Cutaneous leishmaniasis is considered as one of the most concerns of the World Health Organization (WHO). The main objective of this study was to use polycaprolactone (PCL) nanofiber scaffolds in order to provide a topical drug delivery system capable of delivering glucantime (glu) and quercetin (qur) to cutaneous leishmaniasis wounds. First, PCL/glu/qur, PCL/glu, and PCL/qur nanofibers were prepared by an electrospinning method followed by characterization through scanning electron microscopy (SEM) and fourier transform infrared spectroscopy (FTIR). Subsequently, we investigated the release of the drugs from nano-scaffolds and anti-promastigote effects. Lastly, the effect of nanobandage was evaluated on 20 female inbred BALB/c mice infected with the parasite. The nanofibers were bead-free and uniform with an average diameter of 224 ± 25 nm and showed a sustained release. Results from in vivo experiments showed that the number of amastigotes and macrophages infected with the parasite and the infiltration of inflammatory cells in mice treated with PCL/qur and PCL/glu/qur nanofibers significantly decreased as compared with those treated with the PCL/glu and PCL nanofibers. Collectively, PCL/glu/qur and PCL/qur nanofibers have promising therapeutic effects in cutaneous leishmaniasis wound healing.

Eukaryotic chromosomes segregate faithfully prior to nuclear division to ensure genome stability. If segregation becomes defective, the chromosome copy number of the cell may alter leading to aneuploidy and/or polyploidy, both common hallmarks of cancers. In eukaryotes, aurora kinases regulate chromosome segregation during mitosis and meiosis, but their functions in the divergent, single-celled eukaryotic pathogen Trypanosoma brucei are less understood. Here, we focused on one of three aurora kinases in these parasites, TbAUK3, a homologue of the human aurora kinase AURKC, whose functions are primarily restricted to meiosis. We show that RNAi targeted depletion of TbAUK3 correlates with nuclear segregation defects, reduced proliferation, and decreased DNA synthesis, suggestive of a role for TbAUK3 during mitotic, not meiotic, chromosome segregation. Moreover, we uncover a putative role for TbAUK3 during the parasite's response to DNA damage since we show that depletion of TbAUK3 enhances DNA instability and sensitivity to genotoxic agents.

Globally, an estimated 1 billion people reside in endemic areas, and over 12 million individuals are infected with leishmaniasis. Despite its prevalence, leishmaniasis continues to be a neglected disease, mainly affecting underdeveloped countries. In Brazil, the available treatments are pentavalent antimonials and Amphotericin B, which are outdated, toxic, require prolonged parenteral administration and have limited efficacy. The heterocyclic ring oxadiazole has been documented in the literature to possess various biological activities, including leishmanicidal properties, thus positioning it as a potential candidate for further investigation. This study aims to evaluate the in vitro leishmanicidal activity of an oxadiazole compound (2i), explore its mechanism of action through enzymatic inhibition and molecular docking, assess its antioxidant activity, and conduct an in silico pharmacokinetic prediction. Pharmacokinetic predictions via ADME/TOX modeling revealed that the 2i molecule exhibits good intestinal absorption (92%), is water-insoluble (-4 log.mol/L) and demonstrates high permeability in Caco-2 cells (1.35log.Papp10-6cm/s), suggesting potential for oral administration. Metabolic studies indicated that oxadiazole 2i is an inhibitor of cytochrome P450 enzymes CYP1A2 and CYP2C19, necessitating further evaluation of potential drug interactions. Additionally, it did not exhibit hepatotoxicity or cardiotoxicity; however, it demonstrated mutagenic potential in the salmonella reverse mutation test (AMES), which is a genetic method that detects mutagenic chemical agents, thus justifying more complex confirmatory studies. In vitro assays showed that oxadiazole 2i has DPPH (2,2-diphenyl-1-picrylhydrazyl) radical reducing activity, indicating potential antioxidant properties with an IC of 12.10µg/mL. Concerning its leishmanicidal mechanism of action, molecular docking simulations at the active site of acetylcholinesterase demonstrated that the 2i molecule had superior binding energy values compared to the reference drug physostigmine (-7.39kcal/mol versus -6.66kcal/mol, respectively). However, the pharmacophore map revealed that physostigmine had more molecular interactions than oxadiazole 2i. In acetylcholinesterase inhibition assays, the 2i molecule exhibited significant inhibitory activity with an IC of 11.91µg/mL, suggesting a mechanism of action that compromises the parasitic membrane. Moreover, the 2i molecule demonstrated significant leishmanicidal activity against L. infantum with an IC of 30.86μM. Cytotoxicity assays on RAW 264.7 macrophages revealed a high CC value of 485.5µM and a selectivity index (SI) of 17.86. Based on these findings, oxadiazole 2i emerges as a promising candidate for further study, offering prospects for more affordable, selective, and less toxic leishmanicidal agents.

