Metallic nanoparticles and treatment of cutaneous leishmaniasis: A systematic review.

BACKGROUND: Cutaneous leishmaniasis (LC) is an infectious vector-borne disease caused by parasites belonging to the genus Leishmania. Metallic nanoparticles (MNPs) have been investigated as alternatives for the treatment of LC owing to their small size and high surface area. Here, we aimed to evaluate the effect of MNPs in the treatment of LC through experimental, in vitro and in vivo investigations. METHODS: The databases used were MEDLINE/ PubMed, Scopus, Web of Science, Embase, and Science Direct. Manual searches of the reference lists of the included studies and grey literature were also performed. English language and experimental in vitro and in vivo studies using different Leishmania species, both related to MNP treatment, were included. This study was registered in PROSPERO (CRD42021248245). RESULTS: A total of 93 articles were included. Silver nanoparticles are the most studied MNPs, and L. tropica is the most studied species. Among the mechanisms of action of MNPs in vitro, we highlight the production of reactive oxygen species, direct contact of MNPs with the biomolecules of the parasite, and release of metal ions. CONCLUSION: MNPs may be considered a promising alternative for the treatment of LC, but further studies are needed to define their efficacy and safety.

Melatonin: A look at protozoal and helminths.

Melatonin is a pleiotropic neurohormone found in different animal, plant, and microorganism species. It is a product resulting from tryptophan metabolism in the pineal gland and is widely known for its ability to synchronize the circadian rhythm to antitumor functions in different types of cancers. The molecular mechanisms responsible for its immunomodulatory, antioxidant and cytoprotective effects involve binding to high-affinity G protein-coupled receptors and interactions with intracellular targets that modulate signal transduction pathways. In vitro and in vivo studies have reported the therapeutic potential of melatonin in different infectious and parasitic diseases. In this review, the protective and pathophysiological roles of melatonin in fighting protozoan and helminth infections and the possible mechanisms involved against these stressors will be discussed.

RNA vaccines in infectious diseases: A systematic review.

Infectious diseases are a major health concern worldwide, especially as they are one of the main causes of mortality in underdeveloped and developing countries. Those that are considered emerging and re-emerging are characterized by unpredictability, high morbidity and mortality, exponential spread, and substantial social impact. These characteristics highlight the need to create an "on demand" control method, with rapid development, large-scale production, and wide distribution. In view of this, RNA vaccines have been investigated as an effective alternative for the treatment and prevention of infectious diseases since they can meet those needs and are considered safe, affordable, and totally synthetic. Therefore, this systematic review aimed to evaluate the use of RNA vaccines for infectious diseases from experimental, in vivo, and in vitro studies. PubMed, Web of Science, and Embase were searched for suitable studies. Additionally, further investigations, such as grey literature checks, were performed. A total of 723 articles were found, of which only 41 met the inclusion criteria. These studies demonstrated the potential of using RNA vaccines to control 19 different infectious diseases, of which COVID-19 was the most studied. Similarly, viruses comprised the largest number of reported vaccine targets, followed by protozoa and bacteria. The mRNA vaccines were the most widely used, and the intramuscular route of administration was the most reported. Regarding preclinical experimental models, mice were the most used to evaluate the impact and safety of the RNA vaccines developed. Thus, although further studies and evaluation of the subject are necessary, it is evident that RNA vaccines can be considered a promising alternative in the treatment and prophylaxis of infectious diseases.

Cannabis sativa: A look at protozoa, helminths, insect vectors, and pests.

Active principles extracted from plants, such as essential oils, have been commonly described in the literature as therapeutic targets for numerous pathological conditions. Cannabis sativa, which has an ancient and peculiar history, has been used for various purposes, from recreational to compounds of pharmacotherapeutic and industrial importance, such as pesticides based on this plant. It is a plant that contains approximately 500 described cannabinoid compounds and is the target of in vitro and in vivo studies at different locations. This review clarifies the role of cannabinoid compounds in parasitic infections caused by helminths and protozoa. In addition, this study briefly presented the use of C. sativa constituents in the formulation of pesticides for vector control, as the latter topic is justified by the economic burden faced by several regions where vector-borne diseases are a troubling reality. Studies involving cannabis compounds with pesticidal potential should be encouraged, especially those that evaluate their effectiveness against the different life cycles of insects, seeking to interrupt vector proliferation after egg laying. Actions aimed at the management and cultivation of plant species with ecologically correct pharmacotherapeutic and pesticide potentials are becoming urgent.

Organoids as a novel tool in modelling infectious diseases.

Infectious diseases worldwide affect human health and have important societal impacts. A better understanding of infectious diseases is urgently needed. In vitro and in vivo infection models have brought notable contributions to the current knowledge of these diseases. Organoids are multicellular culture systems resembling tissue architecture and function, recapitulating many characteristics of human disease and elucidating mechanisms of host-infectious agent interactions in the respiratory and gastrointestinal systems, the central nervous system and the skin. Here, we discuss the applicability of the organoid technology for modeling pathogenesis, host response and features, which can be explored for the development of preventive and therapeutic treatments.

