Biology-Basel
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2025
·Vol. 14
·期 3
·226
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IF 3.5
Zonghan Jiang,Leisheng Sun,Yuanyuan Li,Haoyu Li,Yu Fu,Jiyun Li,Zhiliang Sun
Simple SummaryEscherichia coliis a ubiquitous pathogen, with certain strains causing severe diarrhea and intestinal illnesses, which pose significant health risks to both children and animals. As antimicrobial resistance continues to rise, traditional antibiotics are increasingly ineffective, highlighting the urgent need for novel therapeutic strategies. In this study, we investigated the antimicrobial peptide D-CONGA-Q7, aiming to evaluate its efficacy and underlying mechanism against drug-resistantE. colistrains. Our results demonstrate that D-CONGA-Q7 effectively disrupts bacterial cell membranes, leading to bacterial death, and exhibits comparable activity against polymyxin- and meropenem-resistant strains. In vivo experiments revealed that D-CONGA-Q7 significantly alleviated intestinal inflammation, reduced inflammatory cytokine levels, and promoted the repair of damaged intestinal tissues. Furthermore, D-CONGA-Q7 displayed good stability. These findings suggest that D-CONGA-Q7 not only represents a promising new approach to combat drug-resistant bacterial infections but also holds potential for clinical application.Escherichia coli(E. coli) is a zoonotic bacterium widespread in the environment, highly transmissible, and responsible for significant economic losses and millions of cases of illness annually. The rise of multidrug-resistant (MDR) strains has rendered last-line antibiotics such as polymyxin and meropenem ineffective, making the development of new antibiotics urgent. Although D-CONGA-Q7 has broad-spectrum bactericidal activity, its underlying mechanism remains poorly understood. In this study, we used in vitro and in vivo experiments to demonstrate that D-CONGA-Q7 effectively kills both antibiotic-sensitive and multidrug-resistant strains ofE. coli. D-CONGA-Q7 disrupts the cell membranes of Gram-negative bacteria, and the treatment ofE. colistrainLN175with D-CONGA-Q7 resulted in a significant up-regulation of theMlacgene, suggesting that D-CONGA-Q7 may interact with phospholipids in the cell membrane. Furthermore, in treatingK88-induced bacterial enteritis in the small intestine, D-CONGA-Q7 significantly reduced intestinal inflammation. In conclusion, this study provides a novel approach to combat drug-resistantE. coli.
研究领域:
微生物学
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药理学
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传染病学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2024
·
IF 8.3
Yanling Wang,Lishi Luo,Tuotuo Zhang,Jun-Rui Hu,Huiling Wang,Feng Bao,Chonglu Li,Yao Sun,Junrong Li
Sonodynamic therapy (SDT) can generate reactive oxygen species (ROS) to combat multidrug-resistant biofilms, which pose significant challenges to human health. As the key to producing ROS in SDT, the design of sonosensitizers with optimal molecular structures for sufficient ROS generation and activity in complex biofilm matrix is essential. In this study, we propose a π-expansion strategy and synthesize a series of small-molecule metal Ru(II) complexes (Ru1–Ru4) as sonosensitizers (Ru1–Ru4) to enhance the efficacy of SDT. Among these complexes, Ru4 demonstrates remarkable ROS generation capability (∼65.5-fold) that surpasses most commercial sonosensitizers (1.3- to 6.7-fold). Through catalyzing endogenous H2O2 decomposition, Ru4 facilitates the production of abundant O2 as a resource for 1O2 and the generation of new ROS (i.e., •OH) for improving SDT. Furthermore, Ru4 maintains the sustained ROS activity via consuming the interferences (e.g., glutathione) that react with ROS. Due to these unique advantages, Ru4 exhibits potent biofilm eradication ability against methicillin-resistant Staphylococcus aureus (MRSA) both in vitro and in vivo, underscoring its potential use in clinical settings. This work introduces a new approach for designing effective sonosensitizers to eliminate biofilm infections, addressing a critical need in healthcare management.
