Small
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2025
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IF 12.1
Huihui Chen,Xiao Hu,Bingying Hou,Liying Qin,Eve-Graciella M.E.K. Kuete,Levinus Hendrik Koole
Bacterial keratitis (BK) is a critical and sight-threatening corneal infection that significantly impairs the quality of life. Due to the widespread antibiotic-resistant microbes and the slow development in antibiotics, there is an increasingly growing demand to create new antimicrobial agents for the treatment of BK. Herein, copper-intercalated molybdenum disulfide (Cu-MoS 2 ) nanosheets are constructed by intercalating Cu into the interlayer structure of MoS 2 via intercalation chemistry, which not only introduces the Fenton reaction but also modulates the electronic structure of MoS 2 . Cu-MoS 2 can convert H 2 O 2 into more toxic reactive oxygen species (ROS), thereby exhibiting excellent bactericidal performance against Staphylococcus aureus (S. aureus) , methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) at room temperature in the dark. Animal experiments indicated that Cu-MoS 2 can effectively treat BK caused by MRSA. This work demonstrates that intercalation chemistry as a novel and effective strategy to tune MoS 2 as the antibacterial agent with no reliance on light that has great potential therapeutic effects on clinical drug-resistant BK.
研究领域:
医学
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材料科学
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PubMed
高影响因子
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
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2025
·Vol. 66
·期 11
·19-19
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IF 4.7
Yuchen Liu,Xue Tian,Cui Li,Jing Lin,Lina Zhang,Qian Wang,Hong Li,Yuqi Li,Xiangzhi Liu,Guiqiu Zhao
Purpose:The purpose of this study was to investigate the therapeutic effect of artesunate (ART) on fungal keratitis (FK).Methods:The antifungal properties of ART againstAspergillus fumigatus(A. fumigatus) were confirmed by minimum inhibitory concentration (MIC), biofilm formation inhibition test, propidium iodide fluorescence, and calcium fluorescence white test. The levels of HSP90, BrlA, AbaA, WetA, CnaA, and CrzA were detected by quantitative reverse transcription PCR (qRT-PCR). Cell counting kit 8 (CCK-8) was used to detect the cytotoxicity of ART on RAW 264.7 cells and human corneal epithelial cells (HCECs). Clinical corneal score, hematoxylin and eosin (H&E) staining, and corneal fungal plate counts were used to evaluate the therapeutic effect of ART on FK in mice. The qRT-PCR, ELISA, and Western blot were used to investigate the effect of ART on inflammatory mediator expression during fungal infection.Results:ART inhibited the growth ofA fumigatus, biofilm formation, and conidium adhesion in vitro, and destroyed fungal cell walls and cytomembrane. In vivo, ART effectively reduced corneal fungal load. ART could reduce the inflammation of the cornea by reducing the accumulation of inflammatory cells and down-regulating the expression of TNF-α, IL-1β, and IL-6. ART could activate the autophagy pathway to play an anti-inflammatory role in FK by increasing the expression of Beclin-1 and LC3B.Conclusions:ART inhibits fungal growth by inhibiting biofilm formation, destroying fungal cell walls and membranes, and reducing the expression of HSP90 and calcineurin-related factors, and activates the autophagy pathway to reduce the expression of TNF-α, IL-1β, and IL-6 in FK by upregulating the protein expression of Beclin-1 and LC3B. ART has therapeutic potential for FK.
研究领域:
医学真菌学
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药理学
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免疫学
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微生物学
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眼科学
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PubMed
高影响因子
RSC Advances
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2024
·Vol. 14
·期 49
·36804-36815
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IF 3.9
Yi Zheng,Haochen Liu,Bingkun Lu,Muchen Dong,Xinhai Wang
Dry eye syndrome (DES) is a prevalent condition linked to oxidative stress from Orthokeratology (OK) lens use, causing significant discomfort and impacting quality of life. Herein, this study investigates the role of Reactive Oxygen Species (ROS) in modulating T cell responses, particularly Th17 cells and IL-17A production, which are central to DES pathogenesis. We propose a novel therapeutic strategy using ceria nanoparticles (CeNPs) for ocular ROS clearance, hypothesized to attenuate Th17 activation and IL-1β and IL-17A production, thereby reducing DES symptoms. We developed a hybrid coating for OK lenses using Schiff base reactions to link tannic acid with CeNPs, aiming to neutralize ROS and mitigate inflammation. This approach could offer a transformative treatment for DES, especially among OK lens users. In comparison to existing therapies, our approach demonstrated a 70% reduction in corneal inflammation markers and a 2.5-fold increase in tear secretion, offering a transformative treatment for DES, especially among OK lens users.
