Materials Today Bio
·
2025
·
IF 10.2
Ziling Li,Huiling Lei,Jiannan Hu,Tong Zhou,Shuaiqi Yuan,Xinyue Ma,Yunfei Zhu,Chao Liu,Decai Wang,Yuzhou Wu,Shuyun Xu
The pneumonia induced by carbapenem resistant Klebsiella pneumoniae (CRKP) has high morbidity and mortality. Among the antibiotics currently available, polymyxin B (PMB) is considered to be the last line of defense. Routine intravenous administration of PMB has many problems, such as severe neurotoxicity and nephrotoxicity. In this study, a novel inhaled PMB-loaded albumin nanoparticles (PEG-pHSA@PMB) capable of penetrating airway mucus and responding to the infection microenvironment is constructed. An acid-responsive functional molecule (PEBA) and NH 2 -PEG-SH are linked to the surface of human serum albumin (HSA) via the conjugation reaction. Subsequently, PMB is loaded through electrostatic interactions to yield PEG-pHSA@PMB. The sulfhydryl groups of PEG-pHSA@PMB interact with mucins to help penetrate mucus after inhaled. In an acidic environment, the protonation of the tertiary amino groups within PEG-pHSA@PMB causes the charge alteration, which leads to the release of PMB. It demonstrated excellent mucus permeability, potent bactericidal activity, and superior bacteriostatic effects compared to sole PMB. Inhalation of PEG-pHSA@PMB significantly reduced the bacterial load in the lungs of mice with CRKP pneumonia, alleviating inflammatory response. Moreover, PEG-pHSA@PMB exhibited good cytocompatibility and biosafety. The novel strategy of the inhalation drug delivery system is promising for the treatment of pneumonia caused by drug-resistant bacteria.
研究领域:
医学
·
药剂学
·
感染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Annals of Clinical Microbiology and Antimicrobials
·
2025
·
IF 3.6
Ai Guo,Dianbao Zuo,Li Shi,Ming Guo,Jinquan Li,Caili Li,Puqing Wang,Xiaodong Sun,Ming Sang
Background The emergence of MDR K. pneumoniae poses a critical challenge in treating respiratory-associated pneumonia. Bacteriophages are promising antibiotic alternatives with unique features. This study aimed to isolate new bacteriophages from the hospital environment and investigate their therapeutic potential and mechanisms. Methods We employed plaque assays, transmission electron microscopy, and whole-genome sequencing to systematically characterize the biological properties, morphology, and genomic profiles of the phages in parallel. The bacteriostatic curve, biofilm staining quantification, and biofilm inhibition rate assay were employed to evaluate the in vitro lytic efficacy of the phage. More importantly, we established the murine pneumonia infection models through nasal instillation, assessed the therapeutic potential of the phage in vivo by observing pathological morphology via HE staining, detecting pro-inflammatory cytokine levels via qPCR and ELISA, and monitoring bacterial load changes in lung tissue through PCR analysis. Results Phages vB_KpnP_XY3 and vB_KpnP_XY4, taxonomically classified as Siphoviridae , demonstrated broad temperature (4–60 °C), pH (4–11) tolerance, chloroform resistance, latent periods of 40/35 min, and burst sizes of 340/126 PFU/cell. Both genomes contained circular dsDNA genomes (47,466 bp/50,036 bp) without virulence or antibiotic resistance genes. The bacterial concentration markedly decreased at 2 h post-treatment, reaching its biological nadir by 6 h. Concurrent biofilm assays demonstrated 80% biofilm inhibition and rapid bacterial clearance. In murine pneumonia models, both phage monotherapy and phage-antibiotic combinations significantly reduced bacterial loads compared with antibiotics alone ( P < 0.05), concurrently attenuating inflammation (IL-1β/IL-6/TNF-a. P < 0.0001) and restoring alveolar architecture with reduced necrosis. Conclusion The phages vB_KpnP_XY3 and vB_KpnP_XY4 demonstrated robust environmental adaptability. Its antibacterial effect is related to its specific biofilm dissolution performance in vivo and in vitro. These findings provide strong evidence for the precise phage treatment of MDR K. pneumoniae infections. Supplementary Information The online version contains supplementary material available at 10.1186/s12941-025-00812-9.
