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Keywords = helminthic therapy

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20 pages, 611 KB  
Review
A Review on Phytochemistry, Ethnopharmacology, and Antiparasitic Potential of Mangifera indica L.
by Diana Mendonça, Yen-Zhi Tan, Yi-Xin Lor, Yi-Jing Ng, Abolghasem Siyadatpadah, Chooi-Ling Lim, Roghayeh Norouzi, Roma Pandey, Wenn-Chyau Lee, Ragini Bodade, Guo-Jie Brandon-Mong, Ryan V. Labana, Tajudeen O. Jimoh, Ajoy Kumar Verma, Tadesse Hailu, Shanmuga S. Sundar, Anjum Sherasiya, Sónia M. R. Oliveira, Ana Paula Girol, Veeranoot Nissapatorn and Maria de Lourdes Pereiraadd Show full author list remove Hide full author list
Pharmaceuticals 2025, 18(10), 1576; https://doi.org/10.3390/ph18101576 - 18 Oct 2025
Viewed by 2466
Abstract
Parasitic infections remain a major global health challenge, particularly in resource-limited settings where they are closely tied to poverty and inadequate sanitation. The increasing emergence of drug resistance and the limited accessibility of current therapies highlight the urgent need for novel, safe, and [...] Read more.
Parasitic infections remain a major global health challenge, particularly in resource-limited settings where they are closely tied to poverty and inadequate sanitation. The increasing emergence of drug resistance and the limited accessibility of current therapies highlight the urgent need for novel, safe, and affordable alternatives. Mangifera indica L. (mango), a widely cultivated fruit tree deeply rooted in traditional medicine, has long been used to treat conditions symptomatic of parasitic diseases, including fever, diarrhea, and dysentery. Phytochemical investigations have revealed a rich spectrum of bioactive compounds, notably mangiferin, phenolic compounds and terpenoids, which exhibit antimicrobial, antioxidant, and immunomodulatory activities. This review critically synthesizes evidence on the antiparasitic potential of M. indica against protozoa, such as Plasmodium, Leishmania, Trypanosoma, Toxoplasma gondii, Entamoeba histolytica, and free-living amoebae, as well as helminths. Strongest evidence exists for malaria and helminth infections, where both crude extracts and isolated compounds demonstrated significant activity in vitro and in vivo. Encouraging but limited findings are available for leishmaniasis and trypanosomiasis, while data on toxoplasmosis and amoebiasis remain largely speculative. Variations in efficacy across studies are influenced by plant parts and extraction methods, with ethanolic extracts and mangiferin often showing superior results. Despite promising findings, mechanistic studies, standardized methodologies, toxicological evaluations, and clinical trials are scarce. Future research should focus on elucidating molecular mechanisms, exploring synergistic interactions with existing drugs, and leveraging advanced delivery systems to enhance bioavailability. Full article
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21 pages, 2253 KB  
Review
Role of the Th2-like Immune Response in Obesity: IL-4 as a Metabolic Regulator and IL-13 as an Effector of Muscle Energy Metabolism
by Lucía A. Méndez-García, Helena Solleiro-Villavicencio, Nallely Bueno-Hernández, Arturo Cérbulo-Vázquez, Galileo Escobedo, Marcela Esquivel-Velázquez and Miguel A. Fonseca-Sánchez
Biomedicines 2025, 13(9), 2208; https://doi.org/10.3390/biomedicines13092208 - 9 Sep 2025
Cited by 1 | Viewed by 1562
Abstract
The Th2 immune response, associated with allergic diseases and helminth infections, has emerged as a significant modulator of metabolic processes in adipose and liver tissues. Th2 cytokines, such as IL-4, IL-5, and IL-13, regulate energy metabolism, insulin resistance, and obesity-related issues. IL-4 and [...] Read more.
