RESUMEN

The vaginal epithelium plays pivotal roles in host defense against pathogen invasion, contributing to the maintenance of an acidic microenvironment within the vaginal lumen through the activity of acid-base transport proteins. However, the precise defense mechanisms of the vaginal epithelium after a bacterial infection remain incompletely understood. This study showed that bacterial lipopolysaccharide (LPS) potentiated net proton efflux by up-regulating the expression of Na+-H+ exchanger 1 (NHE1) without affecting other acid-base transport proteins in vaginal epithelial cells. Pharmacologic inhibition or genetic knockdown of Toll-like receptor-4 and the extracellular signal-regulated protein kinase signaling pathway effectively counteracted the up-regulation of NHE1 and the enhanced proton efflux triggered by LPS in vaginal epithelial cells. In vivo studies revealed that LPS administration led to luminal acidification through the up-regulation of NHE1 expression in the rat vagina. Moreover, inhibition of NHE exhibited an impaired defense against acute bacterial infection in the rat vagina. These findings collectively indicate the active involvement of vaginal epithelial cells in facilitating luminal acidification during acute bacterial infection, offering potential insights into the treatment of bacterial vaginosis.

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This study investigated the impact of high-intensity ultrasound (HIU) treatment on the physiochemical, conformational, and immunomodulatory activity of the OVT-CA complex, emphasizing the structure-function relationship. HIU treatment reduced particle size, improved dispersion, and increased electronegativity of the complex. It facilitated binding between OVT and CA, achieving a maximum degree of 45.22 mg/g CA grafting and reducing interaction time from 2 h to 15 min. HIU-induced cavitation and shear promoted the exposure of -SH and unfolding of OVT, leading to increased surface hydrophobicity of the complex and transformation of its structure from ß-sheet to α-helix. Additionally, CA binds to OVT in the C-lobe region, and HIU treatment modulates the intermolecular forces governing the complex formation, particularly by reinforcing hydrogen bonding, hydrophobic interactions, and introducing electrostatic interactions. Furthermore, HIU treatment increased the immunomodulatory activity of the complex, which was attributed to complex structural changes facilitating enhanced cell membrane affinity, antigen recognition, and B-cell epitope availability. Hierarchical cluster and Pearson correlation analysis confirmed that HIU treatment duration had a greater impact than power on both the structure and activity of the complex, and an optimal HIU treatment duration within 30 min was found to be crucial for activity enhancement. Moreover, structural changes, including ζ-potential, particle size/turbidity, and surface hydrophobicity, were closely correlated with immunomodulatory activity. This study highlights the potential application of HIU in developing protein-polyphenol immunomodulatory agents for public health and food nutrition.

Asunto(s)

Conalbúmina , Relación Estructura-Actividad , Conalbúmina/química , Conalbúmina/farmacología , Ondas Ultrasónicas , Interacciones Hidrofóbicas e Hidrofílicas , Animales , Factores Inmunológicos/química , Factores Inmunológicos/farmacología , Ratones , Agentes Inmunomoduladores/química , Agentes Inmunomoduladores/farmacología , Tamaño de la Partícula

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In this study, the oxidation of egg yolk lipids (EYL) by salt-induced heat and non-heat treatments was investigated for quality and flavor. The correlation between physicochemical properties, lipid oxidation and antioxidant activity was modeled using partial least squares discriminant analysis (PLS-DA). The results indicated that the prolonged salt-induced synergistic heat treatment produced the highest level of lipid oxidation, antioxidant activity and oil exudation, along with the lowest level of polyunsaturated fatty acid content. In addition, higher contents of pyrazines and fewer acid species were detected, which was not the case with the salt-free heat treatment. In total, 14 identical volatile organic compounds (VOCs) were produced, yet their overall flavor profiles determined by the electronic nose would remain dramatically distinguished. Therefore, heat treatment was particularly critical for lipid oxidation and the generation of aromatic compounds, implying that heat-treated EYL induced by salt is a flavor component with good antioxidant potential.

