scholarly journals Radicicol, a Novel Lead Compound against the Migratory-Stage Schistosomula of Schistosoma japonicum

2020 ◽  
Vol 65 (3) ◽  
Author(s):  
Liangxiong Xu ◽  
Qiuli Liu ◽  
Qingren Zeng ◽  
Ping Wu ◽  
Quan Yu ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Schistosoma Japonicum ◽  
Primary Treatment ◽  
Parasitic Disease ◽  
Lead Compound ◽  
Content Type ◽  
Acid Lactone ◽  
Scanning Electron

ABSTRACT Schistosomiasis poses a serious threat to human health and remains a major tropical and parasitic disease in more than 70 countries. Praziquantel (PZQ) has been the primary treatment for schistosomiasis for nearly 4 decades. However, its efficacy against migratory-stage schistosomula is limited. Radicicol (RAD), a β-resorcylic acid lactone derived from Paecilomyces sp. strain SC0924, was investigated as an alternative treatment for Schistosoma japonicum. In vitro tests showed that within 72 h, RAD (10 μmol/liter) completely killed schistosomula of both skin and liver stages with an efficacy significantly higher than that of PZQ, although it was less potent against adult worms than PZQ. In vivo, RAD reduced worm burdens and liver eggs by 91.18% and 86.01%, respectively, by killing migratory-stage schistosomula. Optical microscopy and scanning electron microscopy revealed that RAD damaged the epiderm and tegument morphology of S. japonicum worms at various stages and altered their motility to different degrees. RAD exhibited schistosomicidal effects at different stages in vitro and in vivo, especially at the migratory stage, implying that its mechanism could be different from that of PZQ. Collectively, these results showed that RAD is promising as a lead for the development of drugs to control the migratory-stage schistosomula of S. japonicum.

scholarly journals Synergistic effect of combination chemotherapy with praziquantel and DW-3-15 for Schistosoma japonicum in vitro and in vivo

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Zi-Yin Yang ◽  
Zi-Hao Liu ◽  
Ya-Nan Zhang ◽  
Chen Li ◽  
Lei Liu ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Synergistic Effect ◽  
Schistosoma Japonicum ◽  
Combination Chemotherapy ◽  
Combination Index ◽  
First Choice ◽  
Scanning Electron

Abstract Background Schistosomiasis is a debilitating and neglected tropical disease for which praziquantel (PZQ) remains the first-choice drug for treatment and control of the disease. In our previous studies, we found that the patented compound DW-3-15 (patent no. ZL201110142538.2) displayed significant and stabilized antiparasitic activity through a mechanism that might be distinct from PZQ. Here, we investigated the antischistosomal efficacy of PZQ combined with DW-3-15 against schistosomula and adult worms of Schistosoma japonicum in vitro and in vivo, to verify whether there was a synergistic effect of the two compounds. Methods The antischistosomal efficacy of PZQ combined with DW-3-15 in comparison with an untreated control and monotherapy group against schistosomula and adult worms was assessed both in vitro and in vivo. Parasitological studies, scanning electron microscopy, combination index, and histopathological analysis were used for the assessment. Results The results showed significantly reduced viability of schistosomes, achieving 100% viability reduction for juveniles and males by combination chemotherapy using PZQ together with DW-3-15 in vitro. The combination index was 0.28, 0.27, and 0.53 at the higher concentration of PZQ combined with DW-3-15 against juveniles, males, and females, respectively, indicating that the two compounds display strong synergism. Scanning electron microscopy observations also demonstrated that the compound combination induced more severe and extensive alterations to the tegument and subtegument of S. japonicum than those with each compound alone. In vivo, compared with the single-compound-treated group, the group treated with the higher-dose combination demonstrated the best schistosomicidal efficacy, with significantly reduced worm burden, egg burden, and granuloma count and area, which was evident against schistosomula and adult worms. Conclusions Our study provides a potential novel chemotherapy for schistosomiasis caused by S. japonicum. It would improve the antischistosomal effect on schistosomula and adult worms of S. japonicum, and decrease individual dosages. Graphical Abstract

scholarly journals Tim-3 Induces Th2-Biased Immunity and Alternative Macrophage Activation during Schistosoma japonicum Infection

2015 ◽  
Vol 83 (8) ◽  
pp. 3074-3082 ◽  
Author(s):  
Nan Hou ◽  
Xianyu Piao ◽  
Shuai Liu ◽  
Chuang Wu ◽  
Qijun Chen
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Schistosoma Japonicum ◽  
Immune Cell ◽  
Nk Cell ◽  
Alternative Activation ◽  
Interleukin 12 ◽  
Content Type