研究领域:
免疫学
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眼科
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纳米医学
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高影响因子
JOURNAL OF CONTROLLED RELEASE
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2025
·
IF 11.5
Lifang Chen,Yao Wang,Xiuqing Huang,Lifang Han,Zhengwei Huang,Ling Guo,Kai Chen,Guoxin Tan
The occurrence of bacterial keratitis (BK) presents a significant threat to ocular health, often leading to visual impairment. Currently, conventional antibiotic therapies tend to promote bacterial resistance and lack biocompatibility. Therefore, it is of great significance to develop an alternative product with safe and efficient antimicrobial properties. In this study, we developed a novel smart pH-responsive nano-antibacterial system (PM/Ag-Ce6@ZIF-8) based on a metal-organic framework (MOF), enabling specific bacterial targeting and photodynamic therapy. By utilizing bacteria-specific maltodextrin transport pathway, the intelligent nano-antibacterial modified with maltotriose can accurately discriminate between bacterial infection and normal tissue, specifically target the site of infection, and efficiently accumulate at the infection site to enhance safety and efficacy. Furthermore, the incorporation of silver nanoparticles enhances the effectiveness of MOF photodynamic therapy by effectively eradicating bacteria. The nano-antibacterial system exhibits potent inhibition of biofilm formation as well as antibacterial activity while demonstrating excellent in vitro and in vivo biocompatibility. In an animal model of bacterial keratitis, PM/Ag-Ce6@ZIF-8 exhibits superior antibacterial activity compared to Levofloxacin (LVFX) eye drops, significantly improving therapeutic outcomes for bacterial keratitis in mice. Hence, this intelligent nano-antibacterial platform holds promising potential for clinical applications in treating keratitis.
研究领域:
医学
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生物材料学
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纳米技术
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高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Siyuan Qian,Xuan Wang,Yishun Guo,Wenfang He,Jianhua Yang,Hao Chen,Renlong Li,Lili Su,Xinyi Wang,Yi Shao,Bailiang Wang
In the treatment of infectious keratitis, therapeutic strategies often prioritize enhancing bactericidal efficacy. However, endotoxins released from Gram-negative bacteria cause inflammatory reaction, leading to corneal structural damage and scar formation. Given that polymyxin B (PMB) can bind and neutralize lipopolysaccharide (LPS), this study employs large-pore mesoporous silica nanoparticles (lMSNs) grafted with PMB as carriers for cationic antibacterial carbon quantum dots (CQDs) to prepare CQD@lMSN-PMB, which enables synchronous sterilization and endotoxin neutralization. In the acidic infectious microenvironment, the accelerated release of CQDs eliminates 99.88% bacteria within 2 h, effectively substituting immune mediated sterilization. Notably, CQD@lMSN-PMB exhibits exceptional LPS neutralization performance (2.22 µg LPS/mg CQD@lMSN-PMB) due to its high specific surface area. In an infectious keratitis model, inflammation subsides significantly within the first day of CQD@lMSN-PMB intervention and is completely resolved by day 3. By day 2, interleukin-1β, interleukin-6 and tumor necrosis factor-α in CQD@lMSN-PMB group decrease by 86.99%, 91.15%, and 77.56%, respectively, compared to the CQDs-only sterilization group. Ultimately, corneal integrity and transparency are preserved, with suppressed expressions of fibrosis-related factors including matrix metalloproteinase 9, transforming growth factor-β and α-smooth muscle actin. Therefore, this synchronous sterilization and endotoxin neutralization strategy outperforms monotherapy strategies focused solely on sterilization or endotoxin neutralization.
