Cardiomyocyte death caused by hypoxia is one of the main causes of myocardial infarction or heart failure, and mitochondria play an important role in this process. Agrimonolide (AM) is a monomeric component extracted from Agrimonia pilosa L. and has antioxidant, antitumor, and anti-inflammatory effects. This study aimed to investigate the role and mechanism of AM in improving hypoxia-induced H9c2 cell damage. The results showed that low AM concentrations promote H9c2 cell proliferation and increase cellular ATP content. Transcriptome sequencing showed that AM induces differential expression of genes in H9c2 cells. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that these genes were concentrated in mitochondrial function. Subsequent experiments confirmed that AM regulates hypoxia-induced cell cycle arrest. AM inhibited the rate of apoptosis by regulating the expression of apoptosis-related proteins, reducing the level of cleaved Caspase 3 and Bax, and increasing the level of Bcl2, thereby protecting H9c2 cells from hypoxia-induced apoptosis. AM restored the mitochondrial membrane potential, inhibited the generation of ROS, maintained the normal shape of the mitochondria, improved the level of the mitochondrial functional proteins OPA1, MFN1, MFN2, Tom20, and increased the level of ATP. In conclusion, AM protects H9c2 cells from hypoxia-induced cell damage.
Abstract In recent years, the research on the conversion of chitin to high value-added chemicals has attracted more and more attention. At present, the method of preparing lactic acid from chitin mostly uses strong base or catalyst. These reaction systems have disadvantages such as corrosion of containers and harm to human body. Herein, a simple and effective method to convert chitin to organic acids in catalyst and base-free conditions is developed. The use of H2O2 only can efficiently convert chitin to organic acids in the absence of bases and catalysts. Under the optimal conditions of 30 mg chitin, 2.1 mL water, 0.9 mL H2O2 at 230 oC for 1.5 h, the lactic acid yield of chitin can reach 58.2% and the total organic acid yield can reach 84.0%. This work provides an efficient method for the resource utilization of chitin biomass.
Water blooms caused by cyanobacteria are currently major global environmental issues. The outbreaks induced by nutrient elements have attracted much attention; however, the effects of environmental pollutants on the cyanobacteria are themselves poorly understood, especially those due to chiral chemicals. To explore the enantioselective eco-effects of the chiral herbicide diclofop-methyl (DM) and its major metabolite diclofop acid (DA), the physiological characteristics of Microcystis aeruginosa were investigated. The results showed that using both biomass and protein content as growth parameters is necessary to access the impact of the herbicides, that stimulation biomass production by R-DA and S-DA was apparent (nonessential), and that the concentration of 5 mg/L is worth noting. Ultrastructure changes in gas vacuoles, thylakoids, glycogen, cyanophycin granules, poly beta-hydroxybutyrate, polyhedral body, and lipids indicated different toxicity modes among the four chemicals. The different effects between R-DA and S-DA demonstrated that R-DA probably acts as a proton ionophore shuttling protons across the plasmalemma, whereas S-DA did not demonstrate such action. The toxicity order in the present study is S-DA < R-DA < DM < DA. Stimulation of the growth of M. aeruginosa during the first 3 days by herbicidally inactive S-DA was greater than that due to R-DA, which is adverse to water quality in water bodies. Therefore, using the herbicidally active R-enantiomer is recommended. These results are helpful in understanding the enantioselective effects of chiral pesticides on cyanobacteria, which is important for environmental assessment and protection. It is also helpful for guiding the application of chiral pesticides in agricultural settings.
Abstract Staphylococcus aureus is a common pathogen of bovine mastitis which can induce autophagy and inhibit autophagy flux, resulting in intracellular survival and persistent infection. The aim of the current study was to investigate the role of p38α in the autophagy induced by intracellular S. aureus in bovine mammary epithelial cells. An intracellular infection model of MAC-T cells was constructed, and activation of p38α was examined after S. aureus invasion. Through activating/inhibiting p38α by anisomycin/SB203580, the autophagosomes, LC3 and p62 level were analyzed by immunofluorescence and western blot. To further study the detailed mechanism of p38α, phosphorylation of ULK1ser757 was also detected. The results showed that intracellular S. aureus activated p38α, and the activation developed in a time-dependent manner. Inhibition of p38α promoted intracellular S. aureus -induced autophagy flow, up-regulated the ratio of LC3 II/I, reduced the level of p62 and inhibited the phosphorylation of ULK1ser757, whereas the above results were reversed after activation of p38α. The current study indicated that intracellular S. aureus can inhibit autophagy flow by activating p38α in bovine mammary epithelial cells.
