VIROLOGY
·
2025
·
IF 2.4
Yao Yao,Rui Jing,Xiang Liu,Li Kang,Pinghuang Liu
Feline infectious peritonitis (FIP), a fatal disease in cats caused by feline infectious peritonitis virus (FIPV), has limited treatment options and lacks effective vaccines. Cepharanthine (CEP), a natural isoquinoline alkaloid, possesses many medicinal properties, including antiviral activities. However, the role of CEP in management of FIPV infection remains poorly understood. Here, we identified that CEP had a potent ability to inhibit FIPV infection in vitro . CEP significantly inhibited FIPV infection when administered at different times, with co-treatment showing the most significant inhibitory effect. Time-of-addition assays demonstrated that CEP exerted antiviral activity during the post-entry stages of the FIPV infection. We also verified that CEP inhibited FIPV infection not through affecting type I interferon expression, and it could decrease pro-inflammatory factors expression induced by FIPV infection. The combination of CEP and GS-441524 exhibited synergistic antiviral effects against FIPV infection. Our findings highlight the therapeutic potential of CEP for treatment of FIP.
研究领域:
兽医学
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病毒学
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药理学
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DOI
PubMed
高影响因子
Collagen and Leather
·
2023
·Vol. 5
·期 1
·1-13
·
IF 0
Dong Jinhong,Wang Tianyou,Li Haotian,Zhang Jianhua,Zhang Hengjie,Liu Weijie,You Xinru,Gu Zhipeng,Li Yiwen,Chen Xianchun,Fu Qiang
The development of advanced sustainable biomedical materials with superior biosafety and bioactivity for clinical applications is highly desirable. In the present investigation, biomass-based nanoparticles (NPs) were assembled through the Mannich reaction between the plant polyphenols and the broad-spectrum antibiotic tigecycline (TG). The fabricated NPs with uniform size demonstrated excellent oxidative balance effects, pH-responsive release properties and antibacterial performances. Furthermore, the intracellular and in vivo studies confirmed that the NPs are capable of reducing oxidative damage to cells and significantly repairing tissue injury in mice with peritonitis. This work presents an effective method and idea for constructing biomass-based materials for the treatment of infection-induced diseases. Graphical Abstract
研究领域:
生物医学材料
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药理学
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微生物学
✓ 已验证
DOI
INTERNATIONAL IMMUNOPHARMACOLOGY
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2016
·
IF 2.551
Ping Huang,Xiaoyan Lu,Baohong Yuan,Tao Liu,Liangcheng Dai,Yunjun Liu,Hui Yin
Astragaloside IV (AS-IV), an active saponin purified from Astragali Radix , has been identified with broad biological and pharmacological activities . In the present study, we continue to explore the potential effect of AS-IV on antibacterial response using an acute E. coli peritoneal infection model. Our findings implied that administration of AS-IV decreases mortality in mice challenged by lethal E. coli infection. The protection of AS-IV was related to promotion of neutrophil extravasation into the peritoneum and bacterial clearance . Toll-like receptor (TLR) activation in neutrophils has been reported to reduce CXCR2 expression and subsequent neutrophil migration. Our data indicated that AS-IV prevented the reduction of CXCR2 expression and neutrophil migration induced by LPS, the activator for TLR4 . Moreover, we found that AS-IV blocks LPS-induced suppression of CXCR2 on neutrophils by inhibiting the expression of G protein-coupled receptor kinase-2 (GRK2), an agonist that regulates desensitization and internalization of chemokine receptors . Taken together, these data propose that AS-IV, through modulating GRK2-CXCR2 signal in neutrophils, offers an essential efficacy on host antibacterial immunity.
