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Parasites & Vectors Nov 2023Alveolar echinococcosis (AE) is a lethal zoonosis caused by the fox tapeworm Echinococcus multilocularis. The disease is difficult to treat, and an effective therapeutic...
BACKGROUND
Alveolar echinococcosis (AE) is a lethal zoonosis caused by the fox tapeworm Echinococcus multilocularis. The disease is difficult to treat, and an effective therapeutic drug is urgently needed. Echinococcus multilocularis-associated angiogenesis is required by the parasite for growth and metastasis; however, whether antiangiogenic therapy is effective for treating AE is unclear.
METHODS
The in vivo efficacy of sunitinib malate (SU11248) was evaluated in mice by secondary infection with E. multilocularis. Enzyme-linked immunosorbent assays (ELISAs) were used to evaluate treatment effects on serum IL-4 and vascular endothelial growth factor A (VEGFA) levels after SU11248 treatment. Gross morphological observations and immunohistochemical staining were used to evaluate the impact of SU11248 on angiogenesis and the expression of pro-angiogenic factors VEGFA and VEGF receptor 2 (VEGFR2) in the metacestode tissues. Furthermore, the anthelmintic effects of SU11248 were tested on E. multilocularis metacestodes in vitro. The effect of SU11248 on the expression of VEGFA, VEGFR2, and phosphorylated VEGFR2 (p-VEGFR2) in liver cells infected with protoscoleces in vitro was detected by western blotting, reverse transcription quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA). The influence of SU11248 on endothelial progenitor cell (EPC) proliferation and migration was determined using CCK8 and transwell assays.
RESULTS
In vivo, SU11248 treatment markedly reduced neovascular lesion formation and substantially inhibited E. multilocularis metacestode growth in mice. Further, it exhibited high anti-hydatid activity as efficiently as albendazole (ABZ), and the treatment resulted in reduced protoscolex development. In addition, VEGFA, VEGFR2, and p-VEGFR2 expression was significantly decreased in the metacestode tissues after SU11248 treatment. However, no effect of SU11248 on serum IL-4 levels was observed. In vitro, SU11248 exhibited some anthelmintic effects and damaged the cellular structure in the germinal layer of metacestodes at concentrations below those generally considered acceptable for treatment (0.12-0.5 μM). Western blotting, RT-qPCR, and ELISA showed that in co-cultured systems, only p-VEGFR2 levels tended to decrease with increasing SU11248 concentrations. Furthermore, SU11248 was less toxic to Reuber rat hepatoma (RH) cells and metacestodes than to EPCs, and 0.1 μM SU11248 completely inhibited EPC migration to the supernatants of liver cell and protoscolex co-cultures.
CONCLUSIONS
SU11248 is a potential candidate drug for the treatment of AE, which predominantly inhibits parasite-induced angiogenesis. Host-targeted anti-angiogenesis treatment strategies constitute a new avenue for the treatment of AE.
Topics: Mice; Animals; Echinococcus multilocularis; Sunitinib; Vascular Endothelial Growth Factor A; Interleukin-4; Anthelmintics
PubMed: 37936208
DOI: 10.1186/s13071-023-05999-4 -
Journal of Parasitology Research 2023Goats are an important source of livelihood especially for smallholder communities. But gastrointestinal nematodosis is the greatest threats of goat production. A...
