CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Xiao-Chun Yang,Xiao-Xue Wang,Chen-Yu Wang,Meng Yin,Ke Ma,Yan Li,Ke-Zheng Chen,Sheng-Lin Qiao
Meningitis is a critical condition, particularly prevalent among young children, necessitating prompt diagnosis and intervention to prevent severe complications and mortality. This study presents the design and application of Janus-adhesive ionogels for real-time monitoring of physiological parameters with a focus on the early detection and management of infantile meningitis. The ionogel features a dual-layer structure, with an inner adhesive layer that strongly adheres to the skin and an outer anti-adhesive layer that minimizes external interference, ensuring accurate and reliable monitoring. These ionogels demonstrate superior properties such as high tensile strength, breathability, anti-freezing capabilities, and excellent ionic conductivity, making them ideal for continuous, long-term monitoring. The integrated monitoring system effectively tracks joint activity, body temperature, and ECG signals, providing real-time data critical for early warning and intervention in meningitis cases. This research represents a significant advancement in the field of wearable health monitoring technologies, showcasing the potential of Janus-adhesive ionogels to enhance the performance of wearable devices and contribute to personalized medicine.
研究领域:
医学
·
材料科学
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生物医学工程
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DOI
高影响因子
RARE METALS
·
2025
·
IF 11
Deng Shu-Yue,Zhou Xin-Yu,Zou Xiao-Peng,Tang Fang,Yang Dong,Sun Cai-Xia,Luo Jun,Ge Xing,Zhu Jia-Ying,Fang Tian-Ye,Yue Cai-Feng,Ju Yan-Min,Dai Jian-Jun
The presence of the blood–brain barrier limits the drug concentration in the brain, while low concentrations of antibiotics make it difficult to kill infecting bacteria and tends to induce drug resistance, making the clinical treatment of bacterial meningitis challenging. Herein, a nose-to-brain delivery strategy of small-sized nanozyme has been fabricated for combating bacterial meningitis, to overcome the low drug concentration and drug resistance. This strategy was achieved by a protein-supported Au nanozyme (ANZ). With a particle size of less than 10 nm, it possesses both glucose oxidase-like and peroxidase-like activities and can generate large amounts of reactive oxygen species through a cascade effect without the addition of external H 2 O 2 . Benefiting from the cascade catalytic amplification effect generated by its dual enzyme-like activities, ANZ shows significant broad-spectrum antibacterial activity without inducing bacterial resistance in vitro. Notably, small-sized ANZ exhibits higher brain entry efficiency and greater accumulation after intranasal administration compared to oral or intravenous administration. In a mouse model of bacterial meningitis, the mice treated with ANZ had lower bacterial loads in the brain and higher survival and clinical behavior scores compared to the classical antibiotic ceftriaxone. Additionally, the meningitis mice exhibited undamaged cognitive and behavioral abilities, indicating the excellent biocompatibility of ANZ. The above results demonstrate that nose-to-brain delivery of ANZ exhibits high intracerebral accumulation, strong antibacterial efficacy and does not lead to bacterial resistance. It holds broad prospects for the treatment of bacterial meningitis. Graphical abstract
研究领域:
医学
·
药理学
·
纳米医学
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DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2023
·
IF 4.6
Xinghui Hao,Yuqing Zhang,Yanling Sun,Mengge Liu,Qiru Wang,Xinghua Zhao,Xin He
Two new salt forms of sulfadiazine (SDZ) and piperazine (PIP) were synthesized and characterized. Out of the two polymorphs (SDZ-PIP Ⅰ and SDZ-PIP II), SDZ-PIP Ⅱ is the more stable form at low temperature, room temperature and high temperature. The solution-mediated phase transformation result shows that SDZ-PIP II can transform into pure SDZ within 15 s in phosphate buffer at 37 °C, which leads to a loss in solubility advantage. The addition of 2 mg/mL PVP K30, a polymeric crystallization inhibitor, maintains the solubility advantage and permits supersaturation for a longer period of time. SDZ-PIP II showed 2.5 times the solubility of SDZ alone. The area under the curve (AUC) of SDZ-PIP II with 2 mg/mL PVP K30 was approximately 165% of that of SDZ alone. Moreover, SDZ-PIP II with PVP K30 was more effective than SDZ alone in treating meningitis. Therefore, the SDZ-PIP II salt improves the solubility, bioavailability, and anti-meningitis activity of SDZ.
