scholarly journals Rapamycin inhibits pathogen transmission in mosquitoes by promoting immune activation

2021 ◽  
Vol 17 (2) ◽  
pp. e1009353
Author(s):  
Yuebiao Feng ◽  
Lu Chen ◽  
Li Gao ◽  
Li Dong ◽  
Han Wen ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vector Competence ◽  
Inhibitory Effect ◽  
Pathogen Transmission ◽  
Tor Pathway ◽  
Mosquito Survival ◽  
Coated Surface ◽  
Immune Pathway ◽  
Blood Meals

Repeated blood meals provide essential nutrients for mosquito egg development and routes for pathogen transmission. The target of rapamycin, the TOR pathway, is essential for vitellogenesis. However, its influence on pathogen transmission remains to be elucidated. Here, we show that rapamycin, an inhibitor of the TOR pathway, effectively suppresses Plasmodium berghei infection in Anopheles stephensi. An. stephensi injected with rapamycin or feeding on rapamycin-treated mice showed increased resistance to P. berghei infection. Exposing An. stephensi to a rapamycin-coated surface not only decreased the numbers of both oocysts and sporozoites but also impaired mosquito survival and fecundity. Transcriptome analysis revealed that the inhibitory effect of rapamycin on parasite infection was through the enhanced activation of immune responses, especially the NF-κB transcription factor REL2, a regulator of the immune pathway and complement system. Knockdown of REL2 in rapamycin-treated mosquitoes abrogated the induction of the complement-like proteins TEP1 and SPCLIP1 and abolished rapamycin-mediated refractoriness to Plasmodium infection. Together, these findings demonstrate a key role of the TOR pathway in regulating mosquito immune responses, thereby influencing vector competence.

scholarly journals The seal louse (Echinophthirius horridus) in the Dutch Wadden Sea: investigation of vector-borne pathogens

2021 ◽  
Author(s):  
Jörg Hirzmann ◽  
David Ebmer ◽  
Guillermo J. Sánchez Contreras ◽  
Ana Rubio-García ◽  
Gerd Magdowski ◽  
...  
Keyword(s):  
Wadden Sea ◽  
Vector Competence ◽  
Pathogen Transmission ◽  
Grey Seal ◽  
Harbour Seals ◽  
Wide Range ◽  
Rehabilitation Period ◽  
Phocid Seals ◽  
Vector Borne

Abstract Background: Belonging to the anopluran family Echinophthiriidae, Echinophthirius horridus, the seal louse, has been reported to parasitize a broad range of representatives of phocid seals. So far, only few studies focused on vector function of echinophthiriid lice and knowledge on their role in pathogen transmission is still scarce. The current study aims to investigate the possible vector role of E. horridus parasitizing seals in the Dutch Wadden Sea.Methods: E. horridus seal lice were collected from 54 harbour seals (Phoca vitulina) and one grey seal (Halichoerus grypus) during their rehabilitation period at the Sealcentre Pieterburen, the Netherlands. DNA was extracted from pooled seal lice of individual seals for molecular detection of the seal heartworm Acanthocheilonema spirocauda, the rickettsial intracellular bacterium Anaplasma phagocytophilum, and the cell wall-less bacteria Mycoplasma spp. using PCR assays.Results: Seal lice from 35% of the harbour seals (19/54) and from the grey seal proved positive for A. spirocauda. The seal heartworm was molecularly characterised and phylogenetically analysed (rDNA, cox1). A nested PCR was developed for the cox1 gene to detect A. spirocauda stages in seal lice. A. phagocytophilum and a Mycoplasma species previously identified from a patient with disseminated ‘seal finger’ mycoplasmosis were detected the first time in seal lice. Conclusions: Our findings support the potential vector role of seal lice in transmission of A. spirocauda, and reveal new insights into the spectrum of pathogens occurring in seal lice. Studies on vector competence of E. horridus, especially for bacterial pathogens, are essentially needed in the future as these pathogens might have detrimental effects on the health of seal populations. Further, studies on the vector role of different echinophthiriid species infecting a wide range of pinniped hosts should be conducted to extend the knowledge of vector borne pathogens in seal lice.

scholarly journals The seal louse (Echinophthirius horridus) in the Dutch Wadden Sea: investigation of vector-borne pathogens

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jörg Hirzmann ◽  
David Ebmer ◽  
Guillermo J. Sánchez-Contreras ◽  
Ana Rubio-García ◽  
Gerd Magdowski ◽  
...  
Keyword(s):  
Wadden Sea ◽  
Vector Competence ◽  
Pathogen Transmission ◽  
Grey Seal ◽  
Harbour Seals ◽  
Wide Range ◽  
Rehabilitation Period ◽  
Phocid Seals ◽  
Vector Borne

