MicroRNA-145 plays a role in mitochondrial dysfunction in alveolar epithelial cells in lipopolysaccharide-induced acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) causes substantial mortalities. Alveolar epithelium is one of the main sites of cell injuries in ARDS. As an important kind of microRNAs (miRNAs), microRNA-145 (miR-145) has been studied in various diseases, while its role in ARDS has not been investigated. METHODS: Lipopolysaccharide (LPS) was intratracheally instilled to establish a rat ARDS model. Cytokines from bronchoalveolar lavage fluid (BALF) were measured using rat tumor necrosis factor-α and interleukin-6 enzyme-linked immunosorbent assay kits (R&D Systems), and the pathological structures were evaluated using hematoxylin and eosin (H&E) staining and transmission electron microscope; the lung miR-145 messenger RNA (mRNA) was detected using quantitative polymerase chain reaction. Bioinformatics focused on the target genes and possible pathways of gene regulation. RESULTS: A rat model of LPS-induced ARDS was successfully established. The miR-145 was down-regulated in the LPS-induced ARDS lung, and mitochondrial dysfunction was observed in alveolar epithelial cells, most obviously at 72 hours after LPS. TargetScan and miRDB databases were used to predict the target genes of miR-145. A total of 428 overlapping genes were identified, seven genes were associated with mitochondrial function, and Ogt, Camk2d, Slc8a3, and Slc25a25 were verified. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched in the mitogen-activated protein kinase (MAPK) signaling pathway, and Gene Ontology (GO) biological process was mainly enriched in signal transduction and transcription regulation. CONCLUSIONS: The miR-145 is down-regulated in LPS-induced ARDS, and affects its downstream genes targeting mitochondrial functions.

Gut microbiota modulation and anti-inflammatory properties of Xuanbai Chengqi decoction in septic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Xuanbai Chengqi decoction (XBCQ), a traditional Chinese medicine formulation, was reported to have a protective role in a variety of pulmonary infection diseases. However, its mechanism remains uncertain. In the current study, we investigated the potential mechanism of XBCQ, its therapeutic effects on organ injuries induced by sepsis and gut microbiota modulation. MATERIAL AND METHODS: 80 Male Sprague Dawley rats were performed cecal ligation and puncture (CLP) for sepsis model and 60 of them were treated with different doses of XBCQ (3.78, 7.56, 15.12 g/Kg, 20 rats per group) twice per day. After the most valid dose was determined, another 40 rats were divided randomly into four groups: sham group, sham + XBCQ group, sepsis group, sepsis + XBCQ group. The sepsis + XBCQ group was treated with XBCQ by intragastric administration and then twice per day. Feces of the rats were collected and the gut microbiota constituents were analyzed by 16S rDNA sequencing. Histological changes were observed by H&E staining. Occludin content in the colon was determined by immunohistochemical analysis. The concentrations of cytokines were determined by enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: The survival rate of septic rats was increased significantly at the dose of 7.56 g/Kg from 50% to 80% at 72 h. The gut microbiota richness and composition were disturbed in septic rats. XBCQ altered the gut microbiota, involving alpha diversity changes, significantly reducing the relative abundance of Bacteroidaceae and ClostridiumXI and increasing that of Firmicutes and Actinobacteria. Furthermore, the relative abundances of Lactobacillus, Butyricicoccus and Bifidobacterium were increased by XBCQ. Moreover, the gut barrier dysfunction was improved by XBCQ through restoring the impaired tight conjunction protein Occludin. The concentration of diamine oxidase was decreased, while the D-lactate level was elevated. Meanwhile, the level of myeloperoxidase (MPO) in the lung tissue of the XBCQ-treated group was reduced. Lung injury was also alleviated by decreased levels of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1ß) and interleukin 10 (IL-10) in bronchoalveolar lavage fluids (BALFs). The relative abundance of potential microbial biomarkers in four groups significantly correlated with the concentration of inflammatory factors in BALFs. CONCLUSIONS: Our results suggested that XBCQ had a protective role against sepsis by modulating the gut microbiota, restoring the intestinal epithelial barrier and decreasing inflammatory responses.

Hardness-dependent water quality criteria for cadmium and an ecological risk assessment of the Shaying River Basin, China.