研究领域:
药学
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药物化学
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生物医学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 19
·14554
·
IF 5.6
Fulong Li,Baipeng Chen,Ming Xu,Yang Feng,Yongqiang Deng,Xiaoli Huang,Yi Geng,Ping Ouyang,Defang Chen
Elizabethkingia miricolais an emerging opportunistic pathogen that is highly pathogenic in both immunocompromised humans and animals. Once the disease occurs, treatment can be very difficult. Therefore, a deep understanding of the pathological mechanism ofElizabethkingia miricolais the key to the prevention and control of the disease. In this study, we isolated the pathogenic bacteria from bullfrogs with dark skin color, weak limbs, wryneck, and cataracts. Via subsequent morphological observations and a 16S rRNA gene sequence analysis, the pathogen was identified asElizabethkingia miricola. The histopathological and transmission electron microscopy analysis revealed that the brain was the main target organ. Therefore, brain samples from diseased and healthy bullfrogs were used for the RNA-Seq analysis. The comparative transcriptome analysis revealed that the diseased bullfrog brain was characterized by the immune activation and inflammatory response, which were mediated by the “NOD-like receptor signaling pathway” and the “Toll-like receptor signaling pathway”. We also performed qRT-PCR to examine the expression profile of inflammation-related genes, which further verified the reliability of our transcriptome data. Based on the above results, it was concluded that the NOD/Toll-like receptor-related networks that dominate the immune activation and inflammatory response were activated in the brain ofElizabethkingia miricola-infected bullfrogs. This study contributes to the search for therapeutic targets for bullfrog meningitis and provides basic information for establishing effective measures to prevent and control bullfrog meningitis.Keywords:Elizabethkingia miricola;Lithobates catesbeiana;bacterial meningitis;NOD-like receptor signaling pathway;Toll-like receptor signaling pathway
研究领域:
微生物学
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免疫学
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分子生物学
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兽医学
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DOI
PubMed
高影响因子
JOURNAL OF MEDICAL VIROLOGY
·
2025
·Vol. 97
·期 3
·e70267
·
IF 4.6
Wenting Mao,Yi Wan,Yang Liu,Minmin Zhou,Xiaoying Jia,Yuxia Hou,Wei Wang
The lymphocytic choriomeningitis virus (LCMV) is a widespread pathogen that causes mild-to-severe infections to severe outcomes. In this study, we explored the potential of trametinib, a mitogen-activated protein kinase (MAPK) inhibitor, as an antiviral agent against LCMV. Trametinib demonstrated significant antiviral activity against two distinct LCMV strains, Armstrong and Cl13, with promising half-maximal inhibitory concentrations (IC 50 ) and selectivity indices (SI) indicating its potency and safety profile. Mechanistic investigations revealed that trametinib interfered with multiple stages of the LCMV life cycle, including membrane fusion and genomic replication, leading to the robust inhibition of viral proliferation. Furthermore, trametinib disrupted the MEK/ERK signaling pathway, which is crucial for LCMV infection. In both in vitro and in vivo experiments, trametinib effectively reduced viral loads and mitigated pathological damage to the spleen and liver tissues. Overall, our findings suggest that trametinib is a promising novel therapeutic option for combating LCMV infection by targeting key stages of the viral life cycle and disrupting host cellular signaling pathways. Further exploration of the antiviral properties of trametinib is likely to pave the way for its clinical development as a treatment for LCMV infections.