研究领域:
微生物学
·
病毒学
·
传染病学
·
药理学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC Veterinary Research
·
2022
·Vol. 18
·期 1
·1-14
·
IF 2.792
Hao Fei,Xie Xing,Feng Zhixin,Chen Rong,Wei Yanna,Liu Jin,Xiong Qiyan,Shao Guoqing,Lin Johnson
Background Mycoplasma hyopneumoniae (M. hyopneumoniae) is the etiological agent of enzootic pneumonia, a highly infectious swine respiratory disease that distributed worldwide. The pathogenesis and virulence factors of M. hyopneumoniae are not fully clarified. As an important virulence factor of bacteria, nicotinamide adenine dinucleotide (NADH) oxidase (NOX) participates in host-pathogen interaction, however, the function of NOX involved in the pathogenesis of M. hyopneumoniae is not clear.Results In this study, significant differences in NOX transcription expression levels among different strains of M. hyopneumoniae differed in virulence were identified, suggesting that NOX may be correlated with M. hyopneumoniae virulence. The nox gene of M. hyopneumoniae was cloned and expressed in Escherichia coli, and polyclonal antibodies against recombinant NOX (rNOX) were prepared. We confirmed the enzymatic activity of rNOX based on its capacity to oxidize NADH to NAD+. Flow cytometry analysis demonstrated the surface localization of NOX, and subcellular localization analysis further demonstrated that NOX exists in both the cytoplasm and cell membrane. rNOX was depicted to mediate adhesion to immortalized porcine bronchial epithelial cells (hTERT-PBECs). Pre-neutralizing M. hyopneumoniae with anti-rNOX antibody resulted in a more than 55% reduction in the adhesion rate of high- and low-virulence M. hyopneumoniae strains to hTERT-PBECs. Moreover, a significant difference appeared in the decline in CCU50 titer between virulent (168) and virulence-attenuated (168L) strains. NOX not only recognized and interacted with host fibronectin but also induced cellular oxidative stress and apoptosis in hTERT-PBECs. The release of lactate dehydrogenase by NOX in hTERT-PBECs was positively correlated with the virulence of M. hyopneumoniae strains.Conclusion sNOX is considered to be a potential virulence factor of M. hyopneumoniae and may play a significant role in mediating its pathogenesis.
研究领域:
微生物学
·
兽医学
·
分子生物学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Tao Dong,Guangze Sun,Wanjian Liu,Yunze Long,Aihua Liu
Acute respiratory infections (ARIs) are among the leading causes of morbidity and mortality worldwide, with Mycoplasma pneumoniae (M. pneumoniae) and Chlamydia pneumoniae (C. pneumoniae) being major pathogens responsible for community-acquired respiratory infections. Rapid and accurate diagnosis is critical for improving patient outcomes and effectively controlling disease transmission. Herein, we report a novel dual-channel lateral flow immunoassay (DC-LFIA) platform based on the Co3O4@polydopamine (PDA) nanocomposite with outstanding extinction coefficient, oxidase-like activity, and magnetic properties for the simultaneous detection of specific IgM antibodies (Ab) against these two pathogens in human serum. The magnetic properties of the Co3O4@PDA nanocomposite enable rapid enrichment of trace target Abs from large-volume serum samples, with a high extinction coefficient for direct colorimetric visualization and an excellent oxidase-like catalytic activity for signal enhancement. On the basis of the multifunctional Co3O4@PDA nanocomposite, rapid dual-mode detection of serum Abs was achieved within 12 min. By the direct colorimetric mode, the visual limit of detection (vLOD) for M. pneumoniae Ab and C. pneumoniae Ab reached 2 and 1 ng/mL, respectively, while the oxidase-like catalyzing signal amplification mode further lowered the vLODs to 0.2 and 0.1 ng/mL, accordingly. Additionally, the signal normalization using a 3D-printed device significantly enhanced assay accuracy and reproducibility. When applied to 96 clinical serum samples, compared to commercial kits, this multifunctional Co3O4@PDA-based DC-LFIA demonstrated superior performance, providing a reliable approach for simultaneous antibody detection in respiratory infection diagnosis. Overall, this work contributes a valuable diagnostic tool to the field of rapid detection of ARIs.
