Omega-3 and omega-6 polyunsaturated fatty acids and their potential therapeutic role in protozoan infections.

Protozoa exert a serious global threat of growing concern to human, and animal, and there is a need for the advancement of novel therapeutic strategies to effectively treat or mitigate the impact of associated diseases. Omega polyunsaturated fatty acids (ω-PUFAs), including Omega-3 (ω-3) and omega-6 (ω-6), are constituents derived from various natural sources, have gained significant attention for their therapeutic role in parasitic infections and a variety of essential structural and regulatory functions in animals and humans. Both ω-3 and ω-6 decrease the growth and survival rate of parasites through metabolized anti-inflammatory mediators, such as lipoxins, resolvins, and protectins, and have both in vivo and in vitro protective effects against various protozoan infections. The ω-PUFAs have been shown to modulate the host immune response by a commonly known mechanism such as (inhibition of arachidonic acid (AA) metabolic process, production of anti-inflammatory mediators, modification of intracellular lipids, and activation of the nuclear receptor), and promotion of a shift towards a more effective immune defense against parasitic invaders by regulation the inflammation like prostaglandins, leukotrienes, thromboxane, are involved in controlling the inflammatory reaction. The immune modulation may involve reducing inflammation, enhancing phagocytosis, and suppressing parasitic virulence factors. The unique properties of ω-PUFAs could prevent protozoan infections, representing an important area of study. This review explores the clinical impact of ω-PUFAs against some protozoan infections, elucidating possible mechanisms of action and supportive therapy for preventing various parasitic infections in humans and animals, such as toxoplasmosis, malaria, coccidiosis, and chagas disease. ω-PUFAs show promise as a therapeutic approach for parasitic infections due to their direct anti-parasitic effects and their ability to modulate the host immune response. Additionally, we discuss current treatment options and suggest perspectives for future studies. This could potentially provide an alternative or supplementary treatment option for these complex global health problems.

APDDD: Animal parasitic diseases and drugs database.

Animal parasitic diseases not only have an economic impact, but also have serious social and public health impacts. Although antiparasitic drugs can treat these diseases, it seems difficult for users to comprehensively utilize the information, due to incomplete and difficult data collection. Thus, there is an urgent need to establish a comprehensive database, that includes parasitic diseases and related drugs. In this paper, we develop a knowledge database dedicated to collecting and analyzing animal parasitic diseases and related drugs, named Animal Parasitic Diseases and Drugs Database (APDDD). The current version of APDDD includes animal parasitic disease data of 8 major parasite classifications that cause common parasitic diseases and 96 subclass samples mined from many literature and authoritative books, as well as 182 antiparasitic drugs. Furthermore, we utilized APDDD data to add a knowledge graph representing the relationships between parasitic diseases, drugs, and the targeted gene of drugs acting on parasites. We hope that APDDD will become a good database for animal parasitic diseases and antiparasitic drugs research and that users can gain a more intuitive understanding of the relationships between parasitic diseases, drugs, and targeted genes through the knowledge graph.

Galectins in Protozoan Parasitic Diseases: Potential Applications in Diagnostics and Therapeutics.

Neglected tropical diseases (NTDs) constitute a group of diseases that generally develop in tropical or subtropical climatic conditions and are related to poverty. Within the spectrum of NTDs, diseases caused by protozoa such as malaria, Chagas disease, and leishmaniasis exhibit elevated mortality rates, thereby constituting a substantial public health concern. Beyond their protozoan etiology, these NTDs share other similarities, such as the challenge of control and the lack of affordable, safe, and effective drugs. In view of the above, the need to explore novel diagnostic predictors and therapeutic targets for the treatment of these parasitic diseases is evident. In this context, galectins are attractive because they are a set of lectins bound to ß-galactosides that play key roles in a variety of cellular processes, including host-parasite interaction such as adhesion and entry of parasites into the host cells, and participate in antiparasitic immunity in either a stimulatory or inhibitory manner, especially the galectins-1, -2, -3, and -9. These functions bestow upon galectins significant therapeutic prospects in the context of managing and diagnosing NTDs. Thus, the present review aims to elucidate the potential role of galectins in the diagnosis and treatment of malaria, leishmaniasis, and Chagas disease.

