ACRYLONITRILE HAS DISTINCT HORMETIC EFFECTS ON ACETYLCHOLINESTERASE ACTIVITY IN MOUSE BRAIN AND BLOOD THAT ARE MODULATED BY ETHANOL

Acrylonitrile(AN) is a neurotoxin both in animals and humans, but its effects on acetylcholinesterase (AChE) activity remain controversial. This study aimed to determine the dose-response effects of AN on AChE activity and the modulatory role of ethanol pretreatment. A total of 144 Kunming mice were randomly divided into 18 groups: nine groups received 5% ethanol in their drinking water, and the remaining nine groups received regular tap water. One week later, both the ethanol and tap water only groups were given an intraperitoneal injection of AN at the following doses: 0 (control), 0.156, 0.3125, 0.625, 1.25, 2.5, 5, 10 or 20 mg AN/kg body weight. AChE activity was determined on whole blood and brain 24 h later. Blood AChE activity was higher in AN-injected mice than in controls at all doses. AChE activity in blood increased in a dose-dependent manner, peaking at 0.156 mg/kg, after which a gradual decrease ensued, displaying a β-typed dose-response relationship. In contrast, brain AChE activity, following a single AN injection, was consistently lower than in control mice, and continued to fall up to a dose of 0.313 mg/kg, and thereafter increased gradually with higher doses. Mice receiving a 20 mg/kg dose of AN exhibited AChE brain activity indistinguishable from that of control mice, demonstrating a typical U-typed dose-response relationship. The activity of AChE in the blood and brain of the AN + ethanol-treated groups displayed a shift to the right, and the magnitude of the decrease in AChE activity induced by AN was attenuated relative to the AN-only group. These results suggest that AN affects AChE activity in both mouse blood and brain in a hormetic manner. Pretreatment with ethanol modifies the effect of AN on AChE, indicating that parent AN has a more prominent role than its metabolites in modulating enzyme activity

Interleukin-10 Inhibits Bone Resorption: A Potential Therapeutic Strategy in Periodontitis and Other Bone Loss Diseases

Periodontitis and other bone loss diseases, decreasing bone volume and strength, have a significant impact on millions of people with the risk of tooth loss and bone fracture. The integrity and strength of bone are maintained through the balance between bone resorption and bone formation by osteoclasts and osteoblasts, respectively, so the loss of bone results from the disruption of such balance due to increased resorption or/and decreased formation of bone. The goal of therapies for diseases of bone loss is to reduce bone loss, improve bone formation, and then keep healthy bone density. Current therapies have mostly relied on longterm medication, exercise, anti-inflammatory therapies, and changing of the life style. However there are some limitations for some patients in the effective treatments for bone loss diseases because of the complexity of bone loss. Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine, and recent studies have indicated that IL-10 can contribute to the maintenance of bone mass through inhibition of osteoclastic bone resorption and regulation of osteoblastic bone formation. This paper will provide a brief overview of the role of IL-10 in bone loss diseases and discuss the possibility of IL-10 adoption in therapy of bone loss diseases therapy

Engineered neutrophil-derived exosome-like vesicles for targeted cancer therapy

Neutrophils are the most abundant innate immune cells in human circulation; however, their derived exosomes have been rarely studied for tumor treatment. Here, we reported that exosomes from neutrophils (N-Ex) induce tumor cell apoptosis by delivering cytotoxic proteins and activating caspase signaling pathway. In addition, we decorated N-Ex with superparamagnetic iron oxide nanoparticles ( SPIONs) to achieve higher tumor-targeting therapeutic effect. We further fabricated exosome-like nanovesicles from neutrophils (NNVs) at high yield. Compared with liposome-loaded doxorubicin (DOX) and natural NNVs, DOX-loaded NNVs show an improved inhibition of tumor cell proliferation. Moreover, DOX-loaded, SPION-decorated NNVs selectively accumulate at the tumor sites under an external magnetic field, effectively restraining tumor growth and extensively prolonging the survival rate in mice. Overall, a simple and effective method to engineer N-Ex and NNVs at clinical applicable scale was developed, which enables the efficient and safe drug delivery for targeted and combined tumor therapy.Peer reviewe