This study investigated the effect of dandelion (Taraxacum officinale) leaf aqueous extract (DLE) on the immunological response of mice following infection with Schistosoma mansoni. Mice (in groups of 7) were first experimentally infected with S. mansoni and, 6 weeks later, were treated with praziquantel (PZQ) and/or DLE. Control mice were uninfected. In contrast to the untreated group, animals given PZQ and/or DLE exhibited an enhanced immunological response, as indicated by increased serum IFNγ, TNFα, IL4 and IL10 levels, increased numbers of CD4+ and CD25+ cells in blood and spleen and altered expression of apoptosis-related genes (low Bax and caspase3 and high Bcl2) in the spleen. DLE treatment had a significantly bigger impact in all these parameters compared with PZQ alone and combined DLE/PZQ treatment have the largest effect. While DLE treatment alone significantly decreased parasite burden, it did not improve upon the greater protective effect of PZQ, even when given in combination.

The study aimed to conduct in vitro biological assessments of hydantoin and thiohydantoin compounds against mature Schistosoma mansoni worms, evaluate their cytotoxic effects and predict their pharmacokinetic parameters using computational methods. The compounds showed low in vitro cytotoxicity and were not considered hemolytic. Antiparasitic activity against adult S. mansoni worms was tested with all compounds at concentrations ranging from 200 to 6.25 μM. Compounds SC01, SC02, and SC03 exhibited low activity. Compounds SC04, SC05, SC06 and SC07 caused 100 % mortality within 24 h of incubation at a concentration of 100 and 200 μM. Thiohydantoin SC04 exhibited the highest activity, resulting in 100 % mortality after 24 h of incubation at a concentration of 50 μM and IC of 28 µM. In the ultrastructural analysis (SEM), the compound SC04 (200 µM) induced integumentary changes, formation of integumentary blisters, and destruction of tubercles and spicules. Therefore, the SC04 compound shows promise as an antiparasitic against S. mansoni.

Entamoeba histolytica, an intestinal parasite of global significance, poses substantial health risks with its associated high morbidity and mortality rates. Despite the current repertoire of molecular tools for the study of gene function in, the regulatory mechanisms governing its pathogenicity remain largely unexplored. This knowledge gap underscores the need to elucidate key genetic determinants orchestrating cellular functions critical to its virulence. Previously, our group generated an avirulent strain, termed UG10, with the same genetic background as the HM1:IMSS strain. UG10 strain, despite showing normal expression levels of well-known virulence factors, was unable to perform in-vitro and in-vivo activities related to amoebic virulence. In this study, we aimed to uncover the genome-wide modifications that rendered the avirulent phenotype of the UG10 strain through whole-genome sequencing. As a complementary approach, we conducted Methylated DNA Immunoprecipitation coupled with sequencing (MeDIP-seq) analysis on both the highly virulent HM1:IMSS strain and the low-virulence UG10 strain to uncover the genome-wide methylation profile. These dual methodologies revealed two aspects of the UG10 avirulent strain. One is the random integration of fragments from the ribosomal gene cluster and tRNA genes, ranging from 120 to 400 bp; and secondly, a clear, enriched methylation profile in the coding and non-coding strand relative to the start codon sequence in genes encoding small GTPases, which is associated with the previously described avirulent phenotype. This study provides the foundation to explore other genetic and epigenetic regulatory circuitries in E. histolytica and novel targets to understand the pathogenic mechanism of this parasite.