Therapeutic Potential of Marine-Derived Cyclic Peptides as Antiparasitic Agents.

Parasitic diseases still compromise human health. Some of the currently available therapeutic drugs have limitations considering their adverse effects, questionable efficacy, and long treatment, which have encouraged drug resistance. There is an urgent need to find new, safe, effective, and affordable antiparasitic drugs. Marine-derived cyclic peptides have been increasingly screened as candidates for developing new drugs. Therefore, in this review, a systematic analysis of the scientific literature was performed and 25 marine-derived cyclic peptides with antiparasitic activity (1-25) were found. Antimalarial activity is the most reported (51%), followed by antileishmanial (27%) and antitrypanosomal (20%) activities. Some compounds showed promising antiparasitic activity at the nM scale, being active against various parasites. The mechanisms of action and targets for some of the compounds have been investigated, revealing different strategies against parasites.

Antiparasitic activity of ivermectin: Four decades of research into a "wonder drug".

Parasitic diseases still pose a serious threat to human and animal health, particularly for millions of people and their livelihoods in low-income countries. Therefore, research into the development of effective antiparasitic drugs remains a priority. Ivermectin, a sixteen-membered macrocyclic lactone, exhibits a broad spectrum of antiparasitic activities, which, combined with its low toxicity, has allowed the drug to be widely used in the treatment of parasitic diseases affecting humans and animals. In addition to its licensed use against river blindness and strongyloidiasis in humans, and against roundworm and arthropod infestations in animals, ivermectin is also used "off-label" to treat many other worm-related parasitic diseases, particularly in domestic animals. In addition, several experimental studies indicate that ivermectin displays also potent activity against viruses, bacteria, protozoans, trematodes, and insects. This review article summarizes the last 40 years of research on the antiparasitic effects of ivermectin, and the use of the drug in the treatment of parasitic diseases in humans and animals.

Evaluating the risk of infections under interleukin 23 and interleukin 17 inhibitors relative to tumour necrosis factor inhibitors - A population-based study.

BACKGROUND: The risk of infections among patients with psoriasis undergoing interleukin (IL)-23 inhibitors (IL-23i) and IL-17 inhibitors (IL-17i) is yet to be exhaustively determined. OBJECTIVE: To assess the risk of infectious complications in patients with psoriasis managed by IL-23i and IL-17i with tumour necrosis factor inhibitors (TNFi) as a comparator. METHODS: A global cohort study comprised two distinct analyses comparing patients with psoriasis under different therapeutic modalities; (i) new users of IL-23i (n = 5272) versus TNFi (n = 5272) and (ii) new users of IL-17i (n = 15,160) versus TNFi (n = 15,160). Study groups were compared regarding the risk of 26 different infections. Propensity score matching was conducted to optimize between-group comparability. RESULTS: Patients under IL-23i had a lower risk of otitis media (HR, 0.66; 95% CI, 0.44-0.97), encephalitis (HR, 0.18; 95% CI, 0.04-0.78), herpes zoster (HZ; HR, 0.58; 95% CI, 0.41-0.82), hepatitis B virus (HBV) reactivation (HR, 0.24; 95% CI, 0.12-0.47), cytomegalovirus (HR, 0.25; 95% CI, 0.07-0.86), influenza (HR, 0.52; 95% CI, 0.38-0.71) and parasitic diseases (HR, 0.78; 95% CI, 0.64-0.95). IL-17i was associated with a decreased risk of pneumonia (HR, 0.76; 95% CI, 0.68-0.85), septicaemia (HR, 0.84; 95% CI, 0.72-0.97), upper respiratory tract infection (HR, 0.84; 95% CI, 0.77-0.92), HZ (HR, 0.79; 95% CI, 0.67-0.92), HBV (HR, 0.59; 95% CI, 0.46-0.76) and hepatitis C virus (HR, 0.71; 95% CI, 0.57-0.88) reactivation, cytomegalovirus (HR, 0.58; 95% CI, 0.36-0.93), Epstein-Barr virus (HR, 0.38; 95% CI, 0.19-0.75), influenza (HR, 0.70; 95% CI, 0.61-0.81) and parasitic diseases (HR, 0.80; 95% CI, 0.72-0.88). CONCLUSION: Compared with TNFi, IL-23i and IL-17i are associated with decreased risk of several infectious diseases. These agents might be preferred in patients with susceptibility to infections.

