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Cells May 2024Mutations 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,...
Impact of Oncogenic Changes in p53 and KRAS on Macropinocytosis and Ferroptosis in Colon Cancer Cells and Anticancer Efficacy of Niclosamide with Differential Effects on These Two Processes.
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.
Topics: Humans; Ferroptosis; Pinocytosis; Colonic Neoplasms; Tumor Suppressor Protein p53; Proto-Oncogene Proteins p21(ras); Cell Line, Tumor; Niclosamide; Antineoplastic Agents; Amino Acid Transport System y+; Mutation
PubMed: 38891084
DOI: 10.3390/cells13110951 -
Journal of Medical Case Reports Jun 2024Schistosomiasis is one of the endemic parasitic diseases in many developing countries. Despite this, appendicitis secondary to schistosomiasis is an uncommon condition...
BACKGROUND
Schistosomiasis is one of the endemic parasitic diseases in many developing countries. Despite this, appendicitis secondary to schistosomiasis is an uncommon condition even in some endemic areas. Schistosomal appendicitis, an incidentally discovered appendicitis associated with schistosomiasis histological findings, affects young males predominantly. Timely diagnosis and treatment, including appendectomy and anti-helminthic therapy, are crucial.
CASE REPORT
A 24-year-old Sudanese male patient presented with abdominal pain. Diagnosed with acute appendicitis, he underwent appendectomy, revealing appendix inflammation with Schistosoma ova in histopathology. Abdominal ultrasound detected no complications. Weakly positive Schistosoma serology was noted, but stool and urine analysis showed no infection evidence. Prescribed praziquantel, patient had 3-year post-op follow-up without complications.
CONCLUSIONS
This case report underscores the significance of including schistosomiasis in the differential diagnosis of appendicitis, particularly in regions where the disease is endemic. It underscores the necessity of histopathological evaluations for accurate diagnosis, emphasizing the potential implications for clinical practice in similar settings.
Topics: Humans; Appendicitis; Male; Young Adult; Praziquantel; Appendectomy; Anthelmintics; Schistosomiasis; Diagnosis, Differential; Abdominal Pain; Ultrasonography; Animals; Treatment Outcome; Appendix
PubMed: 38890741
DOI: 10.1186/s13256-024-04610-3 -
PLoS Neglected Tropical Diseases Jun 2024Fasciolosis caused by Fasciola hepatica is a major public health and economic problem worldwide. Due to the lack of a successful vaccine and emerging resistance to the...
Fasciolosis caused by Fasciola hepatica is a major public health and economic problem worldwide. Due to the lack of a successful vaccine and emerging resistance to the drug triclabendazole, alternative phytotherapeutic approaches are being investigated. This study investigated the in vitro anthelmintic activity of Lavender (Lavandula angustifolia) and carob (Ceratonia siliqua L.) essential oils (EOs) against F. hepatica. The in vitro study was based on an egg hatch assay (EHA), adult motility inhibition assays, DNA damage, reactive oxygen species (ROS) level along with several oxidative stress biomarkers including glutathione peroxidase (GSH), and glutathione-S-transferase (GST), superoxide dismutase (SOD) and malondialdehyde (MDA). To this end, different concentrations of L. angustifolia and C. siliqua EOs (1, 5, 10, 25 and 50 mg/mL) were used to assess anthelmintic effects on different life stages including egg, and adults of F. hepatica for 24 hrs. The results indicated that these EOs play a significant role as anthelminthics, and the effect was dependent on time and concentration. The in vitro treatment of F. hepatica worms with both L. angustifolia and C. siliqua EOs increased DNA damage, ROS production and induction of oxidative stress (decreased SOD, GST and GSH, and increased MDA), significantly compared to control. Therefore, it can be concluded that L. angustifolia and C. siliqua EOs have the potential to be used as novel agents for the control and treatment of F. hepatica infections. Further studies are required to investigate their pharmacological potential and effectiveness in vivo for the treatment of parasitic infections.
Topics: Animals; Oxidative Stress; Fasciola hepatica; DNA Damage; Anthelmintics; Plants, Medicinal; Biomarkers; Reactive Oxygen Species; Oils, Volatile; Lavandula; Fascioliasis; Superoxide Dismutase; Glutathione Transferase; Life Cycle Stages
PubMed: 38885188
DOI: 10.1371/journal.pntd.0012251 -
Veterinary Parasitology, Regional... Jul 2024Ancylostoma caninum is a widely prevalent parasitic nematode in dogs across the world. There has been a notable increase in reports of anthelmintic resistance in A....
Surveillance of Ancylostoma caninum in naturally infected dogs in Quebec, Canada, and assessment of benzimidazole anthelmintics reveal a variable efficacy with the presence of a resistant isolate in imported dogs.