研究领域:
医学
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微生物学
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材料科学
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DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2024
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IF 12.2
Xiaoyu Fu,Jingfeng Gao,Qian Wang,Hao Chen,Ying Liu,Liqin Zeng,Yukun Yuan,Hongxin Xu
The existence of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) has been a global public environment and health issue. Due to the different cell structures, gram-positive/negative ARB exhibit various inactivation mechanisms in water disinfection. In this study, a gram-negative ARB Escherichia coli DH5α ( E. coli DH5α) was used as a horizontal gene transfer (HGT) donor, while a gram-positive ARB Bacillus as a recipient. To develop an efficient and engineering applicable method in water disinfection, ARB and ARGs removal efficiency of Fe(VI) coupled peroxydisulfate (PDS) or peroxymonosulfate (PMS) was compared, wherein hydroxylamine (HA) was added as a reducing agent. The results indicated that Fe(VI)/PMS/HA showed higher disinfection efficiency than Fe(VI)/PDS/HA. When the concentration of each Fe(VI), PMS, HA was 0.48 mM, 5.15 log E. coli DH5α and 3.57 log Bacillus lost cultivability, while the proportion of recovered cells was 0.0017 % and 0.0566 %, respectively, and HGT was blocked. Intracellular tetA was reduced by 2.49 log. Fe(IV) and/or Fe(V) were proved to be the decisive reactive species. Due to the superiority of low cost as well as high efficiency and practicality, Fe(VI)/PMS/HA has significant application potential in ARB, ARGs removal and HGT inhibition, offering a new insight for wastewater treatment.
研究领域:
环境科学
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微生物学
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DOI
PubMed
高影响因子
Infectious Microbes & Diseases
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2020
·Vol. 2
·期 1
·26
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IF 0
Feng Xue-Wen,Shao Jun-Dan,Ji Zhong-Kang,Fang Hong,Ding Cheng,Wang Shu-Ting,Shang-Guan Yan-Wan,Shi Pei,Li Lan-Juan,Xu Kai-Jin
Alternative antimicrobial therapies are urgently needed for a variety of multidrug-resistant bacterial pathogens. Faropenem is an orally available β-lactam in the class of carbapenem antibiotics. Thus far, little information is available on faropenem susceptibility of multidrug-resistant clinical isolates from China. Therefore, in the current study 141 contemporary clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA: n = 18), coagulase-negative staphylococci (CNS: n = 16), Enterococcus faecalis ( n = 14), Enterococcus faecium ( n = 7), Pseudomonas aeruginosa ( n = 25), Klebsiella pneumoniae ( n = 21), Escherichia coli ( n = 20), and Acinetobacter baumannii ( n = 20), were collected between March 2018 and March 2019 and tested for susceptibility to faropenem and other antimicrobials using the broth microdilution method. All E. faecium , P. aeruginosa , and A. baumannii isolates were fully resistant to faropenem. However, most of the MRSA, CNS, E. faecalis , K. pneumonia , and E. coli isolates appeared to be susceptible to faropenem, with minimal inhibitory concentration 90 values of 4 mg/L, 2 mg/L, 2 mg/L, 4 mg/L, and 2 mg/L, respectively. Therefore, faropenem could be considered as alternative therapy for future treatment of multidrug-resistant MRSA, CNS, E. faecalis , K. pneumonia , and E. coli infections in China.
研究领域:
微生物学
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传染病学
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药理学
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DOI
Aging-US
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2021
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IF 5.682
Jianhao Xu,Liwei Ni,Fenglun Zhao,Xiaoxiao Dai,Jialong Tao,Jia Pan,Aiming Shi,Zhu Shen,Cunjin Su,Yusong Zhang
Background: This study aimed to investigate the aberrant expression of hsa_circ_0002874 in non-small cell lung cancer (NSCLC) and elucidate associated molecular mechanisms that influence apoptosis and induce paclitaxel (PTX) resistance. Methods: Inhibitors were used to downregulate circRNA or miRNA expression. pCDNA plasmid transfection and mimics were used to upregulate circRNA or miRNA expression. Dual-luciferase reporter assays were conducted to evaluate interactions between miR1273f and MDM2. Xenograft tumor models were used to assess the effect of hsa_circ_0002874 and miR1273f on tumor growth. NSCLC tissues and matched non-cancerous tissues were also collected for correlation analysis. Results: hsa_circ_0002874 acts as a sponge for miR1273f which targets MDM2/P53. The stability of the hsa_circ_0002874/miR1273f/MDM2/P53 pathway was verified by upregulating and downregulating the expression of hsa_circ_0002874 and miR1273f. hsa_circ_0002874 downregulation or miR1273f upregulation reversed the resistance of the A549/Taxol cells in xenograft models. The expression of hsa_circ_0002874 was high, and the level of MDM2 was low in NSCLC tissues. P53 was only weakly expressed in NSCLC tissues with high expression of MDM2. Conclusions: hsa_circ_0002874 is strongly expressed in NSCLC tissues and maybe a potential marker for PTX resistance. hsa_circ_0002874 downregulation could regulate miR1273f/MDM2/P53 signaling pathway to reverse the PTX resistance of NSCLC and induce apoptosis in vitro and vivo .
