Transcriptome analysis reveals limited toxic effects of the UV-filter benzophenone-3 (BP-3) on the hermatypic coral Acropora tenuis and its symbiotic dinoflagellates.

This study aimed to investigate the toxic and transcriptomic effects of the ultraviolet filter benzophenone-3 (BP-3) on Acropora tenuis and its symbiotic dinoflagellates while using acetone as a solvent. Seven-day exposure to 50 and 500 µg/L, which is higher than most BP-3 records from coastal waters, did not affect coral colour or dinoflagellate photosynthesis. Differentially expressed genes (DEGs) between seawater and solvent controls were <20 in both corals and dinoflagellates. Eleven coral DEGs were detected after treatment with 50 µg/L BP-3. Fourteen coral DEGs, including several fluorescent protein genes, were detected after treatment with 500 µg/L BP-3. In contrast, no dinoflagellate DEGs were detected in the BP-3 treatment group. These results suggest that the effects of 50-500 µg/L BP-3 on adult A. tenuis and its dinoflagellates are limited. Our experimental methods with lower acetone toxicity provide a basis for establishing standard ecotoxicity tests for corals.

Low levels of Cd2+ combined with procymidone may cause ovarian damage in mice via unfolded protein response.

As no study about the combined effect of low levels of Cd2+ with procymidone (PCM) on organs and organisms, we investigated their actions on mouse-ovary in vivo and in vitro. Four-week mice were treated with corn oil for the control group, corn oil + 0.0045 mg/L Cd2+ (CdCl2 was dissolved in ultrapure water and freely consumed by mice) for Cd2+ group, 50 mg/kg/d PCM (suspended in corn oil and administered orally to mice) for PCM group, and 50 mg/kg/d PCM + 0.0015 (0.0045 and 0.0135) mg/L Cd2+ for L+ (M+ and H+) PCM group for 21 days. For in vitro experiment, the cultured ovaries were treated with acetone for the control group, 0.1% acetone + 8.4 µg/L Cd2+ for the Cd2+ group, 0.63 mg/L PCM (dissolved in acetone) for the PCM-group, and 0.63 mg/L PCM + 2.8 (8.4 and 25.2) µg/L Cd2+ for L+ (M+ and H+) PCM group for 7 days. Mouse body weight in each treatment group, the weight and volume of ovaries in all PCM groups were lower than the control. Both in vivo and in vitro, all-stage follicle numbers were lower in M+PCM and H+PCM groups, whereas the atretic follicles and CASPASE3/8 were higher; meanwhile, lower estradiol and progesterone and higher unfolded protein response (UPR) members in all PCM groups. L+, M+, and H+PCM groups had further ovarian damage and stronger UPR than PCM groups, as did M+PCM groups over Cd2+ groups. It is hypothesized low-level PCM and Cd2+ may mutually promote each other's triggered UPR and exacerbate ovarian damage.

Formylpeptide receptor 1 contributes to epidermal barrier dysfunction-induced skin inflammation through NOD-like receptor C4-dependent keratinocyte activation.

BACKGROUND: Skin barrier dysfunction may both initiate and aggravate skin inflammation. However, the mechanisms involved in the inflammation process remain largely unknown. OBJECTIVES: We sought to determine how skin barrier dysfunction enhances skin inflammation and molecular mechanisms. METHODS: Skin barrier defect mice were established by tape stripping or topical use of acetone on wildtype mice, or filaggrin deficiency. RNA-Seq was employed to analyse the differentially expressed genes in mice with skin barrier defects. Primary human keratinocytes were transfected with formylpeptide receptor (FPR)1 or protein kinase R-like endoplasmic reticulum (ER) kinase (PERK) small interfering RNA to examine the effects of these gene targets. The expressions of inflammasome NOD-like receptor (NLR)C4, epidermal barrier genes and inflammatory mediators were evaluated. RESULTS: Mechanical (tape stripping), chemical (acetone) or genetic (filaggrin deficiency) barrier disruption in mice amplified the expression of proinflammatory genes, with transcriptomic profiling revealing overexpression of formylpeptide receptor (Fpr1) in the epidermis. Treatment with the FPR1 agonist fMLP in keratinocytes upregulated the expression of the NLRC4 inflammasome and increased interleukin-1ß secretion through modulation of ER stress via the PERK-eIF2α-C/EBP homologous protein pathway. The activation of the FPR1-NLRC4 axis was also observed in skin specimens from old healthy individuals with skin barrier defect or elderly mice. Conversely, topical administration with a FPR1 antagonist, or Nlrc4 silencing, led to the normalization of barrier dysfunction and alleviation of inflammatory skin responses in vivo. CONCLUSIONS: In summary, our findings show that the FPR1-NLRC4 inflammasome axis is activated upon skin barrier disruption and may explain exaggerated inflammatory responses that are observed in disease states characterized by epidermal dysfunction. Pharmacological inhibition of FPR1 or NLRC4 represents a potential therapeutic target.

