Search Results (53)

Background/Objectives: Niclosamide is an U.S. Food and Drug Administration (FDA)-approved antihelminthic drug with a long-established safety profile and demonstrated in vitro antiviral activity against Zika virus. Its evaluation for systemic indications has been limited by its poor oral bioavailability. This Phase I study assessed whether oral administration of the approved niclosamide formulation could achieve plasma concentrations comparable to those with reported antiviral activity. Methods: This single-center, open-label, randomized, two-period crossover Phase I study evaluated the safety, tolerability, and pharmacokinetics of oral niclosamide in healthy adult volunteers. Twelve participants received niclosamide 2 g once daily for three consecutive days under fed or fasted conditions, followed by crossover after a 14-day washout period. Plasma niclosamide concentrations were quantified using a validated Liquid Chromatography-Mass Spectrometry (LC–MS/MS) assay, and pharmacokinetic parameters were derived via non-compartmental analysis. Safety assessments included adverse event monitoring, clinical laboratory testing, vital signs, electrocardiograms, and physical examinations. Results: Nine participants per protocol completed the study. Niclosamide was safe and well tolerated under both fed and fasted conditions, with only mild to moderate, transient adverse events and no serious or severe events. Systemic exposure was markedly higher following fed administration, with mean maximum observed plasma concentration (C_max) and Area Under the Curve (AUC) values several-fold greater than those observed under fasted conditions. Under fed conditions, mean plasma niclosamide concentrations exceeded the reported in vitro Zika virus half-maximal inhibitory concentration (IC₅₀₎ (0.22 µM) for approximately 9 h post-dose on both Day 1 and Day 3. Fasted administration did not consistently achieve this exposure threshold. No unexpected accumulation was observed with repeated once-daily dosing. Conclusions: Oral niclosamide administered at the approved daily dose of 2 g is safe and well tolerated in healthy volunteers. Administration with food substantially enhances systemic exposure and transiently achieves plasma concentrations associated with in vitro antiviral activity against Zika virus. These findings support further development of optimized niclosamide formulations to achieve sustained systemic exposure for antiviral therapeutic applications. Full article

Gastric nematodes can cause severe diarrheal diseases of waterfowl and threaten waterfowl health and productivity. The immune response mechanism of the host against this parasite is unclear. We investigated the transcriptomic changes, immune related pathways and adaptive molecular responses in infected ducks. RNA sequencing of the gastric tissues of infected and control ducks was followed by differential expression using DESeq2, and functional enrichment and protein–protein interaction networks were constructed. There were 1983 differentially expressed genes (DEGs), including 1317 upregulated genes and 666 downregulated genes. GO and KEGG analyses showed considerable enrichment in immune response, extracellular matrix organization, and chemotaxis and cytokine-mediated signaling pathways, suggesting systemic immune activation and tissue remodeling. The protein–protein interaction network indicated several hub genes that might be central to host defense. Validation by RT-qPCR showed consistent expression trends for some DEGs. These results systematically outline the transcriptomic landscape of ducks infected with Eustrongylides tubifex, offering new insights into host–parasite interactions and immune modulation. The results enhance our understanding of anti-helminth immunity in waterfowl and may inform strategies for disease control in poultry production. Full article

Dysphania ambrosioides, commonly known as epazote, is a medicinal plant of great relevance in traditional Latin American medicine. Its cultural roots and pharmacological properties have made it an object of study for phytochemical research. An artificial intelligence (AI) tool was utilized to assist in reviewing scientific information regarding D. ambrosioides. An initial search was conducted in the Scopus database using the keywords epazote, D. ambrosioides, anti-helminthic, antioxidant, and antimicrobial, which yielded a total of 814 publications. To select the most relevant articles, this AI tool based on natural language processing (available online and free of charge) was applied, which analyzed the keywords that appeared in the titles and abstracts of the works and clustered them, leading to a reduction of 86.73% in the number of studies. D. ambrosioides stands out for its rich composition of bioactive compounds, which give the plant a wide range of therapeutic properties, including antiparasitic activity, through which it is effective against several parasites, such as helminths and protozoa, due to its schistosomicidal, nematocidal and antimalarial action. Additionally, it has shown antimicrobial, antioxidant, and anticancer properties as it contains compounds that help fight cell damage caused by free radicals. Epazote represents a rich source of compounds with a wide therapeutic range. However, much research is required to understand the mechanisms of action of these compounds and to evaluate their safety and efficacy in clinical trials. Full article