研究领域:
免疫学
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药理学
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微生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2019
·
IF 3.743
Yanke Lin,Shuai Wang,Zemin Yang,Lu Gao,Ziyue Zhou,Pei Yu,Baojian Wu
Bilirubin is an endogenous substance derived from heme catabolism. In this study, we aimed to assess the anti-inflammatory activity of bilirubin, and to determine the mechanism thereof. The anti-inflammatory activity of bilirubin was evaluated using lipopolysaccharide (LPS)-treated peritoneal macrophages (PMs) and Raw264.7 cells, and mice with alum-induced peritonitis. The mRNA and proteins of NOD-like receptor family pyrin domain containing 3 (Nlrp3) and inflammatory cytokines were determined using qPCR and Western blotting, respectively. Distribution of phosphorylated (p) p65 [a NF-κB (nuclear factor-κB) subunit] in the cytoplasm and nucleus were evaluated by immunofluorescence analysis and electrophoretic mobility shift assay. Bilirubin prior to LPS treatment decreased protein expressions of Nlrp3, pro-interleukin (IL)-1β and mature IL-1β in PMs, whereas bilirubin post LPS treatment showed no effects. Bilirubin prior to LPS treatment dose-dependently repressed expressions of Nlrp3 and IL-1β, and inhibited translocation of p-p65 to nucleus in Raw264.7 cells. Bilirubin treatment decreased myeloperoxidase activity and reduced the levels of inflammatory cytokines (i.e., IL-1β, TNFα and IL-6) in lavage fluid in mice with alum-induced peritonitis. This was accompanied by a lower mortality rate. In addition, the mRNAs of Nlr p3 and IL-1β in peritoneal exudates cells were decreased, and the levels of p-p65 and mature IL-1β proteins were reduced. In conclusion, bilirubin acted on inflammation and alleviated alum–induced peritonitis through inactivation of Nlrp3 inflammasome.
研究领域:
免疫学
·
炎症
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药理学
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产品关联
DOI
PubMed
高影响因子
Animals
·
2025
·Vol. 15
·期 16
·2457
·
IF 2.7
Qirong Lu,Xuwen Liu,Junke Tian,Pu Guo,Chun Ye,Shulin Fu,Yu Liu,Yinsheng Qiu
Simple SummaryGlaesserella parasuis(GPS), a Gram-negative bacterium that colonizes piglets’ upper respiratory tracts, causes Glässer’s disease including peritonitis under stress, though the peritonitis mechanism remains unclear. Baicalin, a main active component of Huangqin (Scutellaria baicalensis), exhibits significant anti-inflammatory effects. This study aimed to investigate the mechanism by which baicalin alleviatesGPS-induced peritonitis in piglets. We examined the effects of baicalin on inflammatory responses and key signaling molecules in both porcine peritoneal mesothelial cells (PPMCs) in vitro and the peritoneum ofGPS-infected piglets in vivo. Our results showed that baicalin significantly reducedGPS-induced expression of pro-inflammatory cytokines (tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6) and inhibited the upregulation of disintegrin and metalloproteinase 17 (ADAM17), phosphorylated epidermal growth factor receptor (EGFR)/EGFR, and phosphorylated extracellular signal-regulated kinase (ERK)/ERK. Mechanistically, baicalin inhibited ADAM17 overexpression-induced upregulation of this pathway and cytokines in PPMCs, while ADAM17 small interfering RNA attenuatedGPS-induced effects. These findings demonstrate that baicalin mitigatesGPS-induced peritonitis by suppressing the ADAM17/EGFR axis and the subsequent cytokine production, thus providing a theoretical basis for novelGPScontrol strategies and the development of novel non-antibiotic strategies, including phytochemical therapeutics and feed additives.Glaesserella parasuis(GPS) is a Gram-negative, pathogenic bacterium that colonizes the upper respiratory tract of piglets and causes Glässer’s disease with peritonitis under stress conditions. The mechanism underlying GPS-induced peritonitis in piglets remains unclear. Baicalin is one of the main active ingredients of Huangqin (Scutellaria baicalensis), which has a significant anti-inflammatory effect on inflammatory diseases. Therefore, this study aimed to elucidate the molecular mechanism by which baicalin alleviatesGPS-induced peritonitis in piglets, specifically focusing on the role of the ADAM17/EGFR signaling axis. We investigated the effects of baicalin in vitro using porcine peritoneal mesothelial cells (PPMCs) and in vivo in GPS-infected piglets. Our results showed that baicalin reduced the expression of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) in PPMCs and the peritoneum of piglets afterGPSinfection. Concurrently, baicalin significantly reduced the upregulation of disintegrin and metalloproteinase 17 (ADAM17), phosphorylated epidermal growth factor receptor (p-EGFR)/EGFR, and phosphorylated extracellular signal-regulated kinase (p-ERK)/ERK induced byGPSinfection in PPMCs and the peritoneum of piglets. Crucially, in vitro mechanistic investigations revealed that baicalin can significantly reduce the upregulation of ADAM17, p-EGFR/EGFR, p-ERK/ERK, TNF-α, IL-1β, and IL-6 induced by ADAM17 overexpression in PPMCs. Furthermore, ADAM17 small interfering RNA can significantly reduce the upregulation of ADAM17, p-EGFR/EGFR, p-ERK/ERK, TNF-α, IL-1β, and IL-6 induced byGPSinfection in PPMCs. These findings demonstrate that baicalin can inhibit the expression of inflammatory factors TNF-α, IL-1β, and IL-6 through the ADAM17/EGFR axis, and then alleviate the peritonitis caused byGPSin piglets. This provides a theoretical basis for developing novel non-antibiotic strategies, including phytochemical therapeutics and feed additives, for preventing and controlling GPS.
