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Aging Nov 2023Head and neck squamous cell carcinomas are the sixth most common malignant tumors worldwide. Tongue squamous cell carcinoma is a common malignant tumor of this type, and...
BACKGROUND
Head and neck squamous cell carcinomas are the sixth most common malignant tumors worldwide. Tongue squamous cell carcinoma is a common malignant tumor of this type, and it is associated with poor prognosis, a high rate of recurrence and a low survival rate. Plumbagin is derived from Plumbago zeylanica L, several studies report that plumbagin could inhibit cell, tumor metastasis, induce apoptosis in various cancer cells. Patient-derived xenograft (PDX) model can maintain the heterogeneity and microenvironment of human tumors, is a powerful research tool for developing potentially effective therapies for TSCC.
METHODS
Tumor tissues obtained from TSCC patients were implanted into immunodeficient mice to establish TSCC PDX models. Subsequently, the PDX models were used to evaluate the anti-tumor effects of plumbagin on TSCC. Furthermore, we conducted next-generation sequencing (NGS) and explored the mRNA expression profiles between the treatment and control groups. We selected eight mRNAs related to the characteristics and prognosis of TSCC patients for further analysis.
RESULTS
Plumbagin could inhibit the growth of TSCC PDX models and inhibit expression of Akt/mTOR pathway. In addition, plumbagin was shown to increase drug sensitivity to cisplatin. The eight mRNAs selected for further analysis, AXL, SCG5, VOPP1, DCBLD2 and DRAM1 are cancer-promoting genes, DUSP1, AQP5 and BLNK are cancer suppressor genes. And they were related to the diagnosis, growth, prognosis, and immune cell infiltration in TSCC patients.
CONCLUSION
Plumbagin exhibits an inhibitory effect on the growth of the PDX model of TSCC. Moreover, plumbagin enhances the inhibitory effects of cisplatin.
Topics: Humans; Animals; Mice; Cisplatin; Carcinoma, Squamous Cell; Tongue Neoplasms; Cell Proliferation; Head and Neck Neoplasms; Cell Line, Tumor; Tumor Microenvironment; Transcription Factors
PubMed: 37925175
DOI: 10.18632/aging.205175 -
Scientific Reports Dec 2023This research aims to study the anthelmintic properties of selected five (5) tropical plant extracts, ascertained margin of fish host safety in reference with...
This research aims to study the anthelmintic properties of selected five (5) tropical plant extracts, ascertained margin of fish host safety in reference with praziquantel, a commonly used chemo-therapeutics. Qualitative and quantitative analysis of Alligator pepper seeds (Aframomum melegueta), Moringa leaves (Moringa oleifera), Neem leaves (Azadirachta indica), Ginger bulbs (Zingiber officinale) and Garlic (Allium sativum) and their potencies in reference to praziquantel against Clarias gariepinus and different classes of helminth parasites were investigated. The results obtained show that the 70% ethanol extract had 80 to 100% presence of the phytochemical content, compared with the 100% aqueous and 100% ethanol extracts with 50 to 80% and 50 to 90%, respectively. Among the five tropical plants, the richest in saponin and flavonoids are alligator pepper and neem with alkaloids, tannin, flavonoid and saponin in ratios 1:1:3:9 and 1:1:4:3 respectively. While, moringa, garlic and ginger are rich in alkaloids with alkaloids, tannin, flavonoid and saponin in ratios, 8:1:10:1, 6:2:1:4 and 6:3:2:1, respectively. Aframomum melegueta and praziquantel showed above 70% potency (at 96 h LC) against all the classes of parasites; Wenyonia spp (cestode), Procamallanus spp (nematode), Tenuisentis spp (acanthocephalan), and Electrotaenia sp (cestode) as compared to the other plant extracts that showed above 70% potency (at 96 h LC) only against Electrotaenia spp. Sub-lethal Concentrations (96 h LC) of praziquantel and Aframomum melegueta on the juvenile fish host (12.36 mg/l and 9.9 mg/l respectively) were found to be 90.9% and 93.5% effective against adult Electrotaenia spp after 8 to 10 min of exposure. These concentrations were 78 to 85.7% and 89.7 to 88.4%, respectively, effective against the other classes of parasites after 18 to 25 min and 15 to 21 min of exposure. These concentrations were tested on the post juvenile of the fish to determine behavioral changes; there were no significant behavioral responses after 24 h of exposure. The effective concentrations indicate the widest margin of safety for the fish host.