The Th2 immune response, associated with allergic diseases and helminth infections, has emerged as a significant modulator of metabolic processes in adipose and liver tissues. Th2 cytokines, such as IL-4, IL-5, and IL-13, regulate energy metabolism, insulin resistance, and obesity-related issues. IL-4 and IL-13 play significant roles, while IL-5 mainly recruits eosinophils in visceral fat. IL-4 influences lipid metabolism via STAT6, promoting adipogenesis, lipolysis, and reducing leptin levels, thereby improving insulin resistance or inducing white adipose browning in the absence of leptin. IL-13 affects glucose metabolism by lowering gluconeogenesis and enhancing glucose control and increases energy expenditure in muscles during exercise via STAT3. Emerging therapies include recombinant cytokines, exosomes, and monoclonal antibodies targeting IL-4/IL-13 or IL-5, which are mostly approved for the treatment of allergic diseases. Their use in metabolic disorders is largely unexplored. Overall, Th2 cytokines are promising targets for obesity and metabolic diseases but require dedicated trials to assess benefits and risks. Full article
(This article belongs to the Special Issue The Role of Cytokines in Health and Disease: 3rd Edition)
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7 pages, 2744 KB  
Case Report
Dirofilaria repens in the Spermatic Cord of a 5-Year-Old Boy: A Rare Pediatric Case in Italy
by Alessandro Franzò, Andrea Marino, Benedetto Maurizio Celesia, Roberto Bruno, Pieralba Catalano, Sebastiano Cacciaguerra, Stefano Reale, Bruno Santi Cacopardo and Giuseppe Nunnari
Trop. Med. Infect. Dis. 2025, 10(7), 184; https://doi.org/10.3390/tropicalmed10070184 - 29 Jun 2025
Viewed by 1000
Abstract
We report the case of a 5-year-old boy from a Sri Lankan migrant family in Catania, Italy, diagnosed with a Dirofilaria repens infection in the spermatic cord. The child presented with pain and swelling in the left inguinal area. Initial evaluation suggested orchiepididymitis, [...] Read more.
We report the case of a 5-year-old boy from a Sri Lankan migrant family in Catania, Italy, diagnosed with a Dirofilaria repens infection in the spermatic cord. The child presented with pain and swelling in the left inguinal area. Initial evaluation suggested orchiepididymitis, which was treated unsuccessfully with amoxicillin/clavulanate and NSAIDs. As symptoms worsened, torsion of the Morgagni hydatid was considered. An exploratory surgery revealed a firm mass in the left spermatic cord. Histopathological examination of the excised lesion showed fragments of a helminth within a granulomatous inflammatory reaction. Subsequent PCR analysis detected D. repens DNA. The patient fully recovered after surgical excision of the mass. Given the increasing incidence of human dirofilariasis, D. repens should be considered in the differential diagnosis of unexplained subcutaneous or inguinal nodules, especially in patients with a relevant travel history. This case highlights the importance of accurate diagnosis to avoid unnecessary invasive procedures or prolonged antimicrobial therapies. It represents one of the youngest pediatric cases with genital involvement reported in Italy, a country that accounts for half of the cases in Europe. Full article
(This article belongs to the Section Vector-Borne Diseases)
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13 pages, 1436 KB  
Case Report
Cutaneous Larva Migrans Refractory to Therapy with Ivermectin: Case Report and Review of Implicated Zoonotic Pathogens, Epidemiology, Anthelmintic Drug Resistance and Therapy
by Bart J. Currie, Jessica Hoopes and Bonny Cumming
Trop. Med. Infect. Dis. 2025, 10(6), 163; https://doi.org/10.3390/tropicalmed10060163 - 12 Jun 2025
Cited by 1 | Viewed by 7900
Abstract
Cutaneous larva migrans (CLM) is attributed to zoonotic infection with animal hookworm larvae penetrating the human skin, usually the feet and legs. There is, however, a broad range of differential diagnoses, with the implicated hookworm species usually remaining speculative. Single-dose ivermectin is the [...] Read more.
