-
Environmental Science and Pollution... Dec 2023Widespread and improper use of various anthelmintics, genetic, and epidemiological factors has resulted in anthelmintic-resistant (AR) helminth populations in livestock.... (Review)
Review
Widespread and improper use of various anthelmintics, genetic, and epidemiological factors has resulted in anthelmintic-resistant (AR) helminth populations in livestock. This is currently quite common globally in different livestock animals including sheep, goats, and cattle to gastrointestinal nematode (GIN) infections. Therefore, the mechanisms underlying AR in parasitic worm species have been the subject of ample research to tackle this challenge. Current and emerging technologies in the disciplines of genomics, transcriptomics, metabolomics, and proteomics in livestock species have advanced the understanding of the intricate molecular AR mechanisms in many major parasites. The technologies have improved the identification of possible biomarkers of resistant parasites, the ability to find actual causative genes, regulatory networks, and pathways of parasites governing the AR development including the dynamics of helminth infection and host-parasite infections. In this review, various "omics"-driven technologies including genome scan, candidate gene, quantitative trait loci, transcriptomic, proteomic, and metabolomic approaches have been described to understand AR of parasites of veterinary importance. Also, challenges and future prospects of these "omics" approaches are also discussed.
Topics: Animals; Cattle; Sheep; Livestock; Proteomics; Nematoda; Nematode Infections; Anthelmintics; Goats; Gastrointestinal Diseases
PubMed: 38015400
DOI: 10.1007/s11356-023-31045-y -
Equine Veterinary Journal May 2024
Topics: Animals; Anthelmintics; Anti-Infective Agents; Drug Resistance
PubMed: 38453425
DOI: 10.1111/evj.14072 -
Journal of Wildlife Diseases Oct 2023Helminths, in particular eyeworms (Oxyspirura petrowi) and cecal worms (Aulonocephalus pennula), may be a factor influencing northern bobwhite (Colinus virginianus)... (Review)
Review
Helminths, in particular eyeworms (Oxyspirura petrowi) and cecal worms (Aulonocephalus pennula), may be a factor influencing northern bobwhite (Colinus virginianus) populations in Texas. Previous research has shown a discrepancy in helminth infections between the Rolling Plains and Rio Grande Plains of Texas, US, potentially caused by differences in intermediate host distribution and abundance. We explored an alternative hypothesis centered on plant diversity, given that many plants possess phytochemicals with anthelmintic properties. We predicted that plant diversity would be greater and bobwhite diet more diverse in the Rio Grande Plains than the Rolling Plains, which in turn would potentially expose bobwhites to more plants with anthelmintic properties and therefore result in lower parasite prevalence and intensity. We conducted a literature review of plant diversity, anthelmintic plants, and bobwhite diet in Texas to explore this hypothesis. We also quantified the relationship between helminth prevalence in bobwhites and latitude. We documented trends for higher plant species richness, greater number of anthelmintic plants, and more diverse bobwhite diet in the Rio Grande Plains compared to the Rolling Plains. In addition, we documented a trend for increasing helminth prevalence with latitude for eyeworms but not cecal worms. Our study provides circumstantial evidence supporting the plant-diversity hypothesis and warrants experimental testing.
Topics: Animals; Colinus; Prevalence; Bird Diseases; Thelazioidea; Anthelmintics
PubMed: 37846916
DOI: 10.7589/JWD-D-22-00124 -
International Journal of Pharmaceutics Nov 2023Thiabendazole is an anthelmintic drug used to treat strongyloidiasis (threadworm), cutaneous and visceral larva migrans, trichinosis, and other parasites. The active...
Thiabendazole is an anthelmintic drug used to treat strongyloidiasis (threadworm), cutaneous and visceral larva migrans, trichinosis, and other parasites. The active pharmaceutical ingredient is typically administered orally as tablets that should be chewed before swallowing. Current formulations combine the active ingredient with excipients, including sodium saccharinate as a sweetener. Thiabendazole's low aqueous solubility hinders fast dissolution and absorption through the mucous membranes. We sought to reformulate this medicine to improve both solubility and palatability. We utilized the possibility of protonation of the azole nitrogen atom and selected four different hydrogen donors: saccharin, fumaric, maleic, and oxalic acids. Solvothermal synthesis resulted in salts with each co-former, whereas neat and liquid-assisted grinding enabled the synthesis of additional formulations. Product formation was observed by powder X-ray diffraction. To better understand the structural basis of the proton transfer, we solved the crystal structures of the salts with saccharin, maleic acid, and oxalic acid using single-crystal X-ray diffraction. The structure of the salt with fumaric acid was solved by powder X-ray diffraction. We further characterized the salts with vibrational spectroscopic and thermoanalytical methods. We report a broad tunability of the aqueous solubility of thiabendazole by salt formation. Reformulation with maleic acid provided a 60-fold increase in solubility, while saccharin and oxalic acid gave a modest improvement. Fumaric acid resulted in a solid with only slightly higher solubility. Furthermore, saccharin is a sweetener, while the acids taste sour. Therefore, the salts formed also result in an intrinsic improvement of palatability. These results can inform new strategies for oral and chewable tablet formulations for treating helminthic infections.