Effect of various concentrations of common organic solvents on the growth and proliferation ability of Candida glabrata and their permissible limits for addition in drug susceptibility testing.

Objectives: Dimethyl sulfoxide (DMSO), acetone, ethanol, and methanol are organic solvents commonly used for dissolving drugs in antimicrobial susceptibility testing. However, these solvents have certain antimicrobial activity. Currently, standardized criteria for the selection and dosage of drug solvents in drug susceptibility testing research are lacking. The study aims to provide experimental evidence for the selection and addition limit of drug solvents for the in vitro antifungal susceptibility test of Candida glabrata (C. glabrata). Methods: According to the recommendation of the Clinical and Laboratory Standards Institute (CLSI) M27-A3, a 0.5 McFarland C. glabrata suspension was prepared and then diluted 1:1,000. Next, a gradient dilution method was used to prepare 20%, 10%, 5%, and 2.5% DMSO/acetone/ethanol/methanol. The mixture was plated onto a 96-well plate and incubated at a constant temperature of 35 °C for 48 h. The inhibitory effects of DMSO, acetone, ethanol, and methanol on C. glabrata growth and proliferation were analyzed by measuring optical density values at 600 nm (OD600 values). Results: After 48 h incubation, the OD600 values of C. glabrata decreased to different extents in the presence of the four common organic solvents. The decrease in the OD600 values was greater with increasing concentrations within the experimental concentration range. When DMSO and acetone concentrations were higher than 2.5% (containing 2.5%) and methanol and ethanol concentrations were higher than 5.0% (containing 5.0%), the differences were statistically significant compared with the growth control wells without any organic solvent (P < 0.05). Conclusion: All four organic solvents could inhibit C. glabrata growth and proliferation. When used as solvents for drug sensitivity testing in C. glabrata, the concentrations of DMSO, acetone, ethanol, and methanol should be below 2.5%, 2.5%, 5%, and 5%, respectively.

Antibacterial Activity of Culinary-Medicinal Polypore Mushroom Lentinus tigrinus (Agaricomycetes).

Medicinal mushrooms belonging to Lentinus spp. exhibit significant antibacterial activities, but little attention has been paid to their efficacy against the food-borne pathogen, Bacillus cereus. The present study for the first time quantitatively evaluated the antibacterial activity of different extracts from fruiting bodies of a well-authenticated Iranian native strain of medicinal mushroom, Lentinus tigrinus, against Gram-positive spore-forming bacterium B. cereus. The findings revealed that the acetone extract inhibited the growth of B. cereus at concentrations as low as 31.25 µg/ML, while it had no effect against Escherichia coli and Staphylococcus aureus even at 10,000 µg/ML. The rest of the bacteria were also susceptible to the acetone extract at concentrations greater than 5 mg/ML. Antibacterial activities of the methanol-ethyl acetate extract and the hot water extract were significantly weaker than that of the acetone extract, which contained high amounts of total phenols (5.83 ± 0.08 mg GAE/g, dw), while Fourier transform infrared spectroscopy (FT-IR) confirmed the presence of functional groups, such as hydroxyl, carbonyl, amide, and amine. Further studies by scanning electron microscopy (SEM) confirmed obvious changes in the morphology of B. cereus in response to the acetone extract of L. tigrinus. This study may suggest that L. tigrinus could be a good natural source for isolating and purifying antibacterial compounds against B. cereus.

Exogenous acetone O-(2-naphthylsulfonyl)oxime improves the adverse effects of excess copper by copper detoxification systems in maize.