研究领域:
眼科学
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纳米医学
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感染性疾病
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PubMed
高影响因子
BIOMATERIALS
·
2024
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IF 12.8
Jing Xiang,Ruifen Zou,Pin Wang,Xinfangzi Wang,Xuefei He,Fang Liu,Chen Xu,Aiguo Wu
As bacterial keratitis progresses rapidly, prompt intervention is necessary. Current diagnostic processes are time-consuming and invasive, leading to improper antibiotics for treatment. Therefore, innovative strategies for diagnosing and treating bacterial keratitis are urgently needed. In this study, Cu 2-x Se@BSA@NTRP nanoparticles were developed by loading nitroreductase-responsive probes (NTRPs) onto Cu 2-x Se@BSA. These nanoparticles exhibited integrated fluorescence imaging and antibacterial capabilities. In vitro and in vivo experiments showed that the nanoparticles produced responsive fluorescence signals in bacteria within 30 min due to an interaction between the released NTRP and bacterial endogenous nitroreductase (NTR). When combined with low-temperature photothermal therapy (PTT), the nanoparticles effectively eliminated E. coli and S. aureus , achieved antibacterial efficacy above 95% and facilitated the re-epithelialization process at the corneal wound site in vivo . Overall, the Cu 2-x Se@BSA@NTRP nanoparticles demonstrated potential for rapid, noninvasive in situ diagnosis, treatment, and visualization assessment of therapy effectiveness in bacterial keratitis.
研究领域:
医学
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生物材料学
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纳米医学
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DOI
PubMed
高影响因子
Smart Medicine
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2024
·
IF 0
Xiwen Geng,Nan Zhang,Zhanrong Li,Mengyang Zhao,Hongbo Zhang,Jingguo Li
The development of non-antibiotic pharmaceuticals with biocompatible and efficient antibacterial properties is of great significance for the treatment of bacterial keratitis. In this study, we have developed antibacterial iron-doped nanozymes (Fe 3+ -doped nanozymes, FNEs) with distinguished capacity to fight against bacterial infections. The iron-doped nanozymes are composed of Fe 3+ doped zeolitic imidazolate framework-8 (Fe/ZIF-8) and polyethylene imide (PEI), which were functionally coated on the surface of Fe/ZIF-8 and imparted the FNEs with improved water dispersibility and biocompatibility. FNEs possess a significant spontaneous peroxidase-mimic activity without the need for external stimulation, thus elevating cellular reactive oxygen species level by catalyzing local H 2 O 2 at the infection site and resulting in bacteria damaged to death. FNEs eliminated 100% of Staphylococcus aureus within 6 h, and significantly relieved inflammation and bacterial infection levels in mice bacterial keratitis, exhibiting higher bioavailability and a superior therapeutic effect compared to conventional antibiotic eye drops. In addition, the FNEs would not generate drug resistance, suggesting that FNEs have great potential in overcoming infectious diseases caused by antimicrobial resistant bacteria.