Cutaneous larva migrans (CLM) is attributed to zoonotic infection with animal hookworm larvae penetrating the human skin, usually the feet and legs. There is, however, a broad range of differential diagnoses, with the implicated hookworm species usually remaining speculative. Single-dose ivermectin is the most recommended current therapy, with repeat ivermectin doses sometimes required. With the massive global expansion of macrocytic lactone use in both livestock and companion animals, ivermectin resistance is being increasingly described in both helminths and ectoparasites. A case of CLM involving the foot of a healthy 37-year-old is described, with the failure of two doses of ivermectin 15 mg (240 μg/kg) a week apart. This occurred in the context of a remote work environment in tropical Australia with both companion animals (dogs and cats) and wildlife exposed to antiparasitic agents including ivermectin. A combination regimen of multiple doses of albendazole and ivermectin was curative. Parasites with multidrug resistance being described from animals now include hookworms in dogs which are resistant to pyrantel, benzimidazoles such as mebendazole and ivermectin. For relapsed CLM we now recommend a combination of ivermectin and albendazole therapy. This report supports the critical role for a One Health/Planetary Health approach to surveillance and response for emerging zoonoses and antimicrobial resistance in human and animal pathogens. This requires support for systematic approaches to foster and normalize communications and collaborations between human and animal health professionals, environmental scientists and ecologists and First Nations scientists who are the holders of Indigenous knowledge. Full article
(This article belongs to the Section One Health)
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20 pages, 3643 KB  
Article
High-Throughput Screens of Repurposing Hub and DOS Chemical Libraries Reveal Compounds with Novel and Potent Inhibitory Activity Against the Essential Non-Neuronal Acetylcholinesterase of Schistosoma mansoni (SmTAChE)
by Patrick J. Skelly and Akram A. Da’dara
Int. J. Mol. Sci. 2025, 26(11), 5415; https://doi.org/10.3390/ijms26115415 - 5 Jun 2025
Viewed by 1126
Abstract
Schistosomiasis is a parasitic disease caused by helminth parasites of the genus Schistosoma, affecting >200 million people worldwide. Current schistosomiasis treatment relies on a single drug, praziquantel, highlighting the urgent need for new therapies. We have identified a non-neuronal tegumental acetylcholinesterase from [...] Read more.
Schistosomiasis is a parasitic disease caused by helminth parasites of the genus Schistosoma, affecting >200 million people worldwide. Current schistosomiasis treatment relies on a single drug, praziquantel, highlighting the urgent need for new therapies. We have identified a non-neuronal tegumental acetylcholinesterase from Schistosoma mansoni (SmTAChE) as a rational and molecularly defined drug target. Molecular modeling reveals significant structural differences between SmTAChE and human AChE, suggesting the potential for identifying parasite-specific inhibitors. Here, we screened recombinant SmTAChE (rSmTAChE) against two chemical libraries: the Broad Institute Drug Repurposing Hub (5440 compounds) and the Diversity-Oriented Synthesis (DOS)-A library (3840 compounds). High-throughput screening identified 116 hits from the Repurposing Hub (2.13% hit rate) and 44 from the DOS-A (1.14% hit rate) library that inhibited rSmTAChE ≥60% at 20 µM. Dose–response assays using both rSmTAChE and recombinant human AChE (rHsAChE) revealed 19 Repurposing Hub compounds (IC50: 0.4–24 µM) and four DOS-A scaffolds (IC50: 13–29 µM), with higher selectivity for rSmTAChE. Selective inhibitors such as cepharanthine, primaquine, mesalazine, and embelin emerged as promising candidates for further evaluation in schistosomiasis treatment. These 23 newly identified selective hits provide a foundation for the further development of novel anti-schistosome therapies. Full article
(This article belongs to the Section Molecular Biology)
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33 pages, 1014 KB  
Systematic Review
The Global Prevalence of and Factors Associated with Parasitic Coinfection in People Living with Viruses: A Systematic Review and Meta-Analysis
by Yan Ge, Huaman Liu, Ningjun Ren, Abdul Qadeer, Ian Kim B. Tabios, Ian Kendrich C. Fontanilla, Lydia R. Leonardo, Banchob Sripa and Guofeng Cheng
Pathogens 2025, 14(6), 534; https://doi.org/10.3390/pathogens14060534 - 27 May 2025
Cited by 4 | Viewed by 6338
Abstract
Coinfection with parasites and viruses can exacerbate disease transmission, outcomes and therapy. This study searched the Web of Science, PubMed, Scopus and JSTOR databases for publications on the prevalence of parasitic coinfection in people living with viruses from 1 January 2005 to 30 [...] Read more.