The current study is to elucidate the responses of maize seedlings to excess copper and acetone O-(2-naphthylsulfonyl)oxime (NS) pretreatment. The study was divided into the following experimental groups: 18 h distilled water (DW) control (C), 6 h 0.3 mM NS + then 12 h DW (NS), 6 h DW + then 12 h 1 mM CuSO4.5H2O (CuS), 0.3 mM NS for 6 h + then 1 mM CuSO4.5H2O (NS + CuS) for 12 h. When the NS + CuS group is compared with the CuS group; It accumulated 10% more copper, while the ABA, H2O2, MDA, and carotenoid contents decreased significantly, the total chlorophyll, proline, gallic acid, ascorbic acid, catechol, trans-P-qumaric acid, and cinnamic acid contents increased. While SOD activity, which is one of the antioxidant system enzymes, decreased with NS application, GPX, CAT, and APX activities increased despite copper stress. When all the findings are evaluated as a whole, exogenous NS, despite excessive copper, ameliorated the adverse effects of copper stress by increasing the effectiveness of the enzymatic and non-enzymatic components of the antioxidant system and the contents of phenolic substances. In addition, increasing the copper content by 10% reveals its importance in terms of NS phytoremediation.Abbreviation: Style-sheet: When full form and abbreviated form both are used as keywords, retain both as provided by the author.

Considering the potential of NS in terms of phytoremediation and phytomining, it was determined that approximately 10% more copper was accumulated.Exogenous acetone O-(2-naphthylsulfonyl)oxime (NS), a synthetic sulfonate derivative oxime, to maize seedlings under copper stress increased the activity of enzymatic and non-enzymatic components of the antioxidant defense system.By increasing the content of phenolic compounds known for their electron-donating properties, NS supported the antioxidant defense system and contributed to the scavenging of radicals.

Methanol and acetone extracts from the leaves of selected aromatic plants affect survival of field collected Anopheles arabiensis (Diptera: Culicidae) from Kisumu, Kenya.

The massive and inappropriate use of synthetic insecticides is causing significant and increasing environmental disruption. Therefore, developing effective natural mosquitocidal compounds could be an alternative tool for malarial vector control. The present study investigates the larvicidal and adulticidal effect of methanol and acetone extracts of leaves from Lippia chevalieri, Lippia multiflora, Cymbopogon schoenanthus, and Lantana camara against Anopheles arabiensis, to control the most widespread vector transmitting malaria in sub-Saharan. Africa. Extracts were evaluated following WHO modified test procedure against third- to fourth-instar larvae and, non-blood-fed females from 3- to 5-day-old field populations of An. arabiensis under laboratory conditions using WHO larval and CDC bottle bioassays, respectively. Mortality was recorded after 24-h exposure and several compounds were identified in the extracts. The methanolic and acetonic extracts of L. camara were effective against larvae showing lethal concentrations to 50% (LC50) of the population, at 89.48 and 58.72 ppm, respectively. The acetonic extracts of C. schoenanthus and L. chevalieri showed higher toxicities LC50s of 0.16% and 0.22% against female adults, respectively. The methanolic extracts of L. multiflora and L. chevalieri LC50s were effective at 0.17% and 0.27%, respectively, against female adults. These results indicate that the plant extracts tested may represent effective means to control An. arabiensis when used to treat the surface of the marshes.

Synthesis of chalcones and their antimicrobial and drug potentiating activities.