研究领域:
肿瘤学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2021
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IF 4.432
Liwei Ni,Jianhao Xu,Fenglun Zhao,Xiaoxiao Dai,Jialong Tao,Jie Pan,Aiming Shi,Zhu Shen,Cunjin Su,Yusong Zhang
MicroRNAs (miRNAs) are involved in the initiation and development of cancer and participate in drug resistance. Paclitaxel (PTX) is a first-line chemotherapy drug for advanced non-small cell lung cancer (NSCLC). The abnormal miRNA expression in NSCLC and its association with chemotherapy drug resistance remains largely unknown. The study aimed to investigate the aberrant expression of miR-221–3p in NSCLC and to elucidate its molecular mechanisms in relation to PTX resistance. PTX increased miR-221–3p expression and regulated MDM2/P53 expression in the PTX-sensitive NSCLC strain (A549). Meanwhile, miR-221–3p was rarely expressed and not interfered by PTX in PTX-resistant A549 cells (A549/Taxol). Dual-luciferase reporter assay confirmed that miR-221–3p specifically binds to MDM2 messenger RNA and inhibited MDM2 expression. The expression of MDM2 and P53 showed a negative correlation in NSCLC cell lines. MiR-221–3p down-regulation reduced the sensitivity of A549 cells to PTX, whereas its up-regulation partially reversed the A549/Taxol cells resistance to PTX and increased the chemosensitivity of A549/Taxol cells to PTX in xenograft models. Quantitative polymerase chain reaction analysis revealed that miR-221–3p expression increased, whereas the MDM2 level decreased in human NSCLC tumor tissues. Moreover, Western bolt analysis showed that P53 was lowly expressed in tumor tissues with MDM2 overexpression. Low expression of miR-221–3p in NSCLC tissues might indicate a poor T staging. In conclusion, miR-221–3p overexpression could regulate MDM2/p53 signaling pathway to reverse the PTX resistance of NSCLC and induce apoptosis in vitro and vivo.
研究领域:
肿瘤学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2016
·Vol. 5
·期 19
·2517-2527
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IF 5.76
Xiaoman Mao,Jingxing Si,Qian Huang,Xuanrong Sun,Qianzhi Zhang,Youqing Shen,Jianbin Tang,Xiangrui Liu,Meihua Sui
Doxorubicin (DOX) is a widely used chemotherapeutic drug to treat a range of cancers. However, its unfavorable effects, particularly the cardiotoxicity and the induction of multidrug resistance (MDR), significantly limit its clinical applications. Herein, a novel doxorubicin prodrug, PEG 2K -DOX, is synthesized by conjugating a deprotonated doxorubicin molecule with the polyethylene glycol (PEG, MW: 2K) chain via pH-responsive hydrazone bond, and its potential as a better alternative than doxorubicin is evaluated. The data show that the amphiphilic PEG 2K -DOX can self-assemble into stable nanoparticles with a high and fixed doxorubicin loading content (≈20 wt%), a favorable size of 91.5 nm with a narrow polydispersity (PDI = 0.14), good stability, and pH-dependent release behavior due to the acid-cleavable linkage between PEG and doxorubicin. Although doxorubicin hardly accumulates in MDR cells, PEG 2K -DOX nanoparticles significantly increase the cellular uptake and cell-killing activity of doxorubicin in two MDR cancer cell lines MCF-7/ADR and KBv200, with the IC 50 values dropped to 1.130% and 42.467% of doxorubicin, respectively. More impressively, PEG 2K -DOX nanoparticles exhibit significantly improved plasma pharmacokinetics, increased in vivo therapeutic efficacy against MDR xenograft tumors, and better in vivo safety compared with doxorubicin. PEG 2K -DOX nanoparticles hold the promise to become a better alternative than doxorubicin for cancer treatment, especially for MDR tumors.