Purpose: Hypoxia is an inevitable consequence of many respiratory diseases resulting from inadequate alveolar ventilation. As pulmonary dysfunction is recently recognized as one of the many clinical features associated with diabetes, this study aims to investigate the effect of streptozotocin (STZ)-induced diabetes on hypoxia-induced lung injury. Materials and Methods: Mice were randomly allocated to four groups (Control, Hypoxia, Diabetes, Diabetes+Hypoxia). Control and type I diabetic (100 mg/kg STZ-treated) mice were followed for 4 weeks and finally exposed to normoxia or hypoxia (8% O2). Twelve hours later, lung tissues were collected for histopathologic examination, and determination of interleukin (IL)-1β, IL-6, myeloperoxidase (MPO), malondialdehyde (MDA), total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, and Toll-like receptor (TLR)4 expression. Results: STZ-induced diabetes aggravated histopathological changes in the lung exposed to acute hypoxia. Hypoxia increased lung MDA level but decreased T-AOC and SOD activity. STZ-induced diabetic mice presented significant increases in MDA level and SOD activity in the lung. Moreover, no difference was found in the levels of both oxidant index (MDA) and anti-oxidant indexes (T-AOC and SOD) between "Hypoxia" group and "Hypoxia plus Diabetes" group. On the other hand, STZ-induced diabetic mice presented significant increases in pulmonary neutrophil infiltration, pro-inflammatory cytokines (IL-1β and IL-6) production, as well as TLR4 expression. Although acute hypoxia alone had no significant effect on pulmonary inflammatory markers, it profoundly increased STZ-diabetes-induced neutrophil infiltration, pro-inflammatory cytokine production, and TLR4 expression in lung tissues. Conclusions: STZ-induced diabetes may aggravate acute hypoxia-induced lung injury through enhancing pulmonary inflammatory responses.
Abstract Background Malignant melanoma (MM) generally presents as a primary neoplasm of the skin, and most MM cases of the respiratory system are metastatic. Primary MM of the lung (PMML) is quite rare, and its diagnosis is relatively difficult. Case presentation We report the case of a 57-year-old male patient with PMML who denied any history of tumours. His initial complaint was frequent coughs with bloody sputum for 4 days. Chest radiography demonstrated a high-density shadow in the lower lobe of the right lung, which was suspected to be a large space-occupying lesion on subsequent computed tomography (CT) and to be a hypermetabolic tumour by positron emission tomography–CT. To confirm the diagnosis, exploratory surgery was performed. Finally, we confirmed the diagnosis of PMML. Conclusions PMML is extremely rare and easily misdiagnosed as lung cancer. Because of its morphological and immunophenotypic variations, the diagnosis of PMML remains difficult. This case report discusses the diagnosis and case management of a patient while referring to the existing literature.
Objective To investigate the curative effect of itraconazole and the complex lotion of ketoconazole.Methods One hundred and forty six patients with Malassezia folliculitis conformed by fungus examination were collected and divided into two groups.The treatment group treated by itraconazole(200 mg/d,per oral for 7 days) and complex lotion of ketoconazole(external application,tid,4 weeks),and the control group only by complex lotion of ketoconazole(external application,tid,4 weeks).Results The curative ratio and effective rate were 69.47% and 95.79% in the treatment group,35.29% and 82.35% in the control group respectively(P0.01).Conclusions The itraconazole per oral combine with complex lotion of ketoconazole external application is safe and effective for Malassezia folliculitis,and it can be generalized.
Despite the fact that the biological processes of chiral compounds are enantioselective, the endocrine disruption activity and uptake of chiral contaminants with respect to enantioselectivity has so far received limited research. In this study, the estrogenic potential and uptake of the enantiomers of a newer pyrethroid insecticide, bifenthrin (BF), were investigated. Significant differences in estrogenic potential were observed between the two enantiomers in the in vitro human breast carcinoma MCF-7 cell proliferation assay (i.e., the E-SCREEN assay) and the in vivo aquatic vertebrate vitellogenin enzyme-linked immunosorbent assay (ELISA). In the E-SCREEN assay, the relative proliferative effect ratios of 1S-cis-BF and 1R-cis-BF were 74.2% and 20.9%, respectively, and the relative proliferative potency ratios were 10% and 1%, respectively. The cell proliferation induced by the two BF enantiomers may be through the classical estrogen response pathway via the estrogen receptor (ER), as the proliferation induced by the enantiomers could be completely blocked when combined with 10-6 mol/L of the ER antagonist ICI 182,780. Measurement of vitellogenin induction in Japanese medaka (Oryzias latipes) showed that, at an exposure level of 10 ng/mL, the response to 1S-cis-BF was about 123 times greater than that to the R enantiomer. Significant selectivity also occurred in the uptake of BF enantiomers in the liver and other tissues of J. medaka. These results together suggest that assessment of the environmental safety of chiral insecticides should consider enantioselectivity in acute and chronic ecotoxicities such as endocrine disruption.
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