Goats are an important source of livelihood especially for smallholder communities. But gastrointestinal nematodosis is the greatest threats of goat production. A repeated cross-sectional and field experimental study design was conducted from December 2020 to August 2021 in Mirab Abaya district, with the aim of seasonal prevalence gastrointestinal nematode infection and assessment of anthelmintic resistance. A systematic random sampling strategy was used to select the study goats. The overall prevalence of gastrointestinal nematode infections of goats in the study area was 57.9% (95% CI: 54.4-61.4), of which 48.7% (95% CI: 43.7-53.7) and 67.2% (95% CI: 62.3-71.7) accounted to dry and wet seasons, respectively. The multivariable logistic regression analysis showed that season, age, sex, and flock size were significantly ( < 0.05) influenced the prevalence of gastrointestinal nematode infection of goats. The number of eggs per gram of faeces (EPG) was ranged from 100 to 2500. The overall mean egg per gram of faeces (EPG) was 461.1 ± 20.9. The mean EPG of wet season (532.7 ± 28.6) was higher than the dry season (362.3 ± 29.1). From faecal culture, 552 nematode larvae were recovered, and the most commonly identified nematode genera were (36.4%) that followed by (28.1%), (15.4%), (11.4), (5.4%), and (3.0%) species. From the anthelmintic resistance test in the field, the percentage reduction and 95% confidence limit of albendazole were 96% (84.2-99.0) and 97.0% (84.6-99.4) in dry and wet seasons, respectively. Here, the lower limit of 95% CI was less than 90% both in dry and wet seasons; and hence, albendazole was suspected for resistance development by gastrointestinal nematode. From a pooled faecal culture that collected from albendazole-treated goats, species was recovered. Therefore, due attention shall be by animal health professionals in the area in the use of albendazole. Animal health extension work to create awareness of how anthelmintic is used is helpful in reducing the risk. Changing the type of anthelmintic drug after using for some period will minimize the risk of anthelmintic resistance development.
PubMed: 37790288
DOI: 10.1155/2023/9945998 -
Veterinary Parasitology Oct 2023While anthelmintic treatment in young calves at first vaccination has not proven repeatedly effective in improving weight gain, there is evidence that treatment 90 day...
While anthelmintic treatment in young calves at first vaccination has not proven repeatedly effective in improving weight gain, there is evidence that treatment 90 day prior to weaning can enhance weight gain. This is difficult in most California cow/calf operations as after initial vaccination, calves are not again handled until preconditioning just prior to weaning. In an attempt to increase weight gain without the need for anthelmintic retreatment prior to preconditioning, 130 cow/calf pairs were stratified and assigned to three treatments of eprinomectin extended release injection (150 d efficacy), doramectin conventional injection, and an untreated control. Dams and calves received the same treatment. All treatments were commingled on irrigated pasture in Northern California. Sampling included weight (d 0, 75, and 145), fecal parasite (d 0, 14, 75, and 145), cow body condition score (d 0, 75, and 145), and cow pregnancy detection (days bred). Calf weight gain was not impacted by anthelmintic treatment (P = 0.44). However, cow weight gain was impacted by treatment (P < 0.01), with eprinomectin extended release showing higher weight gain than both doramectin conventional and the control (ADG kg 0.29, 0.23, 0.22, respectively). Cow weight gain differences were expressed greater toward the end of the trial than early on. Fecal egg count sampling failed to explain the difference in cow weight gain. Cow body condition score (P = 0.15) and days bred (P = 0.50) were not significantly affected by treatment. Although cow weight gain increased with an extended release anthelmintic treatment, this effect did not seem to be evident in suckling calves on high quality irrigated pastures in Northern California when compared to a conventional injectable and control treatments. Neither anthelmintic treatment appeared beneficial over a control when administered to suckling calves during initial vaccination at approximately 90 days of age.
PubMed: 37729829
DOI: 10.1016/j.vetpar.2023.110005 -
International Journal For Parasitology.... Aug 2023Ancylostoma caninum is the most common and important gastrointestinal nematode of dogs in the United States. Despite recent reports of A. caninum isolates resistant to...