Abstract Background Belonging to the anopluran family Echinophthiriidae, Echinophthirius horridus, the seal louse, has been reported to parasitise a broad range of representatives of phocid seals. So far, only a few studies have focused on the vector function of echinophthiriid lice, and knowledge about their role in pathogen transmission is still scarce. The current study aims to investigate the possible vector role of E. horridus parasitising seals in the Dutch Wadden Sea. Methods E. horridus seal lice were collected from 54 harbour seals (Phoca vitulina) and one grey seal (Halichoerus grypus) during their rehabilitation period at the Sealcentre Pieterburen, The Netherlands. DNA was extracted from pooled seal lice of individual seals for molecular detection of the seal heartworm Acanthocheilonema spirocauda, the rickettsial intracellular bacterium Anaplasma phagocytophilum, and the cell wall-less bacteria Mycoplasma spp. using PCR assays. Results Seal lice from 35% of the harbour seals (19/54) and from the grey seal proved positive for A. spirocauda. The seal heartworm was molecularly characterised and phylogenetically analysed (rDNA, cox1). A nested PCR was developed for the cox1 gene to detect A. spirocauda stages in seal lice. A. phagocytophilum and a Mycoplasma species previously identified from a patient with disseminated ‘seal finger’ mycoplasmosis were detected for the first time, to our knowledge, in seal lice. Conclusions Our findings support the potential vector role of seal lice in the transmission of A. spirocauda and reveal new insights into the spectrum of pathogens occurring in seal lice. Studies on vector competence of E. horridus, especially for bacterial pathogens, are essentially needed in the future as these pathogens might have detrimental effects on the health of seal populations. Furthermore, studies on the vector role of different echinophthiriid species infecting a wide range of pinniped hosts should be conducted to extend the knowledge of vector-borne pathogens.

scholarly journals Role of Ferroportin in Macrophage-Mediated Immunity

2010 ◽  
Vol 78 (12) ◽  
pp. 5099-5106 ◽  
Author(s):  
Erin E. Johnson ◽  
Andreas Sandgren ◽  
Bobby J. Cherayil ◽  
Megan Murray ◽  
Marianne Wessling-Resnick
Keyword(s):  
Immune Responses ◽  
Iron Metabolism ◽  
Host Response ◽  
Inhibitory Effect ◽  
Hfe Gene ◽  
Inos Mrna ◽  
No Production ◽  
Transferrin Receptors ◽  
Histocompatibility Complex

ABSTRACT Perturbations in iron metabolism have been shown to dramatically impact host response to infection. The most common inherited iron overload disorder results from defects in the HFE gene product, a major histocompatibility complex class I-like protein that interacts with transferrin receptors. HFE-associated hemochromatosis is characterized by abnormally high levels of the iron efflux protein ferroportin. In this study, J774 murine macrophages overexpressing ferroportin were used to investigate the influence of iron metabolism on the release of nitric oxide (NO) in response to infection. Overexpression of ferroportin significantly impaired intracellular Mycobacterium tuberculosis growth during early stages of infection. When challenged with lipopolysaccharide (LPS) or M. tuberculosis infection, control macrophages increased NO synthesis, but macrophages overexpressing ferroportin had significantly impaired NO production in response to LPS or M. tuberculosis. Increased NO synthesis in control cells was accompanied by increased iNOS mRNA and protein, while upregulation of iNOS protein was markedly reduced when J744 cells overexpressing ferroportin were challenged with LPS or M. tuberculosis, thus limiting the bactericidal activity of these macrophages. The proinflammatory cytokine gamma interferon reversed the inhibitory effect of ferroportin overexpression on NO production. These results suggest a novel role for ferroportin in attenuating macrophage-mediated immune responses.

Effect of Dipyridamole on Spontaneous Platelet Aggregation in Whole Blood Decreases with the Time After Venepuncture: Evidence for the Role of ADP

1987 ◽  
Vol 58 (02) ◽  
pp. 744-748 ◽  
Author(s):  
A R Saniabadi ◽  
G D O Lowe ◽  
J C Barbenel ◽  
C D Forbes
Keyword(s):  
Platelet Aggregation ◽  
Correlation Coefficient ◽  
Whole Blood ◽  
Blood Platelet ◽  
Inhibitory Effect ◽  
Time Interval ◽  
Adp Receptor ◽  
Spontaneous Platelet Aggregation