研究领域:
兽医学
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微生物学
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药理学
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免疫学
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分子生物学
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畜牧学
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2023
·
IF 9.7
Xinshu Zou,Shuang Cai,Tingting Wang,Sidi Zheng,Xilong Cui,Jingyou Hao,Xueying Chen,Yanyan Liu,Zhiyun Zhang,Yanhua Li
Intracellular MRSA is extremely difficult to eradicate by traditional antibiotics, leading to infection dissemination and drug resistance. A general lack of facile and long-term strategies to effectively eliminate intracellular MRSA. In this study, glabridin (GLA)-loaded pH-responsive nanoparticles (NPs) were constructed using cinnamaldehyde (CA)-dextran conjugates as carriers. These NPs targeted infected macrophages/MRSA via dextran mediation and effectively accumulated at the MRSA infection site. The NPs were then destabilized in response to the low pH of the lysosomes, which triggered the release of CA and GLA. The released CA downregulated the expression of cytotoxic pore-forming toxins, thereby decreasing the damage of macrophage and risk of the intracellular bacterial dissemination. Meanwhile, GLA could rapidly kill intracellularly entrapped MRSA with a low possibility of developing resistance. Using a specific combination of the natural antibacterial agents CA and GLA, NPs effectively eradicated intracellular MRSA with low toxicity to normal tissues in a MRSA-induced peritonitis model. This strategy presents a potential alternative for enhancing intracellular MRSA therapy, particularly for repeated and long-term clinical applications. Statement of significance Intracellular MRSA infections are a growing threat to public health, and there is a general lack of a facile strategy for efficiently eliminating intracellular MRSA while reducing the ever-increasing drug resistance. In this study, pH-responsive and macrophage/MRSA-targeting nanoparticles were prepared by conjugating the phytochemical cinnamaldehyde to dextran to encapsulate the natural antibacterial agent glabridin. Using a combination of traditional Chinese medicine, the NPs significantly increased drug accumulation in MRSA and showed superior intracellular and extracellular bactericidal activity. Importantly, the NPs can inhibit potential intracellular bacteria dissemination and reduce the development of drug resistance, thus allowing for repeated treatment. Natural antibacterial agent-based drug delivery systems are an attractive alternative for facilitating the clinical treatment of intracellular MRSA infections.
研究领域:
药学
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纳米技术
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微生物学
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药物递送系统
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传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Maojuan Liu,Yunhe Li,Yang Song,Erqun Song
Peritoneal dialysis-associated peritonitis (PDAP), primarily caused by bacterial infections, is a severe complication and a major contributor to mortality in peritoneal dialysis patients. Early detection of bacterial infections and prompt therapeutic interventions are critical for effective PDAP management. Herein, we report the development of a novel apoptotic body (AB)-hitchhiked manganese-based T1-weighted magnetic resonance imaging (MRI) probe (PMA) for noninvasive and in situ bacterial detection in the abdominal cavity, offering a potential early warning system for PDAP. When administered to PDAP model mice, the PMA probes selectively accumulated in bacteria-infected regions via AB-mediated macrophage targeting. Subsequently, the PMA probes disintegrated in the acidic microenvironment of bacterial infection, which resulted in the MRI signal ON, therefore imaging the bacterial infection in vivo accurately. Remarkably, due to the protein-assisted T1-weighted signal amplification, the PMA probe-based MRI strategy detected bacterial loads in the abdominal cavity approximately 10 times lower than those identified by biochemical analysis for PDAP diagnosis. This approach achieves sensitive bacterial detection, holding great potential for the early diagnosis of PDAP in clinical practice in the future.
