Frontiers in Bioengineering and Biotechnology
·
2019
·
IF 5.122
Pan Xuewei,Sun Changhao,Tang Mi,Liu Chao,Zhang Jianing,You Jiajia,Osire Tolbert,Sun Yang,Zhao Youxi,Xu Meijuan,Yang Taowei,Rao Zhiming
Serratia marcescens, a gram-negative bacterium, found in a wide range of ecological niches can produce several high-value products, including prodigiosin, althiomycin, and serratamolide. Among them, prodigiosin has attracted attention due to its immunosuppressive, antimicrobial, and anticancer properties. However, the regulatory mechanisms behind prodigiosin synthesis in Serratia marcescens remains limited. Here, a transposon mutant library was constructed to identify the genes related to prodigiosin synthesis, and BVG90_02415 gene encoding a peptidoglycan synthesizing enzyme D-Ala-D-Ala carboxypeptidase DacA was found to negatively regulates prodigiosin synthesis. Quantitative measurements revealed that disruption of dacA increased prodigiosin production 1.46-fold that of the wild-type strain JNB5-1 in fermentation medium. By comparing differences in cell growth, pigA gene expression level, cell morphology, membrane permeability, and intracellular prodigiosin concentration between wild-type strain JNB5-1 and dacA mutant SK4-72, results revealed that the mechanism for hyper-producing of prodigiosin by the dacA mutant was probably that dacA disruption enhanced prodigiosin leakage, which in turn alleviated feedback inhibition of prodigiosin and increased expression of pig gene cluster. Collectively, this work provides a novel insight into regulatory mechanisms of prodigiosin synthesis and uncovers new roles of DacA protein in regulating cell growth, cell morphology, and membrane permeability in Serratia marcescens. Finally, this study offers a new strategy for improving production of high-value compounds in Serratia marcescens.
研究领域:
微生物学
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生物化学
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分子生物学
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DOI
PubMed
高影响因子
npj Science of Food
·
2025
·Vol. 9
·期 1
·1-10
·
IF 7.8
Chen Lichun,Yao Feng,Xue Songwen,Yao Kuang,Huang Yun,Zhao Huimin,Shao Qiong
Sugar alcohols are natural sweeteners with various physiological functions, commonly used in low-calorie foods and pharmaceuticals. Current research primarily focuses on their sweetening properties and metabolic effects, often overlooking their interactions with cell membranes. This study built a giant phospholipid vesicle model to examine vesicle deformation in erythritol (Ery) and xylitol (Xyl) environments. The permeation of these sugar alcohols through real cell membranes was also investigated. Fluorescence microscopy and zeta potential measurements showed that osmotic stress from concentration gradients disrupted vesicle membrane structure. Ery and Xyl reduced ROS levels in HEK-293 cells and influenced membrane permeability. Notably, Xyl increased vesicle adsorption on the cell membrane at the same concentration. The findings indicate that sugar alcohols interact with membrane lipids through hydrogen bonds or other non-covalent interactions, modifying cell membrane structure and properties, thus providing a theoretical foundation for understanding their role in physiological environments.
研究领域:
生物物理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Antibiotics-Basel
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2025
·Vol. 14
·期 5
·499
·
IF 4.6
Liyang Wang,Junying He,Hanzhong Feng,Qian Li,Meirong Song,Haoran Gou,Yongxing He,Kui Zhu
Background:Fungal infections pose an increasingly predominant threat to human and animal health. Modified compounds derived from chemo-diverse natural products offer enhanced therapeutic efficacies and promising approaches to combat life-threatening fungal pathogens.Methods:We performed biosynthetic gene clusters analysis of 2,4-diacetylchloroglucoside (DAPG) in 4292 shotgun metagenomes samples from the healthy and diseased skin. Then, we assessed the antifungal activity of DAPG and the derivative 2,4-diproylphloroglucinol (DPPG) against pathogenic fungi by minimum inhibitory concentrations. The inhibitory effects of DPPG were measured using hyphal growth assay and spore germination assay. Concurrently, the mechanism of DPPG onAspergillus fumigatuswas investigated in membrane permeability and fluidity. The therapeutic efficacy was evaluated in aGalleria mellonellainfection model.Results:We observed a significantly higher abundance of bacteria harboring DAPG biosynthetic clusters on healthy skin compared to diseased skin. Further, we designed and synthesized a series of phloroglucinol derivatives based on DAPG and obtained an antifungal candidate DPPG. DPPG not only exhibited robust antifungal activity againstAspergillusspp. andCandidaspp. but also impaired hyphal growth and spore germination ofA. fumigatusin vitro. A mechanism study showed that DPPG reduced membrane fluidity and increased the leakage of cellular contents, resulting in membrane perturbation and fungal death. Lastly, the therapeutic efficacy of DPPG was confirmed in aG. mellonellainfection model.Conclusions:Our study demonstrates that DPPG is a potent scaffold to combat invasive fungal infections.