研究领域:
药学
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肿瘤学
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生物医学工程
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DOI
PubMed
高影响因子
Oncotarget
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2017
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IF 5.168
Jianfa Wu,Lingjie Bao,Zhenbo Zhang,Xiaofang Yi
Induction of Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) has been demonstrated to be involved in cisplatin resistance in ovarian cancer. Solute carrier family 40 member 1 (SLC40A1) is an iron exporter, which possesses many putative Nrf2 binding sites. Here we hypothesize that it may be a possible downstream gene of Nrf2. Elevated level of Nrf2 and reduced level of SLC40A1 were found in cisplatin–resistant ovarian cancer cells as compared with cisplatin-sensitive ovarian cancer cells. Exogenous knockdown of Nrf2 leaded to increased expression of SLC40A1. While overexpression of Nrf2 resulted in decreased expression of SLC40A1. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assay revealed that Nrf2 inhibited the transcription of SLC40A1. Overexpression of SLC40A1 was able to reverse cisplatin resistance induced by Nrf2, while knockdown of SLC40A1 restored cisplatin resistance and increased iron concentration. Desferal, an iron chelator, was found to overcome cisplatin resistance through iron deprivation. Its function was boosted when combined with brusatol, an Nrf2 inhibitor. Taken together, this study first demonstrated that Nrf2 could transcriptionally suppress the expression of SLC40A1. Iron overload induced by SLC40A1 resulted in cisplatin resistance in ovarian cancer. Targeting iron metabolism may be a new therapeutic strategy to reverse drug resistance in ovarian cancer treatment.
研究领域:
肿瘤学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
BIOMATERIALS
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2016
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IF 8.387
Zhi-Ting Cao,Zhi-Yao Chen,Chun-Yang Sun,Hong-Jun Li,Hong-Xia Wang,Qin-Qin Cheng,Zu-Qi Zuo,Ji-Long Wang,Yang-Zhong Liu,Yu-Cai Wang,Jun Wang
Chemotherapy resistance has become a major challenge in the clinical treatment of lung cancer which is the leading cancer type for the estimated deaths. Recent studies have shown that nanoparticles as drug carriers can raise intracellular drug concentration by achieving effectively cellular uptake and rapid drug release, and therefore reverse the acquired chemoresistance of tumors. In this context, nanoparticles-based chemotherapy represents a promising strategy for treating malignancies with chemoresistance. In the present study, we developed cationic lipid assisted nanoparticles (CLAN) to deliver polylactide-cisplatin prodrugs to drug resistant lung cancer cells. The nanoparticles were formulated through self-assembly of a biodegradable poly(ethylene glycol)- block -poly(lactide) (PEG-PLA), a hydrophobic polylactide-cisplatin prodrug, and a cationic lipid. The cationic nanoparticles were proven to significantly improve cell uptake of cisplatin , leading to an increased DNA-Pt adduct and significantly promoted DNA damage in vitro . Moreover, our study reveals that cationic nanoparticles, although are slightly inferior in blood circulation and tumor accumulation, are more effective in blood vessel extravasation. The CLANs ultimately enhances the cellular drug availability and leads to the reversal of cisplatin resistance.
研究领域:
肿瘤学
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药剂学
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纳米技术
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DOI
PubMed
高影响因子
BMJ Open
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2018
·Vol. 8
·期 1
·e017832
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IF 2.413
Qiang Sun,Yang Wang,Anette Hulth,Yonghong Xiao,Lennart E Nilsson,Xuewen Li,Zhenwang Bi,Yuqing Liu,Hong Yin,Yanbo Luo,Maud Nilsson,Chengtao Sun,Yiqing Zhu,Beiwen Zheng,Baoli Chen,Pan Sun,Lilu Ding,Xi Xia,Jakob Ottoson,Sonja Löfmark,Oliver James Dyar,IMPACT Consortium,Stefan Börjesson,Cecilia Stalsby Lundborg
Introduction To effectively minimise the emergence and dissemination of antibiotic resistant bacteria, a holistic One Health approach is called for. The Sino-Swedish Integrated Multisectoral Partnership for Antibiotic Resistance Containment is a cross-sectoral and integrated project on antibiotic resistance, conducted in Shandong Province in China. This paper outlines the overall study protocol for the project. To our knowledge, this is the first research programme aiming to take a true holistic approach across multiple sectors simultaneously in China, and the first to incorporate both antibiotic use and infection prevention and control in addition to antibiotic resistance patterns. The project aims to address gaps in current knowledge and seeks to improve the situation through a system-wide intervention. By using a One Health approach we can address important research questions that individual discipline investigations are unable to. The results obtained should thus more closely reflect the world in which human health, animal health and the environment are inextricably and intimately interlinked. Methods and analysis Both quantitative and qualitative studies are included for households from 12 villages, their surrounding environment and a tertiary care hospital in a nearby town. The studies include analyses of antibiotic consumption for humans and pigs; qualitative and quantitative data on perceptions, knowledge and attitudes; faecal carriage of extended spectrum β-lactamase and carbapenemase-producing Enterobacteriaceae from pigs and humans, and occurrence in household drinking water, surface water, waste water and clinical bacterial isolates from the hospital. Carriage of methicillin-resistant Staphylococcus aureus in humans, household pigs and clinical bacterial isolates is also investigated. Furthermore, potential inter-relationships between these sources are analysed. A multifaceted One Health intervention is designed and implemented in 6 of the 12 villages. Repeated and continuous data collections take place over 2 years, where the repeated data collection is performed after 1 year of intervention. Comparisons are made between intervention and control villages, before and after the intervention. Ethics Ethics approval was obtained from the first Affiliated Hospital, College of Medicine, Zhejiang University, China, reference number 2015#185 and 2015#283.