Ancylostoma caninum is the most common and important gastrointestinal nematode of dogs in the United States. Despite recent reports of A. caninum isolates resistant to all classes of anthelmintics, little is known about the frequency and extent of this anthelmintic resistance. The study aim was to evaluate the efficacy of three commercial anthelmintic products in the treatment of foxhound dogs with a history of persistent A. caninum infections. In the first phase of this study, 35 foxhounds were randomly divided into three treatment groups: moxidectin/imidacloprid (MI), pyrantel pamoate/febantel/praziquantel (PFP), and emodepside/praziquantel (EP). Fecal samples were collected on day 0, 11, and 33 post-treatment (PT), and hookworm eggs were quantified using the mini-FLOTAC technique with a multiplication factor of 5 eggs per gram (EPG). The fecal egg count reduction (FECR) on day 11 PT was 65% (95% CI: 62%-68%) for MI, 69% (95% CI: 66%-72%) for PFP, and 96% (95% CI: 94%-97%) for EP. On day 33 PT, the FEC in the MI and PFP groups returned to almost the same values as on day 0, while in the EP group, the FEC remained low. Since MI and PFP proved ineffective, 32 animals were randomly divided into two groups in the second phase. They were treated either with a combination of MI/PFP or EP. The FECR at day 13 PT for the combination MI/PFP was 89% (95% CI: 87%-91%) and 99% (95% CI: 98%-99%) for EP. These results suggest that this A. caninum population is resistant to multiple anthelmintics. Although the combination of MI/PFP improved the anthelmintic efficacy, the FECR remained below 90%. Future studies are indicated to evaluate further the epidemiology of persistent hookworm infections in dogs in the US and to identify more effective treatment protocols as they pose a significant health risk to canine and human health.
Topics: Animals; Dogs; Ancylostoma; Ancylostomatoidea; Anthelmintics; Dog Diseases; Feces; Hookworm Infections; Nematoda; Parasite Egg Count; Praziquantel
PubMed: 37481894
DOI: 10.1016/j.ijpddr.2023.07.001 -
International Journal For Parasitology.... Dec 2023Reports of Ascaridia galli in laying hens in Europe have increased since the ban on conventional battery cages in 2012. As this parasite is transmitted directly via the... (Review)
Review
Reports of Ascaridia galli in laying hens in Europe have increased since the ban on conventional battery cages in 2012. As this parasite is transmitted directly via the faecal-oral route by parasite eggs containing a larva, it is reasonable to assume that the escalating problem is related to the increased exposure now occurring in modern welfare-friendly cage-free housing systems. On many farms, A. galli reappears in subsequent flocks, even though the birds have no access to the outdoors, biosecurity is high and empty houses are cleaned and disinfected during downtime. Since the egg production cycle lasts only ≈80 weeks and recombinant antigen production for helminth vaccines has not yet been solved, the development of a vaccine seems to be an unrealistic option. Therefore, disrupting the life cycle of the parasite by other means, including the strategic use of dewormers, appears to be the key to controlling infection. Of concern is that only one class of anthelmintics is licenced for poultry in Europe and that are usually administered indiscriminately through the birds' drinking water and often too late when the parasite is already established. If current calendar-based parasite control strategies are not changed, there is a risk that resistance to anthelmintics may develop, as has already been demonstrated with nematodes in livestock. We insist that treatments can be more effective and the risk of developing drug resistance can be mitigated if we invest in a better understanding of A. galli responses to more prudent and judicious use of anthelmintics. This review identifies knowledge gaps and highlights aspects of sustainable parasite control that require further research to support commercial egg producers.
Topics: Animals; Female; Ascaridia; Ascaridiasis; Chickens; Anthelmintics; Feces
PubMed: 37516026
DOI: 10.1016/j.ijpddr.2023.07.003 -
Cancer Biology & Therapy Dec 2023Pancreatic ductal adenocarcinoma (PDAC) is a type of cancer with high morbidity and mortality rates worldwide. Owing to a lack of therapeutic options, the overall...
Combination therapy of niclosamide with gemcitabine inhibited cell proliferation and apoptosis via Wnt/β-catenin/c-Myc signaling pathway by inducing β-catenin ubiquitination in pancreatic cancer.
