Larvicidal activity of the essential oil of Youngia japonica aerial parts and its constituents against Aedes albopictus.

The aim of this study was to evaluate the larvicidal activity of the essential oil of Youngia japonica aerial parts against the larvae of Aedes albopictus and to isolate any active compounds from the oil. Gas chromatography-mass spectrometry (GC-MS) analyses revealed the presence of 31 compounds, with menthol (23.53%), α-asarone (21.54%), 1,8-cineole (5.36%), and caryophyllene (4.45%) as the major constituents. Bioactivity-directed chromatographic separation of the oil led to the isolation of menthol and α-asarone as active compounds. The essential oil of Y. japonica exhibited larvicidal activity against the fourth instar larvae of A. albopictus with an LC50 value of 32.45 µg/mL. α-Asarone and menthol possessed larvicidal activity against the fourth instar larvae of A. albopictus with LC50 values of 24.56 µg/mL and 77.97 µg/mL, respectively. The results indicate that the essential oil of Y. japonica aerial parts and the two constituents can be potential sources of natural larvicides.

Activating transcription factor 6 contributes to cisplatin­induced ototoxicity via regulating the unfolded proteins response.

As a broad-spectrum anticancer drug, cisplatin is widely used in the treatment of tumors in various systems. Unfortunately, several serious side effects of cisplatin limit its clinical application, the most common of which are nephrotoxicity and ototoxicity. Studies have shown that cochlear hair cell degeneration is the main cause of cisplatin-induced hearing loss. However, the mechanism of cisplatin-induced hair cell death remains unclear. The present study aimed to explore the potential role of activating transcription factor 6 (ATF6), an endoplasmic reticulum (ER)-localized protein, on cisplatin-induced ototoxicity in vivo and in vitro. In this study, we observed that cisplatin exposure induced apoptosis of mouse auditory OC-1 cells, accompanied by a significant increase in the expression of ATF6 and C/EBP homologous protein (CHOP). In cell or cochlear culture models, treatment with an ATF6 agonist, an ER homeostasis regulator, significantly ameliorated cisplatin-induced cytotoxicity. Further, our in vivo experiments showed that subcutaneous injection of an ATF6 agonist almost completely prevented outer hair cell loss and significantly alleviated cisplatin-induced auditory brainstem response (ABR) threshold elevation in mice. Collectively, our results revealed the underlying mechanism by which activation of ATF6 significantly improved cisplatin-induced hair cell apoptosis, at least in part by inhibiting apoptosis signal-regulating kinase 1 expression, and demonstrated that pharmacological activation of ATF6-mediated unfolded protein response is a potential treatment for cisplatin-induced ototoxicity.

Activation of Nrf2 inhibits ferroptosis and protects against oxaliplatin-induced ototoxicity.

Oxaliplatin, as a third-generation platinum-based anticancer drug, is widely used in tumor therapy of many systems. Clinically, oxaliplatin has a number of serious side effects, most notably neuropathy and ototoxicity. The degeneration of cochlear hair cells is the main reason for the hearing loss caused by platinum-based drugs. However, the mechanism of oxaliplatin-induced cochlear hair cell death remains unclear. Ferroptosis is a novel cell injury pattern triggered by the accumulation of iron hydroperoxides in lipids and dependent on the participation of iron ions, which plays an important role in a variety of diseases. Whether ferroptosis is involved in oxaliplatin-induced ototoxicity has not been reported. In this study, we observed that oxaliplatin treatment resulted in lipid peroxidation and reactive oxygen species (ROS) accumulation in OC1 cells, which may be an early alteration in the occurrence of ferroptosis. Additional treatment with ferroptosis inducer or inhibitor significantly aggravated or ameliorated oxaliplatin-induced cytotoxicity. Similarly, inhibition of ferroptosis also protected cochlear hair cells against oxaliplatin-induced injury. In addition, the expression of nuclear factor erythroid 2-related factor2 (Nrf2) and heme oxygenase-1 (HO-1) was significantly increased after oxaliplatin treatment, and treatment with the Nrf2 agonist, resveratrol, dramatically attenuated cochlear hair cell damage induced by oxaliplatin. Activation of Nrf2 significantly decreased the expression of iron regulatory protein 2 (IRP-2) and reversed the expression of glutathione peroxidase 4 (GPX4). Collectively, our results demonstrated that activation of Nrf2 alleviates oxaliplatin-induced cochlear hair cell damage by inhibiting ferroptosis, which may be a new mechanism of oxaliplatin-induced ototoxicity.

RNA-seq analysis of the differential response to low-temperature stress in two morphs of mud crabs (Scylla paramamosain).