研究领域:
微生物学
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药理学
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感染病学
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产品关联
DOI
PubMed
高影响因子
Microorganisms
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2020
·Vol. 8
·期 2
·211
·
IF 4.152
Yehao Liu,Yuhui Li,Yuhong Xia,Kaiyong Liu,Lingling Ren,Yanli Ji
Cadmium (Cd), widely present in food and drinking water at low doses, can cause health risks. However, the mechanistic effects of long-term Cd exposure at low dose through dietary intake is poorly studied. The aim of this study is to elucidate whether the dysbiosis of gut microbiota caused by Cd at an environmental low dose can aggravate the injury of mice liver, and the possible mechanism is investigated. In order to explore the potential underlying mechanism, the analyses of the variation of gut microbiota composition, intestinal permeability, and hepatic transcriptome were conducted. Our results showed that gut microbiota was disturbed. The rise of intestinal permeability induced by the dysbiosis of gut microbiota resulted in more Cd ions accumulating in mice liver, but it could be restored partly through depleting gut microbiota by antibiotics cocktail. Transcriptomic analyses indicated that 162 genes were significantly differentially expressed including 59 up-regulated and 103 down-regulated in Cd treatment. These genes were involved in several important pathways. Our findings provide a better understanding about the health risks of cadmium in the environment.Keywords:transcriptome analyses;gut microbiota;cadmium;intestinal permeability
研究领域:
环境健康
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微生物学
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分子生物学
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毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
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2024
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IF 15.8
Di Liu,Na Lu,Fengchao Zang,Mingze Lu,Jingyue Zhang,Ying Zhao,Hao Wan,Mengjun Wang,Qian-Qian Li,Fei Wang,Shouhua Luo,Ming Ma,Fangfang Shi,Haoan Wu,Jing Tu,Yu Zhang
Even though the enhanced permeability and retention (EPR) effect is applicable for the passive targeting of solid tumors, many nanodrugs have failed to achieve meaningful clinical outcomes due to the heterogeneity of EPR effect. Therefore, understanding the mechanism of the EPR effect is crucial to overcome the obstacles nanomedicines face in clinical translation. The aim of this study was to establish a reliable method to increase awareness of the critical influencing factors of nanoparticle (NP) transport into tumors based on the EPR effect using a combined radiogenomics and clinical magnetic resonance imaging (MRI) technique and gene set pathway enrichment analysis. Employing poly(lactic-co-glycolic acid) (PLGA)-coated Fe3O4 NPs as the contrast agent, the monolayer and multilayer distribution of the NPs were observed and quantitatively analyzed by MRI, improving the accuracy of evaluating vascular permeability by MRI. By performing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of genes and pathways, we identified a variety of genes affecting vascular permeability, such as Cldn1, Dlg2, Bves, Prkag3, Cldn10, and Cldn8, which are related to tight junctions and control the permeability of blood vessels in tumors. The method presented here provides an MRI-supported approach to increase the breadth of data collected from genetic screens, reveals genetic evidence of the presence of NPs in tumors and lays a foundation for clinical patient stratification and personalized treatment.
研究领域:
医学影像学
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肿瘤学
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基因组学
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产品关联
DOI
PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
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2020
·
IF 4.006
Bin Ma,Yunxue Guo,Xing Fu,Yongguo Jin
s Ovotransferrin (OVT), displaying multiple bioactivities, is an important egg antimicrobial component. In this study, a novel antimicrobial peptide (OVTp12) was purified from the hydrolysate of OVT by ion-exchange chromatography, Sephadex G-15 gel filtration, and reversed-phase HPLC. The sequence of OVTp12 was identified as AGLAPYKLKPIA using LC-MS/MS with molecular mass of 1240.76 Da. Moreover, OVTp12 showed effective antimicrobial activity against both Gram-positive and Gram-negative bacteria (minimal inhibitory concentrations, MIC values = 32 − 128 μg/mL). The outer/inner cell membrane permeabilization induced by OVTp12 indicated that the isolated peptide exhibited significant membrane permeability of Escherichia coli . To further reveal the antibacterial mechanism, CLSM and flow cytometry analyses demonstrated that OVTp12 could destroy cell membrane integrity and increase the permeability of pathogen's membrane. SEM analyses expressed that OVTp12 caused morphological changes in both Escherichia coli and Staphylococcus aureus . These results suggested that peptide OVTp12 from ovotransferrin may be a promising antimicrobial agent for food preservation or pharmaceuticals.
