In vivo anthelmintic activity of Combretum mucronatum schumach & Thonn leaf extract against Haemonchus contortus in goats.

Parasitic infections with gastrointestinal nematodes are a serious problem for the health and welfare of domestic animals and negatively affect the economics of animal production. Haemonchus contortus is a haematophagous nematode of small ruminants responsible for significant mortality and morbidity. In addition, the widespread resistance to synthetic anthelmintic drugs emphasizes the urgent need of alternative treatment options against haemonchosis.

Phytochemical analysis and anthelmintic activity of Combretum mucronatum leaf extract against infective larvae of soil-transmitted helminths including ruminant gastrointestinal nematodes.

Background: Soil-transmitted helminths (STH) infect more than a quarter of the world's human population. In the absence of vaccines for most animal and human gastrointestinal nematodes (GIN), treatment of infections primarily relies on anthelmintic drugs, while resistance is a growing threat. Therefore, there is a need to find alternatives to current anthelmintic drugs, especially those with novel modes of action.

Anthelmintic Activities of Extract and Ellagitannins from Phyllanthus urinaria against Caenorhabditis elegans and Zoonotic or Animal Parasitic Nematodes.

The aerial parts of are used in traditional medicine in West Africa against helminthiasis, but their anthelmintic potential has not been evaluated until now. Within the current study, a hydroacetonic extract (AWE) and fractions and isolated ellagitannins from were, therefore, tested against and the larvae of the animal parasites and . Compounds 1:  - 13: , mainly representing ellagitannins, were isolated using different chromatographic methods, and their structures were elucidated by HR-MS and H/C-NMR.

Human immune response against filarial HSP70 and its role in the diagnosis of lymphatic filariasis.

A sensitive and specific diagnostic kit is crucial for the detection of human lymphatic filariasis at the early stage of infection as the existing diagnostic tools are inefficient and expensive. In the present study, we have cloned and expressed Brugia malayi HSP70 (BmHSP70) protein and characterized it as a potential antigen for diagnosis of the asymptomatic microfilariae stage of Wuchereria. bancrofti infection using ELISA, western blot, and bioinformatics tools.

Anthelmintic Agents from African Medicinal Plants: Review and Prospects.

Soil-transmitted helminthiasis affects more than 1.5 billion people globally and largely remains a sanitary problem in Africa. These infections place a huge economic burden on poor countries and affect livestock production, causing substantial economic losses and poor animal health.

Condensed tannins act as anthelmintics by increasing the rigidity of the nematode cuticle.

Tannins and tanniferous plant extracts have been discussed as sustainable means for helminth control in the past two decades in response to a dramatic increase of resistances towards standard anthelmintics. While their bioactivities have been broadly investigated in vitro and in vivo, less is known about their mode of action in nematodes, apart from their protein binding properties. In the current study we therefore investigated the impact of a phytochemically well characterized plant extract from Combretum mucronatum, known to contain procyanidins as the active compounds, on the model organism Caenorhabditis elegans.

The Anthelmintic Quassinoids Ailanthone and Bruceine a Induce Infertility in the Model Organism by an Apoptosis-like Mechanism Induced in Gonadal and Spermathecal Tissues.

In continuation of the search for new anthelmintic natural products, the study at hand investigated the nematicidal effects of the two naturally occurring quassinoids ailanthone and bruceine A against the reproductive system of the model nematode to pinpoint their anthelmintic mode of action by the application of various microscopic techniques. Differential Interference Contrast (DIC) and the epifluorescence microscopy experiments used in the presented study indicated the genotoxic effects of the tested quassinoids (c = 50 µM, c = 100 µM) against the nuclei of the investigated gonadal and spermathecal tissues, leaving other morphological key features such as enterocytes or body wall muscle cells unimpaired. In order to gain nanoscopic insight into the morphology of the gonads as well as the considerably smaller spermathecae of , an innovative protocol of polyethylene glycol embedding, ultra-sectioning, acridine orange staining, tissue identification by epifluorescence, and subsequent AFM-based ultrastructural data acquisition was applied.

Using Caenorhabditis elegans to produce functional secretory proteins of parasitic nematodes.

The expression of antigens in their immunologically-active form remains a challenge, both in the analysis of regulatory pathways exploited by parasitic nematodes or in the development of vaccines. Despite the success of native proteins to induce protective immunity, recombinant proteins expressed in bacteria, yeast or insect cells offer only limited protective capacities, presumably due to incorrect folding or missing complex posttranslational modifications. The present study investigates the feasibility of using the free-living nematode Caenorhabditis elegans as an alternative expression system for proteins found in the secretome of parasitic nematodes.

Structure and dynamics of UBA5-UFM1 complex formation showing new insights in the UBA5 activation mechanism.

Ubiquitin fold modifier 1 (UFM1) is an ubiquitin-like protein (Ubl) involved especially in endoplasmic stress response. Activation occurs via a three-step mechanism like other Ubls. Data obtained reveal that UFM1 regulates the oligomeric state of ubiquitin activating enzyme 5 (UBA5) to initiate the activation step.

Homozygous UBA5 Variant Leads to Hypomyelination with Thalamic Involvement and Axonal Neuropathy.

The enzyme ubiquitin-like modifier activating enzyme 5 (UBA5) plays an important role in activating ubiquitin-fold modifier 1 (UFM1) and its associated cascade. is widely expressed and known to facilitate the post-translational modification of proteins. Variants in and are involved in neurodevelopmental disorders with early-onset epileptic encephalopathy as a frequently seen disease manifestation.

Galectins from Onchocerca ochengi and O. volvulus and their immune recognition by Wistar rats, Gudali zebu cattle and human hosts.

