Gold Nanoclusters Exert Bactericidal Activity and Enhance Phagocytosis of Macrophage Mediated Killing of Fusobacterium nucleatum

Fusobacterium nucleatum is a typical periodontal opportunistic pathogen that contributes to inflammatory diseases at oral or extra-oral sites. The emergence of antibiotics resistance calls for a substitute therapeutic strategy to control bacterial infections effectively. In addition, macrophage is an essential part of host defense against microorganism invasion in vivo. Herein, we synthesized gold nanoclusters (AuNCs) as potent antibacterial material to kill F. nucleatum through bactericidal behavior and pro-phagocytic activity. Firstly, we evaluated the bactericidal effect of AuNCs on F. nucleatum by the means of plate counting, growth curve measurement, bacterial viability analysis, and live/dead fluorescent imaging. Morphological changes and the intracellular reactive oxygen species levels of bacteria were further analyzed to explore the possible mechanisms. Additionally, the impact of AuNCs on the ability of macrophages to uptake bacteria under normal and inflammatory circumstance was also evaluated by fluorescent imaging. We found that AuNCs exhibited superior antibacterial performance on F. nucleatum in vitro by a combination of membrane disruption and oxidative stress. Furthermore, in the presence of AuNCs, macrophages displayed enhanced phagocytosis against F. nucleatum without inducing any significant cytotoxicity. Therefore, AuNCs are providing a new platform for the prevention and treatment of F. nucleatum-associated diseases.

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Integrated endotoxin-adsorption and antibacterial properties of platelet-membrane-coated copper silicate hollow microspheres for wound healing

Journal of Nanobiotechnology ◽

10.1186/s12951-021-01130-w ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Zaihui Peng ◽

Xiaochun Zhang ◽

Long Yuan ◽

Ting Li ◽

Yajie Chen ◽

...

Keyword(s):

Wound Healing ◽

Bacterial Infections ◽

Antibacterial Properties ◽

Platelet Membrane ◽

Gram Negative Bacteria ◽

Gram Negative ◽

The Impact ◽

Copper Silicate

AbstractSerious infection caused by drug-resistant gram-negative bacteria and their secreted toxins (e.g., lipopolysaccharide) is a serious threat to human health. Thus, treatment strategies that efficiently kill bacteria and reducing the impact of their toxins simultaneously are urgently required. Herein, a novel antibacterial platform composed of a mesoporous copper silicate microsphere (CSO) core and a platelet membrane (PM) shell was prepared (CSO@PM). CSO@PM specifically targets bacteria owing to formyl peptide receptors on the PM and, combined with photothermal therapy (PTT), exhibits highly effective bacter icidal activity. Importantly, CSO@PM can adsorb lipopolysaccharide secreted by gram-negative bacteria, resulting in inflammation reduction. Thus, CSO@PM stimulates re-epithelialization and granulation-tissue formation, promoting wound healing. Moreover, this antibacterial platform exhibits no obvious toxicity at all the test concentrations in vitro and in vivo. Thus, CSO@PM exhibits a robust antibacterial effect and a strong toxin-adsorption capacity, facilitating the clinical treatment of many bacterial infections and the development of next-generation antibacterial nanoagents. Graphical Abstract

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Quantitative Impact of Neutrophils on Bacterial Clearance in a Murine Pneumonia Model

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00508-11 ◽

2011 ◽

Vol 55 (10) ◽

pp. 4601-4605 ◽

Cited By ~ 18

Author(s):

Beining Guo ◽

Kamilia Abdelraouf ◽

Kimberly R. Ledesma ◽

Kai-Tai Chang ◽

Michael Nikolaou ◽

...