Cysteine Proteases as Validated Targets for the Treatment of Neglected and Poverty-Related Parasitic Diseases.

Neglected tropical diseases (NTDs) include 20 diverse infections mainly prevalent in tropical areas that mostly affect disadvantaged communities and women and children [...].

Vanadium compounds as antiparasitic agents: An approach to their mechanisms of action.

BACKGROUND: Parasitic infections are a public health problem since they have high morbidity and mortality worldwide. In parasitosis such as malaria, leishmaniasis and trypanosomiasis it is necessary to develop new compounds for their treatment since an increase in drug resistance and toxic effects have been observed. Therefore, the use of different compounds that couple vanadium in their structure and that have a broad spectrum against different parasites have been proposed experimentally. OBJECTIVE: Report the mechanisms of action exerted by vanadium in different parasites. CONCLUSION: In this review, some of the targets that vanadium compounds have were identified and it was observed that they have a broad spectrum against different parasites, which represents an advance to continue investigating therapeutic options.

Employing "Red Flags" to Fight the Most Neglected Diseases: Nitroaromatic as Still Suitable Tools to Treat Human and Veterinary Parasitosis.

Nitroaromatic compounds have been used for treating parasitic diseases since the 1960s. Pharmacological alternatives to treat them are under observation. However, for the most neglected diseases, such as those caused by worms and less known protozoans, nitro compounds are still among the drugs of choice, despite their well-known collateral effects. In this review, we describe the chemistry and the uses of the still most employed nitroaromatic compounds for treating parasitosis caused by worms or lesser-known protozoans. We also describe their application as veterinary drugs. The most accepted mechanism of action seems to be the same, leading to collateral effects. For this reason, a special session was dedicated to discussing toxicity, carcinogenicity, and mutagenesis, as well as the most acceptable aspects of the known structure-activity/toxicity relationships involving nitroaromatic compounds. It employed the SciFindern search tool from the American Chemical Society in the search for the most relevant bibliography within the field, exploring keyword expressions such as "NITRO COMPOUNDS" and "BIOLOGICAL ACTIVITY" (within Abstracts or Keywords) and concepts related to parasites, pharmacology and toxicology. The results were classified according to the chemical classes of nitro compounds, being the most relevant studies regarding journal impact and interest of the described results chosen to be discussed. From the found literature, it is easy to notice that nitro compounds, especially the nitroaromatic ones, are still widely used in antiparasitic therapy, despite their toxicity. They also are the best starting point in the search for new active compounds.

Statin and aspirin use in parasitic infections as a potential therapeutic strategy: A narrative review.

Infections, including zoonoses, constitute a threat to human health due to the spread of resistant pathogens. These diseases generate an inflammatory response controlled by a resolving mechanism involving specialized membrane lipid-derived molecules called lipoxins, resolvins, maresins, and protectins. The production of some of these molecules can be triggered by aspirin or statins. Thus, it is proposed that modulation of the host response could be a useful therapeutic strategy, contributing to the management of resistance to antiparasitic agents or preventing drift to chronic, host-damaging courses. Therefore, the present work presents the state of the art on the use of statins or aspirin for the experimental management of parasitic infections such as Chagas disease, leishmaniasis, toxoplasmosis or malaria. The methodology used was a narrative review covering original articles from the last seven years, 38 of which met the inclusion criteria. Based on the publications consulted, modulation of the resolution of inflammation using statins may be feasible as an adjuvant in the therapy of parasitic diseases. However, there was no strong experimental evidence on the use of aspirin; therefore, further studies are needed to evaluate its role inflammation resolution process in infectious diseases.

Medicinal plants as a source of antiparasitics: an overview of experimental studies.