Asunto(s)

Yema de Huevo , Aromatizantes , Calor , Lípidos , Gusto , Yema de Huevo/química , Lípidos/química , Animales , Aromatizantes/química , Oxidación-Reducción , Compuestos Orgánicos Volátiles/química , Antioxidantes/química , Cloruro de Sodio/análisis , Cloruro de Sodio/química , Pollos , Manipulación de Alimentos

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In Parkinson's disease (PD), exogenous ghrelin protects dopaminergic neurons through its receptor, growth hormone secretagogue receptor (GHSR). However, in contrast to the strikingly low levels of ghrelin, GHSR is highly expressed in the substantia nigra (SN). What role does GHSR play in dopaminergic neurons is unknown. In this study, using GHSR knockout mice (Ghsr-/- mice) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model, we found that GHSR deletion aggravated dopaminergic neurons degeneration, and the expression and activity of GHSR were significantly reduced in PD. Furthermore, we explored the potential mechanism that GHSR deficiency aggregated PD-related neurodegeneration. We showed that DEPTOR, a subunit of mTORC1, was overexpressed in Ghsr-/- mice, positively regulating autophagy and enhancing autophagy initiation. The expression of lysosomal markers was abnormal, implying lysosomal dysfunction. As a result, the damaged mitochondria could not be effectively eliminated, which ultimately exacerbated the injury of nigral dopaminergic neurons. In particular, we demonstrated that DEPTOR could be transcriptionally regulated by KLF4. Specific knockdown of KLF4 in dopaminergic neurons effectively alleviated neurodegeneration in Ghsr-/- mice. In summary, our results suggested that endogenous GHSR deletion-compromised autophagy by impairing lysosomal function, is a key contributor to PD, which provided ideas for therapeutic approaches involving the manipulation of GHSR.

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Background: Depression is a chronic psychiatric condition that places significant burdens on individuals, families, and societies. The rapid evolution of non-invasive brain stimulation techniques has facilitated the extensive clinical use of Transcranial Magnetic Stimulation (TMS) for depression treatment. In light of the substantial recent increase in related research, this study aims to employ bibliometric methods to systematically review the global research status and trends of TMS in depression, providing a reference and guiding future studies in this field. Methods: We retrieved literature on TMS and depression published between 1999 and 2023 from the Science Citation Index Expanded (SCIE) and Social Science Citation Index (SSCI) databases within the Web of Science Core Collection (WoSCC). Bibliometric analysis was performed using VOSviewer and CiteSpace software to analyze data on countries, institutions, authors, journals, keywords, citations, and to generate visual maps. Results: A total of 5,046 publications were extracted covering the period from 1999 to 2023 in the field of TMS and depression. The publication output exhibited an overall exponential growth trend. These articles were published across 804 different journals, BRAIN STIMULATION is the platform that receives the most articles in this area. The literature involved contributions from over 16,000 authors affiliated with 4,573 institutions across 77 countries. The United States contributed the largest number of publications, with the University of Toronto and Daskalakis ZJ leading as the most prolific institution and author, respectively. Keywords such as "Default Mode Network," "Functional Connectivity," and "Theta Burst" have recently garnered significant attention. Research in this field primarily focuses on TMS stimulation patterns, their therapeutic efficacy and safety, brain region and network mechanisms under combined brain imaging technologies, and the modulation effects of TMS on brain-derived neurotrophic factor (BDNF) and neurotransmitter levels. Conclusion: In recent years, TMS therapy has demonstrated extensive potential applications and significant implications for the treatment of depression. Research in the field of TMS for depression has achieved notable progress. Particularly, the development of novel TMS stimulation patterns and the integration of TMS therapy with multimodal techniques and machine learning algorithms for precision treatment and investigation of brain network mechanisms have emerged as current research hotspots.

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The specific mechanisms underlying bacteria-triggered cell death and osteogenic dysfunction in host bone marrow mesenchymal stem cells (BMSCs) remain unclear, posing a significant challenge to the repair of infected bone defects. This study identifies ferroptosis as the predominant cause of BMSCs death in the infected bone microenvironment. Mechanistically, the bacteria-induced activation of the innate immune response in BMSCs leads to upregulation and phosphorylation of interferon regulatory factor 7 (IRF7), thus facilitating IRF7-dependent ferroptosis of BMSCs through the transcriptional upregulation of acyl-coenzyme A synthetase long-chain family member 4 (ACSL4). Moreover, it is found that intervening in ferroptosis can partially rescue cell injuries and osteogenic dysfunction. Based on these findings, a hydrogel composite 3D-printed scaffold is designed with reactive oxygen species (ROS)-responsive release of antibacterial quaternized chitosan and sustained delivery of the ferroptosis inhibitor Ferrostatin-1 (Fer-1), capable of eradicating pathogens and promoting bone regeneration in a rat model of infected bone defects. Together, this study suggests that ferroptosis of BMSCs is a promising therapeutic target for infected bone defect repair.

