Search Results (10)

Culex pipiens quinquefasciatus is a notorious vector transmitting severe diseases such as Zika virus and West Nile virus to humans worldwide. Vermistatin is a type of funicon-like compound and was first isolated from Penicillin vermiculatum in the 1970s. Vermistatin has shown promising activity against Cx. p. quinquefasciatus larvae in our previous research. Here, we conducted a transcriptomic analysis of Cx. p. quinquefasciatus larvae treated with a median lethal concentration of 28.13 mg/L vermistatin. Differential expression analysis identified 1055 vermistatin-responsive genes, with 477 downregulated and 578 upregulated. Gene Ontology annotation and enrichment analysis revealed the metabolic process to be the most significantly affected biological process, the membrane to be the most significantly affected cellular component, and catalytic activity to be the most significantly affected molecular function. Kyoto Encyclopedia of Genes and Genomes pathway analysis classified the differential expression genes into six major categories, with metabolism and organismal systems being the most enriched. Fifty-five pathways were significantly enriched, with the hematopoietic cell lineage, renin–angiotensin system, cholesterol metabolism, and peroxisome proliferator-activated receptor signaling pathways among the top altered pathways. Furthermore, 32 potential detoxification-related genes were differentially expressed, with 3 cytochrome P450s, 2 ABC transporters, and 1 UGT induced by vermistatin. This study provides insights into the molecular mechanisms of vermistatin’s action against Cx. p. quinquefasciatus larvae, highlighting potential targets for novel mosquito control strategies. Full article

The pupal parasitoid Trichopria drosophilae (Hymenoptera: Diapriidae) has been evaluated as a biological agent of Drosophila suzukii. Integrated pest management strategies mostly rely on combined application of multiple insecticides and natural enemies. This study assessed the toxicity of eight common insecticides against D. suzukii in fruit orchards and the effects of semilethal and sublethal doses on T. drosophilae. The eight insecticides had higher toxicities to D. suzukii larvae with lower LC₅₀ values than those for adults. Adults and larvae showed high susceptibility to emamectin benzoate, spinetoram, lambda-cyhalothrin, abamectin, and sophocarpidine. The median lethal doses (LC₅₀) of lambda-cyhalothrin and imidacloprid to T. drosophilae adults were 60.41 mg/L and 100.58 mg/L, higher than the toxicities of the other six insecticides. Applying chlorantraniliprole, emamectin benzoate, sophocarpidine, abamectin, azadirachtin, and spinetoram resulted in low toxicity to D. suzukii pupae. However, the exposure of D. suzukii pupae or larvae to these insecticides at semilethal and sublethal doses decreased the parasitism or eclosion rate of T. drosophilae. These results improve our understanding of the effects of insecticide residues on T. drosophilae development and provide a basis for the combined use of chemical and biological options for managing D. suzukii. Full article

The effects of pirimiphos-methyl have previously been assessed on blood-sucking insect species, pollinating insects, and target crop pest species. The sensitivity of non-target zoophagous and saprophage species to this insecticide remains largely unstudied. In laboratory conditions, we assessed the susceptibility of 43 species of invertebrates to pirimiphos-methyl. The most tolerant species to this insecticide were Pyrrhocoris apterus (LC₅₀ measured over 60 mg/m²), Cylindroiulus truncorum, Pterostichus niger, Harpalus rufipes, Lithobius forficatus, and Carabus hortensis (LC₅₀ ranged from 25 to 50 mg/m²). Average tolerance to pirimiphos-methyl was displayed by Ophonus rufibarbis, Teuchestes fossor, Silpha carinata, Badister sodalis, Rugilus rufipes, Phosphuga atrata, Porcellio laevis, Pterostichus oblongopunctatus, Aphodius foetens, Lasius fuliginosus, Oxypselaphus obscurus, Platydracus fulvipes, Myrmica ruginodis, Xantholinus tricolor, and Megaphyllum sp. (LC₅₀ for those species ranged from 12 to 24 mg/m²). Higher sensitivity to this insecticide was seen for Amara nitida, Leistus ferrugineus, Harpalus xanthopus winkleri, Philonthus nitidus, Pterostichus melanarius, Harpalus latus, Limodromus assimilis, Philonthus decorus, Tachinus signatus, Ponera coarctata, Carabus convexus, Philonthus coprophilus, Philonthus laevicollis, Platydracus latebricola, Labia minor, and Carabus granulatus (LC₅₀ for those species ranged from 6 to 12 mg/m²). The greatest sensitivity to pirimiphos-methyl was observed in Hister fenestus, Drusilla canaliculata, Bisnius fimetarius, Oxytelus sculptus, Lasius niger, and Lasius flavus (LC₅₀ ranged from 0.4 to 6 mg/m²). We found a relationship between the parameters of bodies of invertebrates (the average body length and dry body mass) and sensitivity to pirimiphos-methyl. With an increase in body sizes of invertebrates, the tolerance to the insecticide increased (per each mm of body length, LC₅₀ increased by 0.82 mg/m² on average). We identified no relationship between the trophic specialization and sensitivity to the insecticide. Full article