Keyword(s):

Mathematical Model ◽

Bacterial Infections ◽

Dynamic Change ◽

Parameter Estimates ◽

Bacterial Clearance ◽

Content Type ◽

Susceptibility Data ◽

The Impact

ABSTRACTThe rapid increase in the prevalence of antibiotic-resistant pathogens is a global problem that has challenged our ability to treat serious infections. Currently, clinical decisions on treatment are often based onin vitrosusceptibility data. The role of the immune system in combating bacterial infections is unequivocal, but it is not well captured quantitatively. In this study, the impact of neutrophils on bacterial clearance was quantitatively assessed in a murine pneumonia model.In vitrotime-growth studies were performed to determine the growth rate constants ofAcinetobacter baumanniiATCC BAA 747 andPseudomonas aeruginosaPAO1. The absolute neutrophil count in mice resulting from different cyclophosphamide preparatory regimens was determined. The dynamic change of bacterial (A. baumanniiBAA 747) burden in mice with graded immunosuppression over 24 h was captured by a mathematical model. The fit to the data was satisfactory (r2= 0.945). The best-fit maximal kill rate (Kk) of the bacterial population by neutrophils was 1.743 h−1, the number of neutrophils necessary for 50% maximal killing was 190.8/μl, and the maximal population size was 1.8 × 109CFU/g, respectively. Using these model parameter estimates, the model predictions were subsequently validated by the bacterial burden change ofP. aeruginosaPAO1 at 24 h. A simple mathematical model was proposed to quantify the contribution of neutrophils to bacterial clearance and predict the bacterial growth/suppression in animals. Our results provide a novel framework to linkin vitroandin vivoinformation and may be used to improve clinical treatment of bacterial infections.

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Nanomaterial Complexes Enriched With Natural Compounds Used in Cancer Therapies: A Perspective for Clinical Application

Frontiers in Oncology ◽

10.3389/fonc.2021.664380 ◽

2021 ◽

Vol 11 ◽

Author(s):

María Zenaida Saavedra-Leos ◽

Euclides Jordan-Alejandre ◽

César López-Camarillo ◽

Amaury Pozos-Guillen ◽

César Leyva-Porras ◽

...

Keyword(s):

Cancer Treatment ◽

Bacterial Infections ◽

Positive Response ◽

Natural Compounds ◽

Molecular Characteristics ◽

Cancer Therapies ◽

Cancer Types ◽

The Impact

Resveratrol and quercetin are natural compounds contained in many foods and beverages. Reports indicate implications for the health of the general population; on the other hand the use of both compounds has interesting results for the treatment of many diseases as cardiovascular affections, diabetes, Alzheimer’s disease, viral and bacterial infections among others. Based on their capacities described as anti-inflammatory, antioxidant, and anti-aging, resveratrol and quercetin showed antiproliferative and anticancer activity specifically in maligned cells. These molecular characteristics trigger the pharmacological repurposing of both compounds and improved its research for treating different cancer types with interesting results at in vitro, in vivo, and clinical trial studies. Meanwhile, the development of different systems of drug release in specific sites as nanomaterials and specifically the nanoparticles, potentiates the personal treatment perspective in conjunct with the actual cancer therapies; regularly invasive and aggressive, the perspective of nanomedicine as higher effective and lower invasive has gained popularity. Knowledge of molecular interactions of resveratrol and quercetin in diseases confirms the evidence of multiple benefits, while the multiple analyses suggested a positive response for the treatment and diagnostics of cancer in different stages, including at metastatic stage. The present work reviews the reports related to the impact of resveratrol and quercetin in cancer treatment and its effects when the antioxidants are encapsulated in different nanoparticle systems, which improve the prospects of cancer treatment.

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Integrated Endotoxin-Adsorption and Antibacterial Properties of Platelet-Membrane-Coated Copper Silicate Hollow Microspheres for Wound Healing

10.21203/rs.3.rs-903043/v1 ◽

2021 ◽

Author(s):

Zaihui Peng ◽

Xiaochun Zhang ◽

Long Yuan ◽

Yajie Chen ◽

Ting Li ◽

...