Background: During the last two decades research on animal filarial parasites, especially Onchocerca ochengi, infecting cattle in savanna areas of Africa revealed that O. ochengi as an animal model has biological features that are similar to those of O. volvulus, the aetiological agent of human onchocerciasis.

Production of glycosylphosphatidylinositol-anchored proteins for vaccines and directed binding of immunoliposomes to specific cell types.

Background: Liposomes are highly useful carriers for delivering drugs or antigens. The association of glycosylphosphatidylinositol (GPI)-anchored proteins to liposomes potentially enhances the immunogenic effect of vaccine antigens by increasing their surface concentration. Furthermore, the introduction of a universal immunoglobulin-binding domain can make liposomes targetable to virtually any desired receptor for which antibodies exist.

A multilamellar nanoliposome stabilized by interlayer hydrogen bonds increases antimalarial drug efficacy.

Lipid particles for drug delivery can be modified to create multilayer vesicles with higher stability and improved cargo interaction. Here, we used lipids capable of forming hydrogen bonds instead of covalent bonds and designed stable vesicles-inside-vesicles with a high capacity of entrapping antimalarial drugs such as chloroquine (hydrophilic) and Artemisinin (lipophilic). In vitro treatment of the drug-sensitive P.

Interference with Pseudomonas aeruginosa Quorum Sensing and Virulence by the Mycobacterial Quinolone Signal Dioxygenase AqdC in Combination with the -Acylhomoserine Lactone Lactonase QsdA.

The nosocomial pathogen regulates its virulence via a complex quorum sensing network, which, besides -acylhomoserine lactones, includes the alkylquinolone signal molecules 2-heptyl-3-hydroxy-4(1)-quinolone ( quinolone signal [PQS]) and 2-heptyl-4(1)-quinolone (HHQ). subsp. , an emerging pathogen, is capable of degrading the PQS and also HHQ.

Review on medicinal plants and natural compounds as anti-Onchocerca agents.

Onchocerciasis is a filarial vector borne disease which affects several million people mostly in Africa. The therapeutic approach of its control was based on a succession of drugs which always showed limits. The last one: ivermectin is not the least.

The Untapped Pharmacopeic Potential of Helminths.

The dramatic rise in immunological disorders that occurs with socioeconomic development is associated with alterations in microbial colonization and reduced exposure to helminths. Excretory-secretory (E/S) helminth products contain a mixture of proteins and low-molecular-weight molecules representing the primary interface between parasite and host. Research has shown great pharmacopeic potential for helminth-derived products in animal disease models and even in clinical trials.

Onchocerca - infected cattle produce strong antibody responses to excretory-secretory proteins released from adult male Onchocerca ochengi worms.

Background: The front line molecules from filarial worms and other nematodes or helminthes are their Excretory-Secretory (ES) products. Their interaction with the host cells, proteins and immune system accounts for the skin and eye pathology or hyposensitivity observed in human onchocerciasis. ES products and adult worms' crude extracts from Onchocerca ochengi, a filarial nematode that infects the African zebu cattle, were utilized in the present study as a model for studying Onchocerca volvulus that causes river blindness in man.

Abnormal function of the UBA5 protein in a case of early developmental and epileptic encephalopathy with suppression-burst.

Early myoclonic epilepsy (EME) or Aicardi syndrome is one of the most severe epileptic syndromes affecting neonates. We performed whole exome sequencing in a sporadic case affected by EME and his parents. In the proband, we identified a homozygous missense variant in the ubiquitin-like modifier activating enzyme 5 (UBA5) gene, encoding a protein involved in post-translational modifications.

Transcriptome analysis reveals molecular anthelmintic effects of procyanidins in C. elegans.

Worldwide, more than 1 billion people are affected by infestations with soil-transmitted helminths and also in veterinary medicine helminthiases are a severe threat to livestock due to emerging resistances against the common anthelmintics. Proanthocyanidins have been increasingly investigated for their anthelmintic properties, however, except for an interaction with certain proteins of the nematodes, not much is known about their mode of action. To investigate the anthelmintic activity on a molecular level, a transcriptome analysis was performed in Caenorhabditis elegans after treatment with purified and fully characterized oligomeric procyanidins (OPC).

Phytochemical analysis and in vitro anthelmintic activity of Lophira lanceolata (Ochnaceae) on the bovine parasite Onchocerca ochengi and on drug resistant strains of the free-living nematode Caenorhabditis elegans.

Background: Onchocerciasis is one of the tropical neglected diseases (NTDs) caused by the nematode Onchocerca volvulus. Control strategies currently in use rely on mass administration of ivermectin, which has marked activity against microfilariae. Furthermore, the development of resistance to ivermectin was observed.

Anti-Onchocerca and Anti-Caenorhabditis Activity of a Hydro-Alcoholic Extract from the Fruits of Acacia nilotica and Some Proanthocyanidin Derivatives.

fruits with high tannin content are used in the northern parts of Cameroon as anti-filarial remedies by traditional healers. In this study, the hydro-alcoholic fruit extract (crude extract (CE)) and, one of the main constituents in its most active fractions, (+)-catechin-3--gallate (CG), as well as four related proanthocyanidins, (-)-epicatechin-3--gallate (ECG), (+)-gallocatechin (GC), (-)-epigallocatechin (EGC) and (-)-epigallocatechin-3--gallate (EGCG), were assessed for their potential in vitro anthelmintic properties against the free-living model organism and against the cattle filarial parasite . Worms were incubated in the presence of different concentrations of fruit extract, fractions and pure compounds.