Topics: Animals; Parasites; Tannins; Praziquantel; Anthelmintics; Plant Extracts; Alkaloids; Zingiber officinale; Zingiberaceae; Ethanol; Garlic; Fishes; Phytochemicals; Flavonoids; Saponins
PubMed: 38123590
DOI: 10.1038/s41598-023-48164-8 -
PLoS Pathogens Jul 2023Human schistosomiasis is a neglected tropical disease caused by Schistosoma mansoni, S. haematobium, and S. japonicum. Praziquantel (PZQ) is the method of choice for...
Human schistosomiasis is a neglected tropical disease caused by Schistosoma mansoni, S. haematobium, and S. japonicum. Praziquantel (PZQ) is the method of choice for treatment. Due to constant selection pressure, there is an urgent need for new therapies for schistosomiasis. Previous treatment of S. mansoni included the use of oxamniquine (OXA), a drug that is activated by a schistosome sulfotransferase (SULT). Guided by data from X-ray crystallography and Schistosoma killing assays more than 350 OXA derivatives were designed, synthesized, and tested. We were able to identify CIDD-0150610 and CIDD-0150303 as potent derivatives in vitro that kill (100%) of all three Schistosoma species at a final concentration of 71.5 μM. We evaluated the efficacy of the best OXA derivates in an in vivo model after treatment with a single dose of 100 mg/kg by oral gavage. The highest rate of worm burden reduction was achieved by CIDD -150303 (81.8%) against S. mansoni, CIDD-0149830 (80.2%) against S. haematobium and CIDD-066790 (86.7%) against S. japonicum. We have also evaluated the ability of the derivatives to kill immature stages since PZQ does not kill immature schistosomes. CIDD-0150303 demonstrated (100%) killing for all life stages at a final concentration of 143 μM in vitro and effective reduction in worm burden in vivo against S. mansoni. To understand how OXA derivatives fit in the SULT binding pocket, X-ray crystal structures of CIDD-0150303 and CIDD-0150610 demonstrate that the SULT active site will accommodate further modifications to our most active compounds as we fine tune them to increase favorable pharmacokinetic properties. Treatment with a single dose of 100 mg/kg by oral gavage with co-dose of PZQ + CIDD-0150303 reduced the worm burden of PZQ resistant parasites in an animal model by 90.8%. Therefore, we conclude that CIDD-0150303, CIDD-0149830 and CIDD-066790 are novel drugs that overcome some of PZQ limitations, and CIDD-0150303 can be used with PZQ in combination therapy.
Topics: Animals; Humans; Praziquantel; Oxamniquine; Schistosomiasis; Schistosoma mansoni; Combined Modality Therapy; Neglected Diseases; Schistosomiasis mansoni; Anthelmintics
PubMed: 37428793
DOI: 10.1371/journal.ppat.1011018 -
Microbiology Spectrum Aug 2023Schistosomiasis is a parasitic disease that afflicts approximately 250 million people worldwide. There is an urgent demand for new antiparasitic agents because...
Schistosomiasis is a parasitic disease that afflicts approximately 250 million people worldwide. There is an urgent demand for new antiparasitic agents because praziquantel, the only drug available for the treatment of schistosomiasis, is not universally effective and may derail current progress toward the WHO goal of eliminating this disease as a public health problem by 2030. Nifuroxazide (NFZ), an oral nitrofuran antibiotic, has recently been explored to be repurposed for parasitic diseases. Here, , , and studies were conducted to evaluate the activity of NFZ on Schistosoma mansoni. The study showed significant antiparasitic activity, with 50% effective concentration (EC) and 90% effective concentration (EC) values of 8.2 to 10.8 and 13.7 to 19.3 μM, respectively. NFZ also affected worm pairing and egg production and induced severe damage to the tegument of schistosomes. , a single oral dose of NFZ (400 mg/kg of body weight) to mice harboring either prepatent or patent S. mansoni infection significantly reduced the total worm burden (~40%). In patent infection, NFZ achieved a high reduction in the number of eggs (~80%), but the drug caused a low reduction in the egg burden of animals with prepatent infection. Finally, results from target fishing methods predicted that serine/threonine kinases could be one of the potential targets for NFZ in S. mansoni. Overall, the present study revealed that NFZ possesses antischistosomal properties, mainly in terms of egg burden reduction in animals with patent S. mansoni infection. The increasing recognition of the burden imposed by helminthiasis, associated with the limited therapeutic arsenal, has led to initiatives and strategies to research and develop new drugs for the treatment of schistosomiasis. One of these strategies is drug repurposing, which considers low-risk compounds with potentially reduced costs and shorter time for development. In this study, nifuroxazide (NFZ) was evaluated for its anti-Schistosoma mansoni potential through , , and studies. , NFZ affected worm pairing and egg production and induced severe damage to the tegument of schistosomes. , a single oral dose of NFZ (400 mg/kg) to mice harboring either prepatent or patent S. mansoni infection significantly reduced the total worm burden and egg production. investigations have identified serine/threonine kinases as a molecular target for NFZ. Collectively, these results implied that NFZ might be a potential therapeutic candidate for the treatment of schistosomiasis.