Keyword(s):

Wound Healing ◽

Bacterial Infections ◽

Antibacterial Properties ◽

Platelet Membrane ◽

Gram Negative Bacteria ◽

Gram Negative ◽

The Impact ◽

Copper Silicate

Abstract Serious infection caused by drug-resistant gram-negative bacteria and their secreted toxins (e.g., lipopolysaccharide) is a serious threat to human health. Thus, treatment strategies that efficiently kill bacteria and reducing the impact of their toxins simultaneously are urgently required. Herein, a novel antibacterial platform composed of a mesoporous copper silicate microsphere (CSO) core and a platelet membrane (PM) shell was prepared (CSO@PM). CSO@PM specifically targets bacteria owing to formyl peptide receptors on the PM and, combined with photothermal therapy (PTT), exhibits highly effective bactericidal activity. Importantly, CSO@PM can adsorb lipopolysaccharide secreted by gram-negative bacteria, resulting in inflammation reduction. Thus, CSO@PM stimulates re-epithelialization and granulation-tissue formation, promoting wound healing. Moreover, this antibacterial platform exhibits no obvious toxicity at all the test concentrations in vitro and in vivo. Thus, CSO@PM exhibits a robust antibacterial effect and a strong toxin-adsorption capacity, facilitating the clinical treatment of many bacterial infections and the development of next-generation antibacterial nanoagents.

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Hsp90 Induces Acsl4-dependent Glioma Ferroptosis via Dephosphorylate Ser637 at Drp1

10.21203/rs.3.rs-1131699/v1 ◽

2022 ◽

Author(s):

Ning Liu ◽

Zong Miao ◽

Wei Tian ◽

Zhongyuan Bao ◽

Guangchi Sun ◽

...

Keyword(s):

Lipid Peroxidation ◽

Morphological Changes ◽

Heat Shock Protein 90 ◽

Mitochondrial Morphology ◽

Western Blot Assay ◽

Regulated Cell Death ◽

Acyl Coenzyme A ◽

The Impact

Abstract Background: Ferroptosis is a newly identified form of regulated cell death (RCD) characterized by the iron-dependent lipid reactive oxygen species (ROS) accumulation, but its exact mechanism in gliomas remains elusive. Acyl–coenzyme A (CoA) synthetase long-chain family member 4 (Acsl4), a pivotal enzyme in the regulation of lipid biosynthesis, has been found to benefit the initiation of ferroptosis, but its role in gliomas likewise needs clarification. Erastin, widely investigated as an inducer of ferroptosis, was recently found to regulate lipid peroxidation by regulating Acsl4 other than glutathione peroxidase 4 (GPX4) in ferroptosis. Methods: Relationship between Hsp90, Drp1 and Acsl4 was determined by Co-immunoprecipitation/ Mass spectrometry and western blot assay. The impact of Hsp90 and Drp1 on Acsl4-dependent ferroptosis was examined by lipid peroxidation indicators in patient-derived PL1 and PG7 cells. The morphological changes of mitochondria are observed by confocal-fluorescence microscopy and transmission electron microscope. Therapeutic efficacy of Erastin-induced ferroptosis in vivo was examined in xenograft mouse models.Results: In this study, we demonstrated that heat shock protein 90 (Hsp90) and dynamin-related protein 1 (Drp1) actively regulated Acsl4 expression in erastin-induced ferroptosis in gliomas. Hsp90 overexpression and calcineurin (CN)–mediated Drp1 dephosphorylation at serine 637 (Ser637) promoted ferroptosis by altering mitochondrial morphology and increasing Acsl4-mediated lipid peroxidation. Importantly, the Hsp90–Acsl4 pathway mediated Acsl4-dependent ferroptosis, amplifying the anticancer activity of erastin in vitro and in vivo. Conclusions: Our study not only uncovered an important role of Hsp90–Drp1–Acsl4 pathway in erastin-induced ferroptosis but also reveals an efficient mechanism of Acsl4 as a potential therapeutic target to ferroptosis-mediated glioma therapy.

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Influenza-induced oxidative stress sensitizes lung cells to bacterial toxin-mediated necroptosis

10.1101/2020.02.20.957951 ◽

2020 ◽

Cited By ~ 1

Author(s):

Norberto Gonzalez-Juarbe ◽

Ashleigh N. Riegler ◽

Alexander S. Jureka ◽

Ryan P. Gilley ◽

Jeffrey Brand ◽

...

