Activity of terpenes derived from essential oils against Sarcoptes scabiei eggs

Background The limited ovicidal activity of currently available acaricides is a significant obstacle to efficacious scabies treatment. Several essential oils or their respective components have proved to be active against the eggs of arthropods, mainly lice and ticks. Information on the activity of these oils and/or components against the eggs of mites remains very limited. The aim of this study was to assess the activity of six terpenes (carvacrol, eugenol, geraniol, citral, terpinen-4-ol and linalool) commonly found in essential oils against the eggs of Sarcoptes scabiei. Methods Sarcoptes eggs were exposed to paraffin oil containing 1, 2.5, or 5% of each terpene tested. After a 12-h exposure period, the eggs were washed and placed in paraffin oil for hatching. Embryonic development following treatment was assessed every day to determine the stage of developmental arrest. Results The median effective concentration to obtain 50% egg mortality (EC50) was 0.5, 0.9, 2.0, 4.8, 5.1 and 9.8% for carvacrol, eugenol, geraniol, citral, terpinen-4-ol and linalool, respectively. The microscopic images of eggs after each treatment indicated that these six terpenes may act by penetrating through the aeropyles on the egg surface. Conclusions In conclusion, carvacrol, eugenol and geraniol possess significant ovicidal activities, which should be considered as promising ovicidal agents for the treatment of scabies. Graphical Abstract

The Antioxidant Guaiacol Exerts Fungicidal Activity Against Fungal Growth and Deoxynivalenol Production in Fusarium graminearum

The main component of creosote obtained from dry wood distillation—guaiacol—is a natural antioxidant that has been widely used in pharmaceutical and food preservation applications. However, the antifungal mechanism of guaiacol against phytopathogens remains unclear. In this study, we found that guaiacol exerts inhibitory effects against mycelial growth, conidial formation and germination, and deoxynivalenol (DON) biosynthesis in Fusarium graminearum in a dose-dependent manner. The median effective concentration (EC50) value of guaiacol for the standard F. graminearum strain PH-1 was 1.838 mM. Guaiacol strongly inhibited conidial production and germination. The antifungal effects of guaiacol may be attributed to its capability to cause damage to the cell membrane by disrupting Ca2+ transport channels. In addition, the decreased malondialdehyde (MDA) levels and catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) activity by guaiacol treatment indicate that guaiacol displays activity against DON production by modulating the oxidative response in F. graminearum. Taken together, this study revealed the potentials of antioxidant in inhibiting mycotoxins in F. graminearum.

Molecular mechanisms associated with the resistance of Rhizoctonia solani AG-4 isolates to the succinate dehydrogenase inhibitor, thifluzamide

Thifluzamide, a succinate dehydrogenase (SDH) inhibitor, possesses high activity against Rhizoctonia. In this study, 144 R. solani AG-4 (4HGI, 4HGII, and 4HGIII) isolates, the predominate pathogen associated with sugar beet seedling damping-off, were demonstrated to be sensitive to thifluzamide with a calculated mean median effective concentration of 0.0682 ± 0.0025 μg/mL. Thifluzamide-resistant isolates were generated using fungicide-amended media, resulting in four AG-4HGI isolates and eight AG-4HGII isolates with stable resistance and almost no loss in fitness. Evaluation of cross-resistance of the twelve thifluzamide-resistant isolates and their corresponding parental-sensitive isolates revealed a moderately positive correlation between thifluzamide resistance and the level of resistance to eight other fungicides from three groups, the exception being fludioxonil. An active efflux of fungicide through ATP-binding cassette and major facilitator superfamily transporters was found to be correlated to the resistance of R. solani AG-4HGII isolates to thifluzamide based on RNA-sequencing and quantitative reverse transcription-PCR analyses. Sequence analysis of sdhA, sdhB, sdhC, and sdhD revealed replacement of isoleucine by phenylalanine at position 61 in SDHC in nine of the twelve generated thifluzamide-resistant isolates. No other mutations were found in any of the other genes. Collectively, the data indicate that the active efflux of fungicide and a point mutation in sdhC may contribute to the resistance of R. solani AG-4HGI and AG-4HGII isolates to thifluzamide in vitro. This is the first characterization of the potential molecular mechanism associated with the resistance of R. solani AG-4 isolates to thifluzamide, and provides practical guidance for the use of this fungicide.