研究领域:
食品科学
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微生物学
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生物化学
✓ 已验证
产品关联
DOI
高影响因子
Asian Journal of Pharmaceutical Sciences
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2018
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IF 4.56
Chunjuan Zhang,Tonghua Xu,Donglei Zhang,Wei He,Siling Wang,Tongying Jiang
To improve the corneal permeability and water-solubility of disulfiram (DSF), which is an ocular drug for cataract, P188 was selected as a matrix to prepare solid dispersion of DSF (DSF SD ) by hot melt method. The DSF SD was characterized by DSC, XRD, and IR, and the results suggested that DSF was amorphous in DSF SD . The DSF SD was added to borate buffer solution (BBS) contained 20% poloxamer P407 and 1.2% poloxamer P188 to form in-situ gel. In vitro and in vivo experiments revealed that DSF SD combined with in-situ gel (DSF SD /in-situ gel) increased the residence time and the amount of DSF penetrated through the corneal. The pharmacodynamics studies exhibited DSF SD /in-situ gel delayed the development of selenium-induced cataract at some content. These results investigated that DSF SD /in-situ gel as a drug delivery system can improve DSF ocular permeability.
研究领域:
药剂学
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眼科
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药物传递系统
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产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2018
·Vol. 42
·期 17
·14325-14331
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IF 3.201
Ruiqing Feng,Longlong Li,Bing Li,Jinhui Li,Dan Peng,Yitao Yu,Qiuhong Mu,Ning Zhao,Xiaoqiang Yu,Zhenhua Wang
We have synthesized a two-photon organic small-molecule probe (DMI), which has a considerable two-photon absorption cross section (δ) value and selectively stained endogenous RNA in the nucleolus and the cytoplasm of living cells with outstanding membrane permeability. The titrations, fluorescence imaging and RNase digest test indicate markedly higher affinity for endogenous RNA. The double assay of DMI and SYTOX Blue nucleic acid stain (S-11348) showed that the probe possesses excellent membrane permeability to living cells, and a co-staining experiment with the classic DNA-staining dye DAPI indicated that it has excellent counterstain compatibility. Moreover, DMI exhibited good photostability when continuously illuminated by constant femtosecond pulses. These results demonstrate that DMI is an attractive two-photon fluorescent probe for visualizing RNA in living cells.
研究领域:
生物化学
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细胞生物学
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分子影像学
✓ 已验证
产品关联
DOI
高影响因子
DYES AND PIGMENTS
·
2023
·
IF 4.5
Yongfei Huang,Junping Liang,Zhefeng Fan
Hydrazine is widely used as a wide range of industrial chemical reagents. Because of its toxicity and explosiveness, it poses a serious threat to human health and ecological security. Therefore, it is of great significance to develop a real-time tracing method for hydrazine. Here, a novel turn-on fluorescent probe SXNU-1 for the detection of hydrazine was synthesized based on phenothiazine. SXNU-1 showed excellent selectivity toward hydrazine over various competitive species. Vinyl group with cyano and ethylacetate groups in SXNU-1 could react with hydrazine to form Schiff's base , showing bright green fluorescence. The response mechanism was verified by theoretical calculation, 1 H NMR titration and HRMS. In addition, SXNU-1 can determine hydrazine in soil, water samples and test strip. Because SXNU-1 has good cell membrane permeability, it can monitor different concentrations of hydrazine in HeLa cells. Therefore, we believe that SXNU-1 has great potential in the analysis and monitoring of environmental pollutants.