RNA interference (RNAi) on parasitic nematodes has been described as a valuable tool for screening putative targets that could be used as novel drug and/or vaccine candidates. This study aimed to set up a pipeline to identify potential targets using RNAi for vaccine/anti-parasite therapy development against Haemonchus contortus, a blood-feeding abomasal nematode parasite. The available H. contortus sequence data was mined for targets, which were tested for essentiality using RNAi electroporation assays. A total of 56 genes were identified and tested for knockdown using electroporation of first-stage larvae (L1) H. contortus with the target double-stranded RNA. Electroporation of L1 proved to be effective overall; 17 targets had a strong phenotype and significant reduction in alive H. contortus, and another 24 had a moderate phenotype with a significant reduction in larvae development. A total of 28 targets showed a significant reduction in the development of H. contortus larvae to the infective stage (L3) following the RNAi assay. Down-regulation of target transcript levels was evaluated in some targets by semi-quantitative PCR. Four out of five genes tested showed complete knockdown of mRNA levels via semi-quantitative PCR, whereas the knockdown was partial for one. In conclusion, the results indicate that the RNAi pathway is confirmed in H. contortus and that several target genes have the potential to be investigated further as possible vaccine candidates.

Cysteinyl leukotrienes (CysLTs) can induce a disruption of the blood-brain barrier (BBB), and this reaction is mediated by cysteinyl-leukotriene receptors. In this study, we used A. cantonensis-induced eosinophilic meningoencephalitis as a model to investigate whether the CysLT2 receptor involved in the pathogenesis of angiostrongyliasis meningoencephalitis. The present study provides evidence that the CysLT2 receptor antagonist HAMI3379 reduced the number of infiltrated eosinophils and brain edema in eosinophilic meningoencephalitis. Additionally, we found that HAMI3379 significantly decreased the protein levels of M1 polarisation markers (CD80, iNOS, IL-5 and TNF-α), increased the expression of M2 polarisation markers (CD206, IL-10 and TGF-β) both in vivo and in vitro. Matrix metalloproteinase-9, S100B, GFAP, fibronectin, and claudin-5 were markedly lower after HAMI3379 treatment. Therefore, HAMI3379 reduced the BBB dysfunction in angiostrongyliasis meningoencephalitis. We have identified microRNA-155 as a BBB dysfunction marker in eosinophilic meningoencephalitis. The results showed that microRNA-155 was 15-fold upregulated in eosinophilic meningoencephalitis and 20-fold upregulated after HAMI3379 treatment. Our results suggest that CysLT2R may be involved in A. cantonensis-induced brain edema and eosinophilic meningoencephalitis and that down-regulation of CysLT2R could be a novel and potential therapeutic strategy for the treatment of angiostrongyliasis meningoencephalitis.

Most protocols used to study the dynamics of calcium (Ca) in the malaria parasite are based on dyes, which are invasive and do not allow discrimination between the signal from the host cell and the parasite. To avoid this pitfall, we have generated a parasite line expressing the genetically encoded calcium sensor GCaMP3. The PfGCaMP3 parasite line is an innovative tool for studying spontaneous intracellular Ca oscillations without external markers. Using this parasite line, we demonstrate the occurrence of spontaneous Ca oscillations in the ring, trophozoite, and schizont stages in Plasmodium falciparum. Using the Fourier transform to fluorescence intensity data extracted from different experiments, we observe cytosolic Ca fluctuations. These spontaneous cytosolic Ca oscillations occur in the three intraerythrocytic stages of the parasite, with most oscillations occurring in the ring and trophozoite stages. A control parasite line expressing only a GFP control did not reveal such fluctuations, demonstrating the specificity of the observations. Our results clearly show dynamic, spontaneous Ca oscillations during the asexual stage in P. falciparum, independent from external stimuli.