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In order to reduce the quality loss of citrus and extend its storage time after harvest, it is essential to develop coated kraft papers with antibacterial and fresh-keeping properties. In this study, cinnamon essential oil (CEO)/soybean protein isolate (SPI) microcapsules were prepared by the coagulation method, and their properties were optimized. Then, the microcapsules were added to konjac glucomannan (KGM) as a coating solution to enhance the physical, and chemical properties of kraft paper by a coating method. The release behavior of CEO, tensile properties, antibacterial properties and preservation effects of the paper were investigated. The results show that when the ratio of wall to core was 7:3, the highest encapsulation rate was 92.20 ± 0.43 %. The coating treatment significantly reduced the oxygen and water vapor transmission rates of kraft paper. The shelf life of citrus treated with coated Kraft was extended by >10 days. Thus, the CEO/SPI microencapsulation and KGM coating could improve the properties of kraft paper and have the potential for citrus preservation.

Asunto(s)

Cápsulas , Cinnamomum zeylanicum , Citrus , Mananos , Aceites Volátiles , Proteínas de Soja , Citrus/química , Proteínas de Soja/química , Aceites Volátiles/química , Aceites Volátiles/farmacología , Mananos/química , Mananos/farmacología , Cinnamomum zeylanicum/química , Papel , Conservación de Alimentos/métodos , Antibacterianos/química , Antibacterianos/farmacología

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Hyperproliferative keratinocytes and subcutaneous inflammation contribute to the characteristic symptoms of psoriasis, including erythema, scales, or scaly plaques on the skin. These symptoms significantly affect patients' quality of life and cause severe physical and psychological distress. However, current treatment strategies have limited therapeutic effect and may lead to adverse side effects. In this study, we present the novel organic photosensitizer TBTDC [5-(((5-(7-(4-(diphenylamino)phenyl)benzo[c][1,2,5]thiadiazol-4-yl)thiophen-2-yl)methylene)amino)-3-methylthiophene-2,4-dicarbonitrile] nanoparticles (NPs) with aggregation-induced emission (AIE) characteristics to mediate photodynamic therapy (TBTDC NP-PDT) for psoriasis treatment. We demonstrate that TBTDC NPs effectively generate reactive oxygen species upon light irradiation and lead to significant apoptosis of psoriatic keratinocytes. Furthermore, TBTDC NPs exhibit high cellular uptake in diseased keratinocytes and induce endoplasmic reticulum stress (ERS)-mediated autophagy, which can also enhance apoptosis. Importantly, TBTDC NPs show no cytotoxicity toward keratinocytes. These unique properties of TBTDC NPs enable remarkable therapeutic effects against psoriasis-like skin lesions and related inflammation in vivo. Overall, our AIE-active TBTDC NP-PDT represents a promising strategy for treating psoriasis in clinical settings.

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Circular dichroism (CD) spectrum and optical rotation (OR) spectrum, crucial for understanding molecular properties and configurations, present challenges due to limited testing methods and equipment accuracy in the ultraviolet (UV) region. This study proposes a weak measurement system for chiral signals in varying concentrations in the ultraviolet range, optimized using a deep neural network (DNN) model. Introducing different post-selections to detect the circular dichroism spectrum and optical rotation spectrum separately, with contrast as a probe, it achieves a detection resolution of up to 10-6 rad. Moreover, the fitted value of the training data can reach 0.9989, enhancing the prediction accuracy of chiral molecule concentrations. This method exhibits considerable promise for applications in chiral measurement and sensor technologies.

RESUMEN

In this study, a zein-stabilized lemon essential oil Pickering emulsion (ZLPE) was incorporated into a carboxymethyl cellulose/gelatin (CMC/GL) composite film to develop a bio-based packaging material with bioactive properties. The average droplet size of the ZLPE was measured at 3.62 ± 0.08 µm, with a zeta potential of -31.33 ± 0.32 mV, highlighting its excellent stability. The image results of confocal laser microscopy and scanning electron microscopy validated the uniform distribution of ZLPE in the film. The incorporation of ZLPE reduced the water solubility of films by 45.90% and decreased its water vapor permeability by 22.61%, thereby enhancing its hydrophobicity. Additionally, the ZLPE-loaded film improved mechanical properties, enhanced UV-blocking capabilities, and increased thermal stability. The introduction of ZLPE led to the antioxidant activity of the CMC/GL film increasing by six times the original level and endowed it with outstanding antibacterial properties. As a result, cherries packaged with the ZLPE film demonstrated superior preservation performance and extended shelf life in the preservation experiment, exhibiting the film's potential as a food packaging material.

