam/CuO photothermal layer prepared through a low-temperature treatment is combined with the floating and hydrophilic layer to obtain an evaporation rate of 1.53 kg m-2 h-1.

9.
Artigo em Inglês | MEDLINE | ID: mdl-36690854

RESUMO

The seasonal distribution and dynamic evolution of antibiotics in wastewater from main treatment areas and in sludge and their resistance selection potential and ecotoxicological risk were studied at a municipal wastewater treatment plant in Jinan, East China. Ten antibiotics were selected, and all were detected in wastewater and sludge samples, with fluoroquinolones showing the highest detection concentrations and frequencies. Seasonal fluctuations in the antibiotic concentrations in the influent, effluent, and sludge were observed, with the highest values in winter in most cases. The dynamic evolution of antibiotics during the treatment process differed among the seasons. The antibiotic removal efficiencies were incomplete, ranging from - 40.47 to 100%. Mass balance analysis showed that sulfonamides, roxithromycin, and metronidazole were mainly removed through biological processing, whereas fluoroquinolones, doxycycline, and chloramphenicol were removed through sludge adsorption. Levofloxacin, as well as a mixture of the 10 antibiotics from the effluent, could pose a low ecotoxicological risk to Daphnia in the receiving waters. Additionally, levofloxacin and ciprofloxacin in the effluent and ciprofloxacin and metronidazole in the sludge may facilitate the selection of antibiotic-resistant bacteria in the environment.

10.
Sci Total Environ ; 868: 161597, 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36646221

RESUMO

Although zero-valent iron-embedded biochar (ZVI-BC) has been proposed as an effective amendment for arsenic (As)-contaminated soils, the impacts of soil characteristics and treatment conditions on the remediation process remained poorly understood. Herein, the immobilization of As in four As-contaminated soils (i.e., smelting soil, storage soil, agricultural soil, and mining soil) by ZVI-BC under different amendment dosages, cultivation temperatures, and soil moisture contents were investigated. ZVI-BC showed high As immobilization capacity in all four soils via forming the AsFe co-precipitation, and the liable As was reduced by 82.4-97.0 % with a 2 % (w/w) amendment. The higher temperature could raise the concentration of liable As in all four soils, especially for the storage soil, in which liable As at 35 °C was almost 3 times of that at 25 °C after 50-days treatment, because the elevated temperature enhanced the destruction of the generated AsFe coprecipitation as well as the desorption of As in soils. Too much soil moisture was unfavorable for the As immobilization after 50-days treatment. Flooding tended to inhibit the community diversity of As-detoxicated bacteria, e.g., Halomonas, Bryobacter, and Anaerolinea, thus resulting in the release of liable As. According to the correlation analysis, the crucial influencing factor for As immobilization was different in four soils, which was determined by the soil properties and proportion of liable As. Our study indicates that ZVI-BC is an effective amendment for As immobilization under various conditions, and the biogeochemical processes of As-associated Fe minerals determine the As immobilization during amendment.

11.
Cell Host Microbe ; 31(1): 33-44.e5, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-36495868

RESUMO

Diarrhea-predominant irritable bowel syndrome (IBS-D), a globally prevalent functional gastrointestinal (GI) disorder, is associated with elevated serotonin that increases gut motility. While anecdotal evidence suggests that the gut microbiota contributes to serotonin biosynthesis, mechanistic insights are limited. We determined that the bacterium Ruminococcus gnavus plays a pathogenic role in IBS-D. Monocolonization of germ-free mice with R. gnavus induced IBS-D-like symptoms, including increased GI transit and colonic secretion, by stimulating the production of peripheral serotonin. R. gnavus-mediated catabolism of dietary phenylalanine and tryptophan generated phenethylamine and tryptamine that directly stimulated serotonin biosynthesis in intestinal enterochromaffin cells via a mechanism involving activation of trace amine-associated receptor 1 (TAAR1). This R. gnavus-driven increase in serotonin levels elevated GI transit and colonic secretion but was abrogated upon TAAR1 inhibition. Collectively, our study provides molecular and pathogenetic insights into how gut microbial metabolites derived from dietary essential amino acids affect serotonin-dependent control of gut motility.


Assuntos
Síndrome do Intestino Irritável , Animais , Camundongos , Serotonina/metabolismo , Diarreia/metabolismo
12.
Cancer Lett ; 555: 216039, 2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36528182

RESUMO

Gut microbiota play critical roles in the development of colorectal cancer (CRC) metastasis, but the underlying mechanisms remain elusive. This review discusses the molecular mechanisms by which the gut microbiota contribute to a tumor-permissive microenvironment and facilitate malignant transformation and dissemination of tumor cells, thereby mediating CRC metastasis.