Fasciolosis is a neglected tropical disease caused by helminth parasites of the genus Fasciola spp., including Fasciola hepatica (F. hepatica) and Fasciola gigantica (F. gigantica), being a major zoonotic problem of human and animal health. Its control with antihelminthics is becoming ineffective due to the increase in parasite resistance. Developing new therapeutic protocols is crucial to a deeper knowledge of the molecular bases in the host–parasite interactions. The high-throughput omics technologies have dramatically provided unprecedented insights into the complexity of the molecular host–parasite crosstalk. MicroRNAs (miRNAs) are key players as critical regulators in numerous biological processes, modifying the gene expression of cells by degradation of messenger RNA (mRNA), regulating transcription and translation functions, protein positioning, cell cycle integrity, differentiation and apoptosis. The large-scale exploration of miRNAs, including the miRNome, has offered great scientific knowledge of steps in fasciolosis, further scrutinizing the pathogenesis, the growth and development of their strains and their interaction with the host for the survival of the different parasite stages. This review compiles the updated knowledge related to miRNAs involved in fasciolosis and the generated miRNome, highlighting the importance of these key molecules in the host–parasite interactions and the pathogenesis of Fasciola spp. directing towards the development of new biotherapeutic protocols for the control of fasciolosis. Full article

Background/Objectives: Ivermectin gained widespread attention as the “miracle drug” during the coronavirus disease 2019 (COVID-19) pandemic. Its inclusion in the 21st World Health Organization (WHO) List of Essential Medicines is attributed to its targeted anti-helminthic response, high efficacy, cost-effectiveness and favorable safety profile. Since the late 2000s, this bio-inspired active pharmaceutical ingredient (API) gained renewed interest for its diverse therapeutic capabilities. However, producing ivermectin formulations does remain challenging due to its poor water solubility, resulting in low bioavailability after oral administration. Therefore, the transdermal drug delivery of ivermectin was considered to overcome these challenges, which are observed after oral administration. Methods: Ivermectin was incorporated in a nano-emulsion, nano-emulgel and a colloidal suspension as ivermectin-loaded nanoparticles. The nano-drug delivery vehicles were optimized, characterized and evaluated through in vitro membrane release studies, ex vivo skin diffusion studies and tape-stripping to determine whether ivermectin was successfully released from its vehicle and delivered transdermally and/or topically throughout the skin. This study concluded with cytotoxicity tests using the methyl thiazolyl tetrazolium (MTT) and neutral red (NR) assays on both human immortalized epidermal keratinocytes (HaCaT) and human immortalized dermal fibroblasts (BJ-5ta). Results: Ivermectin was successfully released from each vehicle, delivered transdermally and topically throughout the skin and demonstrated little to no cytotoxicity at concentrations that diffused through the skin. Conclusions: The type of nano-drug delivery vehicle used to incorporate ivermectin influences its delivery both topically and transdermally, highlighting the dynamic equilibrium between the vehicle, the API and the skin. Full article

Mutations in p53 and KRAS are seen in most cases of colon cancer. The impact of these mutations on signaling pathways related to cancer growth has been studied in depth, but relatively less is known on their effects on amino acid transporters in cancer cells. This represents a significant knowledge gap because amino acid nutrition in cancer cells profoundly influences macropinocytosis and ferroptosis, two processes with opposing effects on tumor growth. Here, we used isogenic colon cancer cell lines to investigate the effects of p53 deletion and KRAS activation on two amino acid transporters relevant to macropinocytosis (SLC38A5) and ferroptosis (SLC7A11). Our studies show that the predominant effect of p53 deletion is to induce SLC7A11 with the resultant potentiation of antioxidant machinery and protection of cancer cells from ferroptosis, whereas KRAS activation induces not only SLC7A11 but also SLC38A5, thus offering protection from ferroptosis as well as improving amino acid nutrition in cancer cells via accelerated macropinocytosis. Niclosamide, an FDA-approved anti-helminthic, blocks the functions of SLC7A11 and SLC38A5, thus inducing ferroptosis and suppressing macropinocytosis, with the resultant effective reversal of tumor-promoting actions of oncogenic changes in p53 and KRAS. These findings underscore the potential of this drug in colon cancer treatment. Full article

