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Asparagus cochinchinensis is a valuable traditional Chinese medicine that has anti-inflammatory ability and effectively regulates the dysbiosis within the body. Obesity is usually characterized by chronic low-grade inflammation with aberrant gut microbiota. However, the role of Asparagus cochinchinensis against obesity remains unknown. Therefore, a high-fat diet (HFD)-induced obese mouse model with or without aqueous extract from Asparagus cochinchinensis root (ACE) treatment was established herein to determine whether ACE alleviated obesity and its involved mechanisms. Our results showed that ACE administration significantly decreased the weight gain and relieved dyslipidemia induced by HFD Treatment of ACE also improved glucose tolerance and insulin resistance in obese animal model, and remarkably decreased inflammation and lipogenesis in the liver and adipose. Moreover, administration of ACE significantly reshaped the gut microbiota of obese mice. These findings together suggest that ACE has beneficial effect against HFD-induced obesity and will provide valuable insights for the therapeutic potential of ACE against obesity and may aid in strategy-making for weight loss.

Circular RNAs (circRNAs) have shown pivotal regulatory roles in multiple human ocular diseases, including age-related cataract (ARC). Here, we explored the role of circRNA mitogen-activated protein kinase kinase kinase 4 (circMAP3K4, hsa_circ_0078619) in ARC pathology and its associated mechanism. The expression of RNAs and proteins was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assay. Cell viability, senescence, proliferation, and apoptosis were analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, senescence-associated-β-galactosidase (SA-β-Gal) staining, 5-ethynyl-20-deoxyuridine (EdU) assay, and flow cytometry. The oxidative stress status of SRA01/04 cells was analyzed using the commercial kits. The interaction between microRNA-193a-3p (miR-193a-3p) and circMAP3K4 or phospholipase C delta 3 (PLCD3) was verified by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA-pull down assay. CircMAP3K4 was significantly down-regulated in ARC patients and H2O2-induced SRA01/04 cells. H2O2 treatment restrained the viability and proliferation and promoted the senescence, apoptosis, and oxidative stress of SRA01/04 cells, and circMAP3K4 overexpression protected SRA01/04 cells from H2O2-induced dysfunction. MiR-193a-3p was a direct target of circMAP3K4, and circMAP3K4 overexpression-mediated protective effects in H2O2-induced SRA01/04 cells were largely reversed by the accumulation of miR-193a-3p. MiR-193a-3p interacted with the 3’ untranslated region (3’UTR) of PLCD3, and PLCD3 knockdown largely overturned miR-193a-3p silencing-induced protective effects in H2O2-induced SRA01/04 cells. CircMAP3K4 up-regulated the expression of PLCD3 via sponging miR-193a-3p in SRA01/04 cells. In conclusion, circMAP3K4 protected SRA01/04 cells from H2O2-induced dysfunction in ARC through mediating miR-193a-3p/PLCD3 axis.

Additional file 1: Table S1. Primer sequences of target genes.

Bin Han1 ,* Zijie Pei2 ,* Lei Shi,3 Qian Wang,4 Chen Li,1 Boyuan Zhang,1 Xuan Su,1 Ning Zhang,1 Lixiao Zhou,1 Bo Zhao,5 Yujie Niu,3,6 Rong Zhang1,6 1Department of Toxicology, Hebei Medical University, Shijiazhuang 050017, Hebei, People’s Republic of China; 2Department of Pathology, Medical School, China Three Gorge University, Yichang 443002, People’s Republic of China; 3Occupational Health and Environmental Health, Hebei Medical University, Shijiazhuang 050017, Hebei, People’s Republic of China; 4Experimental Center, Hebei Medical University, Shijiazhuang 050017, Hebei, People’s Republic of China; 5Department of Laboratory Diagnosis, Hebei Medical University, Shijiazhuang 050017, Hebei, People’s Republic of China; 6Hebei Key Laboratory of Environment and Human Health, Hebei Medical University, Shijiazhuang 050017, Hebei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rong ZhangDepartment of Toxicology, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, Hebei 050017, People’s Republic of ChinaFax +86-311-86265605Email rongzhang@hebmu.edu.cnIntroduction: Because of the increased production and application of manufactured Nano-TiO2 in the past several years, it is important to investigate its potential hazards. TiO2 is classified by IARC as a possible human carcinogen; however, the potential mechanism of carcinogenesis has not been studied clearly. The present study aimed to investigate the mechanism of DNA damage in rat lung and extra-pulmonary organs caused by TiO2nanoparticles.Methods: In the present study, SD rats were exposed to Nano-TiO2 by intratracheal injection at a dose of 0, 0.2, or 1 g/kg body weight. The titanium levels in tissues were detected by ICP-MS. Western blot was used to detect the protein expression levels. The DNA damage and oxidative stress were detected by comet assay and ROS, MDA, SOD, and GSH-Px levels, respectively.Results: The titanium levels of the 1 g/kg group on day-3 and day-7 were significantly increased in liver and kidney as well as significantly decreased in lung compared to day-1. ROS and MDA levels were statistically increased, whereas SOD and GSH-Px levels were statistically decreased in tissues of rats in dose-dependent manners after Nano-TiO2 treatment. PI3K, p-AKT/AKT, and p-FOXO3a/FOXO3a in lung, liver, and kidney activated in dose-dependent manners. The levels of DNA damage in liver, kidney, and lung in each Nano-TiO2 treatment group were significantly increased and could not recover within 7 days. GADD45α, ChK2, and XRCC1 in liver, kidney, and lung of rats exposed to Nano-TiO2 statistically increased, which triggered DNA repair.Conclusion: This work demonstrated that Ti could deposit in lung and enter extra-pulmonary organs of rats and cause oxidative stress, then trigger DNA damage through activating the PI3K-AKT-FOXO3a pathway and then promoting GADD45α, ChK2, and XRCC1 to process the DNA repair.Keywords: Nano-TiO2, DNA damage, PI3K/AKT/FOXO3a signaling pathway, DNA repair, GADD45α/ChK2/XRCC1 signaling pathway