Topics: Animals; Mice; Schistosomicides; Schistosomiasis mansoni; Schistosoma mansoni; Schistosomiasis; Nitrofurans; Threonine; Serine
PubMed: 37409934
DOI: 10.1128/spectrum.01393-23 -
Pathogens (Basel, Switzerland) Feb 2024is a zoonotic parasitic nematode that lives in the ocular conjunctival sac of domestic and wild carnivores, lagomorphs, and humans, with spp. as its intermediate host....
is a zoonotic parasitic nematode that lives in the ocular conjunctival sac of domestic and wild carnivores, lagomorphs, and humans, with spp. as its intermediate host. At present, the important role that domestic dogs play in thelaziosis has been studied in many countries. However, Beijing, which is the first city in China to experience human thelaziosis, has not yet conducted a comprehensive epidemiological analysis of the disease. In this study, we analyzed risk factors (region, season, age, sex, breed, size, living environment, diet, country park travel history, immunization history, anthelmintic treatment history, and ocular clinical symptoms) associated with the prevalence of thelaziosis in domestic dogs in Beijing. The overall prevalence of in the study area was 3.17% (102/3215 domestic dogs; 95% CI 2.57-3.78%). The results of the risk factor analysis showed that thelaziosis in domestic dogs from Beijing was significantly correlated with regional distribution, seasonal distribution, country park travel history, and anthelmintic treatment history ( < 0.05). In summer and autumn, domestic dogs living in mountainous areas, with a history of country park travel and without deworming were 4.164, 2.382, and 1.438 times more infected with than those living in plain areas without a history of country park travel and with a history of deworming (OR = 4.164, OR = 2.382, OR = 1.438, respectively). -infected domestic dogs did not always show any ocular clinical symptoms, while symptomatic domestic dogs were mainly characterized by moderate symptoms. The results indicate that in summer and autumn, preventive anthelmintic treatment should be strengthened for domestic dogs with a country park travel history or those living in mountain areas. At the same time, we should be vigilant about taking domestic dogs to play in country parks or mountainous areas during summer and autumn because this may pose a potential risk of the owner being infected with .
PubMed: 38392904
DOI: 10.3390/pathogens13020166 -
Veterinary Parasitology Oct 2023Cyathostominae are ubiquitous to grazing horses and regarded the most prevalent internal parasite in the horse. Unfortunately, decades of indiscriminate use of...
Cyathostominae are ubiquitous to grazing horses and regarded the most prevalent internal parasite in the horse. Unfortunately, decades of indiscriminate use of anthelmintic drugs have resulted in the development of resistance in cyathostomins to all currently available drug groups, the most recent being a documented lack of efficacy to the macrocyclic lactones (ML). In vivo determination of anthelmintic resistance in horses most often utilises the faecal egg count reduction test (FECRT). Further, a shortened egg reappearance period (ERP) can indicate a change in response to the applied treatment and suggest an upcoming reduction of efficacy. Although both true resistance as demonstrated by the FECRT and shorter ERPs after ML treatment have now been shown in cyathostomins worldwide, the efficacy of ML as regards to cyathostomins in Sweden is currently unknown. The aim of the present study was therefore to determine FECRTs and ERPs after ivermectin (IVM) treatment in Swedish horses. Sixteen equestrian establishments with a minimum of six horses excreting at least 150 eggs per gram faeces (EPG) at screening were selected. For each establishment, FECRTs and ERPs were determined by collecting faecal samples prior to and 14 days after IVM treatment (200 µg/kg), and thereafter at weekly intervals for a total of eight weeks. All participants responded to a questionnaire detailing pasture management methods and anthelmintic routines.Questionnaire results showed that the majority of establishments (69%) only treated horses with anthelmintic drugs if indicated by faecal diagnostics and all of the establishments had a mean FECRT exceeding 99.0% and ERPs ranging from six to over eight weeks. The ERP was shown to increase with age as young individuals were shown to excrete cyathostomin eggs earlier after treatment compared with older horses (R = 0.21, p = 0.015). Riding schools, stud farms and those declaring not to use separate summer and winter paddocks had significantly shorter ERPs (p <0.01).In conclusion, retained ERPs and no confirmed resistance to IVM were found in Swedish equine establishments practising selective anthelmintic treatment, and supports the use of selective deworming regimens as a means of reducing the risk of anthelmintic resistance development.