Coinfection with parasites and viruses can exacerbate disease transmission, outcomes and therapy. This study searched the Web of Science, PubMed, Scopus and JSTOR databases for publications on the prevalence of parasitic coinfection in people living with viruses from 1 January 2005 to 30 April 2022, and 356 studies were included and systematically reviewed. A meta-analysis was performed to assess the global prevalence of and factors potentially associated with parasitic infection (helminths and protozoa) in virus-infected people, and the infection burden was estimated. A variety of parasites (29 families, 39 genera, and 63 species) and viruses (8 kinds) were identified. The prevalence of parasitic coinfection in (all) virus-infected people was estimated to be 21.34% (95% CI 17.58–25.10, 5593 of 29,190 participants) and 34.13% (95% CI 31.32–36.94, 21,243/76,072 participants) for helminths and protozoa, respectively. Specially, in human immunodeficiency virus (HIV)-infected people, the global prevalence was 19.96% (95% CI 16.18–23.74) for helminths and 34.18% (95% CI 31.33–37.03) for protozoa, respectively. The global prevalence of protozoa was 41.79% (95% CI 15.88–67.69) in hepatitis B virus (HBV)-infected people and 17.75% (95% CI 3.54–31.95) in DENV-infected people, respectively. The global burden of parasitic infections in HIV-infected people was 7,664,640 for helminths and 13,125,120 for protozoa, respectively, and that in HBV- and dengue virus (DENV)-infected people was 137,019,428 and 629,952, respectively. The prevalence of parasitic coinfection at the family, genus, and species levels in virus- or HIV-infected people were comprehensively estimated and further analyzed by subgroups. Among the most commonly identified parasites, the five helminth genera with the highest prevalence in HIV-infected people were Schistosoma (12.46%, 95% CI 5.82–19.10), Ascaris (7.82%, 95% CI 6.15–9.49), Strongyloides (5.43%, 95% CI 4.11–6.74), Trichuris (4·82%, 95% CI 2.48–7.17) and Ancylostoma (2.79%, 95% CI 1.32–4.27), whereas the top five protozoan genera were Toxoplasma (48.85%, 95% CI 42.01–55.69), Plasmodium (34.96%, 95% CI 28.11–41.82), Cryptosporidium (14.27%, 95% CI 11.49–17.06), Entamoeba (12.33%, 95% CI 10.09–14.57) and Blastocystis (10.61%, 95% CI 6.26–14.97). The prevalence of parasitic coinfection in virus-infected people was associated with income level. The findings provide valuable global epidemiological information for informing normative guidance, improving surveillance, and developing public healthcare strategies. Full article
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31 pages, 4011 KB  
Review
Progress and Prospects of Triazoles in Advanced Therapies for Parasitic Diseases
by Jaime A. Isern, Renzo Carlucci, Guillermo R. Labadie and Exequiel O. J. Porta
Trop. Med. Infect. Dis. 2025, 10(5), 142; https://doi.org/10.3390/tropicalmed10050142 - 20 May 2025
Cited by 6 | Viewed by 2978
Abstract
Parasitic diseases represent a severe global burden, with current treatments often limited by toxicity, drug resistance, and suboptimal efficacy in chronic infections. This review examines the emerging role of triazole-based compounds, originally developed as antifungals, in advanced antiparasitic therapy. Their unique structural properties, [...] Read more.
Parasitic diseases represent a severe global burden, with current treatments often limited by toxicity, drug resistance, and suboptimal efficacy in chronic infections. This review examines the emerging role of triazole-based compounds, originally developed as antifungals, in advanced antiparasitic therapy. Their unique structural properties, particularly those of 1,2,3- and 1,2,4-triazole isomers, facilitate diverse binding interactions and favorable pharmacokinetics. By leveraging innovative synthetic approaches, such as click chemistry (copper-catalyzed azide–alkyne cycloaddition) and structure-based design, researchers have repurposed and optimized triazole scaffolds to target essential parasite pathways, including sterol biosynthesis via CYP51 and other novel enzymatic routes. Preclinical studies in models of Chagas disease, leishmaniasis, malaria, and helminth infections demonstrate that derivatives like posaconazole, ravuconazole, and DSM265 exhibit potent in vitro and in vivo activity, although their primarily static effects have limited their success as monotherapies in chronic cases. Combination strategies and hybrid molecules have demonstrated the potential to enhance efficacy and mitigate drug resistance. Despite challenges in achieving complete parasite clearance and managing potential toxicity, interdisciplinary efforts across medicinal chemistry, parasitology, and clinical research highlight the significant potential of triazoles as components of next-generation, patient-friendly antiparasitic regimens. These findings support the further optimization and clinical evaluation of triazole-based agents to improve treatments for neglected parasitic diseases. Full article
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13 pages, 1974 KB  
Review
Navigating the Parasitic Landscape: Insights into Infection Patterns and Public Health Strategies in West Africa
by Patrick F. Ayeh-Kumi, Patience B. Tetteh-Quarcoo, Isabella N. A. Aryee, Peter Nii Apai Baddoo, James Teye Ocansey and Michael Kofi Otoboah
Trop. Med. Infect. Dis. 2025, 10(5), 125; https://doi.org/10.3390/tropicalmed10050125 - 6 May 2025
Cited by 2 | Viewed by 2721
Abstract
Parasitic infections remain a significant public health challenge in West Africa, contributing to high morbidity and mortality rates, economic burdens, and healthcare system strain. Malaria, soil-transmitted helminths, schistosomiasis, and other parasitic diseases persist due to environmental, socio-economic, and healthcare barriers. A systematic literature [...] Read more.