Chen Chu,1,* Lixiao Zhou,1,* Heran Xie,1,* Zijie Pei,2 Mengyue Zhang,1 Mengqi Wu,1 Shaohui Zhang,3 Luqi Wang,4 Chunfang Zhao,5 Lei Shi,6,7 Ning Zhang,1 Yujie Niu,6,7 Yuxin Zheng,8 Rong Zhang1,7,*1Department of Toxicology, Hebei Medical University, Shijiazhuang 050017, People’s Republic of China; 2Department of Pathology, Medical School, China Three Gorge University, Yichang, 443002, People’s Republic of China; 3Department of Experimental Center, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, People’s Republic of China; 4Riodiology, The Third Hospital of Hebei Medical University, Shijiazhuang 050051, People’s Republic of China; 5Histology and Embryology, Hebei Medical University, Shijiazhuang 050017, People’s Republic of China; 6Occupational Health and Environmental Health, Hebei Medical University, Shijiazhuang 050017, People’s Republic of China; 7Hebei Key Laboratory of Environment and Human Health, Hebei Medical University, Shijiazhuang, People’s Republic of China; 8Department of Toxicology, Public Health College, Qingdao University, Qingdao, 266000, People’s Republic of China*These authors contributed equally to this workBackground: Recent years, there occurs heavy haze pollution in northern China during wintertime. The potential influence of airborne particulate matter (PM) on human health attracts great concern. The fuel-derived PM in the inhalable size range is dominated by aggregates of nanoparticles of Carbon black (CB). However, there are still lack of evidences especially regarding long-term exposure to explain the chronic effects of nanoscaled CB and the relative mechanism.Purpose: The objective of this study was to identify the potential mechanism of chronic effects of nanoscale CB. The systemic toxicity, immune suppression or activity and local toxicity were evaluated.Methods: 32 rats were divided into 2 groups: 30 mg/m3 CB exposure (nose only, 90 d, 6h/d) and control (clean air). Half of rats were scarified after exposure and another half of rats recovered for 14 days. Eight rats in each group were executed the lung function tests using a ventilated bias flow whole body plethysmograph (WBP). SDS-PAGE protocol was used to detect the deposition and retention of CB in lung of rats. HE staining was used to observe the changes of histopathology. Cell apoptosis was examined by TUNEL assay or flow cytometry. The levels of IL-6, IL-8, IL-17 and TNF-α in serum and lung tissue were evaluated with commercially available ELISA kit. The peripheral blood cell counts were detected by Auto 5-diff hematology analyzer.Results: The lung burden of CB was 16 mg in lung of rats after a 90-day exposure by MPPD. Fourteen percentages of the amount of CB accumulated at the end of the exposure period was cleared from the lung during the 14 dys recovery period. The lung function was significantly decreased and could not recover after a short time recovery. The fibroblasts and granuloma formation were found in lung. The levels of apoptosis and DNA damages were significantly increased in lung cells after CB inhalation. The cytokines levels in lung but not in serum were significantly increased in CB exposure group. The cell counts of WBC, monocytes and neutrophils had 1.72, 3.13, and 2.73-fold increases after CB exposure, respectively. The percentages of CD4+ lymphocytes and the rates of CD4+/CD8+ were statistically increased after CB exposure. The stimulation indexes of the peripheral blood lymphocytes were significantly decreased after CB exposure. In the CB exposure group, the disrupted histomorphology of thymus and spleen were found as well as the early apoptotic thymocytes had a 2.36-fold increase.Conclusion: CB induced the localized or direct toxicity and systemic immune toxicity. The direct and systemic immune responses had a combined effect on the lung damages caused by CB.Keywords: nanoscale CB particles, pulmonary toxicology, immune toxicity, chronic toxicity, inhalation