PubMed: 37639919
DOI: 10.1016/j.vetpar.2023.110007 -
Helminthologia Sep 2023Oxyuriasis, caused by the nematode is one of the cosmopolitan intestinal infections of humans. commonly infects mice and it is morphologically similar to . Parasitic...
Oxyuriasis, caused by the nematode is one of the cosmopolitan intestinal infections of humans. commonly infects mice and it is morphologically similar to . Parasitic resistance reduces the efficiency of synthetic drugs and poses economic impacts on the dairy sector, thus necessitating novel anthelmintic agents. L. (Olive) is a bioactive plant with potent pharmacological activities. However, its effects on oxyurids are poorly known, and no studies are currently exploring olives' anthelmintic potential. In this study, we investigated the pharmacokinetic behaviors of leaves extract (OLE) and its phenolic compound oleuropein in mice infected with , in comparison with Albendazole (ABZ), a standard drug used to treat parasitic worms. Fecal flotation method was used to identify the infestation with eggs by examining the stool samples from mice. Infected animals were divided into 7 groups. 250 mg/kg, 500 mg/kg, and 1000 mg/kg doses of OLE, 5 mg/kg and 20 mg/kg doses of oleuropein, 10 mg/kg of ABZ and tap water were orally administered by gavage for 7 days during treatments. Drug efficacies and statistical differences between the treatments and controls were evaluated. Our results revealed 92.43 % efficacy of ABZ, similar to 92.19 % efficacy of 1000 mg/kg of OLE. At the same time, 250 mg/kg and 500 mg/kg concentrations of OLE remained 70.03 % and 63.18 % effective in reducing worm counts. Efficacy percentages of 5 mg/kg and 20 mg/kg of oleuropein were 9.27 % and 70.56 %, respectively. Statistical analysis of ABZ was significant compared to 1000 mg/kg of OLE, which was almost equal but insignificant. In general, our results confirm the anthelmintic potential of OLE and oleuropein against mice pinworms and open the way for targeted extraction of bioactive compounds from plants to optimize its use in human and veterinary medicine.
PubMed: 38152475
DOI: 10.2478/helm-2023-0025 -
Food Science & Nutrition Oct 2023An ionic liquid-based dispersive liquid-liquid microextraction (IL-DLLME) of 20 anthelmintic drugs followed and detected by liquid chromatography-tandem mass...
An ionic liquid-based dispersive liquid-liquid microextraction (IL-DLLME) of 20 anthelmintic drugs followed and detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed, optimized, and validated. The parameters affecting the anthelmintic extraction efficiencies such as selection of extraction solvent (ionic liquids), selection of disperser solvent, volume of extraction solvent, volume of disperser solvent, pH of the aqueous phase, extraction time, salt addition, and centrifugation time were optimized. Validation was conducted according to ISO/IEC 17025:2017 and Commission Implementing Regulation (EU) 2021/808 of 22 March 2021. Validation parameters such as calibration function, matrix effect, limit of detection (LOD), limit of quantification (LOQ), decision limit (CCα), accuracy, and precision were established. Coefficient of determination ( ) values ranging from .99938 to .99995 were obtained using the matrix calibration curve spiked at 0, 0.25, 1.0, 1.5, and 2.0 times MRL. The LODs and LOQs were calculated using the standard deviation of the response and the slopes of the calibration curves ranged from 0.35 to 26.1 μg/kg and from 1.2 to 87.0 μg/kg, respectively, and were dependent on calibration range. The CCα values ranged from 23 to 1022.0 μg/kg and are also dependent on the MRL concentration levels. The coefficient of variation (CV) values calculated are within the reproducibility range of 16%-30% adapted from the Horwitz Equation CV = 2 and ranged from 1.7% to 16.9%. The developed and validated and the standard QuEChERS method were compared. The IL-DLLME LC-MS/MS method was applied to 32 small stock (18 caprine [goat] and 14 ovine [sheep]) liver samples received from municipal abattoirs at Botswana National Veterinary Laboratory for the analysis of anthelmintic drug residues. The results obtained indicated that the anthelmintic drug residues were all below the detection capability, and therefore, the samples were passed as fit for human consumption.