研究领域:
病毒学
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药物研发
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医学
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DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Ying Jin,Hongtu Ma,Lisha Fu,Xiaohui Qi,Mengyu Zhang,Xiangjie Di,Li Zheng,Cuiyao He,Zhenlei Wang
Meropenem is an ultrabroad-spectrum antimicrobial agent that is often recommended for the treatment of bacterial meningitis (BM) in children. However, a subtherapeutic phenomenon occurred in BM children complicated with augmented renal clearance (ARC) at the recommended dose of meropenem. To support its pharmacokinetics, a sensitive, fast and robust ultra-liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed to measure meropenem concentrations in serum and cerebrospinal fluid (CSF). The method involved protein precipitation, and samples were diluted with a large proportion of water to eliminate solvent effects. The separation of samples was performed on a Waters Acquity™ BEH C 18 column (2.1 × 50 mm i.d., 1.7 μm) with a gradient profile. The mobile phases were formic acid–water (1:1000, v/v) and acetonitrile. The linear range was good, with a concentration range of 0.100–100 μg/mL for serum and 0.0400–20.0 μg/mL for CSF. The intra-day and inter-day precisions were less than 8.0%, and the intra-day and inter-day accuracies varied −6.6% from 6.5% for the both serum and CSF. The selectivity, carry-over, dilution integrity, matrix effect, recovery and stability were validated according to international guidelines. The developed UPLC–MS/MS method successfully determined the meropenem concentrations in the serum and CSF of children with BM complicated with ARC. The results indicated that under the recommended dosing regimen (40 mg/kg every 8 h), the time to reach the effective treatment target of 50%T > MIC was only approximately 3 h and lower CSF concentrations of meropenem were observed in children with BM with ARC.
研究领域:
药代动力学
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临床药学
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分析化学
·
儿科
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DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2024
·
IF 4.1
Yanghui Chen,Yuan Li,Junliang Luo,Zixin Li,Yu Huang,Jia Cai,Dongneng Jiang,Defeng Zhang,Jichang Jian,Jun Qiang,Bei Wang
The blood-brain barrier (BBB) is mainly composed of specialized endothelial cells , which can resist harmful substances, transport nutrients, and maintain the stability of the brain environment. In this study, an endothelial cell line from tilapia ( Oreochromis niloticus ) named TVEC-01 was successfully established. During the earlier establishment phase of the cell line, the TVEC-01 cells were persistently exposed to an astrocyte-conditioned medium (ACM). TVEC-01 cells were identified as an endothelial cell line. TVEC-01 cells retained the multiple functions of endothelial cells and were capable of performing various experiments in vitro . Furthermore, TVEC-01 cells efficiently expressed BBB-related tight junctions and key efflux transporters. From the results of the qRT-PCR, we found that the TVEC-01 cell line did not gradually lose BBB characteristics after persistent and repetitive passages, which was different from the vast majority of immortalized endothelial cells. The results showed that ACM induced up-regulation of the expression levels of multiple BBB-related genes in TVEC-01 cells. We confirmed that Streptococcus agalactiae was capable of invading the TVEC-01 cells and initiating a series of immune responses, which provided a theoretical basis for S . agalactiae to break through the BBB of teleost through the transcellular traversal pathway. In summary, we have successfully constructed an endothelial cell line of teleost, named TVEC-01, which can be used in many experiments in vitro and even for constructing BBB in vitro . Moreover, it was confirmed that S. agalactiae broke through the BBB of teleost through the transcellular traversal pathway and caused meningitis.
研究领域:
神经科学
·
细胞生物学
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微生物学
·
水产养殖
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DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-16
·
IF 15.7
Bian Xufei,Guo Qian,Yau Lee-Fong,Yang Ling,Wang Xiaoyou,Zhao Shikang,Wu Shiqiong,Qin Xurong,Jiang Zhi-Hong,Li Chong
Lipid nanoparticles have shown success in targeting major organs such as the liver, spleen, and lungs, but crossing the blood-brain barrier (BBB) remains a major challenge. Effective brain-targeted delivery systems are essential for advancing gene therapy for neurological diseases but remain limited by low transport efficiency and poor nucleic acid stability. Here, we report a library of ionizable lipids based on the tetrahydroisoquinoline structure of protoberberine alkaloids, designed to improve BBB penetration via dopamine D3 receptor-mediated endocytosis. These nanoparticles offer three key advantages: enhanced brain uptake, improved nucleic acid stability through poly(A) self-assembly, and minimal immunogenicity with inherent neuroprotective properties. In murine models, they demonstrate therapeutic potential in Alzheimer’s disease, glioma, and cryptococcal meningitis. This berberine-inspired delivery system integrates precise receptor targeting with nucleic acid stabilization, offering a promising platform for brain-targeted therapeutics.