Parasitic infections remain a significant public health challenge in West Africa, contributing to high morbidity and mortality rates, economic burdens, and healthcare system strain. Malaria, soil-transmitted helminths, schistosomiasis, and other parasitic diseases persist due to environmental, socio-economic, and healthcare barriers. A systematic literature search was conducted using databases such as PubMed, Scopus, Web of Science, and Science Direct. Studies published between 2014 and 2024 were screened using predefined eligibility criteria. Cross-sectional and case–control studies reporting on prevalence, diagnostic techniques, and treatment of parasitic infections in West Africa were included. The Rayyan online platform was used for screening, and data extraction focused on study location, prevalence rates, diagnostic methods, and treatment regimens. This review identified the high prevalence rates of malaria, schistosomiasis, and soil-transmitted helminths across various West African countries. Co-infections were frequently reported, particularly among children and pregnant women. Diagnostic methods ranged from traditional microscopy to advanced molecular techniques, though accessibility remained a challenge in resource-limited settings. Treatment strategies, including artemisinin-based combination therapies for malaria and mass drug administration for helminths, showed varying efficacy due to reinfection risks and emerging drug resistance. Factors influencing transmission included environmental conditions, sanitation practices, socio-economic status, and healthcare access. Parasitic infections in West Africa continue to pose significant health and economic challenges. Integrated control programs, enhanced surveillance systems, improved access to diagnostics and treatment, and targeted public health interventions are essential for reducing disease burden. Further research is needed to evaluate the long-term impact of existing interventions and explore innovative solutions for parasite control and elimination. Full article
(This article belongs to the Special Issue Advances in Parasitic Neglected Tropical Diseases)
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14 pages, 608 KB  
Communication
Nematocidal Activity of a Variety of Plants Used in Mexico Against Strongyloides venezuelensis
by Joel H. Elizondo-Luévano, Abelardo Chávez-Montes, Antonio Muro, Belén Vicente-Santiago, Miroslava Kačániová, David G. García-Hernández, Aldo F. Bazaldúa-Rodríguez, Horacio Larqué-García, Uziel Castillo-Velázquez and Julio López-Abán
Parasitologia 2025, 5(2), 18; https://doi.org/10.3390/parasitologia5020018 - 23 Apr 2025
Cited by 1 | Viewed by 2209
Abstract
Strongyloidiasis represents a public health problem in tropical and subtropical regions. The medicinal plants demonstrate the potential of plants as a source of molecules with helminthic activity. In this research, we assessed the potential of five extracts medicinally used in Mexico against Strongyloides [...] Read more.