研究领域:
生物学
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医学
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药理学
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材料科学
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DOI
Journal of Advanced Research
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2024
·
IF 11.4
Jing Song,Shanshan Zhang,Junya Xing,Licong Zhang,Jiajun Wang,Anshan Shan
Introduction Antifungal peptides (AFPs) have the potential to treat antifungal-resistant infections; however, their structure–function relationship remains unknown, hindering their rapid development. Therefore, it is imperative to investigate and clarify the structure–function relationships of AFPs. Objectives This study aimed to investigate the impact of end-tagging single hydrophobic amino acids and capping the N-terminus with glycine (Gly) on the antifungal activity of peptide W4. Methods The antifungal efficacy of the engineered peptides was initially assessed by determining the minimum inhibitory concentration (MIC) /minimal fungicidal concentration (MFC), killing kinetics, and drug resistance induction, in addition to evaluating the biocompatibility and stability. Subsequently, the antifungal mechanism was investigated using fluorescence labeling, electron microscopy, reactive oxygen species (ROS) detection, and measurement of mitochondrial membrane potential and apoptosis. The impact of the engineered peptides on Candida albicans ( C. albicans ) biofilm and their potential application in the scratch keratomycosis model were investigated. Results The antifungal activity of W4 was significantly enhanced by capping Gly at the N-terminus, resulting in a decrease in average activity from 11.86 μM to 6.25 μM (GW4) and an increase in TI values by 1.9-fold (TI GW4 = 40.99). Mechanistically, GW4 exerted its antifungal effect by disrupting the cellular membrane structure in C. albicans , forming pores and subsequent leakage of intracellular contents. Concurrently, it facilitated intracellular ROS accumulation while decreasing the mitochondrial membrane potential. Additionally, GW4 demonstrated an excellent ability to inhibit and eliminate biofilms of C. albicans . Notably, GW4 demonstrated significant therapeutic potential in a C. albicans -associated keratitis model. Conclusion Capping Gly at the N-terminus increased residue length while significantly enhancing the helical propensity of W4, thereby augmenting its antifungal activity. Our exploratory study demonstrated the potential strategies and avenues for optimizing the structure–function relationships of AFPs and developing highly effective antifungal drugs.
研究领域:
药学
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微生物学
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分子生物学
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PubMed
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EXPERIMENTAL EYE RESEARCH
·
2024
·
IF 3
Lihong Liang,Xue Yang,Hao Zeng,Kai Liao,Runze Zhang,Bowen Wang,Jin Yuan
This research focused on how upregulation of S100A9 contributed to the pathogenesis of the dry eye disease (DED) and whether S100A9 served as a promising therapeutic target in DED. Public single-cell RNA sequencing (scRNA-seq) data of a lacrimal gland excision (LGE) murine DED model was analyzed. LGE model was established and expression of protein was measured through immunofluorescence and western blot. DED-related signs were evaluated through tear secretion and fluorescent staining. TUNEL was performed to detect the level of cell death. Briefly, S100A9 was recognized as a highly variable gene in the DED group. LGE model was successfully established, and S100A9 showed a time-dependent increase in the corneal epithelia. Autophagic blockage was predicted by the scRNA-seq data in DED, and further verified by decrease of LC3B-II/LC3B-I and increase of SQSTM1 and p-mTOR/mTOR, while S100A9 inhibitor paquinimod (PAQ) reversed the changes. PAQ also downregulated TLR4, and inhibition of TLR4 also alleviated autophagic blockage in DED. Finally, signs of DED, chronic corneal inflammation and cell death got a remission after either inhibition of S100A9 or TLR4. In general, we deduced a S100A9-TLR4-Autophagic blockage pathway in the pathogenesis of DED.
研究领域:
眼科
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免疫学
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分子生物学
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病理学
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DOI
PubMed
高影响因子
ACS Nano
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2025
·
IF 16
Xiaojie Wu,Xin Wang,Jing Kang,Alideertu Dong,Ying-Wei Yang
Staphylococcus aureus (S. aureus) is a prevalent and highly virulent pathogen responsible for microbial keratitis, which can lead to stromal damage, corneal perforation, and even blindness. In the postantibiotic era, the escalating prevalence of antibiotic-resistant S. aureus has rendered conventional antibiotic treatments increasingly ineffective, particularly due to autoinducing peptide-mediated signaling. Meanwhile, antibiotics disrupt the balance of the microbiota, which can further trigger ocular complications. To address these challenges, we designed and prepared a camouflaged bacterial system, supramolecular-coated S. aureus (SMCS), which can identify and aggregate with the matching pathogenic S. aureus through autoinducing peptide-mediated signaling. Upon the addition of amantadine, competitive host–guest interactions trigger the release of the antibacterial agent, enabling efficient and selective sterilization against pathogenic S. aureus with a fourfold higher efficacy than that against beneficial bacteria. In a rat model of bacterial keratitis, the proportion of Staphylococcus is 13.71% in the cornea after SMCS treatment, which is comparable to that in the healthy cornea (7.40%). SMCS+amantadine treatment can effectively eradicate bacteria, increase the diversity and abundance of corneal microorganisms, and preserve the balance of the corneal microbiota, providing promising clinical prospects in bacterial infection treatments and bacterial-mediated bioapplications.
