-
Nanomaterials (Basel, Switzerland) Mar 2021Nanoparticles (NPs) are promising platforms for the development of diagnostic and therapeutic tools. One of the main hurdle to their medical application and translation... (Review)
Review
Nanoparticles (NPs) are promising platforms for the development of diagnostic and therapeutic tools. One of the main hurdle to their medical application and translation into the clinic is the fact that they accumulate in the spleen and liver due to opsonization and scavenging by the mononuclear phagocyte system. The "protein corona" controls the fate of NPs in vivo and becomes the interface with cells, influencing their physiological response like cellular uptake and targeting efficiency. For these reasons, the surface properties play a pivotal role in fouling and antifouling behavior of particles. Therefore, surface engineering of the nanocarriers is an extremely important issue for the design of useful diagnostic and therapeutic systems. In recent decades, a huge number of studies have proposed and developed different strategies to improve antifouling features and produce NPs as safe and performing as possible. However, it is not always easy to compare the various approaches and understand their advantages and disadvantages in terms of interaction with biological systems. Here, we propose a systematic study of literature with the aim of summarizing current knowledge on promising antifouling coatings to render NPs more biocompatible and performing for diagnostic and therapeutic purposes. Thirty-nine studies from 2009 were included and investigated. Our findings have shown that two main classes of non-fouling materials (i.e., pegylated and zwitterionic) are associated with NPs and their applications are discussed here highlighting pitfalls and challenges to develop biocompatible tools for diagnostic and therapeutic uses. In conclusion, although the complexity of biofouling strategies and the field is still young, the collective data selected in this review indicate that a careful tuning of surface moieties is a pivotal step to lead NPs through their future clinical applications.
PubMed: 33803884
DOI: 10.3390/nano11030780 -
Frontiers in Immunology 2021Trypanosomatids are protozoa responsible for a wide range of diseases, with emphasis on Chagas Disease (CD) and Leishmaniasis, which are in the list of most relevant...
Methodological Appraisal of Literature Concerning the Analysis of Genetic Variants or Protein Levels of Complement Components on Susceptibility to Infection by Trypanosomatids: A Systematic Review.
BACKGROUND
Trypanosomatids are protozoa responsible for a wide range of diseases, with emphasis on Chagas Disease (CD) and Leishmaniasis, which are in the list of most relevant Neglected Tropical Diseases (NTD) according to World Health Organization (WHO). During the infectious process, immune system is immediately activated, and parasites can invade nucleated cells through a broad diversity of receptors. The complement system - through classical, alternative and lectin pathways - plays a role in the first line of defense against these pathogens, acting in opsonization, phagocytosis and lysis of parasites. Genetic modifications in complement genes, such as Single Nucleotide Polymorphisms (SNPs), can influence host susceptibility to these parasites and modulate protein expression.
METHODS
In March and April 2021, a literature search was conducted at the PubMed and Google Scholar databases and the reference lists obtained were verified. After applying the inclusion and exclusion criteria, the selected studies were evaluated and scored according to eleven established criteria regarding their thematic approach and design, aiming at the good quality of publications.
RESULTS
Twelve papers were included in this systematic review: seven investigating CD and five focusing on Leishmaniasis. Most articles presented gene and protein approaches, careful determination of experimental groups, and adequate choice of experimental techniques, although several of them were not up-to-date. Ten studies explored the association of polymorphisms and haplotypes with disease progression, with emphasis on lectin complement pathway genes. Decreased and increased patient serum protein levels were associated with susceptibility to CD and Visceral Leishmaniasis, respectively.
CONCLUSION
This systematic review shows the influence of genetic alterations in complement genes on the progression of several infectious diseases, with a focus on conditions caused by trypanosomatids, and contributes suggestions and evidence to improve experimental design in future research proposals.
Topics: Chagas Disease; Complement Activation; Complement System Proteins; Disease Progression; Genetic Predisposition to Disease; Genetic Variation; Host-Parasite Interactions; Humans; Leishmania; Leishmaniasis; Phenotype; Risk Assessment; Risk Factors; Trypanosoma cruzi
PubMed: 34899745
DOI: 10.3389/fimmu.2021.780810 -
MSphere Jul 2020An -cluster based system was proposed as a standard typing scheme to facilitate and enhance future studies of group A (GAS) epidemiological surveillance, M protein... (Meta-Analysis)
Meta-Analysis
An -cluster based system was proposed as a standard typing scheme to facilitate and enhance future studies of group A (GAS) epidemiological surveillance, M protein function, and vaccine development strategies. We provide an evidence-based distribution of GAS clusters in Africa and assess the potential coverage of the new 30-valent vaccine in terms of an cluster-based approach. Two reviewers independently assessed studies retrieved from a comprehensive search and extracted relevant data. Meta-analyses were performed (random-effects model) to aggregate cluster prevalence estimates. Eight studies ( = 1,595 isolates) revealed the predominant clusters as E6 (18%; 95% confidence interval [CI], 12.6% to 24.0%), followed by E3 (14%; 95% CI, 11.2% to 17.4%) and E4 (13%; 95% CI, 9.5% to 16.0%). There was negligible variation in clusters with regard to regions, age, and socioeconomic status across the continent. Considering an cluster-based vaccine strategy, which assumes cross-protection within clusters, the 30-valent vaccine currently in clinical development would provide hypothetical coverage to 80.3% of isolates in Africa. This systematic review indicates the most predominant GAS cluster in Africa is E6 followed by E3, E4, and D4. The current 30-valent vaccine would provide considerable coverage across the diversity of cluster types in Africa. Future efforts could be directed toward estimating the overall potential coverage of the new 30-valent vaccine based on cross-opsonization studies with representative panels of GAS isolates from populations at highest risk for GAS diseases. Low vaccine coverage is of grave public health concern, particularly in developing countries where epidemiological data are often absent. To inform vaccine development for group A (GAS), we report on the epidemiology of the M protein clusters from GAS infections in Africa, where GAS-related illnesses and their sequelae, including rheumatic fever and rheumatic heart disease, are of a high burden. This first report of clusters across the continent indicates a high probably of coverage by the M protein-based vaccine currently undergoing testing were an -cluster based approach to be used.