In Vitro Evaluation of the Antiviral Activity of Methylene Blue Alone or in Combination against SARS-CoV-2

A new severe acute respiratory syndrome coronavirus (SARS-CoV-2) causing coronavirus diseases 2019 (COVID-19), which emerged in Wuhan, China in December 2019, has spread worldwide. Currently, very few treatments are officially recommended against SARS-CoV-2. Identifying effective, low-cost antiviral drugs with limited side effects that are affordable immediately is urgently needed. Methylene blue, a synthesized thiazine dye, may be a potential antiviral drug. Antiviral activity of methylene blue used alone or in combination with several antimalarial drugs or remdesivir was assessed against infected Vero E6 cells infected with two clinically isolated SARS-CoV-2 strains (IHUMI-3 and IHUMI-6). Effects both on viral entry in the cell and on post-entry were also investigated. After 48 h post-infection, the viral replication was estimated by RT-PCR. The median effective concentration (EC50) and 90% effective concentration (EC90) of methylene blue against IHUMI-3 were 0.41 ± 0.34 µM and 1.85 ± 1.41 µM, respectively; 1.06 ± 0.46 µM and 5.68 ± 1.83 µM against IHUMI-6. Methylene blue interacted at both entry and post-entry stages of SARS-CoV-2 infection in Vero E6 cells as retrieved for hydroxychloroquine. The effects of methylene blue were additive with those of quinine, mefloquine and pyronaridine. The combinations of methylene blue with chloroquine, hydroxychloroquine, desethylamodiaquine, piperaquine, lumefantrine, ferroquine, dihydroartemisinin and remdesivir were antagonist. These results support the potential interest of methylene blue to treat COVID-19.

Comparative Analysis of Intracellular and in vitro Antioxidant Activities of Essential Oil From White and Black Pepper (Piper nigrum L.)

Ethnopharmacological Relevance: Pepper essential oils have potential immunomodulatory, anti-tumor, and anti-cancer activities. Pepper exhibits the potential to prevent or attenuate carcinogenesis as therapeutic tools. However, the related mechanism remains unelucidated.Aim of the Study: The present study aims to provide reasonable information for the explanation of the dissimilarity of the essential oils from white (WPEO) and black pepper (BPEO).Materials and Methods: WPEO, BPEO, and their single active component, as well as synthetic antioxidants, were compared by the cell model methods and chemical methods, including intracellular antioxidant activity (CAA), total antioxidant activities (TAA), superoxide radical (SR), hydroxyl radical (HR), DPPH radical (DR) scavenging activities and inhibition ability of lipoprotein lipid peroxidation (ILLP).Results: The median effective concentration (EC50) values (mg/mL) of the WPEO and BPEO of SR, HR, DR, and ILLP were 0.437 and 0.327, 0.486 and 0.204, 7.332 and 6.348, 0.688, and 0.624 mg/mL, respectively. The CAA units of WPEO and BPEO were 50.644 and 54.806, respectively. CAA, DR, and TAA of BPEO were significantly higher than those of WPEO (p < 0.05). The BPEO and WPEO can be differentiated as the former have higher correlations with 3-carene, α-pinene, β-pinene, and limonene while the latter has a higher caryophyllene correlation. The WPEO and BPEO show a good intracellular scavenging ability of reactive oxygen species in HeLa cells.Conclusion: Generally, pepper oil has stronger activities than single components, indicating that pepper is a broad-spectrum natural antioxidant.

The median effective concentration of propofol with different doses of esketamine during gastrointestinal endoscopy in elderly patients：a randomized controlled trial