The increased resistance of microorganisms to antimicrobial drugs makes it necessary to search for new active compounds, such as chalcones. Their simple chemical structure makes them molecules easy to synthesize. Therefore, the aim of this study was to evaluate the antimicrobial and potentiating activity of antibiotics and antifungals by synthetic chalcones against strains of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans and Candida tropicalis. The synthesis of chalcones was carried out by Claisen-Schimidt aldol condensation. Nuclear Magnetic Resonance (NMR) and Gas Chromatography Coupled to Mass Spectrometry (GC/MS) were also performed. Microbiological tests were performed by the broth microdilution method, using gentamicin, norfloxacin and penicillin as standard drugs for the antibacterial assay, and fluconazole for the antifungal assay. Three chalcones were obtained (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one (DB-Acetone), (1E,3E,6E,8E)-1,9-diphenylnone-1,3,6,8-tetraen-5-one (DB-CNM), (1E,4E)-1,5-bis (4-methoxyphenyl) penta-1,4-dien-3-one (DB-Anisal). The compound DB-Acetone was able to inhibit P. aeruginosa ATCC 9027 at a concentration of 1.4 × 102 µM (32 µg/mL), while DB-CNM and DB-Anisal inhibited the growth of S. aureus ATCC 25923 at 17.88 × 102 µM and 2.71 × 101 µM (512 µg/mL and 8 µg/mL) respectively. In the combined activity, DB-Anisal was able to potentiate the effect of the three antibacterial drugs tested against E. coli 06, norfloxacin (128 for 4 µg/mL ±1) against P. aeruginosa 24 and penicillin (1,024 for 16 µg/mL ±1) against S. aureus 10. In antifungal assays, chalcones were not able to inhibit the growth of fungal strains tested. However, both showed potentiating activity with fluconazole, ranging from 8.17 x 10-1 µM (0.4909 µg/mL) to 2.35 µM (13.96 µg/mL). It is concluded that synthetic chalcones have antimicrobial potential, demonstrating good intrinsic activity against fungi and bacteria, in addition to potentiating the antibiotics and antifungal tested. Further studies are needed addressing the mechanisms of action responsible for the results found in this work.

Production of acetone, butanol, and ethanol by electro-fermentation with Clostridium saccharoperbutylacetonicum N1-4.

This manuscript describes the effect of altering the extracellular redox potential during the production of acetone, butanol, and ethanol on a dual chamber H-type microbial fuel cell by fermenting glucose with Clostridium saccharoperbutylacetonicum N1-4. Extracellular redox potential modification was achieved by either supplementing the microbial broth with the redox agent NADH or by poising the cathode potential at -600 mV vs. Ag/AgCl. The addition of NADH was found to foment the production of acetone via fermentation of glucose. The addition of 200 mM of NADH to the catholyte rendered the highest production of acetone (2.4 g L-1), thus outperforming the production of acetone by conventional fermentation means (control treatment) by a factor of 2.2. The experimental evidence gathered here, indicates that cathodic electro-fermentation of glucose favors the production of butanol. When poising the cathode potential at -600 mV vs Ag/AgCl (electro-fermentation), the largest production of butanol was achieved (5.8 g L-1), outperforming the control treatment by a factor of 1.5. The production of ABE solvents and the electrochemical measurements demonstrate the electroactive properties of C. saccharoperbutylacetonicum N1-4 and illustrates the usefulness of bio-electrochemical systems to improve conventional fermentative processes.

Dimethyl Sulfoxide Enhances Acetylcholine-Induced Contractions in Rat Urinary Bladder Smooth Muscle by Inhibiting Acetylcholinesterase Activities.

Dimethyl sulfoxide (DMSO) has been used not only as an experimental solvent, but also as a therapeutic agent for interstitial cystitis. The therapeutic effects of DMSO on interstitial cystitis are presumed to involve anti-inflammatory and analgesic effects. However, the effects of DMSO on urinary bladder smooth muscle (UBSM) have not been fully investigated. Thus, in this study, we investigated the effects of DMSO on rat UBSM contractions, and these effects were compared with those of acetone, which has a structure in which the sulfur of DMSO is replaced with carbon. DMSO (0.5-5%) enhanced acetylcholine (ACh)-induced contractions, whereas acetone (3 and 5%) suppressed them. Additionally, DMSO (5%) suppressed carbachol-induced contractions. DMSO/acetone (0.5-5%) inhibited 80 mM KCl-induced contractions in a concentration-dependent manner; however, the inhibitory effects of DMSO were weaker than those of acetone. The enhancing/suppressing effects of DMSO and acetone were almost completely abolished by wash out. DMSO and acetone (0.5-5%) inhibited recombinant human acetylcholinesterase (rhAChE) activity in a concentration-dependent manner. At 0.5 and 1%, the inhibitory effects of DMSO on rhAChE activity were more potent than those of acetone. These findings suggest that DMSO can enhance ACh-induced UBSM contractions and promote urinary bladder motility by inhibiting acetylcholinesterase (AChE), although DMSO also inhibits Ca2+ influx-mediated UBSM contractions. In addition, the sulfur atom in DMSO might play an important role in its enhancing effect on ACh-induced contractions by inhibiting AChE, as acetone did not enhance these contractions.