Opisthorchis felineus, Opisthorchis viverrini, and Clonorchis sinensis (family Opisthorchiidae) are parasitic flatworms that pose serious threats to humans in certain countries and cause opisthorchiasis/clonorchiasis. Opisthorchiid flukes parasitize the biliary tract of the host, causing cholangitis, cholecystitis, cholelithiasis and cholangiocarcinoma. In this review, we primarily focus on recent microRNAs (miRNAs) studies of opisthorchiid flukes and their definitive hosts. Many miRNAs are conserved and expressed in a developmentally stage specific manner in the three opisthorchiid flukes, which play important roles in the growth and development of Opisthorchiidae spp., as well as host-pathogen interactions. Some miRNAs might be potential biomarkers related to carcinogenesis of cholangiocarcinoma. Therefore, this review provides the basis for further investigating the roles of miRNAs in opisthorchiid flukes and their definitive hosts, as well as promoting the development of novel approaches to prevent and treat opisthorchiasis/clonorchiasis.

The protozoan parasite Trypanosoma brucei possesses a large family of transmembrane receptor-like adenylate cyclases (RACs), primarily located to the flagellar surface and involved in sensing of the extracellular environment. RACs exhibit a conserved topology characterized by a large N-terminal extracellular moiety harbouring two Venus Flytrap (VFT) bilobate structures separated from an intracellular catalytic domain by a single transmembrane helix. RAC activation, which typically occurs under mild acid stress, requires the dimerization of the intracellular catalytic domain. The occurrence of VFT domains in the RAC's extracellular moiety suggests their potential responsiveness to extracellular ligands in the absence of stress, although no such ligands have been identified so far. Herein we report the biophysical characterization of the membrane-proximal VFT2 domain of a bloodstream form-specific RAC called ESAG4, whose ectodomain 3D structure is completely unknown. The paper describes an AlphaFold2-based optimisation of the expression construct, enabling facile and high-yield recombinant production and purification of the target protein. Through an interdisciplinary approach combining various biophysical methods, we demonstrate that the optimised VFT2 domain obtained by recombination is properly folded and behaves as a monomer in solution. The latter suggests a ligand-binding capacity independent of dimerization, unlike typical mammalian VFT receptors, as guanylate cyclase. In silico VFT2 genomic analyses shows divergence among cyclase isoforms, hinting at ligand specificity. Taken together this improved procedure enabling facile and high-yield recombinant production and purification of the target protein could benefit researchers studying trypanosomal RAC VFT domains but also any trypanosome domain with poorly defined boundaries. Additionally, our findings support the stable monomeric VFT2 domain as a useful tool for future structural investigations and ligand screening.

Protein phosphatases Mg/Mn dependent (PPMs), serine/threonine phosphatases, are widely distributed in apicomplexan parasites, and Toxoplasma gondii possesses the largest number of PPMs in the apicomplexan parasites. Though the function of some PPMs has been characterized in T. gondii, much less is known about two phosphatase 2 C domain-containing proteins, PPM2A and PPM2B. PPM2A was identified as one of Toxoplasma Calmodulin's interacting proteins through proximity-based protein interaction BioID technology in the previous study, and PPM2B was the homolog of PPM2A in T. gondii. In this study, PPM2A was distributed in the whole tachyzoite of T. gondii, and PPM2B was mainly distributed in the cytoplasm by inserting a 10HA tag in the C-terminus of the two genes in the RH∆ku80 strain. PPM2A knockout (Δppm2a), PPM2B knockout (Δppm2b), and double knockout (ΔΔ) in RHΔhxgprt type I strain under CRISPR-Cas9 system did not result in intracellular replication defect. Besides, mouse experiments demonstrated that PPM2A, PPM2B, and double knockout did not reduce the pathogenicity of T. gondii compared with the RH∆hxgprt strain. However, the plaque size of these single knockout and double knockout strains were smaller than that in the control RH∆hxgprt strain. Our results provide new insight into the function of PPMs in the pathogenesis of T. gondii.