研究领域:
微生物学
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影像医学
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生物材料
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转化医学
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肾脏病学
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分子诊断
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2024
·
IF 5.5
Huan Cao,Jianhua Zhang,Lei Yang,Haotian Li,Rong Tian,Haoxing Wu,Yiwen Li,Zhipeng Gu
Apart from bacterial growth and endotoxin generation, the excessive production of reactive radicals linked with sepsis also has a substantial impact on triggering an inflammatory response and further treatment failure. Hence, the rational design and fabrication of robust and multifunctional nanoparticles (NPs) present a viable means of overcoming this dilemma. In this study, we used antibiotic polymyxin B (PMB) and antioxidant natural polyphenolic protocatechualdehyde (PCA) to construct robust and multifunctional NPs for sepsis treatment, leveraging the rich chemistries of PCA. The PMB release profile from the NPs demonstrated pH-responsive behavior, which allowed the NPs to exhibit effective bacterial killing and radical scavenging properties. Data from in vitro cells stimulated with H2O2 and lipopolysaccharide (LPS) showed the multifunctionalities of NPs, including intracellular reactive oxygen species (ROS) scavenging, elimination of the bacterial toxin LPS, inhibiting macrophage M1 polarization, and anti-inflammation capabilities. Additionally, in vivo studies further demonstrated that NPs could increase the effectiveness of sepsis treatment by lowering the bacterial survival ratio, the expression of the oxidative marker malondialdehyde (MDA), and the expression of inflammatory cytokine TNF-α. Overall, this work provides ideas of using those robust and multifunctional therapeutic NPs toward enhanced sepsis therapy efficiency.
研究领域:
纳米技术
·
药学
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传染病学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmacology Research & Perspectives
·
2020
·Vol. 8
·期 5
·e00660
·
IF 2.052
Jingyi Zhao,Ying Chen,Lijun Dong,Xin Li,Ruijie Dong,Dongmei Zhou,Chengzhi Wang,Xiangdong Guo,Jieyou Zhang,Zhenyi Xue,Qing Xi,Lijuan Zhang,Guangze Yang,Yan Li,Rongxin Zhang
Acute peritonitis is an acute inflammatory response of the peritoneal cavity to physical injury and chemical stimulation. Timely resolution of this response is critical to prevent further damage to the body, which can eventually lead to more severe chronic inflammation. Arctigenin (ATG) is the main active ingredient of the Chinese medicine Arctium lappa . In recent years, there have been an increasing number of studies on the anti-inflammatory effect of ATG, but there have been few studies on the effect of ATG on acute inflammation, especially in acute peritonitis, which has not been reported. In this study, a mouse model of experimental acute peritonitis induced by thioglycolate (TG) solution was used to study the protective anti-inflammatory effect of ATG against acute peritonitis and the relevant mechanism. Our results showed that, after 12 hours of TG treatment, ATG significantly reduced inflammatory cell infiltration in mouse tissues and inhibited the secretion and expression of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in mice. ATG significantly reduced the percentage of CD11b + Ly6G + neutrophils and F4/80 + macrophages in the spleen and peritoneal exudate. In addition, ATG significantly inhibited the expression of the chemokines CCL3 and CCL4 and the adhesion molecule CD62L on the surface of CD11b-positive monocytes. ATG was observed to inhibit the phosphorylation of p65 and p38 in LPS-stimulated RAW264.7 cells. In conclusion, ATG can improve the symptoms of TG-induced acute peritonitis through immune regulation. ATG can reduce the inflammatory response in TG-induced acute peritonitis in mice.
研究领域:
药理学
·
免疫学
·
炎症性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MicrobiologyOpen
·
2020
·Vol. 10
·期 1
·e1148
·
IF 3.142
Xianghai Zeng,Pengfei She,Linying Zhou,Shijia Li,Zubair Hussain,Lihua Chen,Yong Wu
Graphical Penfluridol shows effective antimicrobial effects against Enterococcus faecalis in vitro and in vivo. The drug prevents biofilm formation and eliminates mature biofilms. The bacterium Enterococcus faecalis has increasingly attracted global attention as an important opportunistic pathogen due to its ability to form biofilms that are known to increase drug resistance. However, there are still no effective antibiofilm drugs in clinical settings. Here, by drug repurposing, we investigated the antibacterial activity of penfluridol (PF), an oral long-acting antipsychotic approved by the FDA, against E . faecalis type strain and its clinical isolates. It was found that PF inhibited the growth of E . faecalis planktonic cells with the MIC and MBC of 7.81 µg/ml and 15.63 ~ 62.50 µg/ml, respectively. Moreover, PF could significantly prevent the biofilm formation of E . faecalis at the concentration of 1 × MIC. Furthermore, PF significantly eradicated 24 h pre-formed biofilms of E . faecalis in a dose-dependent manner, with a concentration range of 1 × MIC to 8 × MIC. Here, through the checkerboard method with other tested conventional antibiotics, we also determined that gentamycin, penicillin G, and amikacin showed partial synergistic antibacterial effects with PF. Also, PF showed almost no hemolysis on human erythrocytes. In a mouse peritonitis model, a single dose of 20 mg/kg of PF treatment could significantly reduce the bacterial colonization in the liver (~5-fold reduction) and spleen (~3-fold reduction). In conclusion, these findings indicated that after structural optimization, PF has the potential as a new antibacterial agent against E . faecalis .