Ivermectin is a an anti-helminthic that is critical globally for both human and veterinary care. To the best of our knowledge, information available regarding the influence of ivermectin (IVM) on the gut microbiota has only been collected from diseased donors, who were treated with IVM alone or in combination with other medicines. Results thus obtained were influenced by multiple elements beyond IVM, such as disease, and other medical treatments. The research presented here investigated the impact of IVM on the gut microbial structure established in a Triple-SHIME^® (simulator of the human intestinal microbial ecosystem), using fecal material from three healthy adults. The microbial communities were grown using three different culture media: standard SHIME media and SHIME media with either soluble or insoluble fiber added (control, SF, ISF). IVM introduced minor and temporary changes to the gut microbial community in terms of composition and metabolite production, as revealed by 16S rRNA amplicon sequencing analysis, flow cytometry, and GC-MS. Thus, it was concluded that IVM is not expected to induce dysbiosis or yield adverse effects if administered to healthy adults. In addition, the donor’s starting community influences the relationship between IVM and the gut microbiome, and the soluble fiber component in feed could protect the gut microbiota from IVM; an increase in short-chain fatty acid production was predicted by PICRUSt2 and detected with IVM treatment. Full article

The existing treatment strategy for Schistosomiasis centers on praziquantel, a single drug, but its effectiveness is limited due to resistance and lack of preventive benefits. Thus, there is an urgent need for novel antischistosomal agents. Schistosoma glutathione S-transferase (GST) is an essential parasite enzyme, with a high potential for targeted drug discovery. In this study, we conducted a screening of compounds possessing antihelminth properties, focusing on their interaction with the Schistosoma mansoni glutathione S-transferase (SmGST) protein. We demonstrated the unique nature of SmGST in comparison to human GST. Evolutionary analysis indicated its close relationship with other parasitic worms, setting it apart from free-living worms such as C. elegans. Through an assessment of binding pockets and subsequent protein–ligand docking, we identified Scutiaquinone A and Scutiaquinone B, both naturally derived Perylenequinones, as robust binders to SmGST. These compounds have exhibited effectiveness against similar parasites and offer promising potential as antischistosomal agents. Full article

Levamisole is an anti-helminthic drug with immunomodulatory properties that is added to cocaine to increase its potency and weight. Levamisole-adulterated cocaine (LAC) may cause an antineutrophil cytoplasmic antibody (ANCA)-associated systemic small vessel vasculitis (AAV). We aimed to characterize the phenotype of persons developing pulmonary-renal syndrome (PRS) in LAC-induced AAV and summarize its treatment and outcomes. Pubmed and Web of Science were searched (until September 2022). Reports that described co-existing diffuse alveolar hemorrhage and glomerulonephritis in an adult (age ≥ 18) with confirmed or suspected LAC exposure were included. Reports, demographics, clinical and serologic features, treatment and outcome characteristics were extracted. Of the 280 records identified, eight met the inclusion criteria, including eight unique cases. Persons were aged 22–58 years, and 50% were women. Cutaneous involvement occurred in only half of the cases. Other associated vasculitis findings and serologies were heterogeneous. All patients received immunosuppression with steroids, with cyclophosphamide and rituximab commonly added. We concluded that PRS could occur from LAC-induced AAV. Distinguishing LAC-induced AAV from primary AAV is challenging as clinical and serologic presentations overlap. Asking about cocaine use is requisite in persons presenting with PRS to guide diagnosis and appropriately counsel on cocaine cessation in conjunction with immunosuppression as treatment. Full article