研究领域:
神经科学
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药物学
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基因治疗
·
纳米技术
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产品关联
DOI
PubMed
高影响因子
VETERINARY MICROBIOLOGY
·
2021
·
IF 3.293
Hexiang Jiang,Tong Wu,Jianan Liu,Xibing Yu,Hongtao Liu,Chuntong Bao,Mengmeng Liu,Yalu Ji,Xin Feng,Jingmin Gu,Wenyu Han,Na Li,Liancheng Lei
Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that causes meningitis. The ubiquitously expressed 40S ribosome protein SA (RPSA) is a multifunctional protein involved in the pathogenesis of multiple pathogens, especially those causing meningitis. However, the role of RPSA in SS2-induced meningitis is not clear. In this study, immunofluorescence staining revealed that SS2 infection promoted the intracellular transfer of RPSA to the surface of human cerebral microvascular endothelial cells (HCMECs). Moreover, SS2 infection promoted the accumulation of caveolin 1 (CAV1) and the formation of membrane bulges where RPSA enveloped CAV1 on the cell surface. SS2 infection also caused dynamic changes in the localization of RPSA and CAV1 on the cell surface which could be eliminated by disruption of caveolae/rafts by addition of methyl-β-cyclodextrin (MβCD). Co-immunoprecipitation analysis demonstrated that α-enolase (ENO), a key virulence factor of SS2, interacted with RPSA, and promoted the interaction between RPSA and CAV1. Immunofluorescence staining, western blotting and flow cytometry analyses showed that damaged caveolae/rafts significantly enhanced ENO adhesion to HCMECs, promoted the “destruction” of RPSA by ENO, and enhanced the toxic effect of ENO on HCMECs. Importantly, these effects could be relieved upon the addition of cholesterol. We conclude that caveolae/rafts weaken the toxic effect of SS2 ENO on RPSA-mediated events in HCMECs. Our study has led to better understanding of the roles of RPSA and caveolae/rafts upon SS2 infection, and a new pathological role for RPSA in infection.
研究领域:
微生物学
·
细胞生物学
·
传染病学
·
神经科学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2022
·
IF 6.064
Olasunkanmi Oluwatayo Israel,Mageto James,Avala Ntsigouaye Juval,Yi Ming,Fei Yanru,Chen Yang,Chen Sijia,Xu Weizhen,Lin Lexun,Zhao Wenran,Wang Yan,Zhong Zhao-Hua
Coxsackievirus group B (CVB) is a member of the genus Enterovirus in the family Picornaviridae. CVB infection has been implicated as a major etiologic agent of viral myocarditis, dilated cardiomyopathy, meningitis, and pancreatitis among children and young adults. Until date, no antiviral agent has been licensed for the treatment of Coxsackievirus infection. In an effort to identify antiviral agents against diseases caused by the CVB, we found that ethyl 3-hydroxyhexanoate (EHX), a volatile compound present in fruits and food additives, is a potent antiviral compound. In this study, we demonstrated that EHX treatment significantly inhibits CVB replication both in vivo and in vitro. Furthermore, EHX possesses antiviral activity at 50% effective concentration (EC50) of 1.2 μM and 50% cytotoxicity (CC50) of 25.6 μM, yielding a selective index (SI) value as high as 20.8. Insights into the mechanism of antiviral activity of EHX showed that it acts at the step of viral RNA replication. Since EHX has received approval as food additives, treatment of CVB-related infections with EHX might be a safe therapeutic option and may be a promising strategy for the development of semi-synthetic antiviral drugs for viral diseases.