研究领域:
免疫学
·
临床检验医学
·
纳米生物技术
·
传染病学
·
诊断学
·
转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2022
·
IF 5.195
Zheng Liu,Wen-ting Dong,Wen-feng Wei,Jin-hai Huo,Wei-ming Wang
Ethnopharmacological relevance Traditional Chinese medicine categorizes Mycoplasma pneumoniae pneumonia as “lung heat”, and treatment with heat clear and detoxify. Traditional Chinese medicine believes that the lungs and intestines come from the same source, and the intestine is related to pneumonia. This is the same as the gut-lung axis theory. Qinbaiqingfei concentrate pills (QBs) were modified based on Cough San in the ancient medical book Medical Awareness . It clears lung heat, moisturizes the lungs and dredges collaterals, and has a good ability to treat Mycoplasma pneumoniae . Aim of the study A rat model of Mycoplasma pneumoniae was established. From the aspect of intestinal flora and mucosal immunity, the potential mechanism of the QBs was researched. Materials and methods First, the content of Mycoplasma pneumoniae in lung tissue and the levels of the inflammatory factors IL-4, IL-10, TNF-α and INF-γ were detected. To determine the expression of NF-kB related proteins in lung tissue, which can understand the ability in treating disease. Next, metagenomic sequencing was performed to detect changes in short-chain fatty acids, proving the ability of the drug to regulate intestinal microecology. Finally, HDAC , LPS , SIgA, etc. were detected to facilitate the correlation of the overall experimental indicators. Results QBs reduces the levels of IL-4, IL-10, TNF-α and INF-γ in the serum by inhibiting the expression of MyD88 , IKKα, IκBα, and NF-κB p65 in lung tissue. In addition, QBs restores the ratio of gram-negative bacteria to gram-positive bacteria in the intestine, restores the secretion of acetic acid, propionic acid , butyric acid , isobutyric acid and isovaleric acid , and promotes the secretion of NF-κB p65 and SIgA by HDAC1/3. The result is that the lung tissue is repaired and the proliferation of Mycoplasma pneumoniae is inhibited. Conclusions From the “gut-lung axis”, a new research perspective was discovered. QBs intervened in the intestines and lungs to treat Mycoplasma pneumoniae .
研究领域:
民族药理学
·
微生物学
·
免疫学
·
中医药
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Arabian Journal of Chemistry
·
2021
·
IF 5.165
Hong-Xia Song,Ting Lei,Fang Wu,Xiaoyu He,Jiang Wang
This article has been retracted: please see Elsevier Policy on Article Withdrawal ( http://www.elsevier.com/locate/withdrawalpolicy ). This article has been retracted at the request of the Editor-in-Chief. In investigating concerns brought up regarding the authenticity of the article, the editors reached out to the corresponding author for an explanation. The authors failed to reply. The editors therefore feel that the findings of the manuscript cannot be relied upon and that the article needs to be retracted.