Despite advances in modern human and veterinary medicine, gastrointestinal (GI) parasitic infections remain a significant health issue worldwide, mainly in developing countries. Increasing evidence of the multi-drug resistance of these parasites and the side effects of currently available synthetic drugs have led to increased research on alternative medicines to treat parasitic infections. The exploration of potential botanical antiparasitics, which are inexpensive and abundant, may be a promising alternative in this context. This study summarizes the in vitro/in vivo antiparasitic efficacy of different medicinal plants and their components against GI parasites. Published literature from 1990-2020 was retrieved from Google Scholar, Web of Science, PubMed and Scopus. A total of 68 plant species belonging to 32 families have been evaluated as antiparasitic agents against GI parasites worldwide. The majority of studies (70%) were conducted in vitro. Most plants were from the Fabaceae family (53%, n = 18). Methanol (37%, n = 35) was the most used solvent. Leaf (22%, n = 16) was the most used plant part, followed by seed and rhizome (each 12%, n = 9). These studies suggest that herbal medicines hold a great scope for new drug discoveries against parasitic diseases and that the derivatives of these plants are useful structures for drug synthesis and bioactivity optimization.

Drug discovery for parasitic diseases: powered by technology, enabled by pharmacology, informed by clinical science.

While prevention is a bedrock of public health, innovative therapeutics are needed to complement the armamentarium of interventions required to achieve disease control and elimination targets for neglected diseases. Extraordinary advances in drug discovery technologies have occurred over the past decades, along with accumulation of scientific knowledge and experience in pharmacological and clinical sciences that are transforming many aspects of drug R&D across disciplines. We reflect on how these advances have propelled drug discovery for parasitic infections, focusing on malaria, kinetoplastid diseases, and cryptosporidiosis. We also discuss challenges and research priorities to accelerate discovery and development of urgently needed novel antiparasitic drugs.

Salt-Tolerant Plants as Sources of Antiparasitic Agents for Human Use: A Comprehensive Review.

Parasitic diseases, especially those caused by protozoans and helminths, such as malaria, trypanosomiasis, leishmaniasis, Chagas disease, schistosomiasis, onchocerciasis, and lymphatic filariasis, are the cause of millions of morbidities and deaths every year, mainly in tropical regions. Nature has always provided valuable antiparasitic agents, and efforts targeting the identification of antiparasitic drugs from plants have mainly focused on glycophytes. However, salt-tolerant plants (halophytes) have lately attracted the interest of the scientific community due to their medicinal assets, which include antiparasitic properties. This review paper gathers the most relevant information on antiparasitic properties of halophyte plants, targeting human uses. It includes an introduction section containing a summary of some of the most pertinent characteristics of halophytes, followed by information regarding the ethnomedicinal uses of several species towards human parasitic diseases. Then, information is provided related to the antiprotozoal and anthelmintic properties of halophytes, determined by in vitro and in vivo methods, and with the bioactive metabolites that may be related to such properties. Finally, a conclusion section is presented, addressing perspectives for the sustainable exploitation of selected species.

Modular nanotheranostic agents for protistan parasitic diseases: Magic bullets with tracers.

Protistan parasitic infections contribute significantly to morbidity and mortality, causing more than 2 billion human infections annually. However, current treatments are often limited; due to ineffective drugs and drug resistance, thus better options are urgently required. In the present context, theranostics agents are those that offer simultaneous detection, diagnosis and even treatment of protistan parasitic diseases. "Nanotheranostics" is the term used to describe such agents, that are around 100 nm or less in size. Anti-parasitic activity of nanoparticles (NPs) has been reported, and many have useful intrinsic imaging properties, but it is perhaps their multifunctional nature that offers the greatest potential. NPs may be used as adapters onto which various subunits with different functions may be attached. These subunits may facilitate targeting parasites, coupled with toxins to eradicate parasites, and probe subunits for detection of particles and/or parasites. The modular nature of nano-platforms promises a "mix and match" approach for the construction of tailored agents by using combinations of these subunits against different protistan parasites. Even though many of the subunits have shown promise alone, these have not yet been put together convincingly enough to form working theranostics against protistan parasites. Although the clinical application of nanotheranostics to protistan parasitic infections in humans requires more research, we conclude that they offer not just a realisation of Paul Ehrlich's long imagined "magic bullet" concept, but potentially are magic bullets combined with tracer bullets.