Strongyloidiasis represents a public health problem in tropical and subtropical regions. The medicinal plants demonstrate the potential of plants as a source of molecules with helminthic activity. In this research, we assessed the potential of five extracts medicinally used in Mexico against Strongyloides venezuelensis third-stage infective larvae (L3). Plant methanol (MeOH) extracts of Argemone mexicana (chicalote), Jatropha dioica (Sangre de Drago), Lippia graveolens (oregano), Thymus vulgaris (tomillo), and Kalanchoe daigremontiana (aranto) were prepared by the maceration technique. The toxicity of the extracts was evaluated in human red blood cells by the hemolysis test and in monkey kidney epithelial cells (Vero cells) using the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, we showed their antioxidant potential by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. The methanolic extracts of A. mexicana, J. dioica, L. graveolens, and T. vulgaris exhibited significant activity against L3 cultures at 72 and 96 h post-incubation. None of the extracts showed hemolytic effects on red cells or Vero cells. L. graveolens demonstrated the strongest antioxidant activity, with an EC50 of 19.80 µg/mL. Plant MeOH extracts used in this study showed a promising anthelmintic effect in vitro, making it a suitable candidate for future research in nematocidal therapies. Full article
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25 pages, 2772 KB  
Review
Natural Alternatives in the Treatment of Colorectal Cancer: A Mechanisms Perspective
by Karen Vanessa Fernandez-Muñoz, Cuauhtémoc Ángel Sánchez-Barrera, Marco Meraz-Ríos, Jose Luis Reyes, Eloy Andrés Pérez-Yépez, Maria Teresa Ortiz-Melo, Luis I. Terrazas and Monica Graciela Mendoza-Rodriguez
Biomolecules 2025, 15(3), 326; https://doi.org/10.3390/biom15030326 - 24 Feb 2025
Cited by 8 | Viewed by 6837
Abstract
Colorectal cancer (CRC) is one of the deadliest neoplasia. Intrinsic or acquired resistance is the main cause of failure of therapy regimens that leads to relapse and death in CRC patients. The widely used chemotherapeutic agent 5-fluorouracil (5-FU) remains the mainstay for therapeutic [...] Read more.
Colorectal cancer (CRC) is one of the deadliest neoplasia. Intrinsic or acquired resistance is the main cause of failure of therapy regimens that leads to relapse and death in CRC patients. The widely used chemotherapeutic agent 5-fluorouracil (5-FU) remains the mainstay for therapeutic combinations. Unfortunately, chemotherapeutic resistance and side effects are frequent events that compromise the success of these therapies; the dysregulation of enzymes that regulate 5-FU metabolism increases the expression and activity of efflux pumps. Additional tumor cell adaptations such as epithelial–mesenchymal transition (EMT), autophagy shaping of the tumor microenvironment, and inflammation contribute to chemoresistance. Finding new strategies and alternatives to enhance conventional chemotherapies has become necessary. Recently, the study of natural compounds has been gaining strength as an alternative to chemotherapeutics in different cancers. Curcumin, trimethylglycine, resveratrol, artemisinin, and some helminth-derived molecules, among others, are some natural compounds studied in the context of CRC. This review discusses the main benefits, mechanisms, advances, and dark side of conventional chemotherapeutics currently evaluated in CRC treatment. We also analyzed the landscape of alternative non-conventional compounds and their underlying mechanisms of action, which could, in the short term, provide fundamental knowledge to harness their anti-tumor effects and allow them to be used as alternative adjuvant therapies. Full article
(This article belongs to the Special Issue Natural Bioactives as Leading Molecules for Drug Development)
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18 pages, 5056 KB  
Article
A Small Intestinal Helminth Infection Alters Colonic Mucus and Shapes the Colonic Mucus Microbiome
by Thomas C. Mules, Francesco Vacca, Alissa Cait, Bibek Yumnam, Alfonso Schmidt, Brittany Lavender, Kate Maclean, Sophia-Louise Noble, Olivier Gasser, Mali Camberis, Graham Le Gros and Stephen Inns
Int. J. Mol. Sci. 2024, 25(22), 12015; https://doi.org/10.3390/ijms252212015 - 8 Nov 2024
Cited by 2 | Viewed by 3106
Abstract
Infecting humans with controlled doses of small intestinal helminths, such as human hookworm, is proposed as a therapy for the colonic inflammatory disease ulcerative colitis. Strengthening the colonic mucus barrier is a potential mechanism by which small intestinal helminths could treat ulcerative colitis. [...] Read more.