Topics: Salts; Saccharin; Powders; Thiabendazole; X-Ray Diffraction; Solubility; Anti-Infective Agents; Sweetening Agents; Tablets; Anthelmintics; Oxalic Acid
PubMed: 37863447
DOI: 10.1016/j.ijpharm.2023.123516 -
Molecules (Basel, Switzerland) Sep 2023It is estimated that 250 million people worldwide are affected by schistosomiasis. Disease transmission is related to the poor sanitation and hygiene habits that affect... (Review)
Review
It is estimated that 250 million people worldwide are affected by schistosomiasis. Disease transmission is related to the poor sanitation and hygiene habits that affect residents of impoverished regions in tropical and subtropical countries. The main species responsible for causing disease in humans are , , and , each with different geographic distributions. Praziquantel is the drug predominantly used to treat this disease, which offers low effectiveness against immature and juvenile parasite forms. In addition, reports of drug resistance prompt the development of novel therapeutic approaches. Natural products represent an important source of new compounds, especially those obtained from plant sources. This review compiles data from several in vitro and in vivo studies evaluating various compounds and essential oils derived from plants with cercaricidal and molluscicidal activities against both juvenile and adult forms of the parasite. Finally, this review provides an important discussion on recent advances in molecular and computational tools deemed fundamental for more rapid and effective screening of new compounds, allowing for the optimization of time and resources.
Topics: Humans; Animals; Anthelmintics; Schistosoma haematobium; Biological Products; Schistosomiasis; Praziquantel; Schistosoma mansoni
PubMed: 37836650
DOI: 10.3390/molecules28196807 -
The FEBS Journal Nov 2023Transthyretin (TTR) is a carrier protein for thyroid hormone thyroxine (T ) in plasma, placental cytosol, and cerebrospinal fluid. While the potential toxicity of small...
Transthyretin (TTR) is a carrier protein for thyroid hormone thyroxine (T ) in plasma, placental cytosol, and cerebrospinal fluid. While the potential toxicity of small molecules that compete with T for binding to TTR should be carefully studied, these small molecules can also serve as anti-ATTR amyloidosis drugs by stabilizing the TTR structure. Here, we demonstrated that rafoxanide, an EU-approved anthelmintic drug for domesticated animals, binds to the T -binding site of TTR. An intrinsic fluorescence quenching assay showed that rafoxanide also binds to the thyroid hormone-related proteins, including serum albumin and thyroid hormone receptor β. Rafoxanide strongly inhibited TTR amyloidogenesis in fibrillization assay, but the binding of rafoxanide to TTR was interfered with in human plasma, probably due to interactions with thyroid hormone-related proteins. Protein crystallography provided clues for the optimization of binding affinity and selectivity. Our findings emphasize the importance of considering rafoxanide as both a possible thyroid-disrupting chemical and a lead compound for the development of new ATTR amyloidosis inhibitors.
Topics: Animals; Humans; Female; Pregnancy; Prealbumin; Rafoxanide; Placenta; Thyroid Hormones; Amyloidosis; Anthelmintics; Anti-Infective Agents
PubMed: 37522420
DOI: 10.1111/febs.16915 -
Experimental Cell Research Sep 2023Glioblastoma multiform (GBM), one of the most common, aggressive primary brain tumours, demonstrates resistance to radiotherapy and chemotherapy after surgical resection...
Glioblastoma multiform (GBM), one of the most common, aggressive primary brain tumours, demonstrates resistance to radiotherapy and chemotherapy after surgical resection and treatment failure. Metformin (MET) has been shown to suppress the proliferative capacity and invasion ability of GBM cells by activating AMPK and inhibiting mTOR, but the effective dose exceeded the maximum tolerated dose. Artesunate (ART) can exert certain anti-tumour effects by activating the AMPK-mTOR axis and inducing autophagy in tumour cells. Therefore, this study investigated the effects of MET combined with ART combination therapy on autophagy and apoptosis in GBM cells. MET combined with ART treatment effectively suppressed the viability, mono-cloning ability, migration and invasion capacities, as well as metastatic ability of GBM cells. The underlying mechanism involved modulation of the ROS-AMPK-mTOR axis, which was confirmed using 3-methyladenine and rapamycin to inhibit or promote the effects of MET combined with ART, respectively. The study findings suggest that MET used in combination with ART can induce autophagy-dependent apoptosis in GBM cells by activating the ROS-AMPK-mTOR pathway, providing a potential new treatment for GBM.