研究领域:
分析化学
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环境科学
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生物医学
✓ 已验证
DOI
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2020
·
IF 2.365
Bing Zhang,Wenli Pan,Yaxin Deng,Haibing He,Jingxin Gou,Yanjiao Wang,Yu Zhang,Tian Yin,Dongchun Liu,Xing Tang
Panax quinquefolium saponin (PQS) composed of 45% pseudo-ginsenoside F11 (PF11), is a natural mixture of sterol compounds obtained from the American ginseng plant, having numerous promising benefits for health. However, low solubility and permeability limit the development of PQS as a therapeutic agent for oral administration. In this study, PQS liposomes (PQS-Lips) were prepared by thin layer hydration, an in situ single-pass intestinal perfusion (SPIP) model was used to verify the improvement of membrane permeability of PQS-Lips. PQS-Lips had a high encapsulation efficiency (EE) of 65%∼70%, a particle size about 100.0 nm, and a zeta potential of −60 mV with regular spherical surface. FTIR and DSC showed the PQS in liposomes were amorphous, indicating that hydrogen bonds formed between one or several hydroxyl groups in PQS and C-O group at the phospholipid polar terminal. In addition, PQS-Lips showed sustained release in vitro than PQS at pH 1.2 and pH 6.8, and PQS-Lips had good stability in simulated gastric and intestinal fluid. Then, the absorption rate (Ka) and effective permeability coefficient (Peff) of PQS-Lips in the whole small intestine were significantly higher than those in PQS solution (PQS-Sol), which proved that the PQS-Lips could significantly increase the membrane permeability of PQS and promote its absorption in the small intestine. From the experimental results, it could be known that liposome technology could effectively improve the absorption of PQS in the small intestine.
研究领域:
药剂学
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生物药剂学
·
中药学
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产品关联
DOI
PubMed
高影响因子
Food Science & Nutrition
·
2020
·Vol. 8
·期 9
·4843-4856
·
IF 1.797
Muhammad Umair,Saqib Jabbar,Tayyaba Sultana,Zubaria Ayub,Sheikheldin A. Abdelgader,Zhu Xiaoyu,Zhang Chong,Lu Fengxia,Bie Xiaomei,Lu Zhaoxin
The present study explores the effect of chirality of the biological macromolecules, its functional aspects, and its interaction with other food components. Dihydromyricetin (DHM) is a natural novel flavonol isolated from the vine tea ( Ampelopsis grossedentata) leaves. However, limited progress in enantiopure separation methods of such compounds hinder in the development of enantiopure functional studies. This study is an attempt to develop a simple, accurate, and sensitive extraction method for the separation of the enantiopure DHM from vine tea leaves. In addition, the identification and purity of the extracted enantiopure (−)-DHM were further determined by the proton nuclear magnetic resonance ( 1 H-NMR) and the carbon nuclear magnetic resonance ( 13 C-NMR). The study further evaluates the antimicrobial activity of isolated (-)-DHM in comparison with racemate (+)-DHM, against selected foodborne pathogens, whereas the action mode of enantiopure (−)-DHM to increase the integrity and permeability of the bacterial cell membrane was visualized by confocal laser scanning microscopy using green fluorescence nucleic acid dye (SYTO-9) and propidium iodide (PI). Moreover, the morphological changes in the bacterial cell structure were observed through field emission scanning electron microscope. During analyzing the cell morphology of B. cereus (AS11846), it was confirmed that enantiopure (−)-DHM could increase the cell permeability that leads to the released of internal cell constituents and, thus, causes cell death. Therefore, the present study provides an insight into the advancement of enantiopure isolation along with its antimicrobial effect which could be served as an effective approach of biosafety.
研究领域:
食品科学
·
生物化学
·
微生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF RARE EARTHS
·
2012
·
IF 0.901
Aimei CHEN,Qingshan SHI,Yousheng OUYANG,Yiben CHEN
This study aimed to delineate the antibacterial mechanism of rare-earth ion Ce 3+ to the target organism Escherichia coli cell, and the most important purpose was to identify its biological effect of increasing the E. coli cell membrane permeability. The antibacterial activities of Ce 3+ to E. coli cells were tested, and then the permeability of outer membrane (OM) and inner membrane (IM) were studied by N-phenyl-1-naphthylamine (NPN) and o -nitrophenyl-β-D-galactopyranoside (ONPG) methods separately. Through these experiments we concluded that the E. coli cells grown to log phage were more sensitive to Ce 3+ than the ones not at this stage; the structure of membrane was destroyed and the permeability of both OM and IM was obviously increased by Ce 3+ ; there should be certain interactions between Ce 3+ and some proteins inside the cell, which impeded the physiological activities of bacteria.
研究领域:
微生物学
·
分子生物学
·
生物化学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）