SummarySpontaneous platelet aggregation (SPA) was studied in human whole blood at 3, 5, 10, 20, 30, 40 and 60 minutes after venepuncture. Using a whole blood platelet counter, SPA was quantified by measuring the fall in single platelet count upon rollermixing aliquots of citrated blood at 37° C. The extent of SPA increased with the time after venepuncture, with a correlation coefficient of 0.819. The inhibitory effect of dipyridamole (Dipy) on SPA was studied: (a) 10 μM at each time interval; (b) 0.5-100 μM at 3 and 30 minutes and (c) 15 μM in combination with 100 μM adenosine, 8 μM 2-chloroadenosine (2ClAd, an ADP receptor blocker) and 50 μM aspirin. There was a rapid decrease in the inhibitory effect of Dipy with the time after venepuncture; the correlation coefficient was -0.533. At all the concentrations studied, Dipy was more effective at 3 minutes than at 30 minutes after venepuncture. A combination of Dipy with adenosine, 2ClAd or aspirin was a more effective inhibitor of SPA than either drug alone. However, when 15 μM Dipy and 10 μM Ad were added together, the inhibitory effect of Dipy was not increased significantly, suggesting that Dipy inhibits platelet aggregation independent of Ad. The increase in SPA with the time after venepuncture was abolished when blood was taken directly into the anticoagulant containing 5 μM 2ClAd. It is suggested that ADP released from the red blood cells is responsible for the increased platelet aggregability with the time after venepuncture and makes a serious contribution to the artifacts of in vitro platelet function studies.

Platelet Accumulation on Fibrin-coated Polyethylene: Role of Platelet Activation and Factor XIII

1995 ◽  
Vol 73 (05) ◽  
pp. 850-856 ◽  
Author(s):  
F D Rubens ◽  
D W Perry ◽  
M W C Hatton ◽  
P D Bishop ◽  
M A Packham ◽  
...  
Keyword(s):  
Factor Xiii ◽  
Cross Linking ◽  
Internal Diameter ◽  
Static System ◽  
Graft Occlusion ◽  
Platelet Binding ◽  
Coated Surface ◽  
Platelet Accumulation ◽  
Polyethylene Tubing

SummaryPlatelet accumulation on small- and medium-calibre vascular grafts plays a significant role in graft occlusion. We examined platelet accumulation on the surface of fibrin-coated polyethylene tubing (internal diameter 0.17 cm) during 10 min of flow (l0ml/min) at high wall shear rate (764 s-1). Washed platelets labelled with 51Cr were resuspended in Tyrode solution containing albumin, apyrase and red blood cells (hematocrit 40%). When the thrombin that was used to form the fibrin-coated surface was inactivated with FPRCH2C1 before perfusion of the tubes with the platelet:red blood cell suspension, the accumulation of platelets was 59,840 ± 27,960 platelets per mm2, whereas accumulation on fibrin with residual active thrombin was 316,750 ± 32,560 platelets per mm2 (n = 4). When the fibrin on the surface was cross-linked by including recombinant factor XIII (rFXIII) in the fibrinogen solution used to prepare the fibrin-coated surface, platelet accumulation, after thrombin neutralization, was reduced by the cross-linking from 46,974 ± 9702 to 36,818 ± 7964 platelets per mm2 (n = 12, p <0.01). Platelet accumulation on tubes coated with D-dimer was ten times less than on tubes coated with D-domain; this finding also supports the observation that cross-linking of fibrin with the formation of γ-γ dimers reduces platelet accumulation on the fibrin-coated surface. Thrombin-activated platelets themselves were shown to cross-link fibrin when they had adhered to it during perfusion, or in a static system in which thrombin was used to form clots from FXIII-free fibrinogen in the presence of platelets. Thus, cross-linking of fibrin by FXIII in plasma or from platelets probably decreases the reactivity of the fibrin-containing thrombi to platelets by altering the lysine residue at or near the platelet-binding site of each of the γ-chains of the fibrinogen which was converted into the fibrin of these thrombi.

Effect of human galanin on the response of circulating catecholamines to hypoglycemia in man