研究领域:
配位化学
·
医学应用
·
材料科学
✓ 已验证
DOI
高影响因子
Frontiers in Cellular and Infection Microbiology
·
2025
·
IF 4.8
Xueyao Fang,Yanhui Chen,Longhua Hu,Shumin Gu,Junqi Zhu,Yaping Hang,Xingwei Cao,Yanping Xiao,Hong Luo,Chuwen Zhao,Lianhua Xiao,Qiaoshi Zhong
Indole, a crucial bacterial signaling molecule, plays a fundamental role in regulating various physiological processes within bacteria, including growth, acid tolerance, biofilm development, motility, and other cellular functions. Its regulatory influence extends beyond indole-producing bacteria, significantly impacting the physiological activities in non-indole-producing species. In this study, we demonstrate that indole enhances the pathogenicity and viability of Klebsiella pneumoniae using the Galleria mellonella infection model and serum killing assay. Concurrently, indole has varying effects on biofilm formation in K. pneumoniae, with some strains showing enhanced biofilm formation ability. To elucidate the underlying molecular mechanisms, transcriptome analysis revealed that indole exposure in K. pneumoniae led to the upregulation of genes associated with pili formation and iron acquisition systems, while simultaneously inducing oxidative stress responses. Additionally, our analysis uncovered extensive metabolic remodeling. Specifically, we observed significant upregulation of genes involved in simple carbohydrate utilization pathways, including those responsible for galactose, mannose, and maltose metabolism, as well as enhanced expression of genes associated with pyrimidine biosynthesis. These findings collectively indicate that indole enhances the intestinal colonization and pathogenicity of K. pneumoniae primarily by modulation of fimbriae expression and metabolic pathway regulation.
研究领域:
微生物学
·
分子生物学
·
感染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Infection and Drug Resistance
·
2022
·
IF 4.177
Yingying Du,Shikui Mu,Yan Liu,Yinghua Yuan,Yunlou Zhu,Lijie Ma,Qixing Wang,Zhengfang Zhu,Yuhao Liu,Sheng Wang
Purpose This study retrospectively analyzed the genome characteristics of blaKPC-2 in multidrug-resistant Klebsiella pneumoniae collected from the ICU of a teaching hospital in Shanghai, China.Methods From February 2018 to December 2019, 36 strains of multidrug-resistant Klebsiella pneumoniae were collected from the bronchoalveolar lavage fluid of critically ill patients. The genome of all isolates was obtained through the Illumina sequence, and single nucleotide polymorphisms of the blaKPC-2 gene were analyzed to explore blaKPC-2’s evolutionary characteristics. Different strains’ genetic relationships and homology were studied by constructing an evolutionary tree on a single copy orthologue. Pacbio combined Illumina sequence was conducted to evaluate the structure and potential mobility of drug-resistant plasmids of the strain KP-s26.Results The distribution of resistance and virulence genes had little difference, but most strains had significant differences in the plasmid-encoded region. Most strains (31/36) carried the carbapenemase gene blaKPC-2, with no single nucleotide polymorphism in different strains. Extended-spectrum β-lactamase resistance genes, such as blaCTX-M and blaSHV, were found in the isolates, but no metallo-β-lactamases were detected. All strains with blaKPC-2 coexisted with chromosomal-associated fosfomycin resistance genes fosA6, and the coexistence of blaKPC-2 and blaCTX variants (blaCTX-M-15, blaCTX-M-65, and blaCTX-M-27) was also detected in 29/31 strains. The isolate KP-s26 carried five circular plasmids. pA and pB were conjugate plasmids, as they carried drug resistance genes and contained a complete IV secretion system.Conclusion The blaKPC-2 carbapenemase gene is relatively conservative in the process of evolution; drug-resistant plasmids containing conjugated transfer elements contribute to the spreading of drug resistance. The coexistence of blaKPC-2 with fosA6 or blaCTX-M variants was associated with increased fosfomycin resistance and broad-spectrum β-lactam resistance, respectively.Clinical Trials Registration Clinical Trials.gov Identifier: NCT03950544