Assuntos
Neoplasias Colorretais , Microbioma Gastrointestinal , Humanos , Neoplasias Colorretais/patologia , Microambiente Tumoral
13.
Rice (N Y) ; 15(1): 62, 2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36463341

RESUMO

Previous studies in Arabidopsis reported that the PPR protein SOAR1 plays critical roles in plant response to salt stress. In this study, we reported that expression of the Arabidopsis SOAR1 (AtSOAR1) in rice significantly enhanced salt tolerance at seedling growth stage and promoted grain productivity under salt stress without affecting plant productivity under non-stressful conditions. The transgenic rice lines expressing AtSOAR1 exhibited increased ABA sensitivity in ABA-induced inhibition of seedling growth, and showed altered transcription and splicing of numerous genes associated with salt stress, which may explain salt tolerance of the transgenic plants. Further, we overexpressed the homologous gene of SOAR1 in rice, OsSOAR1, and showed that transgenic plants overexpressing OsSOAR1 enhanced salt tolerance at seedling growth stage. Five salt- and other abiotic stress-induced SOAR1-like PPRs were also identified. These data showed that the SOAR1-like PPR proteins are positively involved in plant response to salt stress and may be used for crop improvement in rice under salinity conditions through transgenic manipulation.

14.
15.
J Autoimmun ; 134: 102949, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36455384

RESUMO

OBJECTIVE: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that commonly affects the kidney. Single-cell RNA sequencing (scRNA-seq) technology is a powerful tool for characterizing individual cells and elucidating biological mechanisms at the cellular level. The purpose of this study was to identify the mechanism underlying kidney injury in SLE using scRNA-seq technology. METHODS: scRNA-seq data of peripheral blood mononuclear cells (PBMCs) in SLE were retrieved from the GEO database, followed by batch effect elimination, dimensionality reduction, cluster analysis, cell annotation and enrichment analysis. A model of SLE was developed in NZB/WF1 mice. Effects of anti-CD45RB antibody on the SLE-induced kidney injury were evaluated, and we measured the distribution of regulatory T cells and B cells in mouse spleen and kidney tissues, levels of kidney function-related indexes, deposition of IgG and C3 in the glomeruli, and the levels of inflammatory cytokines. RESULTS: CD45RB was a specific marker gene of B cell clusters and had influence on the B cells. anti-CD45RB antibody treatment induced regulatory B cells and consequently arrested the kidney injury caused by SLE. In addition, depletion of regulatory T cells was found to partially undermine the alleviatory effect of anti-CD45RB antibody on SLE-induced kidney injury. CONCLUSION: Collectively, our data suggest that anti-CD45RB antibody can prevent the SLE-induced kidney injury, pointing to anti-CD45RB antibody as a potential therapeutic strategy in kidney injury-related disease.

16.
Bioorg Chem ; 131: 106301, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36455485

RESUMO

Alzheimer's disease (AD), characterized by the ß-amyloid protein (Aß) deposition and tau hyperphosphorylation, is the most common dementia with uncertain etiology. The clinical trials of Aß monoclonal antibody drugs have almost failed, giving rise to great attention on the other etiologic hypothesis regarding AD such as metal ions dysmetabolism and chronic neuroinflammation. Mounting evidence revealed that the metal ions (iron, copper, and zinc) were dysregulated in the susceptible brain regions of AD patients, which was highly associated with Aß deposition, tau hyperphosphorylation, neuronal loss, as well as neuroinflammation. Further studies uncovered that iron, copper and zinc could not only enhance the production of Aß but also directly bind to Aß and tau to promote their aggregations. In addition, the accumulation of iron and copper could respectively promote ferroptosis and cuproptosis. Therefore, the metal ion chelators were recognized as promising agents for treating AD. This review comprehensively summarized the effects of metal ions on the Aß dynamics and tau phosphorylation in the progression of AD. Furthermore, taking chronic neuroinflammation contributes to the progression of AD, we also provided a summary of the mechanisms concerning metal ions on neuroinflammation and highlighted the metal ion chelators may be potential agents to alleviate neuroinflammation under the condition of AD. Nevertheless, more investigations regarding metal ions on neuroinflammation should be taken into practice, and the effects of metal ion chelators on neuroinflammation should gain more attention. Running title: Metal chelators against neuroinflammation.