The overuse of synthetic insecticides has led to various negative consequences, including insecticide resistance, environmental pollution, and harm to public health. This may be ameliorated by using insecticides derived from botanical sources. The primary objective of this study was to evaluate the anti-mosquito activity of the essential oil (EO) of Citrus reticulata Blanco cv. Chachiensis (Chachi) (referred to as CRB) at immature, semi-mature, and mature stages. The chemical compositions of the CRB EO were analyzed using GC-MS. The main components were identified to be D-limonene and γ-terpinene. The contents of D-limonene at the immature, semi-mature, and mature stages were 62.35%, 76.72%, and 73.15%, respectively; the corresponding contents of γ-terpinene were 14.26%, 11.04%, and 11.27%, respectively. In addition, the corresponding contents of a characteristic component, methyl 2-aminobenzoate, were 4.95%, 1.93%, and 2.15%, respectively. CRB EO exhibited significant larvicidal activity against Aedes albopictus (Ae. albopictus, Diptera: Culicidae), with the 50% lethal doses being 65.32, 61.47, and 65.91 mg/L for immature, semi-mature, and mature CRB EO, respectively. CRB EO was able to inhibit acetylcholinesterase and three detoxification enzymes, significantly reduce the diversity of internal microbiota in mosquitoes, and decrease the relative abundance of core species within the microbiota. The present results may provide novel insights into the utilization of plant-derived essential oils in anti-mosquitoes. Full article

Para-aminopropiophenone (PAPP) is a potent methaemoglobin (MetHb) forming agent used for the lethal control of exotic carnivores and mustelids. To assess the sensitivity of Australian wildlife to PAPP we developed an in vivo assay that did not use death as an endpoint. Sub-lethal dose-response data were modelled to predict PAPP doses required to achieve an endpoint set at 80% MetHb (MetHb₈₀). The comparative sensitivity of non-target mammals referenced to this endpoint was found to be highly variable, with southern brown bandicoots (Isoodon obesulus) the most sensitive species (MetHb₈₀ = 6.3 mg kg⁻¹) and bush rats (Rattus fuscipes) the most tolerant (MetHb₈₀ = 1035 mg kg⁻¹). Published LD₅₀ estimates were highly correlated with PAPP doses modelled to achieve the MetHb₈₀ endpoint (r² = 0.99, p < 0.001). Most dose-response data for native mammals were collected in the field or in semi-natural enclosures, permitting PAPP and placebo dosed animals to be fitted with tracking transmitters and transponders and released at their point of capture. A protracted morbidity and mortality was observed only in Australian ravens (Corvus coronoides). The combination of sub-lethal dose-response assay and survival data collected in the field provided more relevant information about the actual hazard of pest control agents to non-target wildlife species than laboratory-based lethal-dose bioassays. We discuss the need to replace lethal-dose data with biologically meaningful insights able to define a continuum of toxicological hazards that better serve the needs of conservation and veterinary scientists and wildlife managers. Full article

Natural products (NPs) continue to provide a structural template for the design of novel therapeutic agents and expedite the drug discovery process. The majority of FDA-approved pharmaceuticals used in medical practice can be traced back to natural sources, and NPs play a significant role in drug development. Curcumin, one of the most well-studied chemicals among the NPs, is currently the subject of intense investigation for its biological effects, including the prevention and treatment of cancer. Cancer has overtaken all other causes of death in the world today, with 19.3 million new cases and nearly 10 million deaths predicted in 2020. In the present investigation, we reported the synthesis of three semi-synthetic analogues of curcumin-bearing pyrimidinone moiety by the chemical modification of the diketone function of curcumin followed by their characterization by analytical techniques including infrared (IR), nuclear magnetic resonance (NMR), and mass spectral data. According to the National Cancer Institute (NCI US) methodology, the curcumin analogues (C1-C3) were tested for their anticancer efficacy against 59 cancer cell lines in a single dose assay. 1-(2,6-Dichlorophenyl)-4,6-bis((E)-4-hydroxy-3-methoxystyryl)pyrimidin-2(1H)-one (C2) demonstrated the most promising anticancer activity with mean percent growth inhibition (%GIs) of 68.22 in single dose assay at 10 µM. The compound exhibited >68 %GIs against 31 out of 59 cancer cell lines and was found to be highly active against all leukemia and breast cancer cell lines. The compound C2 showed a lethal effect on HT29 (colon cancer) with %GI of 130.44, while 99.44 %GI was observed against RPMI-8226 (Leukemia). The compound C2 displayed better anticancer activity against the panels of CNS, melanoma, ovarian, prostate, and breast cancer cell lines than curcumin and other anti-EGFR agents gefitinib and imatinib in single dose assay. The compound C2 also demonstrated potent anticancer activity in a 5-dose assay (0.001 to 100 µM) with GI₅₀ values ranging from 1.31 to 4.68 µM; however, it was found to be non-selective with SR values ranging from 0.73 to 1.35. The GI₅₀ values of compound C2 were found to be better than that of the curcumin against all nine panels of cancer cell lines. All of the curcumin analogues were subsequently investigated for molecular docking simulation against EGFR, one of the most attractive targets for antiproliferative action. In molecular docking studies, all the ligands were found to accommodate the active site of EGFR and the binding affinity of ligand C2 was found to be −5.086 kcal/mol. The ligand C2 exhibited three different types of interactions: H-bond (Thr790 and Thr854), π-cationic (Arg841), and aromatic H-bond (Asn842). The curcumin analogues reported in the current investigation may provide valuable therapeutic intervention for the prevention and treatment of cancer and accelerate anticancer drug discovery programs in the future. Full article