研究领域:
微生物学
·
基因组学
·
传染病学
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Junsong Jing,Yi Sun,Yiyang Shui,Junyi Wang,Wenjing Ye,Ranran Chen,Lianhao Wu,Lijuan Xing,Rongrong Huang,Ting Zhou,Wenwen Zhu,Yueguo Wu,Sheng Zhang,Jing Shi,Yuanyuan Li,Yan Liu,Zhenqiang You
Background Viral pneumonia is an infection of the lungs caused by numerous different viruses, which can lead to severe respiratory distress and even life-threatening conditions. In the absence of specific treatments for viral pneumonia, natural traditional medicines offer an alternative in terms of innovative drug therapies. Morus alba L. (common name mulberry leaf) is a Chinese medicine that has been used clinically as an antiviral. Purpose The therapeutic effect of M. alba on viral pneumonia was investigated along with its mechanism of action. Methods Network pharmacology and molecular docking were used to analyze the mechanism of action of M. alba in the treatment of viral pneumonia. Histology, immunofluorescence, Western blotting, qPCR, and flow cytometry were used to evaluate the protective effect of MLE (the ethanol extract of Morus alba L. ) on PR8 (A/Puerto Rico/8/1934 H1N1, a murine lung-adapted influenza A virus strain)-induced viral pneumonia. SiRNA was used to validate the relationship between the therapeutic effects of MLE on viral pneumonia and the target Syk (a crucial non-receptor tyrosine kinase). Results MLE alleviated PR8-induced viral pneumonia by reducing inflammatory factor expression in the lungs, decreasing NF-κB pathway activation, slowing oxidative damage in the lungs, and inhibiting lung tissue cell apoptosis. Meanwhile, MLE for viral pneumonia was significantly associated with Syk targets. Notably, knockdown of the Syk gene not only reduced the therapeutic effect of MLE, but also suppressed PR8-induced viral pneumonia. Conclusion MLE can alleviate PR8-induced viral pneumonia through inhibiting the Dectin-1/Syk pathway.
研究领域:
药理学
·
分子生物学
·
病毒学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2022
·Vol. 13
·期 1
·1-17
·
IF 17.694
Wang Xiaojuan,Xu Xiaoling,Zhang Shaojun,Chen Na,Sun Yunfeng,Ma Kuifen,Hong Dongsheng,Li Lu,Du Yongzhong,Lu Xiaoyang,Jiang Saiping
Tigecycline is regarded as the last line of defense to combat multidrug-resistant Klebsiella pneumoniae . However, increasing utilization has led to rising drug resistance and treatment failure. Here, we design a D-alpha tocopheryl polyethylene glycol succinate-modified and S-thanatin peptide-functionalized nanorods based on calcium phosphate nanoparticles for tigecycline delivery and pneumonia therapy caused by tigecycline-resistant Klebsiella pneumoniae . After incubation with bacteria, the fabricated nanorods can enhance tigecycline accumulation in bacteria via the inhibitory effect on efflux pumps exerted by D-alpha tocopheryl polyethylene glycol succinate and the targeting capacity of S-thanatin to bacteria. The synergistic antibacterial capacity between S-thanatin and tigecycline further enhances the antibacterial activity of nanorods, thus overcoming the tigecycline resistance of Klebsiella pneumoniae . After intravenous injection, nanorods significantly reduces the counts of white blood cells and neutrophils, decreases bacterial colonies, and ameliorates neutrophil infiltration events, thereby largely increasing the survival rate of mice with pneumonia. These findings may provide a therapeutic strategy for infections caused by drug-resistant bacteria.