T cell immunoglobulin- and mucin-domain-containing molecule 3 (Tim-3) has been regarded as an important regulatory factor in both adaptive and innate immunity. Recently, Tim-3 was reported to be involved in Th2-biased immune responses in mice infected withSchistosoma japonicum, but the exact mechanism behind the involvement of Tim-3 remains unknown. The present study aims to understand the role of Tim-3 in the immune response againstS. japonicuminfection. Tim-3 expression was determined by flow cytometry, and increased Tim-3 expression was observed on CD4+and CD8+T cells, NK1.1+cells, and CD11b+cells from the livers ofS. japonicum-infected mice. However, the increased level of Tim-3 was lower in the spleen than in the liver, and no increase in Tim-3 expression was observed on splenic CD8+T cells or CD11b+cells. The schistosome-induced upregulation of Tim-3 on natural killer (NK) cells was accompanied by reduced NK cell numbersin vitroandin vivo. Tim-3 antibody blockade led to upregulation of inducible nitric oxide synthase and interleukin-12 (IL-12) mRNA in CD11b+cells cocultured with soluble egg antigen and downregulation of Arg1 and IL-10, which are markers of M2 macrophages. In summary, we observed schistosome-induced expression of Tim-3 on critical immune cell populations, which may be involved in the Th2-biased immune response and alternative activation of macrophages during infection.

scholarly journals Ambroxol Induces Autophagy and Potentiates Rifampin Antimycobacterial Activity

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Seong Won Choi ◽  
Yuexi Gu ◽  
Ryan Scott Peters ◽  
Padmini Salgame ◽  
Jerrold J. Ellner ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Antimycobacterial Activity ◽  
Lead Compound ◽  
Content Type ◽  
Tuberculosis Model

ABSTRACT Host-directed therapy in tuberculosis is a potential adjunct to antibiotic chemotherapy directed at Mycobacterium tuberculosis. Ambroxol, a lead compound, emerged from a screen for autophagy-inducing drugs. At clinically relevant doses, ambroxol induced autophagy in vitro and in vivo and promoted mycobacterial killing in macrophages. Ambroxol also potentiated rifampin activity in a murine tuberculosis model.

scholarly journals Low-Level Aflatoxin B1 Promotes Influenza Infection and Modulates a Switch in Macrophage Polarization from M1 to M2

2018 ◽  
Vol 49 (3) ◽  
pp. 1151-1167 ◽  
Author(s):  
Yuhang Sun ◽  
Zixuan Liu ◽  
Dandan Liu ◽  
Jin Chen ◽  
Fang Gan ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Influenza Virus ◽  
Matrix Protein ◽  
Macrophage Polarization ◽  
Low Level ◽  
Siv Infection ◽  
Scanning Electron

Background/Aims: Swine influenza virus (SIV) is a major pathogen of both animals and humans. Afatoxin B1 (AFB1) is one of the most common mycotoxins in feed and food. However, the central contribution of AFB1 to SIV infection remains unclear. Methods: Here, TCID50 assays, fluorescence-based quantitative real-time PCR, western blotting, immunofluorescence staining, histopathological examination, flow cytometry and scanning electron microscopy were performed to investigate the involvement and underlying mechanism of AFB1 in SIV infection in vivo and in vitro using mouse models and porcine alveolar macrophage (PAM) models, respectively. Results: The in vivo study showed that low levels of AFB1 promoted SIV infection and increased its severity, as demonstrated by the increased mRNA expression of viral matrix protein (M); by the increased protein expression of nucleoprotein (NP), matrix protein 1 and ion channel protein; and by animal weight loss, lung index and lung histologic damage. In addition, the increased occurrence of SIV infection accompanied by increases in the level of IL-10 in sera and lungs, in the spleen index and in the number of CD206-positive mouse alveolar macrophages but decreases in the level of TNF-α in sera and lungs, in the thymus index and in the number of CD80-positive mouse alveolar macrophages was observed in SIV-infected mice after low-level AFB1 exposure. The in vitro study showed that low concentrations of AFB1 promoted SIV infection, as demonstrated by the increases in viral titers and viral M mRNA and NP expression levels in SIV-infected PAMs as well as by the number of cells positive for NP protein expression. Furthermore, AFB1 promoted the polarization of SIV-infected PAMs to the M1 phenotype at 8 hpi and to the M2 phenotype at 24 hpi, as measured by the increases in IL-10 expression and in the number of CD206-positive PAMs as well as by the morphological changes observed by scanning electron microscopy. The administration of the immune stimulant lipopolysaccharide (LPS) reversed the switch in PAM polarization from M2 to M1 and thereby counteracted the promotion of influenza virus infection induced by AFB1. Conclusion: Our results are the first to confirm that low-level exposure to AFB1 promotes SIV infection and modulates a switch in macrophage polarization from M1 to M2. The work reported here provides important data that point to a role for AFB1 in SIV infection, and it opens a new field of study.