Infecting humans with controlled doses of small intestinal helminths, such as human hookworm, is proposed as a therapy for the colonic inflammatory disease ulcerative colitis. Strengthening the colonic mucus barrier is a potential mechanism by which small intestinal helminths could treat ulcerative colitis. In this study, we compare C57BL/6 mice infected with the small intestinal helminth Heligmosomoides polygyrus and uninfected controls to investigate changes in colonic mucus. Histology, gene expression, and immunofluorescent analysis demonstrate that this helminth induces goblet cell hyperplasia, and an upregulation of mucin sialylation, and goblet-cell-derived functional proteins resistin-like molecule-beta (RELM-β) and trefoil factors (TFFs), in the colon. Using IL-13 knockout mice, we reveal that these changes are predominantly IL-13-dependent. The assessment of the colonic mucus microbiome demonstrates that H. polygyrus infection increases the abundance of Ruminococcus gnavus, a commensal bacterium capable of utilising sialic acid as an energy source. This study also investigates a human cohort experimentally challenged with human hookworm. It demonstrates that TFF blood levels increase in individuals chronically infected with small intestinal helminths, highlighting a conserved mucus response between humans and mice. Overall, small intestinal helminths modify colonic mucus, highlighting this as a plausible mechanism by which human hookworm therapy could treat ulcerative colitis. Full article
(This article belongs to the Special Issue Functional Roles of Epithelial and Endothelial Cells)
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31 pages, 2991 KB  
Review
Unveiling Novel Insights in Helminth Proteomics: Advancements, Applications, and Implications for Parasitology and Beyond
by Nooshinmehr Soleymani, Soheil Sadr, Cinzia Santucciu, Shiva Dianaty, Narges Lotfalizadeh, Ashkan Hajjafari, Fatemeh Heshmati and Hassan Borji
Biologics 2024, 4(3), 314-344; https://doi.org/10.3390/biologics4030020 - 19 Sep 2024
Cited by 2 | Viewed by 5708
Abstract
Helminths have developed intricate mechanisms to survive and evade the host’s immune responses. Hence, understanding the excretory-secretory products (ESPs) by helminths is crucial for developing control tools, including drug targets, vaccines, and potential therapies for inflammatory and metabolic disorders caused by them. Proteomics, [...] Read more.
Helminths have developed intricate mechanisms to survive and evade the host’s immune responses. Hence, understanding the excretory-secretory products (ESPs) by helminths is crucial for developing control tools, including drug targets, vaccines, and potential therapies for inflammatory and metabolic disorders caused by them. Proteomics, the large-scale analysis of proteins, offers a powerful approach to unravel the complex proteomes of helminths and gain insights into their biology. Proteomics, as a science that delves into the functions of proteins, has the potential to revolutionize clinical therapies against parasitic infections that have developed anthelminthic resistance. Proteomic technologies lay a framework for accompanying genomic, reverse genetics, and pharmacokinetic approaches to provide more profound or broader coverage of the cellular mechanisms that underlie the response to anthelmintics. With the development of vaccines against helminth infections, proteomics has brought a major change to parasitology. The proteome of helminths can be analyzed comprehensively, revealing the complex network of proteins that enable parasite survival and pathogenicity. Furthermore, it reveals how parasites interact with hosts’ immune systems. The current article reviews the latest advancements in helminth proteomics and highlights their valuable contributions to the search for anthelminthic vaccines. Full article
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13 pages, 5751 KB  
Brief Report
Schistosoma japonicum sja-let-7 Inhibits the Growth of Hepatocellular Carcinoma Cells via Cross-Species Regulation of Col1α2
by Haoran Zhong, Bowen Dong, Danlin Zhu, Zhiqiang Fu, Jinming Liu, Guiquan Guan and Yamei Jin
Genes 2024, 15(9), 1165; https://doi.org/10.3390/genes15091165 - 4 Sep 2024
Cited by 2 | Viewed by 2166
Abstract
Liver fibrosis, a critical precursor to hepatocellular carcinoma (HCC), results from chronic liver injury and significantly contributes to HCC progression. Schistosomiasis, a neglected tropical disease, is known to cause liver fibrosis; however, this process can be modulated by schistosome-derived miRNAs. Previous studies from [...] Read more.