Development of Ag-ZnO/AgO Nanocomposites Effectives for Leishmania braziliensis Treatment.

Tegumentary leishmaniasis (TL) is caused by parasites of the genus Leishmania. Leishmania braziliensis (L.b) is one of the most clinically relevant pathogens that affects the skin and mucosa, causing single or multiple disfiguring and life-threatening injuries. Even so, the few treatment options for patients have significant toxicity, high dropout rates, high cost, and the emergence of resistant strains, which implies the need for studies to promote new and better treatments to combat the disease. Zinc oxide nanocrystals are microbicidal and immunomodulatory agents. Here, we develop new Ag-ZnO/xAgO nanocomposites (NCPs) with three different percentages of silver oxide (AgO) nanocrystals (x = 49%, 65%, and 68%) that could act as an option for tegumentary leishmaniasis treatment. Our findings showed that 65% and 68% of AgO inhibit the extra and intracellular replication of L.b. and present a high selectivity index. Ag-ZnO/65%AgO NCPs modulate activation, expression of surface receptors, and cytokine production by human peripheral blood mononuclear cells toward a proinflammatory phenotype. These results point to new Ag-ZnO/AgO nanocomposites as a promising option for L. braziliensis treatment.

Neuroprotective Treatments for Digestive Forms of Chagas Disease in Experimental Models: A Systematic Review.

Chagas disease is an anthropozoonosis caused by the protozoan Trypanosoma cruzi and is characterized as a neglected disease. It is currently endemic in 21 countries on the Latin American continent, including Bolivia, Argentina, and Paraguay. Unfortunately, there are no optimally effective treatments that can reduce the damage caused in the digestive form of the disease, such as the neuronal destruction of the myenteric plexus of both the esophagus and the colon. Therefore, the objective of this systematic review was to report the possible pharmacological neuroprotective agents that were tested in murine models of the digestive form of Chagas disease. Inclusion criteria are in vivo experimental studies that used different murine models for digestive forms of Chagas disease related to pharmacological interventions with neuroprotective potential, without year and language restriction. On the other hand, the exclusion criteria were studies that did not approach murine models with the digestive form of the disease or did not use neuroprotective treatments, among others. The search in the PubMed, Web of Science, Embase, and LILACS databases was performed on September 4, 2021. In addition, a manual search was performed using the references of the included articles. The risk of bias assessment of the studies was performed based on the SYRCLE tool guidelines, and the data from the selected articles are presented in this review as a narrative description and in tables. Eight articles were included, 4 of which addressed treatment with acetylsalicylic acid, 3 with cyclophosphamide, and 1 with Lycopodium clavatum 13c. In view of the results of the studies, most of them show neuroprotective activity of the treatments, with the potential to reduce the number of damaged neurons, as well as positive changes in the structure of these cells. However, more studies are needed to understand the mechanisms triggered by each drug, as well as their safety and immunogenicity. Systematic review registration is as follows: PROSPERO database (CRD42022289746).

Metallic Nanoparticles: A New Frontier in the Fight Against Leishmaniasis.

Leishmaniasis, a cutaneous, mucocutaneous, or visceral parasitic disease caused by the protozoa of the genus Leishmania, is responsible for approximately 20-40 thousand deaths annually, with Brazil, India, and certain countries in Africa being the most affected. In addition to the parasite's ability to evade the host's immune system, the incidence of vectors, genetics of different hosts, and several deaths are attributed to the limited conventional treatments that have high toxicity, low effectiveness, and prolonged therapeutic regimens. Thus, the development of new alternative therapeutic strategies remains warranted. Metallic nanoparticles, such as gold, silver, zinc oxide, and titanium dioxide, have shown promising therapeutic tools since they are easily prepared and chemically modified, have a broad spectrum of action and low toxicity, and can generate reactive oxygen species and other immune responses. This review explores the progress of the use of metallic nanoparticles as new tools in the treatment of leishmaniasis and discusses the gaps in knowledge hindering the development of a safe and effective therapeutic intervention against these infections.

Antiprotozoal and Anthelmintic Activity of Zinc Oxide Nanoparticles.

Nanomaterials represent a wide alternative for the treatment of several diseases that affect both human and animal health. The use of these materials consists, mainly, in trying to solve the problem of resistance that pathogenic organisms acquire to conventional drugs. A well-studied example that represents a potential component for biomedical applications is the use of zinc oxide (ZnO) nanoparticles (NPs). Its antimicrobial function is related, especially to the ability to generate/induce ROS that affects the homeostasis of the pathogen in question. Protozoa and helminths that harm human health and the economic performance of animals have already been exposed to this type of nanoparticle. Thus, through this review, our goal is to discuss the state-of-the-art effect of ZnONPs on these parasites.