Vermitoxicity of aged biochar and exploring potential damage factors.

Although biochar is a promising soil amendment, its characteristics change owing to its aging in soil. Studies have shown that some aged biochar is hazardous to plants and soil microbiota. Earthworms are well-known soil ecosystem engineers; nevertheless, the toxic effects of aged biochar on them (vermitoxicity) are yet unknown, and it is necessary to explore the potential risk factors. Here, a series of soil culture experiments were conducted to systematically examine the vermitoxicity of aged biochar at various levels utilizing the earthworm Eisenia fetida and corncob biochar.. Acute toxicity bioassays were also used to evaluate several potential harm factors utilizing modified aged biochar/leaching solutions. The findings showed that both fresh and aged biochar might have adverse effects on earthworms, and that aged biochar was more toxic than fresh biochar with LC50s reduced to 6.89%. Specifically, aged biochar caused earthworm death, growth inhibition with a maximum of 36.6%, and avoidance with 100% avoidance at the application rates of 2% at the individual-behavioral level. At the cellular and physiological-biochemical levels, aged biochar damaged coelomocyte lysosomal membrane stability, disrupted antioxidant enzyme activities, and improved the malondialdehyde (MDA) content in earthworms. Heat-treated and pH-modified aged biochar exhibited less acute toxicity on earthworms than aged biochar, whereas aqueous and acetone extracts showed weak vermitoxicity. As a result, earthworms may be harmed by volatile organic compounds (VOCs), an improper pH, and aqueous and acetone extracts. Additionally, the range of neural red retention times (NRRTs) was reviewed as ∼20-70 min mostly. This study, as far as we know, is the first to evaluate the vermitoxicity of aged biochar and its potential damage factors. The results may enhance our understanding of ecological toxicity of biochar, particularly over the long term, and lead to the development of application standards for biochar amendments to the soil.

Neuropharmacological Effects of Chassalia curviflora (Rubiaceae) Leaves in Swiss Albino Mice Model.

The current study aimed to investigate the neuropharmacological properties of ethanol, acetone, and ethyl acetate leaf extracts of Chassalia curviflora (C. curviflora) in mouse models. The neuropharmacological properties of this plant were studied on Swiss albino mice at dosages of 50, 100, and 200 mg/kg body weight in thiopental sodium-induced sleeping time test, and at dosages of 100 and 200 mg/kg body weight in other tests. The extracts caused a marked reduction in the initiation and sleep length (P<0.05) in studies on thiopental sodium-induced sleeping time at dosages of 100 and 200 mg/kg and a significant decrease (P<0.05) was found in terms of unconstrained locomotor and explorative activities in both hole crossing and open field tests at dosages of 100 and 200 mg/kg. Furthermore, the extracts increased sleeping time with a dosage-dependent onset of action. The hole-board test extracts also reduced the number of head dips at dosages of 100 and 200 mg/kg (P<0.05). It was found in this study that C. curviflora had the best neuropharmacological properties at a dosage of 200 ml/kg. Our findings also showed that all of the extracts from C. curviflora were experimentally active in an in vivo model. The study results suggested that the leaves had strong anti-depressant and hypnotic CNS properties that might be exploited for neuropharmacological adjuvant therapy in conventional medicine. However, pharmacological studies are warranted to explore the active substances and the mode of action.

Mechanistic efficacy assessment of selected novel methanimine derivatives against vincristine induced Neuropathy: In-vivo, Ex-vivo and In-silico correlates.