Ancylostoma caninum is a widely prevalent parasitic nematode in dogs across the world. There has been a notable increase in reports of anthelmintic resistance in A. caninum within the United States of America in recent years, which has led us to investigate the potential of this scenario in Canada. The study objectives were to assess the prevalence of A. caninum in two different groups, including a colony of rescued dogs in Canada and three imported Greyhound dogs from USA, and to evaluate the efficacy of two benzimidazole (BZ) anthelmintics against A. caninum, complemented with a molecular genetic analysis adapted to low prevalence. Fecal samples were collected at pre- and post-treatment with fenbendazole for the native shelters-origin group, and a combination of anthelmintic formulations, including the pro-BZ febantel for the USA-origin group. The coprology analyses found several genera of internal parasites. Canine ancylostomiasis was the most prevalent parasitosis with 30.77% in the native group and 100% in the USA group, but with overall low average of A. caninum eggs per gram. Through the fecal egg count reduction test (FECRT), applying a cut-off at 90% as baseline of egg reduction for successful efficacy, BZ showed variable efficacy. Furthermore, molecular analysis confirmed the presence of A. caninum in both groups of dogs and found differences in the genetics linked to BZ resistance on the A. caninum β-tubulin isotype 1 gene. In the isolate from the native group, both codons 167 and 200 were homozygous without the presence of single nucleotide polymorphism (SNP). In contrast, the selected isolate from the USA group, showed a homozygous allele at position 200 and a heterozygous SNP at position 167. The latter was congruent with the low efficacy in FECRT and agrees with the recent findings of USA A. caninum isolate resistant phenotype to the BZ anthelmintics. The limitations of the study include an overall low eggs-per-gram in both canine groups, and the shortage of additional fecal samples from the USA group, restraining the molecular analysis only to one out of the three Greyhounds. This study provided some insights on the efficacy of BZs against A. caninum and revealed the presence of BZ resistant isolates in imported dogs in Quebec, Canada. All this information should be considered, for choosing the best strategy in the control of A. caninum using anthelmintic drugs.
Topics: Animals; Dogs; Dog Diseases; Benzimidazoles; Ancylostoma; Ancylostomiasis; Anthelmintics; Drug Resistance; Feces; Quebec; Prevalence; Female; Male
PubMed: 38880561
DOI: 10.1016/j.vprsr.2024.101036 -
BMC Ophthalmology Jun 2024Echinococcosis, commonly known as hydatid disease, is a zoonotic infection resulting from the tapeworm Echinococcus granulosus. The occurrence of hydatid cysts in the... (Review)
Review
BACKGROUND
Echinococcosis, commonly known as hydatid disease, is a zoonotic infection resulting from the tapeworm Echinococcus granulosus. The occurrence of hydatid cysts in the orbital region is uncommon, representing less than 1% of all reported hydatid cases. This report details a unique case of an intramuscular hydatid cyst in the orbital region that led to compressive optic neuropathy.
CASE PRESENTATION
A 22-year-old male from Kabul, Afghanistan presented with a five-month history of progressive proptosis in his left eye, associated with a gradual decrease in vision over the past three weeks. The left eye exhibited upward globe dystopia, ocular motility limitation, mild conjunctival injection, and chemosis. Diagnosis was achieved through imaging and histopathological examination. Treatment involves surgical removal of the cyst and prolonged albendazole therapy. The postoperative course showed significant improvement in the patient's condition and restoration of his vision.
CONCLUSIONS
Despite its rarity, this case underscores the importance of awareness and knowledge of hydatid disease among physicians, especially those working in endemic areas. It emphasizes the importance of including hydatid disease in the differential diagnosis of orbital masses, particularly in endemic regions.
Topics: Humans; Male; Echinococcosis; Young Adult; Optic Nerve Diseases; Eye Infections, Parasitic; Orbital Diseases; Magnetic Resonance Imaging; Albendazole; Tomography, X-Ray Computed
PubMed: 38877497
DOI: 10.1186/s12886-024-03502-w -
Infectious Diseases of Poverty Jun 2024Preventive chemotherapy with ivermectin and albendazole (IA) in mass drug administration (MDA) programs for all at-risk populations is the core public health...
Efficacy of ivermectin and albendazole combination in suppressing transmission of lymphatic filariasis following mass administration in Tanzania: a prospective cohort study.
BACKGROUND
Preventive chemotherapy with ivermectin and albendazole (IA) in mass drug administration (MDA) programs for all at-risk populations is the core public health intervention to eliminate lymphatic filariasis (LF). Achieving this goal depends on drug effectiveness in reducing parasite reservoirs in the community to halt transmission. We assessed the efficacy of ivermectin and albendazole in clearing microfilariae and circulating filarial antigens (CFA) following MDA.