Liver fibrosis, a critical precursor to hepatocellular carcinoma (HCC), results from chronic liver injury and significantly contributes to HCC progression. Schistosomiasis, a neglected tropical disease, is known to cause liver fibrosis; however, this process can be modulated by schistosome-derived miRNAs. Previous studies from our laboratory have demonstrated that Schistosoma japonicum extracellular vesicles (EVs) deliver sja-let-7 to hepatic stellate cells, leading to the inhibition of Col1α2 expression and alleviation of liver fibrosis. Given the well-documented antifibrotic and antiproliferative properties of the let-7 miRNA family, this study aims to preliminarily investigate the effects of the sja-let-7/Col1α2 axis on BALB/c mice and HCC cell line SNU387, providing a basis for the potential application of parasite-derived molecules in HCC therapy. In the present study, schistosome-induced fibrosis datasets were analyzed to identify the role of Col1α2 in extracellular matrix organization. Pan-cancer analysis revealed that Col1α2 is upregulated in various cancers, including HCC, with significant associations with immune cell infiltration and clinical parameters, highlighting its diagnostic importance. Functional assays demonstrated that transfection with sja-let-7 mimics significantly reduced Col1α2 expression, inhibited HCC cell proliferation, migration, and colony formation. These findings suggest that sja-let-7, by targeting Col1α2, has the potential to serve as a therapeutic agent in HCC treatment. This study indicates the pivotal role of Col1α2 in liver fibrosis and HCC, and the promising therapeutic application of helminth-derived miRNAs. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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16 pages, 708 KB  
Review
Geohelminths: Use in the Treatment of Selected Human Diseases
by Magdalena Szuba, Weronika Stachera, Adrianna Piwko, Marianna Misiak, Renata Rutkevich, Marcin Sota, Lana Atrushi, Leyla Bennacer, Deborah Nzekea, Yen Ching Wu, Arya Taesung Kim, Subin Yu, Nash Ribeiro and Monika Dybicz
Pathogens 2024, 13(8), 703; https://doi.org/10.3390/pathogens13080703 - 20 Aug 2024
Cited by 3 | Viewed by 5035
Abstract
Research on the therapeutic use of parasites has been ongoing since the development of the “hygiene hypothesis”. Parasites can stimulate the Th2-dependent response and suppress the Th1-dependent response, which is intensified in many diseases, especially allergic and autoinflammatory ones. In this review, we [...] Read more.
Research on the therapeutic use of parasites has been ongoing since the development of the “hygiene hypothesis”. Parasites can stimulate the Th2-dependent response and suppress the Th1-dependent response, which is intensified in many diseases, especially allergic and autoinflammatory ones. In this review, we present the types of parasites used in helminth therapy and the range of diseases in which they may be useful. We also present the results of clinical trials conducted so far, which confirm the safety of such therapy and provide promising outcomes. Full article
(This article belongs to the Special Issue Immune Response of the Host and Vaccine Development—2nd Edition)
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Article
Trichinella spiralis Infection Inhibits the Efficacy of RBD Protein of SARS-CoV-2 Vaccination via Regulating Humoral and Cellular Immunity
by Feifan Zhu, Wenwen Zheng, Yiyan Gong, Jinyuan Zhang, Yihan Yu, Jixian Zhang, Mengjun Liu, Fei Guan and Jiahui Lei
Vaccines 2024, 12(7), 729; https://doi.org/10.3390/vaccines12070729 - 30 Jun 2024
Cited by 1 | Viewed by 2423
Abstract
Vaccines are the most effective and feasible way to control pathogen infection. Helminths have been reported to jeopardize the protective immunity mounted by several vaccines. However, there are no experimental data about the effect of helminth infection on the effectiveness of COVID-19 vaccines. [...] Read more.
Vaccines are the most effective and feasible way to control pathogen infection. Helminths have been reported to jeopardize the protective immunity mounted by several vaccines. However, there are no experimental data about the effect of helminth infection on the effectiveness of COVID-19 vaccines. Here, a mouse model of trichinosis, a common zoonotic disease worldwide, was used to investigate effects of Trichinella spiralis infection on the RBD protein vaccine of SARS-CoV-2 and the related immunological mechanism, as well as the impact of albendazole (ALB) deworming on the inhibitory effect of the parasite on the vaccination. The results indicated that both the enteric and muscular stages of T. spiralis infection inhibited the vaccine efficacy, evidenced by decreased levels of IgG, IgM, sIgA, and reduced serum neutralizing antibodies, along with suppressed splenic germinal center (GC) B cells in the vaccinated mice. Pre-exposure to trichinosis promoted Th2 and/or Treg immune responses in the immunized mice. Furthermore, ALB treatment could partially reverse the inhibitory effect of T. spiralis infection on the efficiency of the vaccination, accompanied by a restored proportion of splenic GC B cells. Therefore, given the widespread prevalence of helminth infections worldwide, deworming therapy needs to be considered when implementing COVID-19 vaccination strategies. Full article
(This article belongs to the Collection Vaccines against Infectious Diseases)
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