1995 ◽  
Vol 133 (6) ◽  
pp. 723-728 ◽  
Author(s):  
Ettore C degli Uberti ◽  
Maria R Ambrosio ◽  
Marta Bondanelli ◽  
Giorgio Transforini ◽  
Alberto Valentini ◽  
...  
Keyword(s):  
Heart Rate ◽  
Healthy Subjects ◽  
Sympathetic Nerve Activity ◽  
Heart Rate Response ◽  
Statistical Significance ◽  
Inhibitory Effect ◽  
Amino Acid Residues ◽  
Nerve Activity ◽  
Receptor Stimulation

degli Uberti EC, Ambrosio MR, Bondanelli M, Trasforini G, Valentini A, Rossi R, Margutti A, Campo M. Effect of human galanin on the response of circulating catecholamines to hypoglycemia in man. Eur J Endocrinol 1995;133:723–8. ISSN 0804–4643 Human galanin (hGAL) is a neuropeptide with 30 amino acid residues that has been found in the peripheral and central nervous system, where it often co-exists with catecholamines. In order to clarify the possible role of hGAL in the regulation of sympathoadrenomedullary function, the effect of a 60 min infusion of hGAL (80 pmol·kg−1 · min−1) on plasma epinephrine and norepinephrine responses to insulin-induced hypoglycemia in nine healthy subjects was investigated. Human GAL administration significantly reduced both the release of basal norepinephrine and the response to insulin-induced hypoglycemia, whereas it attenuated the epinephrine response by 26%, with the hGAL-induced decrease in epinephrine release failing to achieve statistical significance. Human GAL significantly increased the heart rate in resting conditions and clearly exaggerated the heart rate response to insulin-induced hypoglycemia, whereas it had no effect on the blood pressure. We conclude that GAL receptor stimulation exerts an inhibitory effect on basal and insulin-induced hypoglycemia-stimulated release of norepinephrine. These findings provide further evidence that GAL may modulate sympathetic nerve activity in man but that it does not play an important role in the regulation of adrenal medullary function. Ettore C degli Uberti, Chair of Endocrinology, University of Ferrara, Via Savonarola 9, I-44100 Ferrara, Italy

Role of convalescent plasma therapy in new Coronavirus disease (nCOVID-19): A review

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 546-549
Author(s):  
Shweta Dadarao Parwe ◽  
Milind Abhimanyu Nisargandha ◽  
Rishikesh Thakre
Keyword(s):  
Clinical Trial ◽  
Immune Responses ◽  
Indian Population ◽  
Preventive Treatment ◽  
The Body ◽  
Therapeutic Antibodies ◽  
Plasma Therapy ◽  
Host Immune Responses ◽  
Transparent Liquid

Hitherto, there is no proper line of treatment for the new (nCOVID19). The development of unique antiviral drugs has taken precedence. Therapeutic antibodies () will be a significantly beneficial agent against nCOVID-19. Here the host immune responses to new discussed in this review provide strategy and further treatment and understanding of clinical interventions against nCOVID-19. Plasma therapy uses the antibodies found in the blood of people recovering (or convalesced) from an infection to treat infected patients. When an infection occurs, the body begins producing proteins specially made to kill the germ, called antibodies. Those antibodies coat specifically plasma in the blood of survivors, the yellow transparent liquid blood portion for months or even years. research assesses plasma use from Convalescent patients of infected with nCOVID-19 as a possible preventive treatment. But it is not yet recommended as a line of treatment, and it is used as a clinical trial in the new in Indian population.

Biological role of AKT, and regulation of AKT signaling pathway by thymoquinone: perspectives in cancer therapeutics

2020 ◽  
Vol 20 ◽  
Author(s):  
Md. Junaid ◽  
Yeasmin Akter ◽  
Syeda Samira Afrose ◽  
Mousumi Tania ◽  
Md. Asaduzzaman Khan
Keyword(s):  
Clinical Trials ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Inhibitory Effect ◽  
Akt Signaling ◽  
Review Article ◽  
Therapeutic Drug ◽  
Akt Signaling Pathway ◽  
Anti Cancer

Background: AKT/PKB is an important enzyme with numerous biological functions, and its overexpression is related to the carcinogenesis. AKT stimulates different signaling pathways that are downstream of activated tyrosine kinases and phosphatidylinositol 3-kinase, hence functions as an important target for anti-cancer drugs. Objective: In this review article, we have interpreted the role of AKT signaling pathways in cancer and natural inhibitory effect of Thymoquinone (TQ) in AKT and its possible mechanism. Method: We have collected the updated information and data on AKT, their role in cancer and inhibitory effect of TQ in AKT signaling pathway from google scholar, PubMed, Web of Science, Elsevier, Scopus and many more. Results: There are many drugs already developed, which can target AKT, but very few among them have passed clinical trials. TQ is a natural compound, mainly found in black cumin, which has been found to have potential anti-cancer activities. TQ targets numerous signaling pathways, including AKT, in different cancers. In fact, many studies revealed that AKT is one of the major targets of TQ. The preclinical success of TQ suggests its clinical studies on cancer. Conclusion: This review article summarizes the role of AKT in carcinogenesis, its potent inhibitors in clinical trials, and how TQ acts as an inhibitor of AKT and TQ’s future as a cancer therapeutic drug.

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