An Experimental Model for the Study of Venous Thrombosis in Vivo

1975 ◽  
Author(s):  
T. K. Day ◽  
K. G. A. Glark ◽  
V. V. Kakkar
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Experimental Model ◽  
Femoral Vein ◽  
Total Charge ◽  
Small Current ◽  
Group I ◽  
Scanning Electron

The lack of a satisfactory in vivo experimental model has probably been responsible for the delay in the clinical application of recent advances in in vitro research on thrombosis. This paper describes a model in which thrombosis is initiated by an electrical stimulus. The thrombus produced has the histological and biochemical features of human deep vein thrombosis (DVT).The minimum stimulus necessary to induce thrombosis was first determined by passing a fixed current for timed intervals along the femoral veins of 10 rabbits. Thrombi were seen 24 hours later if the total charge passed exceeded a threshold value of 25 millicoulombes. With this small current, no endothelial changes were visible immediately after the passage of the charge on light or scanning electron microscopy. At 24 hours a mural thrombus formed, which had fully cross-linked fibrin and histological features resembling human DVT.In the second series of experiments, the sequence of changes occurring in thrombus production was investigated in 3 groups of 18 rabbits each. After passage of the critical charge along the femoral vein in each animal, veins were removed at fixed intervals, the contralateral vein acting as a control. The veins were examined by scanning electron-microscopy (Group I), transmission electron-microscopy (Group II) and light microscopy (Group III), The earliest changes were detectable at 5 minutes and consisted of the laying down of an organised structure of criss-crossing fibrin strands with small platelet clumps at fibrin intersections. Later the fibrin structure spread towards the lumen; platelet clumps fused and a coralline thrombus was formed by 24 hours. The significance of these changes will be discussed.

scholarly journals Development and Characterization of an In Vivo Central Venous Catheter Candida albicans Biofilm Model

2004 ◽  
Vol 72 (10) ◽  
pp. 6023-6031 ◽  
Author(s):  
D. Andes ◽  
J. Nett ◽  
P. Oschel ◽  
R. Albrecht ◽  
K. Marchillo ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Drug Resistance ◽  
Venous Catheter ◽  
In Vitro Models ◽  
Central Venous ◽  
Biofilm Growth ◽  
Scanning Electron

ABSTRACT Biofilms represent a niche for microorganisms where they are protected from both the host immune system and antimicrobial therapies. Biofilm growth serves as an increasing source of clinical infections. Candida infections are difficult to manage due to their persistent nature and associated drug resistance. Observations made in biofilm research have generally been limited to in vitro models. Using a rat central venous catheter model, we characterized in vivo Candida albicans biofilm development. Time-course quantitative culture demonstrated a progressive increase in the burden of viable cells for the first 24 h of development. Fluorescence and scanning electron microscopy revealed a bilayered architecture. Adjacent to the catheter surface, yeast cells were densely embedded in an extracellular matrix. The layer adjacent to the catheter lumen was less dense. The outermost surface of the biofilm contained both yeast and hyphal forms, and the extracellular material in which they were embedded appeared fibrous. These architectural features were similar in many respects to those described for in vitro models. However, scanning electron microscopy also revealed host cells embedded within the biofilm matrix. Drug susceptibility was determined by using two assays and demonstrated a biofilm-associated drug resistance phenotype. The first assay demonstrated continued growth of cells in the presence of supra-MIC antifungal drug concentrations. The second assay demonstrated reduced susceptibility of biofilm-grown cells following removal from the biofilm structure. Lastly, the model provided sufficient nucleic material for study of differential gene expression associated with in vivo biofilm growth. Two fluconazole efflux pumps, CDR1 and CDR2, were upregulated in the in vivo biofilm-associated cells. Most importantly, the studies described provide a model for further investigation into the molecular mechanisms of C. albicans biofilm biology and drug resistance. In addition, the model provides a means to study novel drug therapies and device technologies targeted to the control of biofilm-associated infections.

scholarly journals Indirect Immunodetection of Fungal Fragments by Field Emission Scanning Electron Microscopy