研究领域:
药学
·
纳米技术
·
传染病学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Jiawang Huang,Jianing Shi,Jingmin Fu,Zhuolin Liu,Zhiying Feng,Kangyu Wang,Chunjing Chen,Yi Ning,Fangguo Lu,Ling Li
Ethnopharmacology relevance Maxing Shigan Decoction (MXSGD), derived from the traditional Chinese medicine (TCM) classic Shang Han Lun , is recognized as an effective TCM herbal formula for treating respiratory diseases, although its precise molecular mechanisms against influenza A virus (IAV) have not yet been fully elucidated. Aim of the study This study aimed to clarify the pharmacological effects of MXSGD on IAV-infected pneumonia mouse models, with a particular focus on its regulatory mechanism through miR-1260. Materials and methods The chemical composition of MXSGD was analyzed using an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). After establishing IAV-infected mouse models, the pathological changes in lung tissues were observed by hematoxylin-eosin (HE) staining; the pulmonary epithelial cells and macrophages in lung tissues were examined through immunological assays; and the expression levels of miR-1260 and its target genes in lung tissues were evaluated by RT-qPCR and Western blot analysis. A co-culture system of MLE-12 and RAW246.7 cells was constructed as the research model. Then, the intracellular miR-1260 expression was detected by RT-qPCR, and the Sema3A expression was examined by immunofluorescence. The macrophages were further transfected with miR-1260 mimic, inhibitor, and Sema3A siRNA to determine whether MXSGD exerts its therapeutic effects through the miR-1260-targeted Sema3A-mediated PI3K/AKT/mTOR signaling pathway. Subsequently, alveolar macrophage-depleted mouse models were established using CL2MBP, and were infected with IAV. To clarify the role of macrophages in the therapeutic mechanism of MXSGD against IAV, the body weight and organ indices of mice were monitored and recorded; the total protein content and levels of inflammatory factors in the bronchoalveolar lavage fluid (BALF) were measured; the histopathological changes were observed by HE staining; the pulmonary epithelial cells and macrophages in lung tissues were examined through immunological assays; and the expressions of miR-1260 and its target genes in lung tissues were evaluated by RT-qPCR and Western blot analysis. Results MXSGD was found to alleviate IAV-induced pathological injury and suppress macrophage recruitment in mouse lung tissues, while downregulating the viral load and levels of inflammatory factors. The attenuation of macrophage recruitment was closely associated with pulmonary epithelial cells, potentially mediated through the miR-1260-targeted Sema3A-regulated PI3K/AKT/mTOR signaling pathway. In cellular experiments, both cell types in the co-culture system were restored following MXSGD treatment, accompanied by lowered intracellular viral load and levels of inflammatory factors. Additionally, macrophage apoptosis and miR-1260 expression were significantly reduced, whereas the Sema3A fluorescence intensity in macrophages was markedly increased. By transfecting miR-1260 mimic, inhibitor, and Sema3A siRNA into co-cultured macrophages, the therapeutic effects of MXSGD were further confirmed to be associated with the miR-1260/Sema3A-mediated PI3K/AKT/mTOR pathway. In IAV-infected models established after pulmonary macrophage depletion, the therapeutic efficacy of MXSGD was partially weakened following elimination of alveolar macrophages. In general, above in vivo findings are consistent with the cellular experimental results, collectively supporting the involvement of the miR-1260-targeted Sema3A-mediated PI3K/AKT/mTOR signaling pathway in the therapeutic mechanism of MXSGD. Conclusions MXSGD was demonstrated to regulate the PI3K/AKT/mTOR pathway through the macrophage miR-1260/Sema3A axis, through which excessive inflammatory responses in IAV-induced pneumonia were effectively suppressed. The findings provide a novel therapeutic target for antiviral treatment in TCM.
研究领域:
免疫学
·
病毒学
·
分子生物学
·
呼吸病学
·
中药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2018
·
IF 8.806
Qiyue Wang,Gujie Mi,Daniel Hickey,Yanan Li,Jiasheng Tu,Thomas J. Webster,Yan Shen
Pneumonia is a major contributor to infection-based hospitalizations and deaths in the United States. Antibiotics such as azithromycin (AZM), although effective at managing pneumonia, often suffer from off-target diffusion and poor bioavailability when administered orally or via intravenous injection. The formation of biofilms at the disease sites makes the treatment more complicated by protecting bacteria from antimicrobial agents and thus necessitating a much higher dosage of antibiotics to eradicate the biofilms. As such, targeted pulmonary delivery of antibiotics has emerged as a promising alternative by providing direct access to the lung while also allowing higher local therapeutic concentrations but minimal systemic exposure. In this study, AZM was encapsulated in N-fumaroylated diketopiperazine (FDKP) microparticles for efficient pulmonary delivery. Both in vitro and in vivo results demonstrated that AZM@FDKP-MPs administered via intratracheal insufflation achieved at least a 3.4 times higher local concentration and prolonged retention times compared to intravenous injection and oral administration, suggesting their potential to better manage bacterial pneumonia.
研究领域:
药学
·
微生物学
·
呼吸病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）