METHODS
This community-based prospective study was conducted in Mkinga district, Tanga region, Tanzania, from November 2018 to June 2019. A total of 4115 MDA-eligible individuals were screened for CFA using Filarial test strips. CFA positives were re-examined for microfilariae by microscopy. CFA and microfilariae positive individuals were enrolled and received IA through MDA campaign. The status of microfilariae and CFA was monitored before MDA, and on day 7 and six-month following MDA. The primary efficacy outcomes were the clearance rates of microfilariae on day 7 and six-months, and CFA at 6 months of post-MDA. The McNemar test assessed the proportions of microfilariae positive pre- and post-MDA, while Chi-square tests were utilized to examine factors associated with CFA status six months post-MDA.
RESULTS
Out of 4115 individuals screened, 239 (5.8%) tested positive for CFA, of whom 11 (4.6%) were also positive for microfilariae. Out of the ten microfilariae-positive individuals available for follow-up on day 7, nine tested negative, yielding a microfilariae clearance rate of 90% [95% confidence interval (CI): 59.6-98.2%]. Participants who tested negative for microfilariae on day 7 remained free of microfilariae six months after MDA. However, those who did not clear microfilariae on day-7 remained positive six-months post-MDA. The McNemar test revealed a significant improvement in microfilariae clearance on day 7 following MDA (P = 0.02). Out of 183 CFA-positive individuals who were available at 6-month follow-up, 160 (87.4%) remained CFA positive, while 23 became CFA negative. The CFA clearance rate at 6 months post-MDA was 12.6% (95% CI: 8.5-8.5%). There was no significant association of variability in ivermectin plasma exposure, measured by maximum concentration or area under the curve, and the clearance status of microfilariae or CFA post-MDA.
CONCLUSIONS
Preventive chemotherapy with IA effectively clears microfilariae within a week. However, it is less effective in clearing CFA at six months of post-MDA. The low clearance rate for filarial antigenemia underscores the need for alternative drug combinations and additional preventive measures to achieve LF elimination by 2030.
Topics: Ivermectin; Albendazole; Tanzania; Humans; Elephantiasis, Filarial; Prospective Studies; Male; Mass Drug Administration; Female; Adult; Middle Aged; Adolescent; Young Adult; Animals; Child; Filaricides; Drug Therapy, Combination; Microfilariae; Aged; Child, Preschool; Antigens, Helminth; Treatment Outcome
PubMed: 38867265
DOI: 10.1186/s40249-024-01214-3 -
Scientific Reports Jun 2024The continuous search for natural product-based biopesticides from fungi isolated from untapped sources is an effective tool. In this study, we studied a pre-selected...
The continuous search for natural product-based biopesticides from fungi isolated from untapped sources is an effective tool. In this study, we studied a pre-selected fungal endophyte, isolate Aa22, from the medicinal plant Artemisia absinthium, along with the antifungal, insect antifeedant and nematicidal compounds present in the extract. The endophyte Aa22 was identified as Stemphylium solani by molecular analysis. The antifungal activity was tested by broth microdilution against Fusarium solani, F. oxysporum, F. moniliforme and Botrytis cinerea, the insect antifeedant by choice bioassays against Spodoptera littoralis, Myzus persicae and Rhopalosiphum padi and the in vitro mortality against the root-knot nematode Meloiydogyne javanica. The structures of bioactive compounds were determined on the basis of 1D and 2D NMR spectroscopy and mass spectrometry. The ethyl acetate extract obtained from the solid rice fermentation showed mycelial growth inhibition of fungal pathogens (EC 0.08-0.31 mg/mL), was antifeedant to M. persicae (99%) and nematicidal (68% mortality). A bioguided fractionation led to the isolation of the new compound stempholone A (1), and the known stempholone B (2) and stemphol (3). These compounds exhibited antifeedant (EC 0.50 mg/mL), antifungal (EC 0.02-0.43 mg/L) and nematicidal (MLD 0.5 mg/mL) activities. The extract activities can be explained by 3 (antifungal), 1-3 (antifeedant) and 1 (nematicidal). Phytotoxicity tests on Lolium perenne and Lactuca sativa showed that the extract and 1 increased L. sativa root growth (121-130%) and 1 reduced L. perenne growth (48-49%). These results highlight the potential of the endophytic fungi Aa22 as biotechnological source of natural product-based biopesticides.
Topics: Animals; Endophytes; Antifungal Agents; Antinematodal Agents; Fusarium; Spodoptera; Ascomycota; Botrytis; Microbial Sensitivity Tests; Tylenchoidea
PubMed: 38867066
DOI: 10.1038/s41598-024-64467-w -
PloS One 2024Haemonchus contortus is a blood-feeding gastrointestinal parasite that impacts grazing sheep, causing economic losses in animal production. Due to its anthelmintic...