2015 ◽  
Vol 81 (17) ◽  
pp. 5794-5803 ◽  
Author(s):  
Komlavi Anani Afanou ◽  
Anne Straumfors ◽  
Asbjørn Skogstad ◽  
Ajay P. Nayak ◽  
Ida Skaar ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Field Emission ◽  
Polyclonal Antibodies ◽  
Detection Methods ◽  
Indoor Environments ◽  
Content Type ◽  
Freeze Dried ◽  
Scanning Electron

ABSTRACTSubmicronic fungal fragments have been observed inin vitroaerosolization experiments. The occurrence of these particles has therefore been suggested to contribute to respiratory health problems observed in mold-contaminated indoor environments. However, the role of submicronic fragments in exacerbating adverse health effects has remained unclear due to limitations associated with detection methods. In the present study, we report the development of an indirect immunodetection assay that utilizes chicken polyclonal antibodies developed against spores fromAspergillus versicolorand high-resolution field emission scanning electron microscopy (FESEM). Immunolabeling was performed withA. versicolorfragments immobilized and fixed onto poly-l-lysine-coated polycarbonate filters. Ninety percent of submicronic fragments and 1- to 2-μm fragments, compared to 100% of >2-μm fragments generated from pure freeze-dried mycelial fragments ofA. versicolor, were positively labeled. In proof-of-concept experiments, air samples collected from moldy indoor environments were evaluated using the immunolabeling technique. Our results indicated that 13% of the total collected particles were derived from fungi. This fraction comprises 79% of the fragments that were detected by immunolabeling and 21% of the spore particles that were morphologically identified. The methods reported in this study enable the enumeration of fungal particles, including submicronic fragments, in a complex heterogeneous environmental sample.

scholarly journals Arsenic Trioxide Negatively Affects Echinococcus granulosus

2015 ◽  
Vol 59 (11) ◽  
pp. 6946-6951 ◽  
Author(s):  
Bo Wang ◽  
Yufeng Jiang ◽  
Zhuo Wang ◽  
Fangfang Li ◽  
Guoqiang Xing ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Arsenic Trioxide ◽  
Echinococcus Granulosus ◽  
Treatment Options ◽  
Small Sample ◽  
Content Type ◽  
Transmission Electron ◽  
New Strategy

ABSTRACTSpillage of cyst contents during surgery is the major cause of recurrences of hydatidosis, also called cystic echinococcosis (CE). Currently, many scolicidal agents are used for inactivation of the cyst contents. However, due to complications in the use of those agents, new and more-effective treatment options are urgently needed. The aim of this study was to investigate thein vitroefficacy of arsenic trioxide (ATO) againstEchinococcus granulosusprotoscolices. Protoscolices ofE. granulosuswere incubatedin vitrowith 2, 4, 6, and 8 μmol/liter ATO; viability of protoscolices was assessed daily by microscopic observation of movements and 0.1% eosin staining. A small sample from each culture was processed for scanning and transmission electron microscopy. ATO demonstrated a potent ability to kill protoscolices, suggesting that ATO may represent a new strategy in treating hydatid cyst echinococcosis. However, thein vivoefficacy and possible side effects of ATO need to be explored.

Study of Morphology of Cardiac Valves (Human and Bovine Pericardium) after In Vivo Calcification

2008 ◽  
Vol 396-398 ◽  
pp. 191-194
Author(s):  
Grínia M. Nogueira ◽  
Cassiano Gomes Aimoli ◽  
Raquel Farias Weska ◽  
Adolfo A. Leirner ◽  
Marina J.S. Maizato ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Bovine Pericardium ◽  
Cardiac Valves ◽  
Elemental Analyses ◽  
Calcification Process ◽  
Pathologic Calcification ◽  
Phosphate Deposits ◽  
Scanning Electron

Pathologic calcification can lead to failure or deterioration of cardiac valves. Several researchers have tried alternatives to construct these devices, such as the incorporation or utilization of new biomaterials able to inhibit or decrease the calcification process. In vitro calcification tests can be used to screen new biomaterials regarding their potential to calcify in vivo. However, the mechanisms involved in both cases are not completely understood. In order to collect more information about the calcification process of implanted materials, morphology and elemental analyses of calcified cardiac valve fragments explanted from different patients were investigated and compared to previous reports of in vitro calcification tests. Scanning Electron Microscopy (SEM) and energy dispersive spectroscopy (EDS) analyses indicated that the calcium phosphate deposits from both bovine pericardium and human cardiac valves calcified in vivo were similar to the deposits obtained from in vitro calcification samples as previously reported in the literature.

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