Glycopeptide antibiotics have side effects that limit their clinical use. In view of this, the development of glycopeptides with improved chemotherapeutic properties remains the main direction in the search for new antibacterial drugs. The objective of this study was to evaluate the toxicological characteristics of new semi-synthetic glycopeptide flavancin. Acute and chronic toxicity of antibiotic was evaluated in Wistar rats. The medium lethal dose (LD₅₀) and the maximum tolerated doses (MTD) were calculated by the method of Litchfield and Wilcoxon. In the chronic toxicity study, the treatment regimen consisted of 15 daily intraperitoneal injections using two dosage levels: 6 and 10 mg/kg/day. Total doses were equivalent to MTD or LD₅₀ of flavancin, respectively. The study included assessment of the body weight, hematological parameters, blood biochemical parameters, urinalysis, and pathomorphological evaluation of the internal organs. The results of the study demonstrated that no clinical-laboratory signs of toxicity were found after 15 daily injections of flavancin at a total dose close to the MTD or LD₅₀. The pathomorphological study did not reveal any lesions on the organ structure of animals after low-dose administration of flavancin. Thus, flavancin favorably differs in terms of toxicological properties from the glycopeptides currently used in the clinic. Full article

We present a reproducible procedure for transforming somatic embryos of cork oak with the CsTL1 gene that codes for a thaumatin-like protein, in order to confer tolerance to Phytophthora cinnamomi. Different concentrations/combinations of the antibiotics carbenicillin and cefotaxime, as bacteriostatic agents, and kanamycin, as a selective agent, were tested. A lethal dose of 125 mg/L kanamycin was employed to select transgenic somatic embryos, and carbenicillin was used as a bacteriostatic agent at a concentration of 300 mg/L, which does not inhibit somatic embryo proliferation. The transformation efficiency was clearly genotype-dependent and was higher for the TGR3 genotype (17%) than for ALM80 (4.5%) and ALM6 (2%). Insertion of the transgenes in genomic DNA was confirmed by PCR analysis, whereas expression of the CsTL1 gene was evaluated by semi-quantitative real-time PCR (qPCR) analysis. A vitrification treatment successfully cryopreserved the transgenic lines generated. The antifungal activity of the thaumatin-like protein expressed by the gene CsTL1 was evaluated in an in vitro bioassay with the oomycete P. cinnamomi. Of the eight transgenic lines analyzed, seven survived for between one or two times longer than non-transgenic plantlets. Expression of the CsTL1 gene and plantlet survival days were correlated, and survival was generally greater in plantlets that strongly expressed the CsTL1 gene. Full article

Rhinella schneideri is a common toad found in South America, whose paratoid toxic secretion has never been explored as an insecticide. In order to evaluate its insecticidal potential, Nauphoeta cinerea cockroaches were used as an experimental model in biochemical, physiological and behavioral procedures. Lethality assays with Rhinella schneideri paratoid secretion (RSPS) determined the LD₅₀ value after 24 h (58.07µg/g) and 48 h exposure (44.07 µg/g) (R² = 0.882 and 0.954, respectively). Acetylcholinesterase activity (AChE) after RSPS at its highest dose promoted an enzyme inhibition of 40%, a similar effect observed with neostigmine administration (p < 0.001, n= 5). Insect locomotion recordings revealed that RSPS decreased the distance traveled by up to 37% with a concomitant 85% increase in immobile episodes (p < 0.001, n = 36). RSPS added to in vivo cockroach semi-isolated heart preparation promoted an irreversible and dose dependent decrease in heart rate, showing a complete failure after 30 min recording (p < 0.001, n ≥ 6). In addition, RSPS into nerve-muscle preparations induced a dose-dependent neuromuscular blockade, reaching a total blockage at 70 min at the highest dose applied (p < 0.001, n ≥ 6). The effect of RSPS on spontaneous sensorial action potentials was characterized by an increase in the number of spikes 61% (p < 0.01). Meanwhile, there was 42% decrease in the mean area of those potentials (p < 0.05, n ≥ 6). The results obtained here highlight the potential insecticidal relevance of RSPS and its potential biotechnological application. Full article