The authors have declared that no competing interests exist In a global pandemic involving respiratory pathogens such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), intensified ...scientific research is required to delineate pathways involved in infectivity, transmissibility, and pathogenicity of the causative pathogen. ...these cell lines have been used to evaluate drugs and vaccines response 9. Infected hamsters showed mild–moderate symptoms and elevated inflammatory responses that mirror clinical pathologies observed in humans, and severe symptoms manifest when the animals were infected with high viral dosage 20–22. ...hamsters are useful as preclinical models to screen for therapeutic agents; however, the models may be limited by the availability of hamster-specific reagents for assays 23. Nonhuman primates are attractive models due to their close phylogenetic and physiological similarities to humans; however, differences in the clinical course of disease have been reported.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Together with bound plasma proteins such as albumin, fibrinogen, and orosomucoid, the EGL forms a physiological barrier between the intravascular compartment and the interstitium, and damage and ...degradation may increase vascular permeability 5,6. Furthermore, increased blood levels of HA, syndecan-1 and CS in dengue patients were proportional to disease severity, further suggesting that EGL is damaged in clinical disease 5,6,10. In dengue patients, a significant increase in the peripheral circulation of canonical proteins that are associated with neutrophil degranulation, and granular proteins such as neutrophil elastase and α-defensin 1 were observed in DSS cases compared to either healthy controls or uncomplicated dengue cases 26–28. In a mouse model, simultaneous inhibition of C-type lectin domain family 5 member A (CLEC5A, a pattern recognition receptor) and TLR 2, receptors involved in mediating neutrophil activation and NETs formation, significantly reduced vascular permeability and improved survival 30.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The endothelium is recognized to play an important role in various physiological functions including vascular tone, permeability, anticoagulation, and angiogenesis. Endothelial dysfunction is ...increasingly recognized to contribute to pathophysiology of many disease states, and depending on the disease stimuli, mechanisms underlying the endothelial dysfunction may be markedly different. As such, numerous techniques to measure different aspects of endothelial dysfunction have been developed and refined as available technology improves. Current available reviews on quantifying endothelial dysfunction generally concentrate on a single aspect of endothelial function, although diseases may affect more than one aspect of endothelial function. Here, we aim to provide an overview on the techniques available for the assessment of the different aspects of endothelial function in humans, human tissues or cells, namely vascular tone modulation, permeability, anticoagulation and fibrinolysis, and the use of endothelial biomarkers as predictors of outcomes.The endothelium is recognized to play an important role in various physiological functions including vascular tone, permeability, anticoagulation, and angiogenesis. Endothelial dysfunction is increasingly recognized to contribute to pathophysiology of many disease states, and depending on the disease stimuli, mechanisms underlying the endothelial dysfunction may be markedly different. As such, numerous techniques to measure different aspects of endothelial dysfunction have been developed and refined as available technology improves. Current available reviews on quantifying endothelial dysfunction generally concentrate on a single aspect of endothelial function, although diseases may affect more than one aspect of endothelial function. Here, we aim to provide an overview on the techniques available for the assessment of the different aspects of endothelial function in humans, human tissues or cells, namely vascular tone modulation, permeability, anticoagulation and fibrinolysis, and the use of endothelial biomarkers as predictors of outcomes.
Numerous efforts to understand the functional roles of antibodies demonstrated that they can protect against malaria. However, it is unclear which antibody responses are the best correlates of ...immunity, and which antibody functions are most important in protection from disease. Understanding the role of antibodies in protection against malaria is crucial for antimalarial vaccine design. In this review, the specific functional properties of naturally acquired and vaccine-induced antibodies that correlate to protection from the blood stages of Plasmodium falciparum malaria are re-examined and the gaps in knowledge related to antibody function in malarial immunity are highlighted.
Pregnant women in malaria-endemic regions are susceptible to malaria in pregnancy, which has adverse consequences on birth outcomes, including having small for gestational age and preterm babies. ...These babies are likely to have low birthweights, which predisposes to infant mortality and lifelong morbidities. During malaria in pregnancy,
infected erythrocytes express a unique variant surface antigen, VAR2CSA, that mediates sequestration in the placenta. This process may initiate a range of host responses that contribute to placental inflammation and dysregulated placental development, which affects placental vasculogenesis, angiogenesis and nutrient transport. Collectively, these result in the impairment of placental functions, affecting fetal development. In this review, we provide an overview of malaria in pregnancy and the different pathological pathways leading to malaria in pregnancy-associated low birthweight. We also discuss current prevention and management strategies for malaria in pregnancy, and some potential therapeutic interventions that may improve birth outcomes. Lastly, we outline some priorities for future research that could bring us one step closer to reducing this health burden.
There are seven known species of Plasmodium spp. that can infect humans. The human host can mount a complex network of immunological responses to fight infection and one of these immune functions is ...phagocytosis. Effective and timely phagocytosis of parasites, accompanied by the activation of a regulated inflammatory response, is beneficial for parasite clearance. Functional studies have identified specific opsonins, particularly antibodies and distinct phagocyte sub-populations that are associated with clinical protection against malaria. In addition, cellular and molecular studies have enhanced the understanding of the immunological pathways and outcomes following phagocytosis of malaria parasites. In this review, an integrated view of the factors that can affect phagocytosis of infected erythrocytes and parasite components, the immunological consequences and their association with clinical protection against Plasmodium spp. infection is provided. Several red blood cell disorders and co-infections, and drugs that can influence phagocytic capability during malaria are also discussed. It is hoped that an enhanced understanding of this immunological process can benefit the design of new therapeutics and vaccines to combat this infectious disease.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Malaria remains a global health burden with
accounting for the highest mortality and morbidity. Malaria in pregnancy can lead to the development of placental malaria, where
-infected erythrocytes ...adhere to placental receptors, triggering placental inflammation and subsequent damage, causing harm to both mother and her infant. Histopathological studies of
-infected placentas revealed various placental abnormalities such as excessive perivillous fibrinoid deposits, breakdown of syncytiotrophoblast integrity, trophoblast basal lamina thickening, increased syncytial knotting, and accumulation of mononuclear immune cells within intervillous spaces. These events in turn, are likely to impair placental development and function, ultimately causing placental insufficiency, intrauterine growth restriction, preterm delivery and low birth weight. Hence, a better understanding of the mechanisms behind placental alterations and damage during placental malaria is needed for the design of effective interventions. In this review, using evidence from human studies and murine models, an integrated view on the potential mechanisms underlying placental pathologies in malaria in pregnancy is provided. The molecular, immunological and metabolic changes in infected placentas that reflect their responses to the parasitic infection and injury are discussed. Finally, potential models that can be used by researchers to improve our understanding on the pathogenesis of malaria in pregnancy and placental pathologies are presented.
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