Dalbergia melanoxylon Guill. & Perr (Fabaceae) is widely utilized in the traditional medicine of East Africa, showing effects against a variety of ailments including microbial infections. Phytochemical investigation of the root bark led to the isolation of six previously undescribed prenylated isoflavanones together with eight known secondary metabolites comprising isoflavanoids, neoflavones and an alkyl hydroxylcinnamate. Structures were elucidated based on HR-ESI-MS, 1- and 2-D NMR and ECD spectra. The crude extract and the isolated compounds of D. melanoxylon were tested for their antibacterial, antifungal, anthelmintic and cytotoxic properties, applying established model organisms non-pathogenic to humans. The crude extract exhibited significant antibacterial activity against Gram-positive Bacillus subtilis (97% inhibition at 50 μg/mL) and antifungal activity against the phytopathogens Phytophthora infestans, Botrytis cinerea and Septoria tritici (96, 89 and 73% at 125 μg/mL, respectively). Among the pure compounds tested, kenusanone H and (3R)-tomentosanol B exhibited, in a panel of partially human pathogenic bacteria and fungi, promising antibacterial activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and Mycobacterium showing MIC values between 0.8 and 6.2 μg/mL. The observed biological effects support the traditional use of D. melanoxylon and warrant detailed investigations of its prenylated isoflavanones as antibacterial lead compounds. Full article

Calendula officinalis Linn. (CO) is a popular medicinal plant from the plant kingdom’s Asteraceae family that has been used for millennia. This plant contains flavonoids, triterpenoids, glycosides, saponins, carotenoids, volatile oil, amino acids, steroids, sterols, and quinines. These chemical constituents confer multifaceted biological effects such as anti-inflammatory, anti-cancer, antihelminthic, antidiabetes, wound healing, hepatoprotective, and antioxidant activities. Additionally, it is employed in cases of certain burns and gastrointestinal, gynecological, ocular, and skin conditions. In this review, we have discussed recent research from the last five years on the therapeutic applications of CO and emphasized its myriad capabilities as a traditional medicine. We have also elucidated CO’s molecular mechanisms and recent clinical studies. Overall, this review intends to summarize, fill in the gaps in the existing research, and provide a wealth of possibilities for researchers working to validate traditional claims and advance the safe and effective use of CO in treating various ailments. Full article

Traditional medicines are nature’s gift and our native heritage, which play a vital role in maintaining a disease-free life. Artemisia vestita Wall. ex Besser (family: Asteraceae), popularly known as “Kubsha” or “Russian wormwood”, is a highly enriched folklore medicine with wound- healing, antiphlogistic, antifebrile, antifeedant, anti-helminthic, antimicrobial, antiviral, antitumor, and antiproliferative potential attributed to the presence of various volatile and non-volatile secondary metabolites. A systematic and extensive review of the literature on A. vestita was carried out via the Web of Science, PubMed, INMEDPLAN, EMBASE, Google Scholar, and NCBI, as well as from several websites. The highly relevant literature contained in 109 references was selected for further inclusion in this review. A total of 202 bioactive compounds belonging to different chemical classes such as terpenoids, coumarins, flavonoids, alkaloids, acetylenes, tannins, carotenoids, and sterols have been reported in A. vestita, which are responsible for different pharmacological activities. The chemical structures obtained from the PubChem and Chem Spider databases were redrawn using the software Chem Draw^® version 8.0. This review paper summarizes the distribution, botanical description, phytochemistry, pharmacological activities, and conservation of A. vestita, which will assist scientists for further investigation. Extensive studies on the active constituents, pharmaceutical standardization, mode of action, and sustainable conservation of A. vestita are needed to further explore its wound-healing and allied medicinal properties. Full article

The existence of eosinophils was documented histopathologically in the first half of the 19th century. However, the term “eosinophils” was first used by Paul Ehrlich in 1878. Since their discovery and description, their existence has been associated with asthma, allergies, and antihelminthic immunity. Eosinophils may also be responsible for various possible tissue pathologies in many eosinophil-associated diseases. Since the beginning of the 21st century, the understanding of the nature of this cell population has undergone a fundamental reassessment, and in 2010, J. J. Lee proposed the concept of “LIAR” (Local Immunity And/or Remodeling/Repair), underlining the extensive immunoregulatory functions of eosinophils in the context of health and disease. It soon became apparent that mature eosinophils (in line with previous morphological studies) are not structurally, functionally, or immunologically homogeneous cell populations. On the contrary, these cells form subtypes characterized by their further development, immunophenotype, sensitivity to growth factors, localization, role and fate in tissues, and contribution to the pathogenesis of various diseases, including asthma. The eosinophil subsets were recently characterized as resident (rEos) and inflammatory (iEos) eosinophils. During the last 20 years, the biological therapy of eosinophil diseases, including asthma, has been significantly revolutionized. Treatment management has been improved through the enhancement of treatment effectiveness and a decrease in the adverse events associated with the formerly ultimately used systemic corticosteroids. However, as we observed from real-life data, the global treatment efficacy is still far from optimal. A fundamental condition, “sine qua non”, for correct treatment management is a thorough evaluation of the inflammatory phenotype of the disease. We believe that a better understanding of eosinophils would lead to more precise diagnostics and classification of asthma subtypes, which could further improve treatment outcomes. The currently validated asthma biomarkers (eosinophil count, production of NO in exhaled breath, and IgE synthesis) are insufficient to unveil super-responders among all severe asthma patients and thus give only a blurred picture of the adepts for treatment. We propose an emerging approach consisting of a more precise characterization of pathogenic eosinophils in terms of the definition of their functional status or subset affiliation by flow cytometry. We believe that the effort to find new eosinophil-associated biomarkers and their rational use in treatment algorithms may ameliorate the response rate to biological therapy in patients with severe asthma. Full article