PubMed: 37823093
DOI: 10.1002/fsn3.3568 -
Frontiers in Veterinary Science 2023Nowadays, the exclusive use of commercial anthelmintics for the treatment of gastrointestinal nematode infections in ruminants is less sustainable due to anthelmintic...
Nowadays, the exclusive use of commercial anthelmintics for the treatment of gastrointestinal nematode infections in ruminants is less sustainable due to anthelmintic resistance, as well as the problem of drug residues in animal products and the environment. Therefore, an integrated therapeutic approach is needed, including the search for alternatives to synthetic anthelmintic drugs. The aim of this study was to evaluate the possibility of using the essential oil of peppermint ( L.) in the control of gastrointestinal nematodes in sheep. For this purpose, the and anthelmintic efficacy of this oil and the toxic effects on the hosts were examined. In the egg hatch test, ovicidal activity varied from 21.0-90.3% depending on the concentration of essential oil used (0.0125, 0.025, 0.049, 0.195, 0.781, 3.125, 12.5, and 50 mg/mL). To some extent, anthelmintic efficacy was confirmed in the fecal egg count reduction test at a mean dose of 150 mg/kg, with an average reduction of nematode eggs of 26.9 and 46.0% at Days 7 and 14 after treatment, respectively. Furthermore, no toxic effects of applied oil were observed on sheep behavior, kidney, or liver function. The main compounds identified by gas chromatography-mass spectrometry analyzes were menthol (32.6%), menthone (22.0%), menthyl-acetate (10.0%), and isomenthone (9.39%). Due to their complex chemical compositions, numerous bioactive ingredients, and natural origin, herbal formulations represent a potentially valuable alternative for the control of gastrointestinal nematodes in sheep. In this context, the results of the present study showed that peppermint essential oil is one of the promising candidates. Further studies should be performed to collect more data on the safety profile of EO in treated animals to find the most appropriate formulation for use in field conditions and to test it against resistant gastrointestinal nematode populations.
PubMed: 37662995
DOI: 10.3389/fvets.2023.1232570 -
Reproductive Toxicology (Elmsford, N.Y.) Dec 2023Abamectin is a widely used pesticide and anthelmintic for humans and animals. Previous toxicological studies showed evidence of adverse effects on reproduction, but the...
Abamectin is a widely used pesticide and anthelmintic for humans and animals. Previous toxicological studies showed evidence of adverse effects on reproduction, but the findings were inconclusive. Abamectin is known to exhibit teratogenic activity, causing different malformations during developmental stages in rats and rabbits. The present work aims at combining reproductive and developmental toxicological assessments in a single study to evaluate the impact of abamectin on reproductive, fertility, and developmental functions. Abamectin was administered orally to 20 male and 20 female rats at doses of 0, 0.1, 1.0, and 2.0 mg/kg body weight. Abamectin exposure was prolonged for 11 weeks for males and 10 weeks for females before mating. Females were also treated during mating and pregnancy. In this study, treated animals were mated with untreated intact animals to further assess the potential sex sensitivity effect. The results demonstrate that male rats were more susceptible to general toxic effects such as decreased body weight and showed a more toxic effect on reproductive function and fertility at doses of 1.0 and 2.0 mg/kg/day. Furthermore, stages of gametogenesis and early fetal development are the most vulnerable of the reproductive process to endocrine disruptors' action, leading to changes in the estrous cycle in females and sperm quality in males. Abamectin can produce developmental toxicity in rats at a dose of 2 mg/kg/day, which is not a maternally toxic dose. Accordingly, NOAEL for reproductive toxicity and developmental toxicity with fetotoxic effects were established at the dose level of 0.1 mg/kg/day and 1.0 mg/kg/day, respectively.
Topics: Pregnancy; Humans; Male; Rats; Female; Animals; Rabbits; Rats, Wistar; Pesticides; Semen; Reproduction; Fertility; Body Weight
PubMed: 37832695
DOI: 10.1016/j.reprotox.2023.108487