Topics: Humans; Metformin; Artesunate; AMP-Activated Protein Kinases; Glioblastoma; Reactive Oxygen Species; TOR Serine-Threonine Kinases; Apoptosis; Autophagy
PubMed: 37399981
DOI: 10.1016/j.yexcr.2023.113691 -
International Maritime Health 2024Schistosomiasis, caused by Schistosoma trematode worms, represents a significant global health challenge. This review offers a thorough examination of the disease's... (Review)
Review
Schistosomiasis, caused by Schistosoma trematode worms, represents a significant global health challenge. This review offers a thorough examination of the disease's epidemiology, transmission dynamics, diagnostic modalities, and treatment options. Diagnostic techniques encompass direct parasitological methods, immunological assays, DNA/RNA detection, and biomarker utilization, each with distinct advantages and limitations. There is an urgent need for improved diagnostic tools with enhanced sensitivity and specificity. Praziquantel remains the cornerstone of treatment, exhibiting efficacy against all Schistosoma species, while the potential of artemisin derivatives in combination therapy is also explored. In this review, we focus on the importance of praziquantel administration as the central aspect of schistosomiasis treatment, highlighting ongoing efforts to optimize its utilization for improved patient outcomes.
Topics: Praziquantel; Humans; Schistosomiasis; Anthelmintics; Animals; Schistosoma
PubMed: 38647059
DOI: 10.5603/imh.99453 -
Journal of Fish Diseases Sep 2023Dactylogyrus is one of the most common parasitic diseases in fish and causes huge losses to the aquaculture industry. With the advantages of safety, low toxicity and...
Dactylogyrus is one of the most common parasitic diseases in fish and causes huge losses to the aquaculture industry. With the advantages of safety, low toxicity and easy degradation, plant-derived drugs are ideal for the creation of green aquatic ingredients. The use of plant-derived drugs in aquaculture is limited by their low content and high processing costs, which is a challenge that can be solved by the chemical synthesis of plant-derived drugs. Eleven new coumarin derivatives were synthesized and assessed for their anthelmintic activity in this study. Among them, the derivative 7-((1-tosyl-1H-1,2,3-triazol-4-yl)methoxy)-2H-chromen-2-one (N11) has good anthelmintic activity and its mean anthelmintic efficacy against D. intermedius at a concentration of 10 μM reached 99.84%, which is even better than the anthelmintic activity of the positive control mebendazole. Further studies showed that N11 had concentration values of 3.31 and 1.94 μM for 50% maximal effect (EC ) against D. intermedius at 24 and 48 h, respectively. Furthermore, scanning electron microscopy revealed that N11 caused damage to D. intermedius. What is more noteworthy is that a substantial reduction in the ATP content of the parasite was observed following in vitro and in vivo administration of N11. Moreover, it was also found that N11 was able to inhibit the horizontal transmission of D. intermedius. Furthermore, real-time quantitative PCR analysis was utilized to determine the expression profile of genes associated with anti-inflammatory cytokines (IL-10, TGF-β and IL-4) in goldfish. In all examined organs, it was observed that the expression of anti-inflammatory cytokines increased subsequent to treatment with N11, according to the results. Thus, these results all suggest that N11 possesses good anthelmintic activity and is a potentially effective agent for the control of D. intermedius.
Topics: Animals; Parasites; Fish Diseases; Trematoda; Anthelmintics; Cytokines; Coumarins
PubMed: 37329523
DOI: 10.1111/jfd.13817 -
Frontiers in Veterinary Science 2023is distributed worldwide, causing substantial economic losses in the animal husbandry industry. Human fasciolosis is an emerging zoonosis in Andean America, Asia, and... (Review)
Review
is distributed worldwide, causing substantial economic losses in the animal husbandry industry. Human fasciolosis is an emerging zoonosis in Andean America, Asia, and Africa. The control of the disease, both in humans and animals, is based on using anthelmintic drugs, which has resulted in increased resistance to the most effective anthelmintics, such as triclabendazole, in many countries. This, together with the concerns about drug residues in food and the environment, has increased the interest in preventive measures such as a vaccine to help control the disease in endemic areas. Despite important efforts over the past two decades and the work carried out with numerous vaccine candidates, none of them has demonstrated consistent and reproducible protection in target species. This is at least in part due to the high immunomodulation capacity of the parasite, making ineffective the host response in susceptible species such as ruminants. It is widely accepted that a deeper knowledge of the host-parasite interactions is needed for a more rational design of vaccine candidates. In recent years, the use of emerging technologies has notably increased the amount of data about these interactions. In the present study, current knowledge of host-parasite interactions and their implication in vaccine development is reviewed.
PubMed: 38149297
DOI: 10.3389/fvets.2023.1270064