17.
Front Vet Sci ; 9: 1016191, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36504863

RESUMO

The oviduct consists of three parts: the infundibulum (In), ampulla (Am), and isthmus (Is). These have the same histological structure, but different physiological functions. In this study, transcriptomics was used to analyze mRNA in these three parts of yak oviduct. The results showed that there were 325 up-regulated genes and 282 down-regulated genes in the infundibulum and ampulla. Moreover, there were 234 up-regulated genes and 776 down-regulated genes in the isthmus and ampulla, as well as 873 up-regulated genes and 297 down-regulated genes in the infundibulum and isthmus. The expression of C3 in the infundibulum was significantly higher than that in the ampulla and isthmus. The expression of FAU in the isthmus was significantly lower than that in the ampulla and infundibulum, and the expression of EEF1A1 in the ampulla was significantly higher than that in the ampulla and infundibulum. When the infundibulum was compared with the ampulla and isthmus, it was found that the up-regulated genes were enriched in the lysosome, phagosome, staphylococcus aureus infection, and leishmaniasis pathway. When the isthmus was compared with the ampulla and infundibulum, the up-regulated genes were present in the apoptosis pathway, oxidative phosphorylation, and viral myocarditis pathway. When the isthmus was compared with the infundibulum and ampulla, the down-regulated pathways were protein processing in the endoplasmic reticulum and the endocytosis. The Epstein-Barr virus infection pathway was up-regulated according to a comparison of the isthmus and infundibulum and was down-regulated based on a comparison of the isthmus and ampulla. Transcriptional misregulation in the Middle East pathway was up-regulated based on a comparison of the isthmus and ampulla and was down-regulated based on a comparison of the isthmus and infundibulum. ERBB2, JUP, CTNND1, and KRT7 were defined as the hub genes of the yak oviduct. The results of this study provide sufficient omics data for yak fertilization, which is also of great significance to altitude medicine.

18.
Artigo em Inglês | MEDLINE | ID: mdl-36534259

RESUMO

Heterosigma akashiwo (H. akashiwo), a harmful algal species, has been a global environmental problem. Extracellular algicidal compounds (EACs) extracted from Bacillus sp. B1 exhibited algicidal effects against H. akashiwo. However, little is known about the algicidal mechanism and metabolic process. In this study, metabolomics and physiological analyses were combined to investigate the cellular responses of H. akashiwo when treated with EACs. The results indicated that EACs at 10% (vEACs/vsample) showed more than 90% inhibition of H. akashiwo. EAC treatment resulted in excessive reactive oxygen species (ROS) production in algal cells, causing stress responses such as inhibition of photosynthetic pigment synthesis, reduction of sugar synthesis, imbalance of osmotic pressure in the cell membrane, disruption of cell size and morphology, and eventual cell death. The results reveal the underlying mechanism of the algicidal process and provide new insights into algae-bacteria interactions and the application of metabolomics to algal research.

19.
Zhongguo Zhen Jiu ; 42(12): 1427-30, 2022 Dec 12.
Artigo em Chinês | MEDLINE | ID: mdl-36484198

RESUMO

In view of the core tasks and weak links in the training of medical graduate in the new era, based on the characteristics and development needs of the discipline, a new "three crosses and two integrations" graduate training mode of acupuncture-moxibustion and tuina is proposed, with "equal emphasis on inheritance and innovation, theory and practice" as the core, with "curriculum cross" as the basis, with "academic cross" as the connotation, and with "discipline cross" as the pathway. This new training mode focuses on the comprehensive cultivation of graduates' comprehensive abilities, aiming to achieve the training goal of "strong inheritance ability, excellent innovation ability, good practical ability and broad international perspective".


Assuntos
Currículo , Internacionalidade
20.
Cells ; 11(23)2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36497071

RESUMO

The liver is the most common site for colorectal cancer (CRC)-associated metastasis. There remain unsatisfactory medications in liver metastasis given the incomplete understanding of pathogenic mechanisms. Herein, with an orthotopic implantation model fed either regular or high-fat diets (HFD), more liver metastases were associated with an expansion of conjugated bile acids (BAs), particularly taurocholic acid (TCA) in the liver, and an increased gene expression of Na+-taurocholate cotransporting polypeptide (NTCP). Such hepatic BA change was more apparently shown in the HFD group. In the same model, TCA was proven to promote liver metastases and induce a tumor-favorable microenvironment in the liver, characterizing a high level of fibroblast activation and increased proportions of myeloid-derived immune cells. Hepatic stellate cells, a liver-residing source of fibroblasts, were dose-dependently activated by TCA, and their conditioned medium significantly enhanced the migration capability of CRC cells. Blocking hepatic BA uptake with NTCP neutralized antibody can effectively repress TCA-triggered liver metastases, with an evident suppression of tumor microenvironment niche formation. This study points to a new BA-driven mechanism of CRC-associated liver metastases, suggesting that a reduction of TCA overexposure by limiting liver uptake is a potential therapeutic option for CRC-associated liver metastasis.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Simportadores , Humanos , Transportadores de Ânions Orgânicos Dependentes de Sódio/genética , Transportadores de Ânions Orgânicos Dependentes de Sódio/metabolismo , Simportadores/genética , Simportadores/metabolismo , Ácido Taurocólico/farmacologia , Ácido Taurocólico/metabolismo , Microambiente Tumoral
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