Keyword(s):

Oxidative Stress ◽

Lung Injury ◽

Molecular Basis ◽

Influenza A ◽

Bacterial Infections ◽

Secondary Infection ◽

Lung Cells ◽

The Impact

ABSTRACTRationalePneumonia caused by Influenza A virus (IAV) co- and secondary bacterial infections are characterized by their severity. Previously we have shown that pore-forming toxin (PFT)-mediated necroptosis is a key driver of acute lung injury during bacterial pneumonia. Here, we evaluate the impact of IAV on PFT-induced acute lung injury during co- and secondary Streptococcus pneumoniae (Spn) infection.ObjectivesDetermine the impact of IAV infection on bacterial PFT-mediated lung epithelial cell (LEC) necroptosis. Determine the molecular basis for increased sensitivity and if inhibition of necroptosis or oxidative stress blocks IAV sensitization of LEC to PFT.MethodsMice and cells were challenged with IAV followed by Spn. Necroptosis was monitored by measuring cell death at fixed time points post-infection and immunofluorescent detection of necroptosis. Wildtype mice and LEC were treated with necroptosis inhibitors. Necroptosis effector molecule MLKL deficiency was tested for infection synergy. Oxidative damage to DNA and lipids as result of infection was measured in vitro and in vivo. Necroptosis and anti-oxidant therapy efficacy to reduce disease severity was tested in vivo.Measurements and Main ResultsIAV synergistically sensitized LEC for PFT-mediated necroptosis in vitro and in murine models of Spn co-infection and secondary infection. Pharmacological induction of oxidative stress sans virus sensitized cells for PFT-mediated necroptosis. Necroptosis inhibition reduced disease severity during secondary bacterial infection.ConclusionsIAV-induced oxidative stress sensitizes LEC for PFT-mediated necroptosis. This is a new molecular explanation for severe influenza-associated bacterial infections. Necroptosis inhibitors are potential therapeutic strategies to reduce IAV-primed bacterial pneumonia severity.SummaryHere we demonstrate that Influenza A virus (IAV) infection synergistically sensitizes lung cells to bacterial pore-forming toxin (PFT)-mediated necroptosis. Moreover, this contributes to the severity of lung injury that is observed during co- and secondary infection with Streptococcus pneumoniae. IAV-induced oxidative stress was identified as a key factor contributing to cell sensitization and induction of oxidative stress sans virus was sufficient to synergistically enhance susceptibility to PFT-mediated killing. Our results advance our understanding on the molecular basis of co- and secondary bacterial infection to influenza and identifies necroptosis inhibition and antioxidant therapy as potential intervention strategies.

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The Anti-tumor Activity and Mechanisms of rLj-RGD3 on Human Laryngeal Squamous Carcinoma Hep2 Cells

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666191022160024 ◽

2020 ◽

Vol 19 (17) ◽

pp. 2108-2119

Author(s):

Yang Jin ◽

Li Lv ◽

Shu-Xiang Ning ◽

Ji-Hong Wang ◽

Rong Xiao

Keyword(s):

Wound Healing ◽

Western Blot ◽

Morphological Changes ◽

In Vivo Studies ◽

Migration And Invasion ◽

Tunel Staining ◽

Dna Ladder ◽

Western Blot Assay

Background: Laryngeal Squamous Cell Carcinoma (LSCC) is a malignant epithelial tumor with poor prognosis and its incidence rate increased recently. rLj-RGD3, a recombinant protein cloned from the buccal gland of Lampetra japonica, contains three RGD motifs that could bind to integrins on the tumor cells. Methods: MTT assay was used to detect the inhibitory rate of viability. Giemsa’s staining assay was used to observe the morphological changes of cells. Hoechst 33258 and TUNEL staining assay, DNA ladder assay were used to examine the apoptotic. Western blot assay was applied to detect the change of the integrin signal pathway. Wound-healing assay, migration, and invasion assay were used to detect the mobility of Hep2 cells. H&E staining assay was used to show the arrangement of the Hep2 cells in the solid tumor tissues. Results: In the present study, rLj-RGD3 was shown to inhibit the viability of LSCC Hep2 cells in vitro by inducing apoptosis with an IC50 of 1.23µM. Western blot showed that the apoptosis of Hep2 cells induced by rLj- RGD3 was dependent on the integrin-FAK-Akt pathway. Wound healing, transwells, and western blot assays in vitro showed that rLj-RGD3 suppressed the migration and invasion of Hep2 cells by integrin-FAKpaxillin/ PLC pathway which could also affect the cytoskeleton arrangement in Hep2 cells. In in vivo studies, rLj-RGD3 inhibited the growth, tumor volume, and weight, as well as disturbed the tissue structure of the solid tumors in xenograft models of BALB/c nude mice without reducing their body weights. Conclusion: hese results suggested that rLj-RGD3 is an effective and safe suppressor on the growth and metastasis of LSCC Hep2 cells from both in vitro and in vivo experiments. rLj-RGD3 might be expected to become a novel anti-tumor drug to treat LSCC patients in the near future.