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Paclitaxel and its derivates are the first-line chemotherapeutic agents of breast cancer, which also showed tremendous clinical value in many other diseases including ovarian cancer, lung cancer etc. However, there are many drawbacks for almost all paclitaxel or its derivates, including extremely short half-life, poor solubility and adverse events, which significantly limits their clinical applications. In this work, we designed and constructed a bispecific hydrolysis PAP-SS-PTX (term as PDC), consisting with pro-apoptosis peptide (PAP) and paclitaxel (PTX) that were conjugated together via disulfide and ester bonds. On the one hand, PAP could improve the solubility of PTX and promote cellular uptake for drugs. On the other hand, it was able to prolong the PTX half-life. We performed series of chemo-dynamical assays and showed that PDC would release active drug molecules under micro-acidic and reduction circumstance. The further assays elucidated that PDC could interrupt DNA synthesis and arrest cell division through downregulating CDK4/6 and Histone methylation that inhibit tumor growth in vitro. What's more, it could not only inhibit 4T1 breast tumor growth, but also prolong the survival time of mice and exert antitumor efficacy in vivo. It may provide a new research idea for cancer therapies via controlled release strategy in tumor microenvironment.

RESUMEN

Fms-like tyrosine kinase 3 (FLT3) mutations, present in over 30% of acute myeloid leukemia (AML) cases and dominated by FLT3-internal tandem duplication (FLT3-ITD), are associated with poor outcomes in patients with AML. While tyrosine kinase inhibitors (TKIs; e.g., gilteritinib) are effective, they face challenges such as drug resistance, relapse, and high costs. Here, we report that metformin, a cheap, safe, and widely used anti-diabetic agent, exhibits a striking synergistic effect with gilteritinib in treating FLT3-ITD AML. Metformin significantly sensitizes FLT3-ITD AML cells (including TKI-resistant ones) to gilteritinib. Metformin plus gilteritinib (low dose) dramatically suppresses leukemia progression and prolongs survival in FLT3-ITD AML mouse models. Mechanistically, the combinational treatment cooperatively suppresses polo-like kinase 1 (PLK1) expression and phosphorylation of FLT3/STAT5/ERK/mTOR. Clinical analysis also shows improved survival rates in patients with FLT3-ITD AML taking metformin. Thus, the metformin/gilteritinib combination represents a promising and cost-effective treatment for patients with FLT3-mutated AML, particularly for those with low income/affordability.

Asunto(s)

Compuestos de Anilina , Proteínas de Ciclo Celular , Sinergismo Farmacológico , Leucemia Mieloide Aguda , Metformina , Mutación , Quinasa Tipo Polo 1 , Proteínas Serina-Treonina Quinasas , Proteínas Proto-Oncogénicas , Pirazinas , Transducción de Señal , Tirosina Quinasa 3 Similar a fms , Metformina/farmacología , Metformina/uso terapéutico , Tirosina Quinasa 3 Similar a fms/genética , Tirosina Quinasa 3 Similar a fms/metabolismo , Tirosina Quinasa 3 Similar a fms/antagonistas & inhibidores , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Humanos , Animales , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Transducción de Señal/efectos de los fármacos , Pirazinas/farmacología , Pirazinas/uso terapéutico , Compuestos de Anilina/farmacología , Compuestos de Anilina/uso terapéutico , Ratones , Mutación/genética , Línea Celular Tumoral , Tiofenos/farmacología , Tiofenos/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Factor de Transcripción STAT5/metabolismo , Factor de Transcripción STAT5/genética , Femenino , Ensayos Antitumor por Modelo de Xenoinjerto , Masculino , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Serina-Treonina Quinasas TOR/metabolismo

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Metasurface zone plates exhibit stronger optical control capabilities than traditional Fresnel zone plates, especially in polarization transformation and multiplexing. However, there are still few studies on metasurface zone plates that can be used for simultaneous control of forward and backward waves. In this work, we propose what is to our knowledge a new scheme that utilizes metasurface zone plates for orthogonal linear polarization separation and wavefront manipulation at the same time. We demonstrate the separation of linearly polarized components and transmission-reflection focusing by using the destructive and constructive interference between different meta-atoms in the super-cell, as well as the phase difference between the super-cells. The metasurface not only needs a simple binary phase design but also shows a working bandwidth more than 30 nm with a central wavelength of 875 nm. This scheme can be extended to other electromagnetic bands such as visible and terahertz ones, providing an important way for the multi-dimensional light field manipulations.