Exploration of aminoacyl-tRNA synthetases from eukaryotic parasites for drug development.

Parasitic diseases result in considerable human morbidity and mortality. The continuous emergence and spread of new drug-resistant parasite strains is an obstacle to controlling and eliminating many parasitic diseases. Aminoacyl-tRNA synthetases (aaRSs) are ubiquitous enzymes essential for protein synthesis. The design and development of diverse small molecule, drug-like inhibitors against parasite-encoded and expressed aaRSs have validated this enzyme family as druggable. In this work, we have compiled the progress to date towards establishing the druggability of aaRSs in terms of their biochemical characterization, validation as targets, inhibitor development, and structural interpretation from parasites responsible for malaria (Plasmodium), lymphatic filariasis (Brugia,Wuchereria bancrofti), giardiasis (Giardia), toxoplasmosis (Toxoplasma gondii), leishmaniasis (Leishmania), cryptosporidiosis (Cryptosporidium), and trypanosomiasis (Trypanosoma). This work thus provides a robust framework for the systematic dissection of aaRSs from these pathogens and will facilitate the cross-usage of potential inhibitors to jump-start anti-parasite drug development.

[Anticancer effect of parasites and its underlying mechanisms: a review].

Both parasitic diseases and cancers are disorders that seriously threaten human health. A strong correlation has been recently found between parasitic infections and cancers, and multiple species of parasites and their derived products have shown effective to suppress cancer development, progression and metastasis. Therefore, deciphering the interaction among parasites, cancers and hosts not only provides new insights into the development of cancer therapy, but also provides the basis for screening of parasites-derived active anticancer molecules. This review summarizes the latest advances in the anticancer activity of parasites and underlying mechanisms.

Structural Insights and Pharmaceutical Relevance of Plumbagin in Parasitic Disorders: A Comprehensive Review.

Recently, natural products have been became the center of attraction for the scientific society and exploration of their biologically abilities is proceeding continuously. In search for novel antiparasitic agents with an objective of protecting humans from parasitic infections, the present work was focused on naphthoquinones possessing antiparasitic activity. Among naphthoquinones, plumbagin is one of the secondary metabolites exhibiting diverse biological properties such as antibacterial, antimalarial, antiinflammatory, insecticidal and antiparasitic. Plumbagin is reported to have antischistosomiasis, anti-haemonchosis, anti-fascioliasis, antiotoacariasis, anti-leishmaniasis, antimalaria, antiallergic and anthelmintic activities. Besides, various methods of extraction of plumbagin from different methods, their effectiveness against different parasites, and the structure-activity relationship reported by different researchers. This work highlight on recent advancements in the phytochemistry of plumbagin, studies associated with various biological activities. The structure-activity relationship studies have also been summarized. To conclude, present review could be beneficial for the scientific community to get better insight into medicinal research of plumbagin and may provide a new horizon for the rational design of plumbagin based compounds.

[Other Central Nervous System Infections(Including Fungal Infection, Tuberculosis, and Parasitic Infection)].

This review describes cryptococcal meningoencephalitis, tuberculous meningitis, neurosyphilis, and toxoplasma encephalitis. Central nervous system infections are neurological emergencies associated with mortality or other outcomes. Therefore, early diagnosis and treatment are critical. Fungal or gondii infections are rare and affect compromised hosts who are HIV positive, have diabetes, or take immunosuppressive or anticancer drugs. Cryptococcal antigens in the serum and cerebrospinal fluid are useful for the diagnosis of cryptococcal meningoencephalitis. RPR and TPHA tests are useful for the diagnosis of neurosyphilis. Cryptococcal meningoencephalitis and tuberculous meningitis often develop into hydrocephalus, making VP shunt necessary. Antifungal drugs for cryptococcal meningitis are limited by the blood-brain barrier, making a full recovery difficult; in such situations, intraventricular antifungal treatment is required.