Phosphosphingolipids (PSL) are essential components of eukaryotic membranes. The major PSL in fungi and protists is inositol phosphorylceramide (IPC), while sphingomyelin (SM), and to a lesser extent ethanolamine phosphorylceramide (EPC) predominate in mammals. Most kinetoplastid protozoa have a syntenic locus that encodes a single sphingolipid synthase (SLS) gene. Uniquely, among the kinetoplastids, the salivarian (African) trypanosomes have expanded this locus from a single gene in Trypanosoma vivax (TvSLS) to four genes in T. brucei (TbSLS1-4). We have previously shown that one of these is an IPC synthase, while the others are SM/EPC synthases, and that specificity is controlled by a single signature residue (IPC, serine; SM/EPC, phenylalanine). This residue is serine in T. cruzi and Leishmania major SLSs, both of which are demonstrated IPC synthases. However, T. vivax has a tyrosine at this residue raising the issue of specificity. Using a liposome-supplemented in vitro translation system we now show that T. vivax SLS is an SM/EPC synthase, and that the basal kinetoplastid Bodo saltans SLS is an IPC synthase (serine). We use these data, and a multiple alignment of available sequences, to discuss the evolution of kinetoplastid SLSs and their unique expansion in T. brucei and related salivarian trypanosomes.

The parasite Toxoplasma gondii, or T. gondii, is zoonotic that both individuals as well as animals can contract resulting in toxoplasmosis, a life-threatening illness. We used an immunoinformatic technique in our research to construct a vaccine with multi-epitopes so that it can decrease the devastating impact caused by this dangerous parasite. In order to construct the vaccine, GRA6 and MIC3 proteins were targeted, which are engaged in T. gondii identification, infection, and immune response. Novel epitopes for linear B lymphocytes (LBL), cytotoxic T lymphocytes (CTL), and helper T lymphocytes (HTL) were found by epitope mapping, every anticipated epitope was assessed through rigorous screening to determine the top choices for epitopes which were entirely preserved, very antigenic in nature, nonallergenic, and nontoxic. 4 CTLs, 3 HTLs and 4 LBL epitopes were chosen and combined along with proper linkers and adjuvants to design a vaccine with several epitopes. Linkers as well as adjuvants were provided to make the vaccine more immunogenic, antigenic, and stable. The proposed vaccination was identified to possess the necessary biophysical properties, be soluble, extremely antigenic, and non-allergic. Reliability of the vaccine design was demonstrated by secondary along with tertiary structure prediction. It was anticipated that the vaccine's three-dimensional structure would likely link up with TLR-2 and TLR-4 via the investigation of molecular docking. TLR-2 and TLR-4 are crucial for the parasite's invasion and the body's response. In our docking investigation, both TLRs demonstrated strong binding affinities utilizing the vaccine structure. After that, the vaccine construct's elevated expression rate, which was observed in Escherichia coli strain K12, was confirmed by an investigation using in silico cloning and codon adaptation. The results of the research are really encouraging and some properties of the vaccine were found to be significantly better than existing the T. gondii multi-epitope vaccination based on the same proteins. Nonetheless, in vivo trials are strongly suggested for potential future studies.