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Rapid industrialization and urbanization have caused severe soil contamination with cadmium (Cd) necessitating effective remediation strategies. Phytoremediation is a widely adopted technology for remediating Cd-contaminated soil. Previous studies have shown that Abelmoschus manihot has a high Cd accumulation capacity and tolerance indicating its potential for Cd soil remediation. However, the mechanisms underlying its response to Cd stress remain unclear. In this study, physiological, transcriptomic, and metabolomic analyses were conducted to explore the response of A. manihot roots to Cd stress at different time points. The results revealed that Cd stress significantly increased malondialdehyde (MDA) levels in A. manihot, which simultaneously activated its antioxidant defense system, enhancing the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) by 19.73%-50%, 22.87%-38.89%, and 32.31%-45.40% at 12 h, 36 h, 72 h, and 7 days, respectively, compared with those in the control (CK). Moreover, transcriptomic and metabolomic analyses revealed 245, 5,708, 9,834, and 2,323 differentially expressed genes (DEGs), along with 66, 62, 156, and 90 differentially expressed metabolites (DEMs) at 12 h, 36 h, 72 h, and 7 days, respectively. Through weighted gene coexpression network analysis (WGCNA) of physiological indicators and transcript expression, eight hub genes involved in phenylpropanoid biosynthesis, signal transduction, and metal transport were identified. In addition, integrative analyses of metabolomic and transcriptomic data highlighted the activation of lipid metabolism and phenylpropanoid biosynthesis pathways under Cd stress suggesting that these pathways play crucial roles in the detoxification process and in enhancing Cd tolerance in A. manihot. This comprehensive study provides detailed insights into the response mechanisms of A. manihot to Cd toxicity.

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Objective: To compare the efficacy and postoperative infection rate of super mini percutaneous nephrolithotomy (SMP) and flexible ureteroscopic lithotripsy (FURL) in patients with diabetic nephrolithiasis and to explore the risk factors associated with postoperative infection following these two procedures. Methods: The medical history and surgery details of 252 patients with diabetic nephrolithiasis who underwent lithotripsy in our hospital between January 2018 and May 2023, including 144 SMP and 108 FURL, were reviewed and compared. Perioperative outcomes were compared between the two groups. Logistic regression was performed to identify the significant risk factors for infection after each procedure. Results: SMP achieved a higher stone-free rate (SFR) on postoperative day 1 and postoperative day 30 compared with FURL (p < 0.05). The mean operative time was shorter in SMP (p < 0.01). FURL was associated with less hemoglobin drop (p < 0.01) and shorter length of stay (p < 0.01). The incident rate of systemic inflammatory response syndrome (SIRS) was higher after SMP (p = 0.019), while the incident rate of urinary tract infection (UTI) was higher after FURL (p = 0.021). Overall postoperative infection and sepsis rates were similar between the two procedures. Logistic regression analysis revealed that gender odds ratio [OR]: 0.225, 95% confidence interval [CI]: 0.079-0.639), HbA1c (OR: 3.516, 95% CI: 1.841-6.716), and operation time (OR: 1.037, 95% CI: 1.008-1.066) were independent risk factors for infection after FURL, while operation time (OR: 1.063, 95% CI: 1.022-1.106) and HbA1c (OR: 7.443, 95% CI: 2.956-18.742) significantly predicted SMP-associated infections. Conclusion: In diabetic patients, SMP demonstrated higher SFR and shorter operation time, whereas FURL was associated with less bleeding and shorter hospitalization. SMP had a higher incident rate of SIRS and FURL had a higher incident rate of UTI. Elevated HbA1c and prolonged operative duration increased infection risk after both procedures, while female gender was an additional risk factor for FURL-related infections.