Hardness is one important water quality parameter that influences the toxicity of cadmium. Several studies have derived water quality criteria (WQC) for cadmium, but most of these studies did not consider environmental factors. Moreover, few studies considered environmental factors when carrying out ecological risk assessments (ERA) based on environmental factors. In this research, six native aquatic organisms in the Shaying River were adopted to conduct toxicity tests for cadmium. By combining published toxicity data for cadmium with hardness values and toxicity data from this study, hardness-dependent WQC were established. When normalized to a hardness of 100 mg/L CaCO3, the criterion maximum concentration (CMC) of 6.46 µg/L and criterion continuous concentration (CCC) of 1.49 µg/L in the Shaying River Basin were derived according to the USEPA guidelines. The acute predicted no effect concentrations (PNECs) derived by species sensitivity distribution (SSD) methods based on log-logistic, log-normal and Burr Type III models were 1.03, 2.41 and 1.66 µg/L, respectively. Recommended WQC values finally expressed as a function of hardness: (1) CMC=(1.136672-0.041838 × lnH) × e0.9969×lnH-2.6676; and (2) CCC=(1.101672-0.041838 × lnH) × e1.0083×lnH-6.1156. In addition, three tiers of ERA of cadmium in surface waters were conducted based on hardness obtained during different seasons in the Shaying River using the hazard quotient (HQ), the margin of safety (MOS10), and the joint probability (JPC) methods. In tiered 1, 2, and 3 ERA, cadmium exposure concentrations were standardized to a hardness of 100 mg/L. The three levels of the ERA method in the tiered framework gave consistent results: the ecological risks of cadmium in the Shaying River Basin were at acceptable levels. The present study provides a reference for the derivation of WQC and risk assessment of pollution affected by differences in aquatic species and water quality factors such as hardness.

Traditional Chinese medicine targeting cancer stem cells as an alternative treatment for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a prevalent and highly malignant cancer throughout the world. Effective treatment of this disease is impeded by the high rate of metastasis, recurrence, and chemoresistance. Recent studies have revealed the close relationship between the malignant phenotype of HCC and cancer stem cells (CSCs). Therefore, CSC-targeted therapy is considered a promising strategy to eradicate HCC. Traditional Chinese medicine (TCM) can be effective in preventing recurrence and metastasis of some advanced HCC. A growing amount of literature has discovered that extracts or compounds derived from TCM exert an anti-CSC effect. This review introduces some formulas and chemical compounds derived from TCMs that have been reported to inhibit CSCs of HCC; these TCM-related drugs may help to provide an alternative approach to help manage cancers, especially for HCC which has a great potential of metastasis, recurrence, and chemoresistance.

Pulmonary-Affinity Paclitaxel Polymer Micelles in Response to Biological Functions of Ambroxol Enhance Therapeutic Effect on Lung Cancer.

PURPOSE: Cancer chemotherapy effect has been largely limited by cell autophagy and little drug accumulation at the action sites. Herein, we designed an intelligent strategy involving paclitaxel (PTX) polymer micelles in response to biological functions of ambroxol (Ax). The amphiphilic polymers polyethyleneglycol-polylactic acid (PEG-PLA) and Pluronic P105 were selected as nanocarriers to encapsulate PTX to form into lung affinity PEG-PLA/P105/PTX micelles. Ax which can up-regulate the secretion of pulmonary surfactant (PS) and inhibit autophagy was hired to change the microenvironment of the lung, thereby promoting the lung accumulation and increasing cell-killing sensitivity of the micelles. METHODS: The physical and chemical properties of the micelles were characterized including size, morphology, critical micellar concentration (CMC) and in vitro drug release behavior. The therapeutic effects of the combination regimen were characterized both in vitro and in vivo including study on Ax in promoting the secretion of pulmonary surfactant, in vitro cytotoxicity, cellular uptake, Western blotting, in vivo biodistribution, in vivo pharmacokinetics and in vivo antitumor efficacy. RESULTS: The PEG-PLA/P105/PTX micelles showed a particle size of 16.7 ± 0.5 nm, a nearly round shape, small CMC and sustained drug release property. Moreover, the in vitro results indicated that Ax could increase PS and LC3 protein secretion and enhance the cytotoxicity of PEG-PLA/P105/PTX micelles toward A549 cells. The in vivo results indicated that the combination therapeutic regimen could promote the micelles to distribute in lung and enhance the therapeutic effect on lung cancer. CONCLUSION: This multifunctional approach of modulating the tumor microenvironment to enhance drug transportation and cell-killing sensitivity in the action sites might offer a new avenue for effective lung cancer treatment.

Deriving water quality criteria for China for the organophosphorus pesticides dichlorvos and malathion.

Organophosphorus pesticides are effective, cheap, and used extensively but can harm aquatic organism and human health. Here, water quality criteria (WQCs) for dichlorvos (DDVP) and malathion (MAL) were derived. Nine aquatic organisms native to China were used in toxicity tests. Published toxicity data for aquatic organisms native and non-native to China were also analyzed. DDVP and MAL WQCs were derived using (log-normal model) species sensitivity distributions. Species sensitivity distribution curves indicated native and non-native species have different sensitivities to DDVP. The sensitivities of native and non-native species to MAL were not different because non-native species data for fewer than eight genera were available, so further research is required. The results indicated that native species need to be considered when deriving WQCs. The criteria maximum concentration (CMC) and criteria continuous concentration (CCC) were 1.33 and 0.132 µg/L, respectively, for DDVP, and 0.100 and 0.008 µg/L, respectively, for MAL. The CMCs for DDVP and MAL derived using ETX 2.0 software and species sensitivity ranks were different from the CMCs obtained using the SSD method because of parameter uncertainties. The DDVP and MAL WQCs were significantly lower than Chinese surface water quality standard thresholds. The results provide basic data for revising these thresholds.