Vincristine induced peripheral neuropathy (VIPN) is a serious untoward side effect suffered by cancer patients, which still lacks an adequate therapeutic approach. This study examined the alleviating potential of novel methanimine derivatives i.e. (E)-N-(4-nitrobenzylidene)-4-chloro-2-iodobenzamine (KB 9) and (E)-N-(2-methylbenzylidene)-4-chloro-2-iodobenzamine (KB 10) in VIPN. Vincristine was injected in BALB/c mice for 10 days to instigate nociceptive neuropathy. Dynamic and static allodynia, thermal (hot and cold) hyperalgesia were evaluated at 0, 5, 10 and 14 days using cotton brush, Von Frey filament application, hot plate test, acetone drop and cold water respectively. Tumour necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), lipid peroxide (LPO), glutathione-S-transferase (GST), catalase (CAT), superoxide dismutase (SOD) and reactive oxygen species (ROS) assays were performed to assess the efficacy of KB9 and KB10 against neuroinflammation and oxidative stress utilizing ELISA, immunohistochemistry and western blot analysis in brain and sciatic nerve tissues. Computational studies were executed to determine the stable binding conformation of both compounds with respect to COX-2 and NF-κB. Interestingly, both compounds substantially reduced protein expression related to neuroinflammation, oxidative stress (LPO, GST, SOD, CAT) and pain (NF-κB, COX-2, IL-1ß and TNF-α). This molecular analysis suggested that the neuroprotective effect of KB9 and KB10 was mediated via regulation of inflammatory signaling pathways. Overall, this study demonstrated that KB9 and KB10 ameliorated vincristine induced neuropathy, through anti-inflammatory, anti-nociceptive and antioxidant mechanisms.

Cleaning and microstructural effects of amyl acetate on pulp chamber dentin impregnated with epoxy resin-based endodontic sealer.

OBJECTIVE: To evaluate the cleaning potential of 95% ethanol, acetone, and amyl acetate solutions used solely or in association, to remove epoxy resin-based sealer residues from pulp chamber dentin and their microstructural effects. MATERIALS AND METHODS: One hundred and eighty bovine incisor specimens were divided into nine groups according to the cleaning protocol: ET (ethanol); AC (acetone); AA (amyl acetate); E1: AA+AC; E2: AA+ET; E3: AC+ET; E4: AA+AC+ET; PC (positive control), and NC (negative control). All groups were impregnated with epoxy resin-sealer, except NC. Ninety specimens were divided into groups (n = 10) for evaluation of persistence of residues and amount of open dentinal tubules by SEM analysis and evaluation of chemical compounds on the dentin surface after cleaning with electron dispersive spectroscopy. The others 90 specimens were submitted to Knoop microhardness evaluation. Persistence of residues data were submitted to the Kruskal Wallis and Dunn tests (α = 0.05). Open dentinal tubules and microhardness data were submitted to one-way ANOVA and Mann Whitney tests (α = 0.05). RESULTS: AA and E4 protocols showed the lowest persistence of residues. E4 group had the highest incidence of open dentinal tubules. E3 and E4 groups showed no changes in the atomic ratio Ca/P, which was similar to NC group. E4 group did not present W, an element presents in all the other groups. ET and E4 protocols showed the smallest reduction in dentin microhardness. CONCLUSIONS: The combination of amyl acetate, acetone and ethanol is the most effective and safe protocol to remove epoxy sealer residues on pulp chamber dentin. Moreover, it has the lowest microhardness reduction. CLINICAL SIGNIFICANCE: The combined use of amyl acetate, acetone, and ethanol enhanced the cleaning of pulp chamber dentin with minimal microstructural damage.

Protective effect of kavain in meristematic cells of Allium cepa L.

Kavain is one of the main kavalactones of Piper methysticum (Piperaceae) with anxiolytic, analgesic, and antioxidant activities. Therefore, the aim of the study was to evaluate the cytotoxic, mutagenic, and antimutagenic potential of kavain in Allium cepa cells. Roots of A. cepa were transferred to the negative (2% acetone) and positive (10 µg/mL of Methylmethanesulfonate, MMS) controls and to the concentrations of kavain (32, 64 and 128 µg/mL) for 48 h. A total of 5,000 meristematic cells were analyzed under an optical microscope to determine the mitotic index, mean number of chromosomal alterations and percentage of damage reduction. Data were analyzed by Kruskal-Wallis test (p <0.05). All concentrations of kavain were not cytotoxic and did not show significant chromosomal changes when compared to 2% acetone. Kavain showed a cytoprotective effect in the pre (128 µg/mL) and in the post-treatment (32 and 64 µg/mL) and reduced damage against the mutagenic action of MMS in all concentrations of the pre and simultaneous and at the highest of post (128 µg/mL). Kavain promoted a significant reduction in micronuclei, nuclear buds and chromosomal losses in relation to MMS. The observed data indicate the importance of kavain for the inhibition of damage and chemoprevention.

Comparative study of the effect of solvents on the efficacy of neonicotinoid insecticides against malaria vector populations across Africa.