Pancreatic ductal adenocarcinoma (PDAC) is a type of cancer with high morbidity and mortality rates worldwide. Owing to a lack of therapeutic options, the overall survival rate of patients with pancreatic cancer is low. Gemcitabine has been mainly used to treat patients with pancreatic cancer, but its efficacy is limited by chemoresistance. Therefore, a novel therapeutic agent for PDAC therapy is urgently needed. An anthelminthic drug, niclosamide, has already been researched in breast, lung, colon, and pancreatic cancer as an anti-cancer purpose by re-positioning its original purpose. However, combination therapy of gemcitabine and niclosamide was not informed yet. Here, we found that niclosamide co-administered with gemcitabine significantly inhibited tumorigenesis of pancreatic cancer compared to gemcitabine alone. Further, combining niclosamide and gemcitabine inhibited cell proliferation and induced apoptosis. Niclosamide induced cell cycle arrest at the G phase, and the levels of CDK4/6 and cyclin D1 were lowered after gemcitabine treatment. In addition, the combination of these chemical compounds more effectively increased the binding level of activated β-catenin destruction complex and β-catenin to enable phosphorylation, compared to gemcitabine alone. After phosphorylation, niclosamide - gemcitabine upregulated the ubiquitin level, which caused phosphorylated β-catenin to undergo proteasomal degradation; the combination was more potent than gemcitabine alone. Finally, the combination more effectively suppressed tumor growth in vivo, compared to gemcitabine alone. Altogether, our results indicate that niclosamide synergistically enhances the antitumor effect of gemcitabine in pancreatic cancer, by inducing the degradation of β-catenin with ubiquitination. Therefore, this drug combination can potentially be used in PDAC therapy.
Topics: Humans; Gemcitabine; Niclosamide; Proto-Oncogene Proteins c-myc; beta Catenin; Pancreatic Neoplasms; Cell Proliferation; Carcinoma, Pancreatic Ductal; Wnt Signaling Pathway; Ubiquitination; Apoptosis; Cell Line, Tumor
PubMed: 37917550
DOI: 10.1080/15384047.2023.2272334 -
Annual Review of Genomics and Human... Aug 2023Continued advances in precision medicine rely on the widespread sharing of data that relate human genetic variation to disease. However, data sharing is severely limited... (Review)
Review
Continued advances in precision medicine rely on the widespread sharing of data that relate human genetic variation to disease. However, data sharing is severely limited by legal, regulatory, and ethical restrictions that safeguard patient privacy. Federated analysis addresses this problem by transferring the code to the data-providing the technical and legal capability to analyze the data within their secure home environment rather than transferring the data to another institution for analysis. This allows researchers to gain new insights from data that cannot be moved, while respecting patient privacy and the data stewards' legal obligations. Because federated analysis is a technical solution to the legal challenges inherent in data sharing, the technology and policy implications must be evaluated together. Here, we summarize the technical approaches to federated analysis and provide a legal analysis of their policy implications.
Topics: Humans; Privacy; Fenbendazole; Health Facilities; Information Dissemination; Policy
PubMed: 37253596
DOI: 10.1146/annurev-genom-110122-084756 -
Parasitology Oct 2023In June 2022, at the XXXII Conference of the Italian Society of Parasitology, the parallels of the main endoparasitic infections of horses and donkeys were discussed.... (Review)
Review
In June 2022, at the XXXII Conference of the Italian Society of Parasitology, the parallels of the main endoparasitic infections of horses and donkeys were discussed. Although these 2 species are genetically different, they can be challenged by a similar range of parasites (i.e. small and large strongyles, and spp.). Although equids can demonstrate some level of resilience to parasites, they have quite distinct helminth biodiversity, distribution and intensity among different geographical locations and breeds. Heavily infected donkeys may show fewer clinical signs than horses. Although parasite control is primarily provided to horses, we consider that there may be a risk of drug-resistance parasitic infection through passive infection in donkeys when sharing the same pasture areas. Knowing the possible lack of drug efficacy (<90 or 80%), it is advocated the use of selective treatment for both species based on fecal egg counts. Adult horses should receive treatment when the threshold exceeds 200–500 eggs per gram (EPG) of small strongyles. Moreover, considering that there are no precise indications in donkeys, a value >300 EPG may be a safe recommendation. We have highlighted the main points of the discussion including the dynamics of helminth infections between the 2 species.