Pebrine disease, caused by Nosema bombycis (N. bombycis), is the most important pathogen known to the silk industry. Historical evidence from several countries shows that the outbreaks of pebrine disease have largely caused the decline of the sericulture industry. Prevention is the first line to combat pebrine as a deadly disease in silkworm; however, no effective treatment has yet been presented to treat the disease. Many different methods have been used for detection of pebrine disease agent. This review focuses on the explanation and comparison of these methods, and describes their advantages and/or disadvantages. Also, it highlights the ongoing advances in diagnostic methods for N. bombycis that could enable efforts to halt this microsporidia infection. The detection methods are categorized as microscopic, immunological and nucleic acid-based approaches, each with priorities over the other methods; however, the suitability of each method depends on the available equipment in the laboratory, the mass of infection, and the speed and sensitivity of detection. The accessibility and economic efficiency are compared as well as the speed and the sensitivity for each method. Although, the light microscopy is the most common method for detection of N. bombycis, qPCR is the most preferred method for large data based on speed and sensitivity as well as early detection ability.

The protozoan protein kinase calcium-dependent protein kinase 1 (CDPK1) has emerged as a potential therapeutic target for the treatment of cryptosporidiosis. A focused screen of known kinase inhibitors identified a pyridopyrimidinone as a new chemotype of Cryptosporidium parvum (Cp) CDPK1 inhibitors. Structural comparison of CpCDPK1 to two representative human kinases, RIPK2 and Src, revealed differences in the positioning of the αC-helix that was used in the design of a potent pyridopyrimidinone-based CpCDPK1 inhibitor 7 (a.k.a. UH15-16, IC = 10 nM), which blocked the growth of three C. parvum strains (EC = 12-40 nM) as well as C. hominis (EC = 85 nM) in HCT-8 host cells. Pharmacokinetic and tissue distribution analyses indicated that 7 had low systemic exposure after oral administration, but high gastrointestinal concentration, as well as good Caco-2 cell permeability. Finally, 7 demonstrated partial efficacy in an IL-12 knock-out mouse model of acute cryptosporidiosis.

The scabies mite is known to induce a complicated immune response that involves both innate and long-term adaptive immunity. Many immune effectors and pathways are involved. Th17/Treg balance can influence the complex immune response to scabies. The immunological effectors including IL-17A, as a pro-inflammatory cytokine, and Treg cells, anti-inflammatory regulatory T cells, are essential for preserving cutaneous immunological homeostasis. So, evaluating these immune effectors may help in comprehending the pathophysiology of scabies and facilitate the development of new treatment approaches. This study examined the expression of IL-17A and FoxP3 in the skin and serum of 50 scabies patients and 25 healthy controls. An assessment of their correlation with clinical features was performed. Regarding tissue response, scabietic patients exhibited a significant increase in IL-17A and FoxP3 expression in their epidermis and dermis compared to controls (P<0.001), but the correlation between these factors was not significant in either area (P>0.05). Also, patients showed a significant increase in serum IL-17A levels compared to controls (P<0.001), with a significant association between serum IL-17A levels and lesion severity, but no significant correlation was observed between skin and serum responses (P>0.05). In conclusion, there was increased expression of both IL-17A and FoxP3, with FoxP3 being significantly more abundant than IL17A in the skin of scabies patients. Skin FoxP3 up-regulation has been linked to the severity of the condition.