Haemonchus contortus is a blood-feeding gastrointestinal parasite that impacts grazing sheep, causing economic losses in animal production. Due to its anthelmintic resistance, alternative antiparasitic treatments like plant-based anthelmintics are necessary to explore. Artemisia cina (Asteraceae) is a plant whose n-hexane extract and ethyl acetate extract exhibit anthelmintic activity against H. contortus, the n-hexane more active. To discover additional bioactive metabolites, a chemical analysis was performed on ethyl acetate extract, which presented an LC90 of 3.30 mg/mL and allowed the isolation of 11-[(1R,5S,7R,8R,10S,)-1,8-dihydroxy-5,10-dimethyl-4-oxodecahydroazulen-7-yl] acrylic acid. This new sesquiterpene was identified through one and two-dimensional NMR. The compound was named cinic acid and displayed an LC50 of 0.13 (0.11-0.14) mg/mL and LC90 of 0.40 (0.37-0.44) mg/mL, which, compared with ethyl acetate extract larvicidal activity, was 256-fold more active at LC50 and 15.71-fold at LC90. In this study, a new sesquiterpene with larvicidal activity against H. contortus L3 infective larvae was isolated from the ethyl acetate extract of Artemisia cina.
Topics: Artemisia; Haemonchus; Animals; Anthelmintics; Larva; Plant Extracts; Sesquiterpenes; Sheep; Magnetic Resonance Spectroscopy
PubMed: 38865346
DOI: 10.1371/journal.pone.0305155 -
Journal of Cellular and Molecular... Jun 2024Chemotherapy resistance remains a significant challenge in treating ovarian cancer effectively. This study addresses this issue by utilizing a dual drug-loaded...
Chemotherapy resistance remains a significant challenge in treating ovarian cancer effectively. This study addresses this issue by utilizing a dual drug-loaded nanomicelle system comprising albendazole (ABZ) and paclitaxel (PTX), encapsulated in a novel carrier matrix of D-tocopheryl polyethylene glycol 1000 succinate vitamin E (TPGS), soluplus and folic acid. Our objective was to develop and optimize this nanoparticulate delivery system using solvent evaporation techniques to enhance the therapeutic efficacy against ovarian cancer. The formulation process involved pre-formulation, formulation, optimization, and comprehensive characterization of the micelles. Optimization was conducted through a 32 factorial design, focusing on the effects of polymer ratios on particle size, zeta potential, polydispersity index (PDI) and entrapment efficiency (%EE). The optimal formulation demonstrated improved dilution stability, as indicated by a critical micelle concentration (CMC) of 0.0015 mg/mL for the TPGS-folic acid conjugate (TPGS-FOL). Extensive characterization included differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR), and Fourier-transform infrared spectroscopy (FTIR). The release profile exhibited an initial burst followed by sustained release over 90 h. The cytotoxic potential of the formulated micelles was superior to that of the drugs alone, as assessed by MTT assays on SKOV3 ovarian cell lines. Additionally, in vivo studies confirmed the presence of both drugs in plasma and tumour tissues, suggesting effective targeting and penetration. In conclusion, the developed TPGS-Fol-based nanomicelles for co-delivering ABZ and PTX show promising results in overcoming drug resistance, enhancing solubility, sustaining drug release, and improving therapeutic outcomes in ovarian cancer treatment.
Topics: Female; Paclitaxel; Micelles; Albendazole; Ovarian Neoplasms; Humans; Animals; Cell Line, Tumor; Drug Carriers; Polyethylene Glycols; Vitamin E; Folic Acid; Mice; Drug Liberation; Particle Size; Polyvinyls; Polymers; Xenograft Model Antitumor Assays
PubMed: 38864691
DOI: 10.1111/jcmm.18389 -
Veterinary Medicine and Science Jul 2024Sarcoptic mange is rare in cats. The main symptoms reported in cases of feline sarcoptic mange include crusty lesions and pruritus, although these may vary in severity...
BACKGROUND
Sarcoptic mange is rare in cats. The main symptoms reported in cases of feline sarcoptic mange include crusty lesions and pruritus, although these may vary in severity among individuals.
OBJECTIVES
This report describes three cats infested with Sarcoptes scabiei, all presenting with pruritus and excoriation.
METHODS
The diagnosis was confirmed by microscopic observation of skin scrape samples.
RESULTS
All three cats were treated successfully using moxidectin and imidacloprid, selamectin and ivermectin, respectively.
CONCLUSIONS
The clinical presentation of feline scabies appears to be more variable in cats than in dogs. Infestation with S. scabiei should be considered a differential diagnosis for cats presenting with pruritic inflammatory skin disease.
Topics: Animals; Scabies; Cat Diseases; Cats; Male; Female; Poland; Sarcoptes scabiei; Ivermectin; Nitro Compounds; Neonicotinoids; Insecticides; Macrolides
PubMed: 38864312
DOI: 10.1002/vms3.1500