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Rice bran is an important byproduct of the rice polishing process, rich in nutrients, but it is underutilized and often used as feed or discarded, resulting in a huge amount of waste. In this study, rice bran was fermented by Lactobacillus fermentum MF423 to obtain a product with high antioxidant activity. First, a reliable and efficient method for assessing the antioxidant capacity of the fermentation products was established using high-performance liquid chromatography (HPLC), which ensured the consistency of the batch fermentation. The fermented rice bran product (FLRB) exhibited significant antioxidant activity in cells, C. elegans, and hyperlipidemic mice. Transcriptome analysis of mouse livers showed that the expression of plin5 was upregulated in diabetic mice administered FLRB, thereby preventing the excessive production of free fatty acids (FFAs) and the subsequent generation of large amounts of reactive oxygen species (ROS). These studies lay the foundation for the application of rice bran fermentation products.

RESUMEN

Fusarium verticillioides (F. verticillioides) is a globally recognized and highly impactful fungal pathogen of maize, causing yield losses and producing harmful mycotoxins that pose a threat to human and animal health. However, the genetic tools available for studying this crucial fungus are currently limited in comparison to other important fungal pathogens. To address this, an efficient CRISPR/Cas9 genome editing system based on an autonomously replicating plasmid with an AMA1 sequence was established in this study. First, gene disruption of pyrG and pyrE via nonhomologous end-joining (NHEJ) pathway was successfully achieved, with efficiency ranging from 66 to 100%. Second, precise gene deletions were achieved with remarkable efficiency using a dual sgRNA expression strategy. Third, the developed genome editing system can be applied to generate designer chromosomes in F. verticillioides, as evidenced by the deletion of a crucial 38 kb fragment required for fumonisin biosynthesis. Fourth, the pyrG recycling system has been established and successfully applied in F. verticillioides. Lastly, the developed ΔFUM1 and ΔFUM mutants can serve as biocontrol agents to reduce the fumonisin B1 (FB1) contamination produced by the toxigenic strain. Taken together, these significant advancements in genetic manipulation and biocontrol strategies provide valuable tools for studying and mitigating the impact of F. verticillioides on maize crops.

Asunto(s)

Sistemas CRISPR-Cas , Proteínas Fúngicas , Fusarium , Edición Génica , Micotoxinas , Zea mays , Fusarium/genética , Fusarium/metabolismo , Edición Génica/métodos , Zea mays/microbiología , Micotoxinas/metabolismo , Micotoxinas/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Fumonisinas/metabolismo , Contaminación de Alimentos/análisis , Contaminación de Alimentos/prevención & control

RESUMEN

BACKGROUND AND AIMS: Chemotherapy resistance in colorectal cancer have been faced with significant challenges in recent years. Particular interest is directed to tumor microenvironment function. Recent work has, identified a small molecule named Divertin that prevents myosin light chain kinase 1(MLCK1) recruitment to the perijunctional actomyosin ring(PAMR), restores barrier function after tumor necrosis factor(TNF)-induced barrier loss and prevents disease progression in experimental inflammatory bowel disease. Studies have shown that MLCK is a potential target for affecting intestinal barrier function, as well as for tumor therapy. However, the relative contributions of MLCK expression and chemotherapy resistance in colorectal cancers have not been defined. METHODS: Statistical analysis of MYLK gene expression differences in colorectal cancer patients and normal population and prognosis results from The Cancer Genome Atlas(TCGA) data. Cell activity was detected by Cell counting Kit-8. Cell proliferation was detected by monoclonal plate. The apoptosis was detected by flow cytometry and western blot. Determine the role of MLCK1 in inducing 5-Fluorouracil(5-Fu) resistance in colorectal cancer cells was detected by overexpression of MLCK1 and knock-down expression of MLCK1. RESULTS: MLCK1 is expressed at different levels in different colorectal cancer cells, high MLCK1 expressing cell lines are less sensitive to 5-Fu, and low MLCK1 expressing cell lines are more sensitive to 5-Fu. MLCK1 high expression enhances resistance to 5-Fu in colorectal cancer cells and the sensitivity to 5-Fu was increased after knocking down the expression of MLCK1, that might be closely correlated to TNFR2/NF-κB pathway. CONCLUSIONS: MLCK1 high expression can enhance resistance to 5-Fu in colorectal cancer cells and the sensitivity to 5-Fu was increased after knocking down the expression of MLCK1, that might be closely correlated to TNFR2/NF-κB pathway, which will provide a new method for the treatment of colorectal cancer patients who are resistant to 5-Fu chemotherapy.

Asunto(s)

Insuficiencia Cardíaca , Células Mieloides , Humanos , Insuficiencia Cardíaca/patología , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/fisiopatología , Células Mieloides/patología