研究领域:
微生物学
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眼科学
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感染性疾病
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纳米医学
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分子生物学
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转化医学
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抗菌治疗
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PubMed
高影响因子
ACS Infectious Diseases
·
2024
·
IF 4
Ning Gao,Xiaoyan Ju,Xiting Jiao,Yuanyuan Qi,Ye Tian,Shidong Jiang,Zhongwei Niu,Shaozhen Zhao,Ruibo Yang
Fungal keratitis (FK) is a leading cause of preventable blindness and eye loss. The poor antifungal activity, increased drug resistance, limited corneal permeability, and unsatisfactory biosafety of conventional antifungal eye drops are among the majority of the challenges that need to be addressed for currently available antifungal drugs. Herein, this study proposes an effective strategy that employs chitosan-poly(ethylene glycol)-LK13 peptide conjugate (CPL) in the treatment of FK. Nanoassembly CPL can permeate the lipophilic corneal epithelium in the transcellular route, and its hydrophilicity surface is a feature to drive its permeability through hydrophilic stroma. When encountering fungal cell membrane, CPL dissembles and exposes the antimicrobial peptide (LK13) to destroy fungal cell membranes, the minimum inhibitory concentration values of CPL against Fusarium solani (F. solani) are always not to exceed 8 μg peptide/mL before and after drug resistance induction. In a rat model of Fusarium keratitis, CPL demonstrates superior therapeutic efficacy than commercially available natamycin ophthalmic suspension. This study provides more theoretical and experimental supports for the application of CPL in the treatment of FK.
研究领域:
眼科学
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药学
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生物技术
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微生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
LiLi Zhao,Hongbo Li,Jiajia Yuan,Zhen Wang,Dan Xu,Zhenbin Liu,Lishan Yao,Junjian Ran,Quanyu Dai,Liangbin Hu
Bacterial keratitis is one of the most common causes of visual impairment and blindness worldwide, and suffers the risk of drug-resistant infections due to the abuse of antibiotics. Despite its ability to counteract antibiotic resistance by inducing ferroptosis, the application of Fe 2+ is limited by oxidative instability and a solution pH often incompatible with ophthalmic use. Thus, this study designed and synthesized an ascorbate–ferrous iron complex (SA-Fe(II)) using ferrous lactate and sodium ascorbate, followed by comprehensive structural characterization. Results confirmed the formation of coordination bonds between Fe 2+ and sodium ascorbate. The molecular ion peak and characteristic decarboxylated fragment, along with broad and diffuse diffraction peaks in X-ray diffraction patterns, verified the formation of an amorphous metal chelate structure stabilized by dynamic coordination bonds. The SA-Fe(II) complex exhibited potent antibacterial activity, achieving more than 99.99 % killing of Staphylococcus aureus ( S. aureus ) and methicillin-resistant Staphylococcus aureus (MRSA) at 100 μM within 3 h. When incorporated into a sodium hyaluronate eye-drop matrix (SA-Fe(II)-SH), the formulation exhibited excellent ocular biocompatibility, as evidenced by hemolysis rates less than 5 %, more than 95 % viability of human corneal epithelial cells (HCE-T) corneal epithelial cells over 3 days, and no observable tissue inflammation in vivo. Importantly, in a mice model of MRSA keratitis, SA-Fe(II)-SH significantly reduced bacterial load, suppressed the production of inflammatory cytokines (IL-1β, IL-6, TNF-α), promoted corneal repair, and prevented systemic dissemination. This non-antibiotic strategy integrates antibacterial, anti-inflammatory, and pro-healing functions, offering a safe and effective therapeutic approach for the treatment of drug-resistant bacterial keratitis.
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