研究领域:
病毒学
·
药理学
·
传染病学
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DOI
PubMed
高影响因子
CNS Neuroscience & Therapeutics
·
2020
·Vol. 26
·期 12
·1288-1302
·
IF 4.074
Meng Gao,Weitian Lu,Yue Shu,Zhengyu Yang,Shanquan Sun,Jin Xu,Shengwei Gan,Shujuan Zhu,Guoping Qiu,Fei Zhuo,Shiye Xu,Yiying Wang,Junhong Chen,Xuan Wu,Juan Huang
Background Specific highly polarized aquaporin-4 (AQP4) expression is reported to play a crucial role in blood-brain barrier (BBB) integrity and brain water transport balance. The upregulation of polymerase δ-interacting protein 2 (Poldip2) was involved in aggravating BBB disruption following ischemic stroke. This study aimed to investigate whether Poldip2-mediated BBB disruption and cerebral edema formation in mouse bacterial meningitis (BM) model occur via induction of AQP4 polarity loss. Methods and Results Mouse BM model was induced by injecting mice with group B hemolytic streptococci via posterior cistern. Recombinant human Poldip2 (rh-Poldip2) was administered intranasally at 1 hour after BM induction. Small interfering ribonucleic acid (siRNA) targeting Poldip2 was administered by intracerebroventricular (i.c.v) injection at 48 hours before BM induction. A specific inhibitor of matrix metalloproteinases (MMPs), UK383367, was administered intravenously at 0.5 hour before BM induction. Western blotting, immunofluorescence staining, quantitative real-time PCR, neurobehavioral test, brain water content test, Evans blue (EB) permeability assay, transmission electron microscopy (TEM), and gelatin zymography were carried out. The results showed that Poldip2 was upregulated and AQP4 polarity was lost in mouse BM model. Both Poldip2 siRNA and UK383367 improved neurobehavioral outcomes, alleviated brain edema, preserved the integrity of BBB, and relieved the loss of AQP4 polarity in BM model. Rh-Poldip2 upregulated the expression of MMPs and glial fibrillary acidic protein (GFAP) and downregulated the expression of β-dystroglycan (β-DG), zonula occludens-1 (ZO-1), occludin, and claudin-5; whereas Poldip2 siRNA downregulated the expression of MMPs and GFAP, and upregulated β-DG, ZO-1, occludin, and claudin-5. Similarly, UK383367 downregulated the expression of GFAP and upregulated the expression of β-DG, ZO-1, occludin, and claudin-5. Conclusion Poldip2 inhibition alleviated brain edema and preserved the integrity of BBB partially by relieving the loss of AQP4 polarity via MMPs/β-DG pathway.
研究领域:
神经科学
·
药理学
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分子生物学
·
传染病学
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DOI
PubMed
高影响因子
MICROBIAL PATHOGENESIS
·
2022
·
IF 3.848
Bei-Bei Dou,Xia Yang,Feng-Ming Yang,Kang Yan,Wei Peng,Jia Tang,Ming-Zheng Peng,Qi-Yun He,Huan-Chun Chen,Fang-Yan Yuan,Wei-Cheng Bei
Streptococcus suis ( S. suis ) is an important zoonotic pathogen that can cause high morbidity and mortality in both humans and swine. As the most important life-threatening infection of the central nervous system (CNS), meningitis is an important syndrome of S. suis infection. The vancomycin resistance associated sensor/regulator (VraSR) is a critical two-component signal transduction system that affects the ability of S. suis to resist the host innate immune system and promotes its ability to adhere to brain microvascular endothelial cells (BMECs). Prior work also found mice infected with Δ vraSR had no obvious neurological symptoms , unlike mice infected with wild-type SC19. Whether and how VraSR participates in the development of S. suis meningitis remains unknown. Here, we found Δ vraSR -infected mice did not show obvious meningitis, compared with wild-type SC19-infected mice. Moreover, the proinflammatory cytokines and chemokines in serum and brains of Δ vraSR- infected mice, including IL-6, TNF-α, MCP-1 and IFN-γ, were significantly lower than wild-type infected group. Besides, blood-brain barrier (BBB) permeability also confirmed that the mutant had lower ability to disrupt BBB. Furthermore, in vivo and in vitro experiments showed that SC19 could increase BBB permeability by downregulating tight junction (TJ) proteins such as ZO-1, β-Catenin, Occludin , and Clauidn-5, compared with mutant Δ vraSR . These findings provide new insight into the influence of S. suis VraSR on BBB disruption during the pathogenic process of streptococcal meningitis, thereby offering potential targets for future preventative and therapeutic strategies against this disease.
研究领域:
微生物学
·
传染病学
·
神经科学
·
病理学
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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）