Background: Propofol may result in hypotension, bradycardia, and loss of protective reflexes, especially in elderly patients, while esketamine, a N-methyl-D-aspartate receptor antagonists, has analgesic, anaesthetic and sympathomimetic properties and is known to cause less cardiorespiratory depression. We hypothesized that esketamine may reduce the median effective concentration (EC50) of propofol and cause more stable haemodynamic responses during gastrointestinal endoscopy in elderly patients. Methods: Ninety elderly patients, aged 65-89 years, undergoing gastrointestinal endoscopy were randomly assigned into three groups: SK0.25 group (0.25 mg/kg esketamine), SK0.5 group (0.5 mg/kg esketamine) and saline control group. Anaesthesia was achieved by target-controlled infusion of propofol with an initial plasma concentration of 2.5 μg/ml with different bolus doses of esketamine during gastrointestinal endoscopy. The EC50 of propofol for gastrointestinal endoscopy was determined by using an up-and-down method of Dixon with an adjacent concentration gradient at 0.5μg/mL to prohibit purposeful movements. Cardiovascular parameters were also measured and recorded. Results: Propofol EC50 and its 95% confidence interval for gastrointestinal endoscopy in elderly patients were 1.71 (1.15-2.27) μg/mL in SK0.5 group, 2.45 (1.85-3.05) μg/mL in SK0.25 group and 3.69 (2.59-4.78) μg/mL in control group respectively (P < 0.05). The average percent change to baseline mean arterial pressure (MBP) was -19.7 (7.55), -15.2 (7.14) and -10.1 (6.73) with P＜0.001, in the control group, the SK0.25 group and the SK0.5 group, respectively. Conclusions: Combination medication of propofol with esketamine reduced the propofol EC50 during gastrointestinal endoscopy in elderly patients and caused more stable haemodynamic responses compared with single administration of propofol.

Multi-Layer Graphene Oxide in Human Keratinocytes: Time-Dependent Cytotoxicity, Proliferation, and Gene Expression

Few-layer graphene oxide (GO) has shown no or very weak cytotoxicity and anti-proliferative effects in a wide range of cell lines, such as glioma cells and human skin HaCaT cells at concentrations up to 100 µg/mL. However, as multi-layer GO has hardly been explored in the biomedical field, in this study, this other type of GO was examined in human keratinocyte HaCaT cells treated with different concentrations, ranging from 0.01 to 150 µg/mL, for different periods of time (3, 12, and 24 h). The results revealed a time–concentration dependence with two non-cytotoxic concentrations (0.01 and 0.05 µg/mL) and a median effective concentration value of 4.087 µg/mL at 24 h GO exposure. Contrary to what has previously been reported for few-layer GO, cell proliferation of the HaCaT cells in contact with the multi-layer GO at 0.01 μg/mL showed identical proliferative activity to an epidermal growth factor (1.6-fold greater than the control group) after 96 h. The effects of the multi-layer GO on the expression of 13 genes (SOD1, CAT, MMP1, TGFB1, GPX1, FN1, HAS2, LAMB1, LUM, CDH1, COL4A1, FBN, and VCAN) at non-cytotoxic concentrations of GO in the HaCaT cells were analyzed after 24 h. The lowest non-cytotoxic GO concentration was able to upregulate the CAT, TGFB1, FN1, and CDH1 genes, which confirms multi-layer GO’s great potential in the biomedical field.

Small Molecule Inhibitors of White Spot Syndrome Virus: Promise in Shrimp Seedling Culture

Rapid production of prawn (Litopenaeus vannamei) under artificial pressure can result in a series of obvious challenges and is vulnerable to serious losses related to aquatic environmental issues and the unrestrained outbreak of white spot syndrome (WSS). However, to date, there are no therapeutic strategies to contain the spread of the virus. Here, we synthesized 27 coumarin deriv-atives and evaluated their anti-white spot syndrome virus (WSSV) activity in L. vannamei larvae. We demonstrated that electron-withdrawing and electron-giving substituent groups play an im-portant role in reducing toxicity and WSSV replication, respectively. Two coumarin C2 (2-amino-5-oxo-4-(p-tolyl)-4H,5H-pyrano[3,2-c]chromene-3-carbonitrile) and C7 (2-amino-4-(4-chlorophenyl)-5-oxo-4H,5H-pyrano[3,2-c]chromene-3-carbonitrile) were regarded as the most promising anti-WSSV compounds with maximum antiviral response <5% and median effective concentration <10 mg/L. The mortality of WSSV-infected larvae decreased by more than 60% after exposure to C2 and C7. With continuous immersion of C2 and C7 exchange, the mortality further decreased to 40% at 120 h.Additionally, C2 and C7 are the relatively stable in aquacultural water, making these agents