Human Umbilical Cord MSC-Derived Exosomes Suppress the Development of CCl 4

Mesenchymal stem cells (MSCs) have been increasingly applied into clinical therapy. Exosomes are small (30–100 nm in diameter) membrane vesicles released by different cell types and possess the similar functions with their derived cells. Human umbilical cord MSC-derived exosomes (hucMSC-Ex) play important roles in liver repair. However, the effects and mechanisms of hucMSC-Ex on liver injury development remain elusive. Mouse models of acute and chronic liver injury and liver tumor were induced by carbon tetrachloride (CCl4) injection, followed by administration of hucMSC-Ex via the tail vein. Alleviation of liver injury by hucMSC-Ex was determined. We further explored the production of oxidative stress and apoptosis in the development of liver injury and compared the antioxidant effects of hucMSC-Ex with frequently used hepatic protectant, bifendate (DDB) in liver injury. hucMSC-Ex alleviated CCl4-induced acute liver injury and liver fibrosis and restrained the growth of liver tumors. Decreased oxidative stress and apoptosis were found in hucMSC-Ex-treated mouse models and liver cells. Compared to bifendate (DDB) treatment, hucMSC-Ex presented more distinct antioxidant and hepatoprotective effects. hucMSC-Ex may suppress CCl4-induced liver injury development via antioxidant potentials and could be a more effective antioxidant than DDB in CCl4-induced liver tumor development

Engineered neutrophil-derived exosome-like vesicles for targeted cancer therapy

Neutrophils are the most abundant innate immune cells in human circulation; however, their derived exosomes have been rarely studied for tumor treatment. Here, we reported that exosomes from neutrophils (N-Ex) induce tumor cell apoptosis by delivering cytotoxic proteins and activating caspase signaling pathway. In addition, we decorated N-Ex with superparamagnetic iron oxide nanoparticles ( SPIONs) to achieve higher tumor-targeting therapeutic effect. We further fabricated exosome-like nanovesicles from neutrophils (NNVs) at high yield. Compared with liposome-loaded doxorubicin (DOX) and natural NNVs, DOX-loaded NNVs show an improved inhibition of tumor cell proliferation. Moreover, DOX-loaded, SPION-decorated NNVs selectively accumulate at the tumor sites under an external magnetic field, effectively restraining tumor growth and extensively prolonging the survival rate in mice. Overall, a simple and effective method to engineer N-Ex and NNVs at clinical applicable scale was developed, which enables the efficient and safe drug delivery for targeted and combined tumor therapy

How Rural Residents Access News and Its Influence on Social Trust: Based on the Data of the China Family Panel Studies

The Internet is bound to profoundly impact public social trust. This study empirically investigated the impact of rural residents’ access to information on social trust based on the tracking survey data of Chinese households, which covered a sample size of 12,042 rural residents from 25 provinces and cities. We found that: (1) The modes of access to information had a significant positive impact on rural residents’ social trust. Specifically, as the time spent using the Internet or television for news increased, rural residents’ trust in others also increased, which is known as the “media propaganda and mobilization effect.” The use of the Internet had a higher impact coefficient than the use of TV. (2) A substitution effect was detected between the ways rural residents accessed news via the Internet and television. (3) Rural residents used the Internet less frequently than urban residents to obtain news but were more influenced by the Internet regarding social trust. (4) The information-disadvantaged groups among rural residents were mainly women, old people, and people with low education. The government should attach great importance to the influence of media on social trust and needs to actively improve the digital literacy of disadvantaged groups of rural residents and combat and eliminate the “digital divide” to enhance rural residents’ social trust

Effect of Internet Use to Obtain News on Rural Residents’ Satisfaction with the Social Environment: Evidence from China

The deterioration of satisfaction with the social environment in rural areas recently has become a major issue in the rural governance of China. This study examined if using the Internet to obtain news would affect rural residents’ satisfaction with their social environment. It used data from the China Family Panel Studies to determine the influencing factors of rural residents’ satisfaction with their social environment in the Internet era. The research found that: (1) The Internet has become the main medium for rural residents to obtain news, which affects rural residents’ satisfaction with the social environment. Specifically, as the number of days rural residents use the Internet to obtain weekly news increased, their satisfaction with China’s social environment worsened. Internet use also affected satisfaction with the social environment more than traditional media, such as TV. (2) The influencing factors of rural residents’ social environment satisfaction were heterogeneous among groups with different characteristics, with the phenomenon of the “digital divide” emerging. Women, middle-aged and older adults, and illiterate/semi-illiterate people used the Internet to obtain news less frequently. Based on the above research conclusions, governments should focus on and be vigilant against false public opinions disseminated online as well as improve the digital literacy of vulnerable rural groups

The Impact of Non-Agricultural Employment on Farmland Transfer and Investment in Agricultural Assets: Evidence from China

This study aimed to determine the impact of non-agricultural employment of peasants on their farmland transfer and investment in agricultural assets by using theoretical models and empirical analysis. The Heckman two-step approach and ordinary least squares method of econometric estimation were used to analyze the questionnaire survey data collected from Jiangxi Province in China. Non-agricultural employment led to reduction of investment in agricultural assets and renting of land. The remittance flows from non-farm income were mainly used to improve the current quality of life, particularly housing condition, rather than to invest in agricultural assets. Migration of laborers caused farmers to rent out farmland, but the inflow of remittances from non-farm income, which increased the capital stock, did not increase the renting in of farmland