Topics: Horses; Animals; Equidae; Horse Diseases; Parasite Egg Count; Helminthiasis; Helminths; Feces; Anthelmintics
PubMed: 37221816
DOI: 10.1017/S0031182023000525 -
International Journal of Oncology Nov 2023Chloroxylenol is the active ingredient of the antibacterial agent Dettol. The anticancer effect and underlying mechanisms of this compound and other common antimicrobial...
Chloroxylenol is the active ingredient of the antibacterial agent Dettol. The anticancer effect and underlying mechanisms of this compound and other common antimicrobial agents have not been clearly elucidated. In the present study, the effects of chloroxylenol, benzalkonium chloride, benzethonium chloride, triclosan and triclocarban on β‑catenin‑mediated Wnt signaling in colorectal cancer were evaluated using the SuperTOPFlash reporter assay. It was demonstrated that chloroxylenol, but not the other antimicrobial agents tested, inhibited the Wnt/β‑catenin signaling pathway by decreasing the nuclear translocation of β‑catenin and disrupting β‑catenin/T‑cell factor 4 complex, which resulted in the downregulation of the Wnt target genes Axin2, Survivin and Leucine‑rich G protein‑coupled receptor‑5. Chloroxylenol effectively inhibited the viability, proliferation, migration and invasion, and sphere formation, and induced apoptosis in HCT116 and SW480 cells. Notably, chloroxylenol attenuated the growth of colorectal cancer in the MC38 cell xenograft model and inhibited organoid formation by the patient‑derived cells. Chloroxylenol also demonstrated inhibitory effects on the stemness of colorectal cancer cells. The results of the present study demonstrated that chloroxylenol could exert anti‑tumor activities in colorectal cancer by targeting the Wnt/β‑catenin signaling pathway, which provided an insight into its therapeutic potential as an anticancer agent.
Topics: Humans; beta Catenin; Wnt Signaling Pathway; Anti-Infective Agents; Colorectal Neoplasms
PubMed: 37681484
DOI: 10.3892/ijo.2023.5569 -
Infection and Immunity Jul 2023Parasitic diseases are a major public health problem worldwide. Plant-derived products appear to be ideal candidates from a biotechnological perspective, being...
Parasitic diseases are a major public health problem worldwide. Plant-derived products appear to be ideal candidates from a biotechnological perspective, being sustainable and environmentally friendly. The antiparasitic properties of have been attributed to some of its components, including papain and other compounds that are concentrated in the latex and seeds. This study demonstrated a high and insignificantly different cysticidal activity of soluble extract that was obtained after the disruption of nontransformed wild-type (WT) cells as well as transformed papaya calluses (PC-9, PC-12, and PC-23) and papaya cell suspensions (CS-9, CS-12, and CS-23). , cell suspensions of CS-WT and CS-23 that had been previously lyophilized were tested with respect to their cysticidal effects, compared with those of three commercial antiparasitic drugs. CS-WT and CS-23 together reduced the number of cysticerci, the number of buds, and the percentage of calcified cysticerci in a similar extent to albendazole and niclosamide, whereas ivermectin was less effective. Mice were then orally immunized with CS-23 that expressed the anti-cysticercal KETc7 antigen (10 μg/mouse), CS-WT (10 mg/mouse), or both together to evaluate their preventive properties. CS-23 and CS-WT significantly reduced the expected parasite and increased the percentage of calcified cysticerci as well as recovery, being more effective when employed together. The results reported in this study support the feasibility of the development of an anti-cysticercosis vaccine from cells of in cultures, as they are a source of an anthelmintic, natural, and reproducible product.
Topics: Mice; Animals; Carica; Suspensions; Albendazole; Plant Extracts; Seeds
PubMed: 37341599
DOI: 10.1128/iai.00517-22