Tectona grandis is a traditional Dai medicine plant belonging to the Lamiaceae family, which can be used to treat malaria, inflammation, diabetes, liver disease, bronchitis, tumors, cholelithiasis, jaundice, skin disease and as an anti-helminthic. To find more novel therapeutic agents contained in this medicinal plant, the antioxidant, anti-inflammatory and anti-diabetic activities of T. grandis methanolic extract, fractions and compounds were evaluated. In this study, 26 compounds were isolated from the leaves and branches of T. grandis. Their structures were identified based on extensive spectral experiments, including NMR, ESI-MS and comparison with published spectral data. Among them, compounds 1–2, 4–6, 9–14 and 16–22 were reported for the first time for this plant. The antioxidant activity screening results showed that compounds 5, 15 and 23 had potent antioxidant capacities, with SC₅₀ values from 0.32 to 9.92 µmol/L, 0.92 to 1.10 mmol Trolox/L and 1.02 to 1.22 mmol Trolox/L for DPPH, ABTS and FRAP, respectively. In addition, their anti-inflammatory effects were investigated by releasing TNF-α, IL-1β and IL-6 through the use of mouse monocytic macrophages (RAW 264.7). Compounds 1, 13, 18 and 23 had the effects of reducing the expression of inflammatory factors. Compounds 13 and 18 were reported for the first time for their anti-inflammatory activities. Furthermore, the methanolic extract (ME), petroleum ether extract (PEE) and EtOAc extract (EAE) of T. grandis showed significant glucose uptake activities; compounds 21 and 23 significantly promoted glucose uptake of 3T3-L1 adipocytes at 40 µM. Meanwhile, compounds 4, 5 and 7 showed significant inhibitory activities against α-glucosidase, with IC₅₀ values of 14.16 ± 0.34 µmol/L, 19.29 ± 0.26 µmol/L and 3.04 ± 0.08 µmol/L, respectively. Compounds 4 and 5 were reported for the first time for their α-glucosidase inhibitory activities. Our investigation explored the possible therapeutic material basis of T. grandis to prevent oxidative stress and related diseases, especially inflammation and diabetes. Full article

Retama monosperma L. (Boiss.) or Genista monosperma L. (Lam.), known locally as “R’tam”, is a spontaneous and annual herb that belongs to the Fabaceae family. It is native to the Mediterranean regions, specifically in the desert areas and across the Middle Atlas in Morocco. This plant has been extensively used in folk medicine and it is rich in bioactive compounds, including polyphenols, flavonoids, and alkaloids. Current research efforts are focusing on the development of novel natural drugs as alternatives to various organic and non-organic chemical products from Retama monosperma. In addition, extract, and isolated compounds obtained from different parts of the chosen plant have been described to exhibit multiple biological and pharmacological properties such as antioxidant, anti-aging, anti-inflammatory, antihypertensive, anti-helminthic, disinfectant, diuretic, and hypoglycemic effects. The plant-derived extract also acts as an antimicrobial agent, which is highly efficient in the treatment of bacterial, viral, and fungal infections. Its antiproliferative effects are associated with some mechanisms, such as the inhibition of cell cycle arrest and apoptosis. In light of these assessments, we critically highlight the beneficial effects of the flowers, stems, seeds extracts, and isolated compounds from R. monosperma (L.) Boiss in human health care, industrial, and other applications, as well as the possible ways to be employed as a potential natural source for future drug discovery. Full article