The mud crab (Scylla paramamosain) is an economically important crab species that is distributed along the southern coast of China. Previously we reported that various morphological types of mud crabs differentially adapt to temperature changes. This study investigates the effects of temperature on morphs with one or two spines (Sp1 and Sp2, respectively) on the outer margin of the carpus of cheliped at a low temperature (8 °C) and a control temperature (20 °C). The hepatopancreas were the transcriptome source, and a total of 81,853 unigenes were obtained by sequencing, with an average length of 420 bp, and an N50 of 1460 bp. Of these, 22.33 % were known genes. Under low-temperature stress, there were 361 differentially expressed genes (DEGs) between the two morphs; 96 and 265 were up- and down-regulated genes, respectively. There were no DEGs between the morphs at 20 °C. Functional enrichment analysis revealed that the DEGs encoded abundant metallocarboxypeptidase activity, extracellular space, proteolysis, and sequence-specific DNA binding, and were further enriched in signal pathway components, including ubiquinone and other terpenoid-quinone biosynthesis, phenylalanine metabolism, MAPK signaling pathway, apoptosis, and other signaling pathways. The gene expressions of acid phosphatase (ACP), chymotrypsin (CHY), serine carboxypeptidase (SCP), and trypsin (TRY) under low-temperature stress were detected. The expressions of ACP, CHY, and SCP gradually decreased with time. The ACP, CHY, SCP, and TRY gene expression of the Sp1 morph was lower than that of the Sp2 morph; however, the ACP gene expression of the Sp1 morph was higher than that of the Sp2 morph at several time points. In conclusion, adaptability differences between the morphs to low-temperature stress were confirmed, which will enable the selection of cold-tolerant, high-quality varieties of mud crabs for breeding.

Larvicidal activity of the essential oil from Tetradium glabrifolium fruits and its constituents against Aedes albopictus.

BACKGROUND: In our screening programme for new agrochemicals from wild plants, the essential oil of Tetradium glabrifolium (Champ. ex Benth.) T.G. Hartley fruits was found to possess strong larvicidal activity against the Asian tiger mosquito, Aedes albopictus L. The essential oil was extracted via hydrodistillation, and the constituents were determined by GC-MS analysis. The active compounds were isolated and identified by bioassay-directed fractionation. RESULTS: GC-MS analyses revealed the presence of 19 components with 2-tridecanone (43.38%), 2-undecanone (24.09%), D-limonene (13.01%), caryophyllene (5.04%) and ß-elemene (4.07%) being the major constituents. Bioactivity-directed chromatographic separation of the oil led to the isolation of 2-tridecanone, 2-undecanone and D-limonene as active compounds. The essential oil of T. glabrifolium exhibited larvicidal activity against the early fourth-instar larvae of A. albopictus, with an LC50 value of 8.20 µg mL(-1). The isolated constituent compounds, 2-tridecanone, 2-undecanone and D-limonene, possessed strong larvicidal activity against the early fourth-instar larvae of A. albopictus, with LC50 values of 2.86, 9.95 and 41.75 µg mL(-1) respectively. CONCLUSION: The findings indicated that the essential oil of T. glabrifolium fruits and the three constituents have an excellent potential for use in control of A. albopictus larvae and could be useful in the search for newer, safer and more effective natural compounds as larvicides.

Chemical Composition and Insecticidal Activities of the Essential Oil of Clinopodium chinense (Benth.) Kuntze Aerial Parts against Liposcelis bostrychophila Badonnel.

Water-distilled essential oil from Clinopodium chinense (Labiatae) aerial parts at the flowering stage was analyzed by gas chromatography-mass spectrometry. Thirty-five compounds, accounting for 99.18% of the total oil, were identified, and the main components of the essential oil of C. chinense were spathulenol (18.54%), piperitone (18.9%), caryophyllene (12.04%), and bornyl acetate (8.14%). Based on bioactivity-directed fractionation, bornyl acetate, caryophyllene, and piperitone were identified from the essential oil. The essential oil possessed fumigant toxicity against booklice (Liposcelis bostrychophila) with a 50% lethal concentration (LC50) value of 423.39 µg/liter, while the isolated constituents, bornyl acetate and piperitone, had LC50 values of 351.69 and 311.12 µg/liter against booklice, respectively. The essential oil also exhibited contact toxicity against L. bostrychophila with an LC50 value of 215.25 µg/cm(2). Bornyl acetate, caryophyllene, and piperitone exhibited acute toxicity against booklice with LC50 values of 321.42, 275.00, and 139.74 µg/cm(2), respectively. The results indicated that the essential oil and its isolated constituents have potential for development into natural insecticides or fumigants for control of insects in stored grains.

Age-related changes in mitochondrial antioxidant enzyme Trx2 and TXNIP-Trx2-ASK1 signal pathways in the auditory cortex of a mimetic aging rat model: changes to Trx2 in the auditory cortex.

Age-associated degeneration in the central auditory system, which is defined as central presbycusis, can impair sound localization and speech perception. Research has shown that oxidative stress plays a central role in the pathological process of central presbycusis. Thioredoxin 2 (Trx2), one member of thioredoxin family, plays a key role in regulating the homeostasis of cellular reactive oxygen species and anti-apoptosis. The purpose of this study was to explore the association between Trx2 and the phenotype of central presbycusis using a mimetic aging animal model induced by long-term exposure to d-galactose (d-Gal). We also explored changes in thioredoxin-interacting protein (TXNIP), apoptosis signal regulating kinase 1 (ASK1) and phosphorylated ASK1 (p-ASK1) expression, as well as the Trx2-TXNIP/Trx2-ASK1 binding complex in the auditory cortex of mimetic aging rats. Our results demonstrate that, compared with control groups, the levels of Trx2 and Trx2-ASK1 binding complex were significantly reduced, whereas TXNIP, ASK1 p-ASK1 expression, and Trx2-TXNIP binding complex were significantly increased in the auditory cortex of the mimetic aging groups. Our results indicated that changes in Trx2 and the TXNIP-Trx2-ASK1 signal pathway may participate in the pathogenesis of central presbycusis.