Members of the Anopheles gambiae complex vary in their vector competence, and this is often attributed to behavioural differences. Similarly, there are differences in transmission capabilities of the zoophilic members of this complex despite exhibiting similar behaviours. Therefore, behavioural differences alone cannot fully explain vector competence variation within members of the An. gambiae complex. The immune system of mosquitoes plays a key role in determining susceptibility to parasite infection and consequently transmission capacity. This study aimed to examine variations in the immune response of An. arabiensis, An. merus and An. quadriannulatus, a major, minor, and non-vector respectively. The global epigenetic landscape was characterised and the expression of Defensin-1 and Gambicin was assessed in response to Gram-positive (Streptococcus pyogenes) and Gram-negative (Escherichia coli) bacterial infections. The effect of insecticide resistance in An. arabiensis on these aspects was also assessed. The immune system was stimulated by a blood-borne bacterial supplementation. The 5mC, 5hmC, m6A methylation levels and Histone Acetyl Transferase activity were assessed with commercial ELISA kits. The transcript levels of Defensin-1 and Gambicin were assessed by quantitative Real-Time Polymerase Chain Reaction. Species-specific differences in 5mC and m6A methylation existed both constitutively as well as post immune stimulation. The epigenetic patterns observed in the laboratory strains were largely conserved in F1 offspring of wild-caught adults. The methylation patterns in the major vector typically differed from that of the minor/non-vectors. The differences between insecticide susceptible and resistant An. arabiensis were more reflected in the expression of Defensin-1 and Gambicin. The expression of these peptides differed in the strains only after bacterial stimulation. Anopheles merus and An. quadriannulatus expressed significantly higher levels of antimicrobial peptides, both constitutively and after immune stimulation. These findings suggest molecular variations in the immune response of members of the An. gambiae complex.

The Leishmania life cycle alternates between promastigotes, found in the sandfly, and amastigotes, found in mammals. When an infected sandfly bites a host, promastigotes are engulfed by phagocytes (i.e., neutrophils, dendritic cells, and macrophages) to establish infection. When these phagocytes die or break down, amastigotes must be re-internalized to survive within the acidic phagolysosome and establish disease. To define host kinase regulators of Leishmania promastigote and amastigote uptake and survival within macrophages, we performed an image-based kinase regression screen using a panel of 38 kinase inhibitors with unique yet overlapping kinase targets. We also targeted inert beads to complement receptor 3 (CR3) or Fcγ receptors (FcR) as controls by coating them with complement/C3bi or IgG respectively. Through this approach, we identified several putative host kinases that regulate receptor-mediated phagocytosis and/or the uptake of L. amazonensis. Findings included kinases previously implicated in Leishmania uptake (such as Src family kinases (SFK), Abl family kinases (ABL1/c-Abl, ABL2/Arg), and spleen tyrosine kinase (SYK)), but we also uncovered many novel kinases. Our methods also predicted host kinases necessary for promastigotes to convert to amastigotes or for amastigotes to survive within macrophages. Overall, our results suggest that the concerted action of multiple interconnected networks of host kinases are needed over the course of Leishmania infection, and that the kinases required for the parasite's life cycle may differ substantially depending on which receptors are bound and the life cycle stage that is internalized. In addition, using our screen, we identified kinases that appear to preferentially regulate the uptake of parasites over beads, indicating that the methods required for Leishmania to be internalized by macrophages may differ from generalized phagocytic mechanisms. Our findings are intended to be used as a hypothesis generation resource for the broader scientific community studying the roles of kinases in host-pathogen interactions.

Malaria, a parasitic infection caused by the genus Plasmodium, results to over 20 million reported cases annually worldwide. Most individuals exhibit various symptoms, and blood analysis plays a crucial role in determining the appropriate treatment approach. This study discusses various hematologic complications associated with different Plasmodium species. A review of scientific databases including PubMed, Science Direct, Web of Science, Scopus, EMBASE, Magiran, SID, IranMedex was conducted using standard keywords such as Plasmodium, malaria, anemia and blood disorders (hematologic disorder) between 2000 and 2024. The review focused on articles pertaining to clinical trials, prospective cohort, retrospective, cross-sectional and case-control studies. Articles evaluating the effects of malaria on blood cells and indices, with target groups including human and animals, were included. Articles not written in English or Farsi were excluded. Our review revealed that, apart from iron deficiency anemia and vascular dysfunction contributed in part by adhesion of infected RBC to endothelium, decreases in hematocrit and hemoglobin levels, as part of pancytopenia and thrombocytopenia, are characteristic of Plasmodium infection. Additionally, the occurrence of inflammation due to the release of inflammatory cytokines and complement activation can complicate the clinical features of malaria in individuals with hematologic conditions.