BACKGROUND: New insecticides with a novel mode of action such as neonicotinoids have recently been recommended for public health by WHO. Resistance monitoring of such novel insecticides requires a robust protocol to monitor the development of resistance in natural populations. In this study, we comparatively used three different solvents to assess the susceptibility of malaria vectors to neonicotinoids across Africa. METHODS: Mosquitoes were collected from May to July 2021 from three agricultural settings in Cameroon (Njombe-Penja, Nkolondom, and Mangoum), the Democratic Republic of Congo (Ndjili-Brasserie), Ghana (Obuasi), and Uganda (Mayuge). Using the CDC bottle test, we compared the effect of three different solvents (ethanol, acetone, MERO) on the efficacy of neonicotinoids against Anopheles gambiae s.l. In addition, TaqMan assays were used to genotype key pyrethroid-resistant markers in An. gambiae and odds ratio based on Fisher exact test were used to evaluate potential cross-resistance between pyrethroids and clothianidin. RESULTS: Lower mortality was observed when using absolute ethanol or acetone alone as solvent for clothianidin (11.4‒51.9% mortality in Nkolondom, 31.7‒48.2% in Mangoum, 34.6‒56.1% in Mayuge, 39.4‒45.6% in Obuasi, 83.7‒89.3% in Congo and 71.1‒95.9% in Njombe pendja) compared to acetone + MERO for which 100% mortality were observed for all the populations. Similar observations were done for imidacloprid and acetamiprid. Synergist assays (PBO, DEM and DEF) with clothianidin revealed a significant increase of mortality suggesting that metabolic resistance mechanisms are contributing to the reduced susceptibility. A negative association was observed between the L1014F-kdr mutation and clothianidin resistance with a greater frequency of homozygote resistant mosquitoes among the dead than among survivors (OR = 0.5; P = 0.02). However, the I114T-GSTe2 was in contrast significantly associated with a greater ability to survive clothianidin with a higher frequency of homozygote resistant among survivors than other genotypes (OR = 2.10; P = 0.013). CONCLUSIONS: This study revealed a contrasted susceptibility pattern depending on the solvents with ethanol/acetone resulting to lower mortality, thus possibly overestimating resistance, whereas the MERO consistently showed a greater efficacy of neonicotinoids but it could prevent to detect early resistance development. Therefore, we recommend monitoring the susceptibility using both acetone alone and acetone + MERO (4 µg/ml for clothianidin) to capture the accurate resistance profile of the mosquito populations.

Acetone extracts of three selected plants induce toxicological and biological effects against the house mosquito, Culex pipiens (Diptera: Culicidae).

The biological effect of acetone extracts from three selected plants, Lantana camara, Rhazya astricta, and Citrullus colocynthis, on the egg hatch rate, larvicidal activity, and larval development of Culex pipiens L. was investigated. The egg hatch rate of Cx. pipiens was significantly reduced (P<0.01) when the extracts of L. camara were used. Moreover, the used extracts significantly exhibited a variable larvicidal activity against the Cx. pipiens (P<0.001). The most toxicity was observed when the larvae were treated with the acetonic extract of L. camara, showing different toxicities with lower LC50s at 140.1 ppm after two days and 51.3 ppm after ten days. In this observed time, larvae suffered chronic toxicities (increased mortality with increasing exposure time and sublethal endpoints, such as decreased larvae development) when treated with used plant extracts, leading to 96.7% mortality with L. camara and 91.5% and 85.7% mortalities with C. colocynthis and Rh. stricta, respectively. All concentrations significantly obstructed larvae development, causing significant reductions in both the proportion of pupation (P<0.001) and the emergence of adults (P<.001). The larval development reduction was observed under the L. camara extracts treatment, where only 15.2% and 9.7% of the larvae managed to reach pupal and adult stages, respectively. In conclusion, applying acetone extracts from L. camara to immature mosquito breeding sites may efficiently control mosquitoes to reduce the reliance on insecticides against these disease vectors.

Reproductive Toxicity of Furfural Acetone in Meloidogyne incognita and Caenorhabditis elegans.