研究领域:
药理学
·
微生物学
·
传染病
·
药物开发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2016
·
IF 8.387
Yao Wang,Xiali Ding,Yuan Chen,Mingquan Guo,Yan Zhang,Xiaokui Guo,Hongchen Gu
Drug-resistant bacterial infections have become one of the most serious risks in public health as they make the conventional antibiotics less efficient. There is an urgent need for developing new generations of antibacterial agents in this field. In this work, a nanoplatform of LEVO-loaded and silver core-embedded mesoporous silica nanovehicles (Ag@MSNs@LEVO) is demonstrated as a synergistic antibacterial agent for the treatment of drug-resistant infections both in vitro and in vivo. The combination of the inner Ag core and the loaded antibiotic drug in mesopores endows the single-particle nanoplatform with a synergistic effect on killing the drug-resistant bacteria. The nanoplatform of Ag@MSNs@LEVO exhibits superior antibacterial activity to LEVO-loaded MSNs (MSNs@LEVO) and silver core-embedded MSNs (Ag@MSNs) in vitro. In the in vivo acute peritonitis model, the infected drug-resistant Escherichia coli GN102 in peritoneal cavity of the mice is reduced by nearly three orders of magnitude and the aberrant pathological feature of spleen and peritoneum disappears after treatment with Ag@MSNs@LEVO. Importantly, this nanopaltform renders no obvious toxic side effect to the mice during the tested time. There is no doubt that this study strongly indicates a promising potential of Ag@MSNs@LEVO as a synergistic and safety therapy tool for the clinical drug-resistant infections.
研究领域:
纳米技术
·
药学
·
微生物学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioengineered
·
2022
·
IF 6.832
Xiao-Yi Chen,Qian-Long Wang,Wei-Xue Huang,Long-Wei Li,Lan-Cong Liu,Yi Yang,You-Jiao Wu,Shan-Shan Song,Hao Ma,Hua Zhou,Pei Luo
Bacterial peritonitis is a severe disease that diagnosis remains challenging for clinicians. Measuring biomarkers might be a rapid diagnostic method. The objective of this study was to analyze and evaluate the dynamic changes in HIF-1α concentration in serum exosomes during bacterial peritonitis. The pre-clinical application value of serum exosomal HIF-1α was evaluated via imipenem and cilastatin sodium (ICS) intervention in the bacterial peritonitis model. The new colorimetric method to quantitate dynamic expression changes of HIF-1α in serum exosomes during bacterial peritonitis was established by our team via using the gold seed-coated with aptamer-functionalized Au @ Au core-shell peroxidase mimic. The typical inflammatory cytokines of bacterial peritonitis were also measured. Following intramuscular administration with ICS, In-Vivo Xtreme imaging system was used to visualize abdominal infection extent. Meanwhile, HIF-1α concentration in rat serum exosomes and pro-inflammatory factors levels in serum were detected. The serum typical inflammatory cytokines levels were elevated in GFP-labeled E.coli induced bacterial peritonitis. The serum exosomal HIF-1α levels clearly increased at 12 h, reached the peak during 24–48 h, and then gradually decreased at 72 h. Following intramuscular administration with ICS, the abdominal infection extent, HIF-1α concentration in serum exosomes, and the serum pro-inflammatory factors levels were reduced at 24 h in GFP-labeled E. coli induced bacterial peritonitis model. The serum exosomal HIF-1α can be used as a biomarker in the early stage of bacterial peritonitis, which might provide the basic research in the pre-clinical for further predicting and monitoring the pathological process of bacterial peritonitis.
研究领域:
医学诊断
·
药理学
·
传染病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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