研究领域:
公共卫生
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微生物学
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流行病学
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
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2022
·Vol. 10
·期 33
·6296-6306
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IF 7.571
Yao Lu,Qingqing Pan,Wenxia Gao,Yuji Pu,Bin He
Platinum-based chemotherapy is widely used to treat various cancers. However, exogenous platinum is likely to cause severe side effects and drug resistance induced by upregulated glutathione (GSH) in cancer cells poses a threat to the management of cancer progression and recurrence. Anticancer copper–organic complexes are excellent candidates to substitute platinum-based chemotherapeutics, exhibiting lower systemic toxicity and even overcoming platinum-based chemotherapy resistance. Here, we report the GSH-resistance of copper(II) bis(diethyldithiocarbamate) (CuET) and its reversal of cisplatin resistance in non-small-cell lung cancer via cuproptosis. Electrochemistry and UV-vis spectroscopy studies demonstrate that CuET possesses a lower reduction potential and the reaction inertness with GSH. Importantly, CuET overcomes the drug resistance of A549/DDP cells and the anticancer effect is hardly affected by intracellular GSH levels. To improve the solubility and bioavailability, bovine serum albumin-stabilized CuET nanoparticles (NPs) are prepared and they have a high drug loading content of 27.5% and excellent physiological stability. In vitro studies manifest that CuET NPs augment the distributions in the cytosol and cytoskeleton, inducing cell death via cuproptosis in A549/DDP cells, which is distinctly different from the apoptosis pattern induced by cisplatin. In vivo antitumor evaluation shows that the nanomedicine has superior biosafety and potent antitumor activity in a cisplatin-resistant tumor model. Our study suggests that copper–organic complex-based nanosystems could be a powerful toolbox to tackle the platinum-based drug resistance and systemic toxicity concerns.
研究领域:
肿瘤学
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药理学
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生物化学
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DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
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2022
·Vol. 32
·期 29
·2202887
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IF 19.924
Congyang Mao,Wanyu Jin,Yiming Xiang,Yizhou Zhu,Jun Wu,Xiangmei Liu,Shuilin Wu,Yufeng Zheng,Kenneth M.C. Cheung,Kelvin Wai Kwok Yeung
Multidrug-resistant (MDR) bacteria are emerging and disseminating rapidly, undoubtedly posing an urgent threat to global public health. One particular concern is that MDR Gram-negative bacteria are immunized to available antibiotics owing to a series of biogenetic effects, including the β-barrel assembly machine (BAM complex) in the outer membrane, MDR efflux pumps, and enzymatic degradation/modification, which are known to induce antibiotic resistance (AbR). Here, this work identifies that the AbR mechanisms of MDR Escherichia coli become compromised and sensitive again to conventional antibiotics, when the temperature of infected tissues is elevated to ≈50 °C in situ. This thought is realized by the microwave-driven poly(lactic- co -glycolic acid) microparticles that may effectively convert electromagnetic radiation to thermal energy. The microwave hyperthermia (MWH) therapy not only interrupts the essential surface-exposed BamA protein of the BAM complex, but also enhances the permeability of the outer membrane and inhibits the action of MDR efflux pumps. MWH also impairs the hydrogen bond interaction between the catalytic residues of bacterial enzymes and functional groups of antibiotic molecules. Lastly, this work demonstrates these combined inhibitors can revitalize the bactericidal effects of conventional antibiotics in MDR Escherichia coli -associated deep tissue infections.
研究领域:
微生物学
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医学
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感染病学
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DOI
高影响因子
危险品化学品经营许可证（带存储）