Furfural acetone (FAc) is a promising alternative to currently available nematicides, and it exhibits equivalent control efficiency on root-knot nematodes with avermectin in fields. However, its effect on the reproduction of root-knot nematode is poorly understood. In this study, the natural metabolite FAc was found to exhibit reproductive toxicity on Meloidogyne incognita and Caenorhabditis elegans. The number of germ cells of C. elegans was observed to decrease after exposure to FAc, with a reduction of 59.9% at a dose of 200 mg/L. FAc in various concentrations induced the germ-cell apoptosis of C. elegans, with an increase over six-fold in the number of apoptotic germ cells at 200 mg/L. These findings suggested that FAc decreased the brood size of nematode by inducing germ-cell apoptosis. Moreover, FAc-induced germ-cell apoptosis was suppressed by the mutation of gene hus-1, clk-2, cep-1, egl-1, ced-3, ced-4, or ced-9. The expression of genes spo-11, cep-1, and egl-1 in C. elegans was increased significantly after FAc treatment. Taken together, these results indicate that nematode exposure to FAc might inflict DNA damage through protein SPO-11, activate CEP-1 and EGL-1, and induce the core apoptosis pathway to cause germ-cell apoptosis, resulting in decreased brood size of C. elegans.

Could acetone O-(4-chlorophenylsulfonyl)oxime be a copper chelating and antioxidative molecule on maize seedlings?

The main purpose of study is to determine if Acetone O- (4-chlorophenylsulfonyl) oxime (AO) has a positive effect on maize seedlings under copper (Cu) stress or not. Seedlings were allocated to following experimental groups: 18-hour distilled water (DW) Control (C), ago 6-hour 0.66 mM AO + later 12-hour DW (AO), ago 6-hour DW + later 12-hour 1 mM Cu (Cu), ago 6-hour 0.66 mM AO + later 12-hour 1 mM Cu (AO + Cu). The results showed that AO + Cu caused approximately three times more copper accumulation compared to Cu treatment. AO and AO + Cu treatments significantly decreased membrane damage and H2O2 formation compared to its control. The proline content was significantly increased in AO and AO + Cu compared to its control. While the highest catalase, Guaiacol Peroxidase and superoxide dismutase activity was observed in Cu application, the highest ascorbate peroxidase activity was determined in AO application. It was observed that AO had a protective effect on chlorophyll content and RWC, but a positive effect on carotenoid content could not be determined. In addition, the effects of AO on the content of 17 phenolic substances in maize leaves were determined. In the light of the current findings, AO may prevent the formation of radical compounds.

The fact that Acetone O-(4 chlorophenylsulfonyl) oxime (AO) caused approximately three times more copper accumulation indicates that it has a significant potential for phytoremediation studies. Despite the fact that AO resulted in approximately three times more copper accumulation, it is surprising that the Maize plant was able to continue its almost normal metabolic activities. AO alleviated the adverse effects of stress by affecting the hormones and antioxidant system of the plant. If AO is used with hyper accumulator plants, it may have the potential to obtain effective solutions in heavily copper-contaminated soils.

Effects of Solvents, Emulsions, Cosolvents, and Complexions on Ex Vivo Mouse Myometrial Contractility.

A great need exists to develop tocolytic and uterotonic drugs that combat poor, labor-related maternal and fetal outcomes. A widely utilized method to assess novel compounds for their tocolytic and uterotonic efficacy is the isometric organ bath contractility assay. Unfortunately, water-insoluble compounds can be difficult to test using the physiological, buffer-based, organ bath assay. Common methods for overcoming solubility issues include solvent variation, cosolvency, surfactant or complexion use, and emulsification. However, these options for drug delivery or formulation can impact tissue function. Therefore, the goal of this study was to evaluate the ability of common solvents, surfactants, cosolvents, and emulsions to adequately solubilize compounds in the organ bath assay without affecting mouse myometrial contractility. We found that acetone, acetonitrile, and ethanol had the least effect, while dimethylacetamide, ethyl acetate, and isopropanol displayed the greatest inhibition of myometrial contractility based on area under the contractile curve analyses. The minimum concentration of surfactants, cosolvents, and human serum albumin required to solubilize nifedipine, a current tocolytic drug, resulted in extensive bubbling in the organ bath assay, precluding their use. Finally, we report that an oil-in-water base emulsion containing no drug has no statistical effect beyond the control (water), while the drug emulsion yielded the same potency and efficacy as the freely solubilized drug.