Topics: Africa; Antigens, Bacterial; Bacterial Outer Membrane Proteins; Carrier Proteins; Humans; Prevalence; Streptococcal Infections; Streptococcal Vaccines; Streptococcus pyogenes
PubMed: 32669471
DOI: 10.1128/mSphere.00429-20 -
The Cochrane Database of Systematic... Jan 2020Neonates are at higher risk of infection due to immuno-incompetence. Maternal transport of immunoglobulins to the fetus mainly occurs after 32 weeks' gestation, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Neonates are at higher risk of infection due to immuno-incompetence. Maternal transport of immunoglobulins to the fetus mainly occurs after 32 weeks' gestation, and endogenous synthesis begins several months after birth. Administration of intravenous immunoglobulin (IVIG) provides immunoglobulin G (IgG) that can bind to cell surface receptors, provide opsonic activity, activate complement, promote antibody-dependent cytotoxicity and improve neutrophilic chemo-luminescence. Theoretically, infectious morbidity and mortality could be reduced by the administration of IVIG.
OBJECTIVES
To assess the effects of IVIG on mortality and morbidity caused by suspected or proven infection at study entry in neonates. To assess in a subgroup analysis the effects of IgM-enriched IVIG on mortality from suspected infection.
SEARCH METHODS
For this update, MEDLINE, EMBASE, The Cochrane Library, CINAHL, trial registries, Web of Science, reference lists of identified studies, meta-analyses and personal files were searched in 2013. No language restrictions were applied.
SELECTION CRITERIA
Randomised or quasi-randomised controlled trials involving newborn infants (< 28 days old); IVIG for treatment of suspected or proven bacterial or fungal infection compared with placebo or no intervention; and where one of the following outcomes was reported, mortality, length of hospital stay or psychomotor development at follow-up.
DATA COLLECTION AND ANALYSIS
Statistical analyses included typical risk ratio (RR), risk difference (RD), weighted mean difference (WMD), number needed to treat for an additional beneficial outcome (NNTB) or an additional harmful outcome (NNTH), all with 95% confidence intervals (CIs), and the I statistic to examine for statistical heterogeneity.
MAIN RESULTS
The updated search identified one published study that was previously ongoing. A total of 9 studies evaluating 3973 infants were included in this review. Mortality during hospital stay in infants with clinically suspected infection was not significantly different after IVIG treatment (9 studies (n = 2527); typical RR 0.95, 95% CI 0.80 to 1.13; typical RD -0.01, 95% CI - 0.04 to 0.02; I = 23% for RR and 29% for RD). Death or major disability at 2 years corrected age was not significantly different in infants with suspected infection after IVIG treatment (1 study (n = 1985); RR 0.98, 95% CI 0.88 to 1.09; RD -0.01, 95% CI -0.05 to 0.03). Mortality during hospital stay was not significantly different after IVIG treatment in infants with proven infection at trial entry (1 trial (n = 1446); RR 0.95, 95% CI 0.74 to 1.21; RD -0.01, 95% CI -0.04 to 0.03). Death or major disability at 2 years corrected age was not significantly different after IVIG treatment in infants with proven infection at trial entry (1 trial (n = 1393); RR 1.03, 95% CI 0.91 to 1.18; RD 0.01, 95% CI -0.04 to 0.06). Mortality during hospital stay in infants with clinically suspected or proven infection at trial entry was not significantly different after IVIG treatment (1 study (n = 3493); RR 1.00, 95% CI 0.86 to 1.16; RD 0.00, 95% CI - 0.02 to 0.03). Death or major disability at 2 years corrected age was not significantly different after IVIG treatment in infants with suspected or proven infection at trial entry (1 study (n = 3493); RR 1.00, 95% CI 0.92 to 1.09; RD -0.00, 95% CI -0.03 to 0.03). Length of hospital stay was not reduced for infants with suspected or proven infection at trial entry (1 study (n = 3493); mean difference (MD) 0.00 days, 95% CI -0.61 to 0.61). No significant difference in mortality during hospital stay after administration of IgM-enriched IVIG for suspected infection at trial entry was reported in 4 studies (n = 266) (typical RR 0.68, 95% CI 0.39 to 1.20; RD -0.06, 95% CI -0.14 to 0.02; I = 17% for RR and 53% for RD).
AUTHORS' CONCLUSIONS
The undisputable results of the INIS trial, which enrolled 3493 infants, and our meta-analyses (n = 3973) showed no reduction in mortality during hospital stay, or death or major disability at two years of age in infants with suspected or proven infection. Although based on a small sample size (n = 266), this update provides additional evidence that IgM-enriched IVIG does not significantly reduce mortality during hospital stay in infants with suspected infection. Routine administration of IVIG or IgM-enriched IVIG to prevent mortality in infants with suspected or proven neonatal infection is not recommended. No further research is recommended.
Topics: Humans; Immunoglobulins, Intravenous; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infections; Length of Stay; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31995649
DOI: 10.1002/14651858.CD001239.pub6