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The impact of Zataria multiflora Boiss extract on in vitro and in vivo Th1/Th2 cytokine (IFN-γ/IL4) balance

Journal of Ethnopharmacology ◽

10.1016/j.jep.2013.10.003 ◽

2013 ◽

Vol 150 (3) ◽

pp. 1024-1031 ◽

Cited By ~ 35

Author(s):

Mohammad Hossein Boskabady ◽

Sakine Shahmohammadi Mehrjardi ◽

Abadorrahim Rezaee ◽

Houshang Rafatpanah ◽

Sediqeh Jalali

Keyword(s):

Zataria Multiflora ◽

Th2 Cytokine ◽

Ifn Γ ◽

The Impact

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Carbon dots derived from Fusobacterium nucleatum for intracellular determination of Fe3+ and bioimaging both in vitro and in vivo

Analytical Methods ◽

10.1039/d1ay00020a ◽

2021 ◽

Author(s):

Lijuan Liu ◽

Shengting Zhang ◽

Xiaodan Zheng ◽

Hongmei Li ◽

Qi Chen ◽

...

Keyword(s):

Carbon Dots ◽

Fusobacterium Nucleatum ◽

Living Cells ◽

First Time ◽

Fluorescent Carbon Dots ◽

Fluorescent Carbon

Fusobacterium nucleatum has been employed for the first time to synthesize fluorescent carbon dots which could be applied for the determination of Fe3+ ions in living cells and bioimaging in vitro and in vivo with excellent biocompatibility.

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The impact of FGF19/FGFR4 signaling inhibition in antitumor activity of multi-kinase inhibitors in hepatocellular carcinoma

Scientific Reports ◽

10.1038/s41598-021-84117-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hiroaki Kanzaki ◽

Tetsuhiro Chiba ◽

Junjie Ao ◽

Keisuke Koroki ◽

Kengo Kanayama ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Molecular Mechanisms ◽

Kinase Inhibitors ◽

Progression Free Survival ◽

Erk Signaling ◽

Enzyme Linked Immunosorbent Assay ◽

Antitumor Effects ◽

The Impact

AbstractFGF19/FGFR4 autocrine signaling is one of the main targets for multi-kinase inhibitors (MKIs). However, the molecular mechanisms underlying FGF19/FGFR4 signaling in the antitumor effects to MKIs in hepatocellular carcinoma (HCC) remain unclear. In this study, the impact of FGFR4/ERK signaling inhibition on HCC following MKI treatment was analyzed in vitro and in vivo assays. Serum FGF19 in HCC patients treated using MKIs, such as sorafenib (n = 173) and lenvatinib (n = 40), was measured by enzyme-linked immunosorbent assay. Lenvatinib strongly inhibited the phosphorylation of FRS2 and ERK, the downstream signaling molecules of FGFR4, compared with sorafenib and regorafenib. Additional use of a selective FGFR4 inhibitor with sorafenib further suppressed FGFR4/ERK signaling and synergistically inhibited HCC cell growth in culture and xenograft subcutaneous tumors. Although serum FGF19high (n = 68) patients treated using sorafenib exhibited a significantly shorter progression-free survival and overall survival than FGF19low (n = 105) patients, there were no significant differences between FGF19high (n = 21) and FGF19low (n = 19) patients treated using lenvatinib. In conclusion, robust inhibition of FGF19/FGFR4 is of importance for the exertion of antitumor effects of MKIs. Serum FGF19 levels may function as a predictive marker for drug response and survival in HCC patients treated using sorafenib.

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